URINARY TRACT INFECTIONS

COMMON AND UNCOMMON KIDNEY DISEASES

JASSIN M. JOURIA, MD

Dr. Jassin M. Jouria is a practicing Emergency Medicine physician, professor of academic medicine, and medical author. He graduated from Ross University School of Medicine and has completed his clinical clerkship training in various teaching hospitals throughout New York, including King’s County Hospital Center and Brookdale Medical Center, among others. Dr. Jouria has passed all USMLE medical board exams, and has served as a test prep tutor and instructor for Kaplan. He has developed several medical courses and curricula for a variety of educational institutions. Dr. Jouria has also served on multiple levels in the academic field including faculty member and Department Chair. Dr. Jouria continues to serve as a Subject Matter Expert for several continuing education organizations covering multiple basic medical sciences. He has also developed several continuing medical education courses covering various topics in clinical medicine. Recently, Dr. Jouria has been contracted by the University of Miami/Jackson Memorial Hospital’s Department of Surgery to develop an e-module training series for trauma patient management. Dr. Jouria is currently authoring an academic textbook on Human Anatomy & Physiology.

Abstract

The kidneys serve as the body’s filtration system. Waste and excess fluids are filtered out of the blood and excreted through the . When the kidneys are not working as they should, fluid, electrolytes, and wastes can build up to dangerous levels in the body, even to the point of being fatal. Because kidney disease often does not create noticeable symptoms until the disease is advanced, it is important that medical clinicians are able to recognize the symptoms as soon as they are present and take immediate steps to resolve or mitigate the impact.

1 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Policy Statement

This activity has been planned and implemented in accordance with the policies of NurseCe4Less.com and the continuing nursing education requirements of the American Nurses Credentialing Center's Commission on Accreditation for registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity, transparency, and best practice in clinical education for all continuing nursing education (CNE) activities.

Continuing Education Credit Designation

This educational activity is credited for 3 hours. Nurses may only claim credit commensurate with the credit awarded for completion of this course activity.

Pharmacology hours include .5 hours (30 minutes).

Statement of Learning Need

Clinicians need to understand the symptoms of the varied stages of kidney disease and the types of blood or urine laboratory testing that are available to detect abnormalities indicating early stages of kidney disease in order to take immediate steps to resolve or mitigate serious health outcomes.

Course Purpose

To provide health clinicians with knowledge about the varied types of kidney disease, as well as diagnostic methods to achieve early recognition of and to initiate and effectively treat kidney disease.

2 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Target Audience

Advanced Practice Registered Nurses and Registered Nurses

(Interdisciplinary Health Team Members, including Vocational Nurses and Medical Assistants may obtain a Certificate of Completion)

Course Author & Planning Team Conflict of Interest Disclosures

Jassin M. Jouria, MD, William S. Cook, PhD, Douglas Lawrence, MA

Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures

Acknowledgement of Commercial Support

There is no commercial support for this course.

Please take time to complete a self-assessment of knowledge, on page 4, sample questions before reading the article.

Opportunity to complete a self-assessment of knowledge learned will be provided at the end of the course.

3 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 1. The most common organism causing is ______, which is responsible for up to 80% of kidney and urinary infections.

a. Klebsiella b. Enterococcus c. Staphylococcus saprophyticus d. Escherichia coli (E. coli)

2. True or False: Kidney stones do not increase the development of urinary tract infections because the mineral and salt deposits that usually compose kidney stones inhibit the growth of infections.

a. True b. False

3. Urinary tract infections are more common in women than in men because

a. the length of the is shorter in women. b. the hormone estrogen makes women more susceptible. c. of gastrointestinal tract bacteria. d. of the higher incidence of epispadias in women.

4. When a patient presents with symptoms of pyelonephritis (kidney infection) the clinician will perform two common laboratory tests, which are examining a urine specimen for red and white blood cell counts and

a. a urine culture. b. a helical (spiral) computed tomography. c. a . d. a urethral swab for STD testing.

5. If a clinician suspects a patient has pyelonephritis,

a. antibiotics are started after laboratory test results are reviewed. b. antibiotics are started immediately only if the patient may have contracted the infection in the hospital. c. antibiotics are started immediately only if the patient’s immune system is impaired. d. antibiotics are started immediately.

4 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Introduction

A urinary tract infection can develop in any part of the , including the urethra, bladder, , or kidneys. A person’s body is able to defend against a urinary tract infection if urine is able to flow normally from the kidneys, through the ureters to the bladder. This allows bacteria that enters the urinary system to be flushed out when a person urinates. Bacteria are able to remain in the urinary tract and cause infection when there is an obstruction to the flow of urine, or if urine flow is slowed. The classification of urinary tract infections is based on clinical assessment and existing research. While clinical findings based on urine microscopy and culture tests are the standard for diagnosing a urinary tract infection, the detection of bacteria in sterile (uncontaminated) urine samples and of bacteria that is difficult to culture poses challenges to prior treatment. While future research and efforts are underway to develop improved methods to identify causes of urinary tract infections for effective treatment, existing proven methods to test and diagnose infections in urologic patients are the primary focus.

Etiology And Basic Treatment Strategies For UTI

Urinary tract infections may be caused by bacteria invading the urine, which is normally a sterile body fluid. Bacteria most commonly gain access to the urine through the urethra, which can be exposed to bacteria from outside of the body. Common sources of bacteria that enter the urinary system are from the skin, anus, or vagina. Kidney infection, pyelonephritis, may be facilitated by the introduction of bacteria into the urinary system, from these outside sources, through the urethra.42 Because of the shorter length of the urethra in women, a urinary tract infection (UTI) is more common in women compared to men.

5 nursece4less.com nursece4less.com nursece4less.com nursece4less.com There are some factors that may predispose people to urinary tract infections. Sexual intercourse may increase the risk of urinary tract infections in women. Pregnant women may also be at higher risk for developing urinary tract infections. This may be caused by slower transit of urine from the ureters into the bladder because of increased pressure on the ureters from the enlarged uterus. Approximately 10% of pregnant women may develop urinary tract infections during their pregnancy.43

Kidney stones are another factor that may increase the likelihood of urinary tract infection. Stones can cause partial or complete obstruction to the flow of urine from the kidneys and ureters. This obstruction may act as a focus of infection in the urinary system, leading to urinary tract infections. Bladder catheters (i.e., Foley catheters) are sometimes placed into the bladder in order to aid the outflow of urine from the bladder. These are used in many settings, for example, paralysis with nerve damage to the bladder causing accumulation of urine without adequate emptying, bladder obstruction from an enlarged , or immobilized or hospitalized patients who are not able to independently urinate. These catheters may act as a vehicle for bacteria to gain access to the urine inside the bladder causing urinary infections. In children some risk factors include female gender, an uncircumcised male, or a structural abnormality of the urinary system.44

The most common bacteria causing urinary tract infection are those that are normally seen in the vagina, gastrointestinal tract, or skin. By far, the most common organism causing urinary tract infection is Escherichia coli (E. coli), which is responsible for up to 80% of kidney and urinary infections. Other common bacteria include Klebsiella, Proteus, Pseudomonas, Enterococcus, and Staphylococcus saprophyticus.45

6 nursece4less.com nursece4less.com nursece4less.com nursece4less.com The diagnosis of a urinary tract infection is based on testing of a urinalysis, urine culture and, if needed, imaging tests. Typical symptoms of kidney infection or pyelonephritis lead physicians to do two common laboratory tests to determine whether the kidneys are infected; examining a urine specimen under a microscope to count the number of red and white blood cells and bacteria and a urine culture, in which bacteria from a urine sample are grown in a laboratory setting to identify the numbers and type of bacteria. Blood tests may be done to check for elevated white blood cell levels (suggesting infection), bacteria in the blood, or kidney damage. Imaging tests are done in people who have intense back pain that is typical of and who do not respond to antibiotic treatment within 72 hours, have symptoms return shortly after completion of antibiotic treatment, have long-standing or recurring pyelonephritis, have blood test results indicate kidney damage, and are performed in men (because they rarely develop pyelonephritis). Ultrasonography or helical (spiral) computed tomography (CT) studies done in these situations may reveal kidney stones, structural abnormalities, or other causes of urinary obstruction.46

Treatment of a urinary tract infection includes use of antibiotics and occasionally surgery (to correct abnormality of the urinary tract). Antibiotics are started as soon as the medical clinician suspects pyelonephritis and samples have been taken for laboratory tests. The choice of drug or its dosage may be modified based on the laboratory test results (including culture results), illness severity, and whether the infection started in the hospital, where bacteria tend to be more resistant to antibiotics. Other factors that can alter the choice or dosage of drug treatment include whether the person's immune system is impaired and whether the person has a urinary tract abnormality (such as an obstruction).47

7 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Outpatient treatment with antibiotics given by mouth is usually successful if the person has no nausea or vomiting, signs of dehydration, other disorders that weaken the immune system, such as certain cancers, diabetes mellitus, or AIDS, signs of very severe infection, such as low blood pressure or confusion, and pain that is controlled with drugs taken by mouth.48 Otherwise, the person is usually treated initially in the hospital.

If hospitalization is needed and the person needs antibiotics, the antibiotics are given intravenously for 1 or 2 days, then they can usually be given by mouth. Antibiotic treatment of pyelonephritis is given for 5 to 14 days so that infection will not recur. However, antibiotic therapy may continue for up to 6 weeks for men in whom the infection is due to , which is more difficult to eradicate. A final urine sample is usually taken shortly after the antibiotic treatment is finished to make sure the infection has been eradicated.39,50

Surgery is necessary only occasionally if tests show that something is chronically blocking the urinary tract, such as a structural abnormality or a particularly large stone. Removal of the infected kidney may be necessary for people with chronic pyelonephritis who are about to undergo kidney transplantation since a patient’s kidneys generally are not taken out when a donor kidney is transplanted. Spread of infection to the transplanted kidney is particularly risky because the person takes immunosuppressant drugs, which prevent rejection of the transplanted kidney but also weaken the body's ability to fight infection.51

People who have frequent episodes of a urinary tract infection or whose infection returns after antibiotic treatment is finished may be advised to take a small dose of antibiotic on a long-term basis. The ideal duration of such

8 nursece4less.com nursece4less.com nursece4less.com nursece4less.com therapy is unknown. If the infection returns, preventive therapy may be continued indefinitely. If a woman of child-bearing age is taking an antibiotic, she should avoid pregnancy or talk to her medical clinician about whether to use an antibiotic that is safe during pregnancy in case she becomes pregnant.52

Bacterial Urinary Tract Infections

Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, , lower abdominal pain, and flank pain. Systemic symptoms and even sepsis may occur with kidney infection. Diagnosis is based on analysis and culture of urine. Treatment is with antibiotics and removal of any urinary tract catheters and obstructions. Among adults aged 20 to 50 years, UTIs are about 50-fold more common in women. In women in this age group, most UTIs are cystitis or pyelonephritis. In men of the same age, most UTIs are or prostatitis. The incidence of UTI increases in patients great than 50 years of age, but the female:male ratio decreases because of the increasing frequency of prostate enlargement and instrumentation in men.53

The urinary tract, from the kidneys to the urethral meatus, is normally sterile and resistant to bacterial colonization despite frequent contamination of the distal urethra with colonic bacteria. The major defense against UTI is complete emptying of the bladder during urination. Other mechanisms that maintain the tract’s sterility include urine acidity, vesicoureteral valve, and various immunologic and mucosal barriers.51

About 95% of UTIs occur when bacteria ascend the urethra to the bladder and, in the case of pyelonephritis, ascend the to the kidney. The

9 nursece4less.com nursece4less.com nursece4less.com nursece4less.com remainder of UTIs are hematogenous. Systemic infection can result from UTI, particularly in the elderly. About 6.5% of cases of hospital- acquired bacteremia are attributable to UTI.46

Uncomplicated UTI is usually considered to be cystitis or pyelonephritis that occurs in premenopausal adult women with no structural or functional abnormality of the urinary tract and who are not pregnant and have no significant comorbidity that could lead to more serious outcomes. Also, some experts consider UTIs to be uncomplicated even if they affect postmenopausal women or patients with well-controlled diabetes. In men, most UTIs occur in children or elderly patients, are due to anatomic abnormalities or instrumentation, and are considered complicated.54 The rare UTIs that occur in men aged 15 to 50 years are usually in men who have unprotected anal intercourse or in those who have an uncircumcised penis, and they are generally considered uncomplicated. UTIs in men this age who do not have unprotected anal intercourse or an uncircumcised penis are very rare and, although also considered uncomplicated, warrant evaluation for urologic abnormalities.55

Complicated UTI can involve either sex at any age. It is usually considered to be pyelonephritis or cystitis that does not fulfill criteria to be considered uncomplicated. A UTI is considered complicated if the patient is a child, is pregnant, or has any of the following:56

• A structural or functional urinary tract abnormality and obstruction of urine flow

• A comorbidity that increases risk of acquiring infection or resistance to treatment, such as poorly controlled diabetes, chronic kidney disease, or immunocompromise

• Recent instrumentation or surgery of the urinary tract

10 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Risk factors for development of UTI in women include the following:

• Sexual intercourse

• Diaphragm and spermicide use

• Antibiotic use

• New sex partner within the past year

• History of UTIs in 1st-degree female relatives

• History of recurrent UTIs

• First UTI at early age

Even use of condoms that are spermicide-coated increases risk of UTI in women. The increased risk of UTI in women using antibiotics or spermicides probably occurs because of alterations in vaginal flora that allow overgrowth of Escherichia coli. In elderly women, soiling of the perineum due to fecal incontinence increases risk.47,48

Anatomic, structural, and functional abnormalities are risk factors for UTI. A common consequence of anatomic abnormality is (VUR), which is present in 30 to 45% of young children with symptomatic UTI. Vesicoureteral reflux is usually caused by a congenital defect that results in incompetence of the ureterovesical valve. Vesicoureteral reflux can also be acquired in patients with a flaccid bladder due to spinal cord injury or after urinary tract surgery. Other anatomic abnormalities predisposing to UTI include urethral valves (a congenital obstructive abnormality), delayed bladder neck maturation, bladder diverticulum, and urethral duplications.52

Structural and functional urinary tract abnormalities that predispose to UTI usually involve obstruction of urine flow and poor bladder emptying. Urine flow can be compromised by calculi and tumors. Bladder emptying can be

11 nursece4less.com nursece4less.com nursece4less.com nursece4less.com impaired by neurogenic dysfunction, pregnancy, uterine prolapse, cystocele, and prostatic enlargement. Urinary tract infections caused by congenital factors manifests most commonly during childhood. Most other risk factors are more common in the elderly. Other risk factors for UTI include instrumentation (i.e., bladder catheterization, stent placement, cystoscopy) and recent surgery.57

The bacteria that most often cause cystitis and pyelonephritis include:

• Enteric, usually gram-negative aerobic bacteria (most often)

• Gram-positive bacteria (less often)

In normal genitourinary (GU) tracts, strains of Escherichia coli with specific attachment factors for transitional epithelium of the bladder and ureters account for 75% to 95% of cases. The remaining gram-negative urinary pathogens are usually other enterobacteria, typically Klebsiella or Proteus mirabilis, and occasionally Pseudomonas aeruginosa. Among gram-positive bacteria, Staphylococcus saprophyticus is isolated in 5% to 10% of bacterial UTIs. Less common gram-positive bacterial isolates are Enterococcus faecalis (group D streptococci) and Streptococcus agalactiae (group B streptococci), which may be contaminants, particularly if they were isolated from patients with uncomplicated cystitis.44,46

In hospitalized patients, E. coli accounts for about 50% of cases. The gram- negative species Klebsiella, Proteus, Enterobacter, Pseudomonas, and Serratia account for about 40%, and the gram-positive bacterial cocci, E. faecalis, S. saprophyticus, and Staphylococcus aureus account for the remainder.

12 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Nephritis

Nephritis is used to describe inflammation of one or both kidneys. If a kidney is inflamed, the functions of the kidney are disrupted to varying degrees depending on the type, cause and extent of inflammation. This disturbance is known as nephropathy. While the acute stages may cause only a temporary dysfunction, chronic inflammation can permanently damage kidney tissue, lead to scarring within the kidney, and even result in kidney failure. Both acute and chronic nephritis can be life-threatening if not treated and managed appropriately.75

Nephritis can be classified in several ways but the most common approaches is by the part of the kidney or nephron that is inflamed or by the cause and/or underlying disease responsible for the inflammation.76

• Glomerulonephritis is inflammation of the glomerulus of the nephron.

• Tubulointerstitial nephritis is inflammation of the tubule of the nephron and the surrounding interstitial tissue of the kidney. This is often referred to simply as interstitial nephritis.

• Pyelonephritis is inflammation of the kidney, usually the renal pelvis, and the urinary tract associated with a urinary tract infection (UTI).

All these types of nephritis can be either acute or chronic. When nephritis is classified according to the cause, for example lupus nephritis associated with systemic lupus erythematosus or infectious nephritis associated with an infection, the entire kidney is often affected. If left untreated and depending on the severity and duration of the inflammation, the entire kidney may be destroyed. The following table outlines the varied types of nephritis and the potential health risks and adverse outcomes that can occur.75,77-82

Glomerulonephritis Glomerulonephritis literally means inflammation of the glomerulus

13 nursece4less.com nursece4less.com nursece4less.com nursece4less.com but includes a number of disorders that affect the structure and function of the glomerulus without any prominent inflammation. It is therefore also referred to as glomerular disease or glomerulopathy.

In glomerulonephritis, various known and unknown causes trigger immune activity against the glomeruli which damages it. The glomerulus is the head of the nephron which is responsible for filtering fluid from the blood. This fluid is later processed in the tubule (the rest of the nephron) until urine is eventually formed.

Each kidney has about 1 million nephrons that act together to complete the various functions including removing waste substances from the blood, regulating blood volume and blood pressure. If a significant number of nephrons are damaged, these functions will be significantly hampered.

The kidney is constantly losing nephrons with age. This is a slow process and only commences after the age of 40 years. For every decade of life thereafter, the kidney loses about 10% of its functioning nephrons. Since the progression is so gradual, the remaining healthy nephrons are able to compensate without any significant impairment of normal kidney functioning. In glomerulonephritis, however, there is a more rapid and extensive damage of the nephrons.

Glomerulonephritis is known to be an immune reaction mediated by antigen-antibody complexes. An antigen is the trigger substance against which antibodies are formed by the immune system. The antibodies then bind with the antigen and this antigen-antibody complex can instigate a number of immune activities designed to protect the body. In the process, inflammation arises in whichever tissue that the targeted immune response is occurring. Although the exact cause of glomerulonephritis is not always understood, the mechanism by which it occurs is proposed in two different models –immune complex deposition and circulating immune complexes.

Other mechanisms may involve cell-mediated injury or cytotoxic antibodies. In immune complex deposition, it is believed that antibodies are directed against antigens that are “planted” in the glomerulus or against antigens that are normal components of the glomerulus, specifically the glomerular basement membrane (GBM). The immune activity is therefore specifically targeted at the glomerulus. With circulating immune complexes, the antigen- antibody complexes are circulating in the bloodstream and eventually reach the glomerulus during glomerular filtration. These complexes form in the backdrop of several autoimmune or infectious diseases and the antigen may be endogenous (created within the body) or exogenous (from foreign matter or microorganisms) in nature. In these cases, immune activity is targeted at the circulating immune complex and can lead to inflammation at other sites in

14 nursece4less.com nursece4less.com nursece4less.com nursece4less.com the body as well as the glomerulus. In response to the inflammation, different histologic alterations may be seen in the glomerulus. This includes: • Increase in the number of cells (capillary endothelium or mesangial cells) • Thickening of the basement membrane • Tissue degeneration – hyalinosis and sclerosis

Glomerulonephritis may be primary or secondary. Primary glomerulonephritis arises on its own without any other underlying disease. Secondary glomerulonephritis occurs as a consequence of some other disease, which may not even involve the kidney. Furthermore, glomerulonephritis can be classified as acute or chronic.

In acute glomerulonephritis, the condition starts suddenly and the tissue damage progresses rapidly. With chronic glomerulonephritis, the condition develops gradually and damage becomes extensive after months or years.

There is a wide range of causes of glomerulonephritis. Some may solely involve the kidney while others are due to systemic disease which affect a number of organs simultaneously. Sometimes the cause of glomerulonephritis is unknown – idiopathic. The causes of glomerulonephritis may include: • Infections – post-streptococcal, subacute bacterial endocarditis, viral infections, parasitic infections like malaria and less commonly fungal infections. • Autoimmune diseases – systemic lupus erythematosus (SLE), Goodpasture’s syndrome, vasculitis (Wegener granulomatosis and polyarteritis nodosa), Henoch-Schönlein purpura. • Immune-mediated hypersensitivity (atopy) particularly in children. • Medication like those drugs used in the treatment of SLE and hemolytic-uremic syndrome. • Diabetes mellitus • Malignant hypertension (high blood pressure) • Amyloidosis • Inherited diseases like Alport’s syndrome. • Hodgkin’s lymphoma (mainly in adults).

Tubulointerstitial Tubulointerstitial nephritis is a group of diseases that affect Nephritis the tubule of the nephron and/or surrounding interstitial tissue. It should be differentiated from similar diseases that predominantly affect the glomerulus, known as glomerulonephritis. However, tubulointerstitial disease may sometimes be related to glomerulonephritis but in these cases, the glomerular damage is minimal causing a mild disturbance.

Tubulointerstitial nephritis may be acute or chronic. The acute stages are characterized by rapid onset of inflammation of the renal tubule that compromises its function. This tubular dysfunction is usually temporary. Inflammation is also present in

15 nursece4less.com nursece4less.com nursece4less.com nursece4less.com chronic tubulonephritis along with structural damage to the tubule and/or interstitium. The injury is often irreversible in chronic states.

Tubulointerstitial nephritis is more commonly seen in women as the two most common causes, analgesic use and kidney infections, are more prevalent in females. However, it can affect men with the same risk factors equally. The two most common mechanisms associated with tubulonephritis is cellular injury by bacteria (infection) and toxins, and drug hypersensitivity which leads to an inappropriate immune response.

Acute tubulointerstitial nephritis is marked by inflammation with associated swelling of the affected area.

Leukocyte infiltration of the renal tissue, particularly eosinophils and neutrophils, are prominent and in severe cases there is confined areas of cell death (necrosis). Most cases of acute tubulointerstitial nephritis are largely reversible since the tubules can regenerate if the basement membrane is intact.

With chronic tubulointerstitial nephritis, the long term inflammation and subsequent fibrotic scarring tends to lead to irreversible changes. If a small amount of the total nephrons are affected then kidney function is not severely compromised. However, it tends to lead to progressive chronic renal insufficiency. Infections of the upper urinary tract and kidney (pyelonephritis) accounts for a large number of cases of acute tubulointerstitial nephritis.

Chronic pyelonephritis associated with reflux nephropathy may also be a cause. Most infections are bacterial in nature, although viruses (HIV, HBV, CMV), fungi (histoplasmosis) and parasites can also cause tubulointerstitial nephritis. Drug hypersensitivity is largely responsible for acute tubulointerstitial nephritis and associated with drugs like NSAIDs, certain antibiotics, diuretics, anticonvulsants and proton pump inhibitors. It is known as acute- hypersensitivity interstitial nephritis.

Chronic cases are more often associated with toxicity caused by long term and/or excessive use of drugs like analgesics and lithium. Heavy metal toxicity, lead, mercury and cadmium poisoning may also be responsible for chronic tubulointerstitial nephritis but has decreased substantially with greater awareness of the toxicity associated with these metals.

Other toxins may include fungal toxins like ochratoxin (possibly related to Balkan endemic nephropathy) or plant toxins like aristolochic acid (Chinese herb nephropathy). A number of immunologic diseases can cause acute and chronic tubulointerstitial nephritis. This includes: • Goodpasture syndrome • Systemic lupus erythematosus (SLE)

16 nursece4less.com nursece4less.com nursece4less.com nursece4less.com • Sjogren syndrome • Sarcoidosis • Vasculitis • Wegener’s granulomatosis

Acute transplant rejection and chronic transplant nephropathy also need to be considered in patients following a kidney transplant.

The clinical features of tubulointerstitial nephritis may be non- specific and it is difficult to differentiate with other kidney disorders. It can, however, be differentiated from glomerulonephritis by the absence of nephrotic and nephritic syndrome as discussed under of glomerulonephritis. The clinical presentation may also vary slightly depending on the causative factor and other underlying diseases.

The presentation in tubulointerstitial nephritis includes: • . Passing of large amounts of urine, seen as and waking at night to urinate (). • Hematuria (blood in the urine) may not be seen in every case of tubulointerstitial nephritis. • Metabolic acidosis. Accumulation of acids in the body fluid due to decreased excretion. • Changes in blood pressure – hypertension, hypotension or normal blood pressure. • Congestive heart failure • Headaches • Vomiting and/or diarrhea • Weight loss

Pyelonephritis Pyelonephritis is the medical term for inflammation of the renal pelvis, tubules and interstitium most commonly associated with an infection. It is a serious complication of a urinary tract infection (UTI), typically extending from the infected bladder (cystitis) as a result of an ascending infection.

A kidney infection may vary in severity but can be life-threatening and contribute to a host of other complications involving various systems other than the renal system. Although it can affect any age group and gender, pyelonephritis is more common in women who are generally prone to UTIs in comparison to men, given the shorter urethra. Most urinary tract infections (UTIs) affect the lower tract – urethra, bladder and rarely the lower half of the ureters. Since UTIs are more frequently due to an ascending infection – pathogens gain entry to the urethra and travel higher up the tract – there is risk of kidney infection if treatment is poor or delayed or there are other underlying urinary tract disorders. Typically, an infection of the lower urinary tract, particularly of the urethra (urethritis), is asymptomatic or causes very mild symptoms. Therefore, treatment may be delayed.

17 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Treatment is usually sought early for a bladder infection (cystitis) due to the intensity of symptoms. However, the severity of the clinical presentation in pyelonephritis, which can vary, generally prompts a patient to immediately seek medical treatment. Failure to do so can permanently damage the kidney or even become life-threatening in a short period of time.

Pyelonephrititis (kidney infection) can be acute or chronic. Both cases are most commonly due to a bacterial infection although viruses, fungi and rarely parasites may be responsible. In the majority of the cases, the bacteria originate from the person’s own fecal matter.

It is more likely to occur in women due to a shorter urethra but personal hygiene is a significant contributing factor. The causative bacteria adhere to the urinary tract and its toxins causes localized inflammation.

A kidney infection most commonly occurs when there is an obstruction within the urinary tract which prevents urine outflow to some degree. Usually regular urination prevents an infection by the constant flushing of the urinary tract. Once the bacteria colonizes the distal urethra, it rapidly spreads up the urethra to eventually gain entry into the bladder. The vesicoureteral valve is designed to prevent backward flow of urine up into the ureter from the bladder. However, the inflammation associated with a bladder infection (cystitis) and other contributing factors allows for the backward flow (vesicoureteral reflux) which then introduces the bacteria into the ureters. From here, reflux may push urine n the ureter as high up as the renal pelvis (part of the kidney that communicates with the ureter) thereby allowing bacteria to invade the kidney.

Acute pyelonephritis is mainly due to bacterial invasion of the renal substance, and most commonly a result of E. coli (Escherichia coli) infection. As discussed, a kidney infection may arise as a complication of a UTI, therefore the modes of transmission and causative organisms are the same as the causes of a bladder infection. Less commonly, the causative organism may invade the kidney from surrounding organs or distant sites when it travels through the bloodstream (hematogenous spread). Risk factors include: • Urinary stones • Prostate enlargement (benign prostatic hyperplasia) • Urinary tract obstruction • Pregnancy • Sexually transmitted infections (STIs) • Diabetes mellitus • Immune deficiency • Surgery to the urinary tract • Urinary catheter • Anatomical abnormalities of the kidney and/or urinary tract

18 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Chronic pyelonephritis is due to recurrent kidney infections or a persistent infection. The structural damage to the kidney in chronic pyelonephritis contributes to various other renal disorders like reflux nephropathy and even end-stage renal disease. The risk factors associated with chronic pyelonephritis may be the same as that of acute pyelonephritis and is more likely to occur in a person who is immunocompromised and/or with other urinary tract pathology. The signs and symptoms of pyelonephritis includes: • Back pain and/or flank pain which may extend to the groin. • Urinary frequency – frequent urination • Urinary tenesmus – constant urge to urinate • Dysuria – pain, usually burning, when urinating • – pus in urine which presents as cloudy urine • Hematuria – blood in the urine • Fever • Nausea and vomiting

The presentation may vary in acute and chronic pyelonephritis. The onset of signs and symptoms in acute pyelonephritis is usually sudden. Usually most, if not all, of the signs and symptoms mentioned above are present in acute pyelonephritis and are intense. It will rapidly ease and resolve within a few days if the appropriate antibiotic therapy is commenced as early as possible.

Chronic pyelonephritis is generally more insidious in onset. In some cases, it may remain silent for periods of time, or present with only a few clinical manifestations, until it is diagnosed by the presence of systemic disturbances. Since chronic pyelonephritis is more likely to occur in the presence of pre-existing kidney disease, this may mask the onset of the infection.

The clinical presentation may vary among the different types of nephritis. However, it is characterized by urinary disturbances, changes in blood pressure and volume. Some of the common signs and symptoms includes:75

• Polyuria – passing large volumes of urine in a day which presents as frequent urination.

• Hematuria – microscopic or gross appearance of blood in the urine.

• Nausea and/or vomiting

• Kidney pain

19 nursece4less.com nursece4less.com nursece4less.com nursece4less.com • Hypertension (high blood pressure) or hypotension (low blood pressure)

• Headaches

• Edema – swelling of the limbs, abdomen or the entire body.

Complications of Nephritis

Nephritis may eventually lead to renal failure and end-stage renal disease. This is life-threatening.76

• Waste products rich in nitrogen like urea accumulate in the bloodstream (azotemia).

• Excess fluid in the body leads to high blood pressure, swelling, congestive heart failure and fluid in the lungs (pulmonary edema).

• Loss of electrolytes like sodium, chloride and potassium affects nerve and muscle function, which is dangerous when the normal heart function is affected.

• Decreased excretion of acids causes it to accumulate in the blood (metabolic acidosis) which causes neurological and muscular disturbances.

• Infections may spread throughout the body (septicemia) and lead to death.

Classification And Treatment Of Urinary Tract Infections

The classification of urinary tract infections is based on clinical research and medical observation in clinical practice. The following classifications highlight urinary tract infection symptoms, severity and risk factors.53,58-60 Urinary tract infections that are symptomatic and non-symptomatic, clinical evaluation of symptoms and laboratory testing, such as urinalysis and culture tests, as the standard methods for diagnosing a urinary tract infection are primarily raised here. While there are new improved methods of

20 nursece4less.com nursece4less.com nursece4less.com nursece4less.com testing being studied that may change how urinary tract infections are diagnosed, the detection of bacteria difficult to identify by routine culture has yet to be established through well-designed research trials.

Acute Pyelonephritis

Pyelonephritis is bacterial infection of the kidney parenchyma. The term should not be used to describe tubulointerstitial nephropathy unless infection is documented. In women, about 20% of community acquired bacteremias are due to pyelonephritis. Pyelonephritis is uncommon in men with a normal urinary tract. In 95% of cases of pyelonephritis, the cause is ascension of bacteria through the urinary tract. Although obstruction (i.e., strictures, calculi, tumors, neurogenic bladder, vesicoureteral reflux) predisposes to pyelonephritis, most women with pyelonephritis have no demonstrable functional or anatomic defects. In men, pyelonephritis is always due to some functional or anatomic defect.

Cystitis alone or anatomic defects may cause reflux. The risk of bacterial ascension is greatly enhanced when ureteral peristalsis is inhibited (i.e., during pregnancy, by obstruction, by endotoxins of gram-negative bacteria). Pyelonephritis is common in young girls and in pregnant women after bladder catheterization. Pyelonephritis not caused by bacterial ascension is caused by hematogenous spread, which is particularly characteristic of virulent organisms such as S. aureus, P. aeruginosa, Salmonella species, and Candida species. The affected kidney is usually enlarged because of inflammation and edema. Infection is focal and patchy, beginning in the pelvis and medulla and extending into the cortex as an enlarging wedge.

Cells mediating chronic inflammation appear within a few days, and medullary and subcortical abscesses may develop. Normal parenchymal

21 nursece4less.com nursece4less.com nursece4less.com nursece4less.com tissue between foci of infection is common. Papillary necrosis may be evident in acute pyelonephritis associated with diabetes, obstruction, sickle cell disease, pyelonephritis in renal transplants, pyelonephritis due to candidiasis, or analgesic nephropathy. Although acute pyelonephritis is frequently associated with renal scarring in children, similar scarring in adults is not detectable in the absence of reflux or obstruction.

Diagnosis is made by urinalysis and sometimes urine culture. Diagnosis by culture is not always necessary. If done, diagnosis by culture requires demonstration of significant in properly collected urine.

Urine Collection

If a sexually transmitted disease (STD) is suspected, a urethral swab for STD testing is obtained prior to voiding. Urine collection is then by clean- catch or catheterization. To obtain a clean-catch, midstream specimen, the urethral opening is washed with a mild, nonfoaming disinfectant and air dried. Contact of the urinary stream with the mucosa should be minimized by spreading the labia in women and by pulling back the foreskin in uncircumcised men. The first 5 mL of urine is not captured; the next 5 to 10 mL is collected in a sterile container.

A specimen obtained by catheterization is preferable in older women (who typically have difficulty obtaining a clean-catch specimen) and in women with vaginal bleeding or discharge. Many clinicians also use catheterization to obtain a specimen if evaluation includes a pelvic examination. Diagnosis in patients with indwelling catheters is discussed elsewhere. Testing, particularly culturing, should be done within 2 hours of specimen collection; if not, the sample should be refrigerated.61-63

22 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Urine Testing

Microscopic examination of urine is useful but not definitive. Pyuria is defined as ≥ 8 WBCs/µL of uncentrifuged urine, which corresponds to 2 to 5 WBCs/high-power field in spun sediment. Most truly infected patients have > 10 WBCs/µL. The presence of bacteria in the absence of pyuria, especially when several strains are found, is usually due to contamination during sampling. Microscopic hematuria occurs in up to 50% of patients, but gross hematuria is uncommon. White blood cell (WBC) casts, which may require special stains to differentiate from renal tubular casts, indicate only an inflammatory reaction; they can be present in pyelonephritis, glomerulonephritis, and noninfective tubulointerstitial nephritis.

Pyuria in the absence of bacteriuria and of UTI is possible, for example, if patients have nephrolithiasis, a uroepithelial tumor, appendicitis, or inflammatory bowel disease or if the sample is contaminated by vaginal white blood cells (WBCs). Women who have dysuria and pyuria but without significant bacteriuria have the urethral syndrome or dysuria-pyuria syndrome.57

Dipstick tests are also commonly used. A positive nitrite test on a freshly voided specimen (bacterial replication in the container renders results unreliable if the specimen is not tested rapidly) is highly specific for UTI, but the test is not very sensitive. The leukocyte esterase test is very specific for the presence of > 10 WBCs/µL and is fairly sensitive. In adult women with uncomplicated UTI with typical symptoms, most clinicians consider positive microscopic and dipstick tests sufficient; in these cases, given the likely pathogens, cultures are unlikely to change treatment but add significant expense.

23 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Cultures are recommended in patients whose characteristics and symptoms suggest complicated UTI or an indication for treatment of bacteriuria. Common examples include the following:56,64,65

• Pregnant women

• Postmenopausal women

• Men

• Prepubertal children

• Patients with urinary tract abnormalities or recent instrumentation

• Patients with immunosuppression or significant comorbidities

• Patients whose symptoms suggest pyelonephritis or sepsis

• Patients with recurrent UTIs (≥ 3/yr.)

Samples containing large numbers of epithelial cells are contaminated and unlikely to be helpful. An uncontaminated specimen must be obtained for culture. Culture of a morning specimen is most likely to detect UTI. Samples left at room temperature for > 2 hours can give falsely high colony counts due to continuing bacterial proliferation. Criteria for culture positivity include isolation of a single bacterial species from a midstream, clean catch, or catheterized urine specimen.

For asymptomatic bacteriuria, criteria for culture positivity based on the guidelines of the Infectious Diseases Society of America are:57,66

• Two consecutive clean-catch, voided specimens (for men, one specimen) from which the same bacterial strain is isolated in colony counts of >105/mL

• Among women or men, in a catheter-obtained specimen, a single bacterial species is isolated in colony counts of > 102/mL

For symptomatic patients, culture criteria are:

24 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 3 • Uncomplicated cystitis in women: > 10 /mL 2 • Uncomplicated cystitis in women: > 10 /mL (This quantification may be considered to improve sensitivity to E. coli.) 4 • Acute, uncomplicated pyelonephritis in women: > 10 /mL 5 4 • Complicated UTI: > 10 /mL in women; or > 10 /mL in men or from a catheter-derived specimen in women 2 • Acute urethral syndrome: > 10 /mL of a single bacterial species

Any positive culture result, regardless of colony count, in a sample obtained via suprapubic bladder puncture should be considered a true positive. In midstream urine, E. coli in mixed flora may be a true pathogen. Occasionally, UTI is present despite lower colony counts, possibly because of prior antibiotic therapy, very dilute urine (specific gravity < 1.003), or obstruction to the flow of grossly infected urine. Repeating the culture improves the diagnostic accuracy of a positive result, i.e., may differentiate between a contaminant and a true positive result.56

Treatment includes antibiotics and occasionally surgery (i.e., to drain abscesses, correct underlying structural abnormalities, or relieve obstruction).

All forms of symptomatic bacterial UTI require antibiotics. For patients with troublesome dysuria, phenazopyridine may help control symptoms until the antibiotics do (usually within 48 hours). Choice of antibiotic should be based on the patient’s and adherence history, local resistance patterns (if known), antibiotic availability and cost, and patient tolerance or risk of treatment failure. Propensity for inducing antibiotic resistance should also be considered. When urine culture is done, choice of antibiotic should be

25 nursece4less.com nursece4less.com nursece4less.com nursece4less.com modified when culture and sensitivity results are available to the most narrow-spectrum drug effective against the identified pathogen.46

Surgical correction is usually required for , anatomic abnormalities, and neuropathic urinary tract lesions such as compression of the spinal cord. Catheter drainage of an obstructed urinary tract aids in prompt control of UTI. Occasionally, a renal cortical abscess or perinephric abscess requires surgical drainage. Instrumentation of the lower urinary tract in the presence of infected urine should be deferred if possible. Sterilization of the urine before instrumentation and antibiotic therapy for 3 to 7 days after instrumentation can prevent life-threatening urosepsis.

Antibiotic Treatment

Antibiotics are required for acute pyelonephritis. Outpatient treatment with oral antibiotics is possible if all of the following criteria are satisfied:

• Patients are expected to be adherent

• Patients are immunocompetent

• Patients have no nausea or vomiting or evidence of volume depletion or septicemia

• Patients have no factors suggesting complicated UTI

Ciprofloxacin 500 mg orally bid for 7 days and levofloxacin 750 mg orally once/day for 5 days are 1st-line antibiotics if < 10% of the uropathogens in the community are resistant. A 2nd option is usually trimethoprim/sulfamethoxazole (TMP/SMX) 160/800 mg orally bid for 14 days. However, local sensitivity patterns should be considered because in some parts of the US, > 20% of E. coli are resistant to sulfa.

26 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Patients not eligible for outpatient treatment should be hospitalized and given parenteral therapy selected on the basis of local sensitivity patterns. First-line antibiotics are usually renally excreted fluoroquinolones, such as ciprofloxacin and levofloxacin. Other choices, such as ampicillin plus gentamicin, broad-spectrum cephalosporins (i.e., ceftriaxone, cefepime), aztreonam, beta-lactam/beta-lactam inhibitor combinations (ampicillin/sulbactam, ticarcillin/clavulanate, piperacillin/tazobactam), and imipenem/cilastatin, are usually reserved for patients with more complicated pyelonephritis (i.e., with obstruction, calculi, resistant bacteria, or a hospital-acquired infection) or recent urinary tract instrumentation.

Parenteral therapy is continued until defervescence and other signs of clinical improvement occur. In > 80% of patients, improvement occurs within 72 hours. Oral therapy can then begin, and the patient can be discharged for the remainder of a 7- to14-day treatment course. Complicated cases require longer courses of IV antibiotics with total duration of 2 to 3 weeks. and urologic correction of anatomic defects.

Outpatient management can be considered in pregnant women with pyelonephritis, but only if symptoms are mild, close follow-up is available, and (preferably) pregnancy is < 24 wk. gestation. Outpatient treatment is with cephalosporins (i.e., ceftriaxone 1 to 2 g IV or IM, then cephalexin500 mg po qid for 10 days). Otherwise, 1st-line IV antibiotics include cephalosporins, aztreonam, or ampicillin plus gentamicin. If pyelonephritis is severe, possibilities include piperacillin/tazobactam or meropenem. Fluoroquinolones and TMP/SMX should be avoided. Because recurrence is common, some authorities recommend prophylaxis after the acute infection resolves with nitrofurantoin 100 mg po or cephalexin 250 mg po every night

27 nursece4less.com nursece4less.com nursece4less.com nursece4less.com during the remainder of the pregnancy and for 4 to 6 wk. after pregnancy.55,63,67-72

Cystitis

Cystitis is infection of the bladder. It is common in women, in whom cases of uncomplicated cystitis are usually preceded by sexual intercourse (honeymoon cystitis). In men, bacterial infection of the bladder is usually complicated and usually results from ascending infection from the urethra or prostate or is secondary to urethral instrumentation. The most common cause of recurrent cystitis in men is chronic bacterial prostatitis.

First-line treatment of uncomplicated cystitis is nitrofurantoin 100 mg orally bid for 5 days (it is contraindicated if creatinine clearance is < 60 mL/min), trimethoprim/sulfamethoxazole (TMP/SMX) 160/800 mg orally bid for 3 days, or fosfomycin 3 g orally once. Less desirable choices include a fluoroquinolone or a beta-lactam antibiotic. If cystitis recurs within a week or two, a broader spectrum antibiotic (i.e., a fluoroquinolone) can be used and the urine should be cultured.

Complicated cystitis should be treated with empiric broad-spectrum antibiotics chosen based on local pathogens and resistance patterns and adjusted based on culture results. Urinary tract abnormalities must also be managed.

Urethritis

28 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Infection of the urethra with bacteria (or with protozoa, viruses, or fungi) occurs when organisms that gain access to it acutely or chronically colonize the numerous periurethral glands in the bulbous and pendulous portions of the male urethra and in the entire female urethra. The sexually transmitted pathogens Chlamydia trachomatis, Neisseria gonorrhoeae and herpes simplex virus are common causes in both sexes.

Sexually active patients with symptoms are usually treated presumptively for sexually transmitted diseases (STDs) pending test results. A typical regimen is ceftriaxone 250 mg IM plus either azithromycin 1 g orally once or doxycycline 100 mg orally bid for 7 days. All sex partners within 60 days should be evaluated. Men diagnosed with urethritis should be tested for HIV and syphilis in accordance with the Centers for Disease Control and Prevention's 2015 Sexually Transmitted Diseases Treatment Guidelines.

Acute Urethral Syndrome

Acute urethral syndrome, which occurs in women, is a syndrome involving dysuria, frequency, and pyuria (dysuria-pyuria syndrome), which thus resembles cystitis. However, in acute urethral syndrome (unlike in cystitis), routine urine cultures are either negative or show colony counts that are lower than the traditional criteria for diagnosis of bacterial cystitis.

Urethritis is a possible cause because causative organisms include Chlamydia trachomatis and Ureaplasma urealyticum, which are not detected on routine urine culture. Noninfectious causes have been proposed, but supporting evidence is not conclusive, and most noninfectious causes usually cause little or no pyuria. Possible noninfectious causes include anatomic abnormalities (i.e., urethral stenosis), physiologic abnormalities (i.e., pelvic floor muscle

29 nursece4less.com nursece4less.com nursece4less.com nursece4less.com dysfunction), hormonal imbalances (i.e., atrophic urethritis), localized trauma, gastrointestinal (GI) system symptoms, and inflammation.

Treatment of acute urethral syndrome depends on clinical findings and urine culture results.

2 • Women with dysuria, pyuria, and colony growth of > 10 /mL of a single bacterial species on urine culture can be treated as for uncomplicated cystitis.

• Women who have dysuria and pyuria with no bacteriuria should be evaluated for an STD (including for N. gonorrhoeae and C. trachomatis).

• Women who have dysuria but neither pyuria nor bacteriuria do not have the true urethral syndrome. They should be evaluated for noninfectious causes of dysuria. Evaluation may include therapeutic trials, for example, of behavioral treatments (i.e., biofeedback and pelvic musculature relaxation), surgery (for urethral stenosis), and drugs (i.e., hormone replacement for suspected atrophic urethritis, anesthetics, antispasmodics).

Asymptomatic Bacteriuria

Asymptomatic bacteriuria is absence of UTI signs or symptoms in a patient whose urine culture satisfies criteria for UTI. Pyuria may or may not be present. Because it is asymptomatic, such bacteriuria is found mainly when high-risk patients are screened or when urine culture is done for other reasons.

Screening patients for asymptomatic bacteriuria is indicated for those at risk of complications if the bacteriuria is untreated. Such patients include those listed here.

30 nursece4less.com nursece4less.com nursece4less.com nursece4less.com • Pregnant women at 12 to 16 weeks' gestation or at the first prenatal visit, if later (because of the risk of symptomatic UTI, including pyelonephritis, during pregnancy; and adverse pregnancy outcomes, including low-birth-weight neonate and premature delivery) • Patients who have had a kidney transplant within the previous 6 months • Young children with gross vesicoureteral reflux (VUR) • Before certain invasive genitourinary (GU) procedures that can cause mucosal bleeding (i.e., transurethral resection of the prostate) • Certain patients (i.e., postmenopausal women, patients with controlled diabetes, patients with ongoing use of urinary tract foreign objects such as stents, nephrostomy tubes, and indwelling catheters) often have persistent asymptomatic bacteriuria and sometimes pyuria. However, such patients should not be screened because they are at low risk of complicated UTI due to the bacteriuria and thus do not require treatment. Also, in patients with indwelling catheters, treatment often fails to clear the bacteriuria and only leads to development of highly antibiotic-resistant organisms.

Typically, asymptomatic bacteriuria in patients with diabetes, elderly patients, or patients with chronically indwelling bladder catheters should not be treated. However, patients at risk of complications from asymptomatic bacteriuria may have any treatable causes addressed and be given antibiotics, such as for cystitis.

In pregnant women, only a few antibiotics can be safely used. Oral beta- lactams, sulfonamides, and nitrofurantoin are considered safe in early pregnancy, but trimethoprim should be avoided during the 1st trimester, and sulfamethoxazole should be avoided during the 3rd trimester,

31 nursece4less.com nursece4less.com nursece4less.com nursece4less.com particularly near parturition. Patients with untreatable obstructive problems (i.e., calculi, reflux) may require long-term suppressive therapy.

Fungal Urinary Tract Infections

Fungal infections of the urinary tract primarily affect the bladder and kidneys. Species of Candida, the most common cause, are normal commensals in humans. Candida colonization differs from infection in that infection produces tissue reaction. All invasive fungi (i.e., Cryptococcus neoformans, Aspergillus sp, Mucoraceae sp, Histoplasma capsulatum, Blastomyces sp, Coccidioides immitis) may infect the kidneys as part of systemic or disseminated mycotic infection. Their presence alone indicates infection.72

Lower UTI with Candida usually occurs in patients with urinary catheters, typically after antibiotic therapy, although candidal and bacterial infections frequently occur simultaneously. C. albicansprostatitis occurs infrequently in patients with diabetes, usually after instrumentation.

Renal candidiasis is usually spread hematogenously and commonly originates from the GI tract. Ascending infection is possible and occurs mainly in patients with nephrostomy tubes, other permanent indwelling devices, and stents. At high risk are patients with diabetes and those who are immunocompromised because of tumor, AIDS, chemotherapy, or immunosuppressants. A major source of candidemia in such high-risk hospitalized patients is an indwelling intravascular catheter. Renal transplantation increases the risk because of the combination of indwelling catheters, stents, antibiotics, anastomotic leaks, obstruction, and immunosuppressive therapy. Complications of candidal infection can include emphysematous cystitis or pyelonephritis and fungus balls in the renal

32 nursece4less.com nursece4less.com nursece4less.com nursece4less.com pelvis, ureter, or bladder. Bezoars may form in the bladder. Lower or upper urinary tract obstruction may occur. Papillary necrosis and intrarenal and perinephric abscesses may form. Although renal function often declines, severe renal failure is rare without postrenal obstruction.45,48,73

Most patients with candiduria are asymptomatic. Whether Candida can cause urethral symptoms (mild urethral itching, dysuria, watery discharge) in men is uncertain. Rarely, dysuria in women is caused by candidal urethritis, but it may result from the urine coming into contact with periurethral tissue that is inflamed due to candidal . Among lower UTIs, cystitis due to Candida may result in frequency, urgency, dysuria, and suprapubic pain. Hematuria is common. Emphysematous cystitis is an infection of the bladder produced by gas forming organisms.

In patients with poorly controlled diabetes, pneumaturia (gas in the urine) due to emphysematous cystitis has occurred. Fungus balls or bezoars may cause symptoms of urethral obstruction. Most patients with renal candidiasis that is hematogenously spread lack symptoms referable to the kidneys but may have antibiotic-resistant fever, candiduria, and unexplained deteriorating renal function. Fungus ball elements in the ureter and renal pelvis frequently cause hematuria and urinary obstruction. Occasionally, papillary necrosis or intrarenal or perinephric abscesses cause pain, fever, hypertension, and hematuria. Patients may have manifestations of candidiasis in other sites (i.e., CNS, skin, eyes, liver, spleen).46,60,65,71

Diagnosis is made by urine culture and evidence of tissue reaction (in cystitis) or pyelonephritis.

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Candida UTI is considered in patients with predisposing factors and symptoms suggesting UTI and in all patients with candidemia. Candida should be suspected in men with symptoms of urethritis only when all other causes of urethritis have been excluded. Diagnosis of Candida UTI is by culture, usually from urine. The level at which candiduria reflects true Candida UTI and not merely colonization or contamination is unknown. Differentiating Candida colonization from infection requires evidence of tissue reaction.

Cystitis is usually diagnosed in high-risk patients with candiduria by the presence of bladder inflammation or irritation, as evidenced by pyuria. Cystoscopy and ultrasonography of the kidneys and bladder may help detect bezoars and obstruction. Renal candidiasis is considered in patients with fever, candiduria, or passage of fungus balls.

Severe renal failure suggests postrenal obstruction. Imaging of the urinary tract may help reveal the degree of involvement. Blood cultures for Candida are often negative. Unexplained candiduria should prompt evaluation of the urinary tract for structural abnormalities.74

Treatment

Treatment is done only for symptomatic or high-risk patients and involves Fluconazole or, for resistant organisms, amphotericin B; sometimes flucytosine is added.

Fungal colonization of catheters does not require treatment. Asymptomatic candiduria rarely requires therapy. Candiduria should be treated in the following:

34 nursece4less.com nursece4less.com nursece4less.com nursece4less.com • Symptomatic patients

• Neutropenic patients (i.e., patients with low neutrophilic-white blood cell counts)

• Patients with renal allografts

• Patients who are undergoing urologic manipulation

Urinary stents and Foley catheters should be removed (if possible). For symptomatic cystitis, treatment is with fluconazole 200 mg orally once/day. For pyelonephritis, fluconazole 200 to 400 mg orally once/day is preferred. Therapy in both cases should be for 2 weeks. For fungi resistant to fluconazole, amphotericin B is recommended at dose of 0.3 to 0.6 mg/kg IV once/day for 2 weeks. for cystitis and 0.5 to 0.7 mg/kg IV once/day for 2 weeks for pyelonephritis. For resistant pyelonephritis, flucytosine 25 mg/kg orally qid is added to the regimen if patients have adequate renal function; if not, the dose should be modified based on creatinine clearance.45,46,59

Flucytosine may help eradicate candiduria due to non-albicans species of Candida; however, resistance may emerge rapidly when this compound is used alone. Bladder irrigation with amphotericin B may transiently clear candiduria but is no longer indicated for cystitis or pyelonephritis. Even with apparently successful local or systemic antifungal therapy for candiduria, relapse is frequent, and this likelihood is increased by continued use of a urinary catheter. Clinical experience with using voriconazole to treat UTIs is scant.74

Summary

A urinary tract infection can develop in any part of the urinary tract, including the urethra, bladder, ureters, or kidneys. Laboratory testing

35 nursece4less.com nursece4less.com nursece4less.com nursece4less.com typically involves a urinalysis and urine culture test to identify the organism causing infection and proper treatment. Antibiotics are started as soon as the clinician suspects a urinary tract infection and urinary samples have been obtained for laboratory testing. The choice of drug or its dosage may be modified based on the laboratory test results (including culture results), the patient’s symptoms and the virulence of the organism causing infection. Other factors that can alter the choice or dosage of drug include whether the patient's immune system is impaired and whether the person has a urinary tract abnormality, such as an obstruction.

All forms of symptomatic bacterial urinary tract infection require antibiotics. Surgical correction is uncommon however usually required for obstructive uropathy and anatomic abnormalities. Future research and efforts are underway through improved well-designed research trials to better identify causes of urinary tract infections, such as hard to isolate and resistant organisms, and for more effective treatment options.

Please take time to help NurseCe4Less.com course planners evaluate the nursing knowledge needs met by completing the self-assessment of Knowledge Questions after reading the article, and providing feedback in the online course evaluation.

Completing the study questions is optional and is NOT a course requirement.

1. The most common organism causing urinary tract infection is ______, which is responsible for up to 80% of kidney and urinary infections.

a. Klebsiella b. Enterococcus c. Staphylococcus saprophyticus

36 nursece4less.com nursece4less.com nursece4less.com nursece4less.com d. Escherichia coli (E. coli)

2. True or False: Kidney stones do not increase the development of urinary tract infections because the mineral and salt deposits that usually compose kidney stones inhibit the growth of infections.

a. True b. False

3. Urinary tract infections are more common in women than in men because

a. the length of the urethra is shorter in women. b. the hormone estrogen makes women more susceptible. c. of gastrointestinal tract bacteria. d. of the higher incidence of epispadias in women.

4. When a patient presents with symptoms of pyelonephritis (kidney infection) the clinician will perform two common laboratory tests, which are examining a urine specimen for red and white blood cell counts and

a. a urine culture. b. a helical (spiral) computed tomography. c. a cystoscopy. d. a urethral swab for STD testing.

5. If a clinician suspects a patient has pyelonephritis,

a. antibiotics are started after laboratory test results are reviewed. b. antibiotics are started immediately only if the patient may have contracted the infection in the hospital. c. antibiotics are started immediately only if the patient’s immune system is impaired. d. antibiotics are started immediately.

6. True or False: Pregnant women may also be at higher risk for developing urinary tract infections because transit of urine from the ureters into the bladder may be slower due to the increased pressure on the ureters from the enlarged uterus.

a. True b. False

37 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 7. Which of the following patients is usually treated for pyelonephritis in an outpatient setting?

a. A patient with nausea or vomiting b. A patient with signs of dehydration c. A patient with low blood pressure d. None of the above

8. Antibiotic treatment for a woman with pyelonephritis is given for ______so that infection will not recur.

a. 1 to 2 days b. 6 weeks c. 5 to 14 days d. 4 days

9. People who have frequent episodes of pyelonephritis or whose infection returns after antibiotic treatment is completed

a. may not restart antibiotic treatments. b. may take a small dose of antibiotic on a short-term basis. c. may take a small dose of antibiotic on a long-term basis. d. are limited to kidney transplant to treat the chronic infection.

10. Among women aged 20 to 50 years, most urinary tract infections (UTIs) are cystitis or

a. pyelonephritis. b. urethritis. c. vesicoureteral. d. colonic.

11. True or False: With bacterial urinary tract infections (UTIs) symptoms, such as urinary frequency, urgency, dysuria, lower abdominal pain, and flank pain, are always present.

a. True b. False

12. About 95% of urinary tract infections (UTIs) occur when bacteria ascend the urethra to the bladder or kidney with the remainder of UTIs being

38 nursece4less.com nursece4less.com nursece4less.com nursece4less.com

a. urologic. b. anatomic. c. colonic. d. hematogenous.

13. Vesicoureteral reflux is usually caused by ______that result(s) in incompetence of the ureterovesical valve.

a. spinal cord injury b. infection c. stones d. a congenital defect

14. ______is infection of the bladder.

a. Dysuria-pyuria syndrome b. Chlamydia trachomatis c. Cystitis d. Pyelonephritis

15. In diagnosed cases of ______, a patient’s urine culture will satisfy criteria for urinary tract infection (UTI) even in the absence of urinary tract infection signs or symptoms.

a. asymptomatic bacteriuria b. pyuria c. cystitis d. pyelonephritis

16. True or False: All forms of symptomatic bacterial urinary tract infection (UTI) require antibiotics.

a. True b. False

17. Asymptomatic bacteriuria in patients with diabetes, elderly patients, or patients with chronically indwelling bladder catheters

a. should be treated with fluoroquinolone.

39 nursece4less.com nursece4less.com nursece4less.com nursece4less.com b. should be treated with a beta-lactam antibiotic. c. should not be treated. d. should be treated with nitrofurantoin.

18. In pregnant women, which of the following antibiotics should be avoided during the first trimester?

a. Sulfonamides b. Beta-lactams c. Trimethoprim d. Nitrofurantoin

19. Candiduria causes urethral symptoms, mild urethral itching, dysuria, watery discharge, in ______of men.

a. 5% b. 2% c. 10% d. None of the above

20. Emphysematous cystitis is an infection of the ______produced by gas forming organisms.

a. bladder b. kidney c. urethra d. spleen

21. Candiduria should be treated in

a. cases of fungal colonization of catheters. b. asymptomatic candiduria. c. neutropenic patients. d. All of the above

22. Tubulointerstitial nephritis is inflammation of the tubule of the ______and the surrounding interstitial tissue of the kidney.

a. glomerulus

40 nursece4less.com nursece4less.com nursece4less.com nursece4less.com b. urethra c. nephron d. renal hilus

23. The appearance of microscopic or gross amounts of blood in the urine is referred to as

a. azotemia. b. edema. c. anemia. d. hematuria.

24. Complications of nephritis include ______, which is the accumulation of waste products rich in nitrogen in the bloodstream.

a. azotemia b. pneumaturia c. anemia d. hematuria

25. ______is caused by decreased excretion of acids, which leads to their accumulation in the blood, causing neurological and muscular disturbances in the body.

a. Metabolic acidosis b. Azotemia c. Septicemia d. Hyponatremia

CORRECT ANSWERS:

1. The most common organism causing urinary tract infection is ______, which is responsible for up to 80% of kidney and urinary infections.

d. Escherichia coli (E. coli)

“By far, the most common organism causing urinary tract infection is Escherichia coli (E. coli), which is responsible for up to 80% of kidney and urinary infections.”

41 nursece4less.com nursece4less.com nursece4less.com nursece4less.com

2. True or False: Kidney stones do not increase the development of urinary tract infections because the mineral and salt deposits that usually compose kidney stones inhibit the growth of infection.

b. False

“Kidney stones are another factor that may increase the likelihood of urinary tract infection.”

3. Urinary tract infections are more common in women than in men because

a. the length of the urethra is shorter in women.

“Because of the shorter length of the urethra in women, urinary tract infections are more common in women compared to men.”

4. When a patient presents with symptoms of pyelonephritis (kidney infection) the clinician will perform two common laboratory tests, which are examining a urine specimen for red and white blood cell counts and

a. a urine culture.

“The typical symptoms of pyelonephritis lead doctors to do two common laboratory tests to determine whether the kidneys are infected: examining a urine specimen under a microscope to count the number of red and white blood cells and bacteria and a urine culture, in which bacteria from a urine sample are grown in a laboratory to identify the numbers and type of bacteria.”

5. If a clinician suspects a patient has pyelonephritis,

d. antibiotics are started immediately.

“Antibiotics are started as soon as the doctor suspects pyelonephritis and samples have been taken for laboratory tests. The choice of drug or its dosage may be modified based on the laboratory test results (including culture results), how sick the person is, and whether the infection started in the hospital, where bacteria tend to be more resistant to antibiotics. Other factors that can alter the choice or dosage of drug include whether the person's

42 nursece4less.com nursece4less.com nursece4less.com nursece4less.com immune system is impaired and whether the person has a urinary tract abnormality (such as an obstruction).”

6. True or False: Pregnant women may also be at higher risk for developing urinary tract infections because transit of urine from the ureters into the bladder may be slower due to the increased pressure on the ureters from the enlarged uterus.

a. True

“Pregnant women may also be at higher risk for developing urinary tract infections. This may be caused by slower transit of urine from the ureters into the bladder because of increased pressure on the ureters from the enlarged uterus. Approximately 10% of pregnant women may develop kidney and urinary tract infections during their pregnancy.”

7. Which of the following patients is usually treated for pyelonephritis in an outpatient setting?

a. A patient with nausea or vomiting b. A patient with signs of dehydration c. A patient with low blood pressure d. None of the above [correct answer]

“Outpatient treatment with antibiotics given by mouth is usually successful if the person has: No nausea or vomiting; No signs of dehydration; ... No signs of very severe infection, such as low blood pressure or confusion.... Otherwise, the person is usually treated initially in the hospital.”

8. Antibiotic treatment for a woman with pyelonephritis is given for ______so that infection will not recur.

c. 5 to 14 days

“If hospitalization is needed and the person needs antibiotics, the antibiotics are given intravenously for 1 or 2 days, then they can usually be given by mouth. Antibiotic treatment of pyelonephritis is given for 5 to 14 days so that infection will not recur. However, antibiotic therapy may continue for up to 6 weeks for men in whom the infection is due to prostatitis, which is more difficult to eradicate.”

43 nursece4less.com nursece4less.com nursece4less.com nursece4less.com

9. People who have frequent episodes of pyelonephritis or whose infection returns after antibiotic treatment is completed

c. may take a small dose of antibiotic on a long-term basis.

“People who have frequent episodes of pyelonephritis or whose infection returns after antibiotic treatment is finished may be advised to take a small dose of antibiotic on a long-term basis. The ideal duration of such therapy is unknown. If the infection returns, preventive therapy may be continued indefinitely.”

10. Among women aged 20 to 50 years, most urinary tract infections (UTIs) are cystitis or

a. pyelonephritis.

“Among adults aged 20 to 50 yr., UTIs are about 50-fold more common in women. In women in this age group, most UTIs are cystitis or pyelonephritis. In men of the same age, most UTIs are urethritis or prostatitis.”

11. True or False: With bacterial urinary tract infections (UTIs) symptoms, such as urinary frequency, urgency, dysuria, lower abdominal pain, and flank pain, are always present.

b. False

“Bacterial urinary tract infections (UTIs) can involve the urethra, prostate, bladder, or kidneys. Symptoms may be absent or include urinary frequency, urgency, dysuria, lower abdominal pain, and flank pain.”

12. About 95% of urinary tract infections (UTIs) occur when bacteria ascend the urethra to the bladder or kidney with the remainder of UTIs being

d. hematogenous.

“About 95% of UTIs occur when bacteria ascend the urethra to the bladder and, in the case of pyelonephritis, ascend the ureter to the kidney. The remainder of UTIs are hematogenous.”

44 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 13. Vesicoureteral reflux is usually caused by ______that result(s) in incompetence of the ureterovesical valve.

d. a congenital defect

“Vesicoureteral reflux is usually caused by a congenital defect that results in incompetence of the ureterovesical valve.”

14. ______is infection of the bladder.

c. Cystitis

“Cystitis is infection of the bladder.”

15. In diagnosed cases of ______, a patient’s urine culture will satisfy criteria for urinary tract infection (UTI) even in the absence of urinary tract infection signs or symptoms.

a. asymptomatic bacteriuria

“Asymptomatic bacteriuria is absence of UTI signs or symptoms in a patient whose urine culture satisfies criteria for UTI.”

16. True or False: All forms of symptomatic bacterial urinary tract infection (UTI) require antibiotics.

a. True

“All forms of symptomatic bacterial UTI require antibiotics.”

17. Asymptomatic bacteriuria in patients with diabetes, elderly patients, or patients with chronically indwelling bladder catheters

c. should not be treated.

“Asymptomatic bacteriuria - Typically, asymptomatic bacteriuria in patients with diabetes, elderly patients, or patients with chronically indwelling bladder catheters should not be treated.”

18. In pregnant women, which of the following antibiotics should be avoided during the first trimester?

45 nursece4less.com nursece4less.com nursece4less.com nursece4less.com c. Trimethoprim

“In pregnant women, only a few antibiotics can be safely used. Oral beta-lactams, sulfonamides, and nitrofurantoin are considered safe in early pregnancy, but trimethoprim should be avoided during the 1st trimester, and sulfamethoxazole should be avoided during the 3rd trimester, particularly near parturition.”

19. Candiduria causes urethral symptoms, mild urethral itching, dysuria, watery discharge, in ______of men.

a. 5% b. 2% c. 10% d. None of the above [correct answer]

“Most patients with candiduria are asymptomatic. Whether Candida can cause urethral symptoms (mild urethral itching, dysuria, watery discharge) in men is uncertain.”

20. Emphysematous cystitis is an infection of the ______produced by gas forming organisms.

a. bladder

“Emphysematous cystitis is an infection of the bladder produced by gas forming organisms. In patients with poorly controlled diabetes, pneumaturia (gas in the urine) due to emphysematous cystitis has occurred.”

21. Candiduria should be treated in

c. neutropenic patients.

“Fungal Urinary Tract Infections ... Treatment: Only for symptomatic or high-risk patients. Fluconazole or, for resistant organisms, amphotericin B; sometimes flucytosine is added. Fungal colonization of catheters does not require treatment. Asymptomatic candiduria rarely requires therapy. Candiduria should be treated in the following: Symptomatic patients; Neutropenic patients; Patients with renal allografts; Patients who are undergoing urologic manipulation.”

46 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 22. Tubulointerstitial nephritis is inflammation of the tubule of the ______and the surrounding interstitial tissue of the kidney.

c. nephron

“Glomerulonephritis is inflammation of the glomerulus of the nephron. Tubulointerstitial nephritis is inflammation of the tubule of the nephron and the surrounding interstitial tissue of the kidney. This is often referred to simply as interstitial nephritis.”

23. The appearance of microscopic or gross amounts of blood in the urine is referred to as

d. hematuria.

“Hematuria – microscopic or gross appearance of blood in the urine.”

24. Complications of nephritis include ______, which is the accumulation of waste products rich in nitrogen in the bloodstream.

a. azotemia

“Complications of Nephritis ... Waste products rich in nitrogen like urea accumulate in the bloodstream (azotemia).”

25. ______is caused by decreased excretion of acids, which leads to their accumulation in the blood, causing neurological and muscular disturbances in the body.

a. Metabolic acidosis

“Decreased excretion of acids causes it to accumulate in the blood (metabolic acidosis) which causes neurological and muscular disturbances.”

Reference Section

47 nursece4less.com nursece4less.com nursece4less.com nursece4less.com The References below include published works and in-text citations of published works that are intended as helpful material for your further reading. [References are for a multi-part series on Common And Uncommon Kidney Diseases].

1. Webster AC, Nagler E V., Morton RL, Masson P. (2017). Chronic Kidney Disease. Vol. 389, The Lancet. 2017. p. 1238–52. 2. The National Kidney Foundation (2013). Kidney Disease. NKF. 3. Centers for Disease Control and Prevention. (2014). National Chronic Kidney Disease Fact Sheet. CKD Surveill Proj. 2014;1–4. 4. Little MH, Brown D, Humphreys BD, McMahon AP, Miner JH, Sands JM, et al. (2014). Defining kidney biology to understand renal disease. Clin J Am Soc Nephrol; 9(4):809–11. 5. Said A, Desai C, Lerma E V. (2015). Chronic kidney disease. Disease-a- Month. Vol. 61;p. 374–7. 6. Ahmed SA bdalla, de Hoog GS, Stevens DA, Fahal AH, van de Sande (2015). Renal Stones. Med Mycol.; 53(3):295–301. 7. Victoria SG (2015). Kidney stones. Better Health Victoria; p. 1–2. 8. Khan SR, Pearle MS, Robertson WG, Gambaro G, Canales BK, Doizi S, et al. (2016). Kidney stones. Nat Rev Dis Prim.; 16008. 9. Asplin JR. (2013). Treatment of Renal Stones. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism; p. 878–883. 10. Eisner BH, Goldfarb DS, Pareek G. (2013). Pharmacologic treatment of . Urol Clin North Am.; 40(1):21–30. 11. Johansson ME, Axelson H. (2013). Kidney cancer. Seminars in Cancer Biology; 23(1):1–2. 12. Motzer RJ, Jonasch E, Agarwal N, Beard C, Bhayani S, Bolger GB, et al. (2015). Kidney cancer. J Natl Compr Canc Netw.; 13(2):151–9. 13. UK CR. (2015). Advanced kidney cancer. 14. Wilson KM, Cho E. (2016). Obesity and kidney cancer. Recent Results in Cancer Research; p. 81–93. 15. American Society of Clinical Oncology (2013). Kidney Cancer Types. Cancer.net; 28(11):19. 16. Linehan WM, Ricketts CJ. (2013). The metabolic basis of kidney cancer. Seminars in Cancer Biology. Vol. 23;p. 46–55. 17. Motzer RJ, Jonasch E, Agarwal N, Beard C, Bhayani S, Bolger GB, et al. (2014). Kidney cancer. JNCCN Journal of the National Comprehensive Cancer Network. Vol. 12; p. 175–82. 18. Hancock SB, Georgiades CS. (2016). Kidney Cancer. Cancer J. 22(6):387–92. 19. Hancock SB and Georgiades CS. (2016). Kidney Cancer. Cancer J.; 22(6):387–92.

48 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 20. Delacroix SE, Matin SF, Araujo J, Wood CG. (2013). Kidney cancer. 60 Years of Survival Outcomes at the University of Texas MD Anderson Cancer Center. Vol. 9781461451. 21. Sudarshan S, Karam JA, Brugarolas J, Thompson RH, Uzzo R, Rini B, et al. (2013). Metabolism of kidney cancer: From the lab to clinical practice. European . Vol. 63; p. 244–51. 22. Jones JM, Bhatt J, Avery J, Laupacis A, Cowan K, Basappa NS, et al. (2017). Setting Research Priorities for Kidney Cancer. European Urology. 23. Wang Z, Choi ME. (2013). Autophagy in Kidney Health and Disease. Antioxid Redox Signal.; 20(3):1–52. 24. El Zorkany K, Bridson J-M, Sharma A, Halawa A. (2017). Transplant Renal Vein Thrombosis. Exp Clin Transplant.; 15(2):123–9. 25. J. O, A. G, K.K. L. (2013). Current reviews on renal vein thrombosis in neonates. Current Pediatric Reviews. Vol. 9; p. 195–9. 26. J.L. H, S.J. R, S.G. Y, J.A. J, T.M. S, S.C. K, et al. (2015). Late-onset renal vein thrombosis: A case report and review of the literature. Int J Surg Case Rep.; 6:73–6. 27. M. O, C. A, O. B, B. D, H. E, K. T. (2014). Acute renal artery thrombosis after kidney transplantation. J Vasc Bras.; 13(4):345–7. 28. Haridasan S, Sharma A, Rathi M. (2014). Treatment of membranous lupus nephritis. Clin Queries Nephrol.; 3(2–4):106–13. 29. A.N. J. (2015). Perinatal renal vein thrombosis; review of 6 cases. Ultrasound Med Biol.; 41(4):S88. 30. T. C, Arun, et al. (2014). Acute renal vein thrombosis in an adult-rare clinical entity. Indian Journal of Urology. Vol. 30, p. S164. 31. Galanaud J-P, Laroche J-P, Righini M. (2013). The history and historical treatments of deep vein thrombosis. Journal of thrombosis and haemostasis : Vol. 11, p. 402–11. 32. Balducci L. (2015). Anemia, fatigue and aging. Management of Hematological Cancer in Older People. p. 35–48. 33. The global issue of kidney disease. The Lancet. 2013;382(9887):101. 34. Nemati E, Einollahi B, Pezeshki ML, Porfarziani V, Fattahi MR. (2014). Does kidney transplantation with deceased or living donor affect graft survival? Nephrourol Mon.; 6(4). 35. Togan T, Turan H, Cifci E, Çiftci C. (2015). Ovarian and Renal Vein Thrombosis: A Rare Cause of Fever Outer the Postpartum Period. Case Rep Obstet Gynecol: 1–4. 36. Afsar B, Turkmen K, Covic A, Kanbay M. (2014). An update on coronary artery disease and chronic kidney disease. International Journal of Nephrology. 37. Cook HT. (2013). Complement and kidney disease. Curr Opin Nephrol Hypertens.; 22(3):295–301. 38. C. D, M.A. C, A. M, R. P, F. C, A. M, et al. (2014). Portal vein

49 nursece4less.com nursece4less.com nursece4less.com nursece4less.com thrombosis with renal cell carcinoma: A case report. Urologia Internationalis. Vol. 93, p. 241–3. 39. Sweeney C, Kirby JM. (2013). Radiological diagnosis of renal thrombosis in children. Curr Pediatr Rev.; 9(3):225–39. 40. Saoraya J, Inboriboon PC. (2013). Pulmonary vein thrombosis associated with a large hiatal hernia. J Emerg Med.; 44(3):e299-301. 41. Thajudeen B, Budhiraja P, Bracamonte ER. (2013). Bilateral renal artery thrombosis secondary to acute necrotizing pancreatitis. Clin Kidney J.; 6(5):503–6. 42. Stapleton AE. (2014). Urinary tract infection pathogenesis. Host factors. Infectious Disease Clinics of North America. Vol. 28, p. 150–9. 43. Kidney Infection [Internet]. [cited 2014 Jan 24]. Available from: http://my.clevelandclinic.org/urology-kidney/diseases- conditions/kidney-infection.aspx 44. Gupta K, Trautner BW. (2015). Urinary Tract Infections, Pyelonephritis, and Prostatitis. Harrison’s Princ Intern Med.; (1):861–8. 45. Moore K, Spence K. (2014). Urinary tract infection. Hospital Medicine Clinics, Vol. 3. 46. Saadeh S, Mattoo TK. (2011). Managing urinary tract infections. Pediatr Nephrol.; 26:1967–76. 47. Foxman B. (2014). Urinary Tract Infection Syndromes. Infect Dis Clin North Am.; 28(1):1–13. 48. Flores-Meireles A, Walker J, Caparon M, Hultgren S. (2015). Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol.; 13(5):269–84. 49. Rowe TA, Juthani-Mehta M. (2013). Urinary tract infection in older adults. Aging health.; 9(5):519–28. 50. Chenoweth CE, Saint S. (2011). Urinary tract infections. Infect Dis Clin North Am.; 25:103–15. 51. Foxman B. (2014). Urinary tract infection syndromes. Occurrence, recurrence, bacteriology, risk factors, and disease burden. Infectious Disease Clinics of North America. Vol. 28, p. 1–13. 52. Finucane TE. (2017). “Urinary Tract Infection”—Requiem for a Heavyweight. J Am Geriatr Soc.; 65(8):1650–5. 53. McKibben MJ, Seed P, Ross SS, Borawski KM. (2015). Urinary Tract Infection and Neurogenic Bladder. Urologic Clinics of North America. Vol. 42, p. 527–36. 54. Sheerin NS. (2015). Urinary tract infection. Medicine (Baltimore); 43(8):435–9. 55. Raynor MC, Carson CC. (2011). Urinary infections in men. Med Clin North Am.; 95:43–54. 56. DiVito M. (2014). Management of urinary tract infection (UTI) in the community. J Community Nurs.; 28(3):18–27. 57. Foxman B. (2013). Urinary Tract Infection. Women and Health. p. 553–

50 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 564. 58. Nicolle LE. (2014). Urinary tract infections in special populations. diabetes, renal transplant, HIV infection, and spinal cord injury. Infectious Disease Clinics of North America. Vol. 28, p. 91–104. 59. Storm A, Bhasin B, Rangachari D, Sperati CJ. (2014). Cachexia, Urinary Tract Infection, Nephromegaly, and Kidney Failure. American Journal of Kidney Diseases. Vol. 63, p. xviii–xxi. 60. Hickling DR, Sun T-T, Wu X-R. (2015). Anatomy and Physiology of the Urinary Tract: Relation to Host Defense and Microbial Infection. Microbiol Spectr.;3(4):10.1128/microbiolspec.UTI-0016-2012. 61. Dielubanza EJ, Mazur DJ, Schaeffer AJ. (2014). Management of non- catheter-associated complicated urinary tract infection. Infectious Disease Clinics of North America. Vol. 28, p. 122–34. 62. Rosen JM, Klumpp DJ. (2014). Mechanisms of pain from urinary tract infection. Int J Urol.; 21 Suppl 1:26–32. 63. Ali A Ben, Bagnis CI. (2014). Recurrent urinary tract infection. Rev Prat.; 64(7):969–71. 64. Glissmeyer EW, Korgenski EK, Wilkes J, Schunk JE, Sheng X, Blaschke AJ, et al. (2014). Dipstick screening for urinary tract infection in febrile infants. Pediatrics.; 133(5):e1121-7. 65. Rowe TA, Juthani-Mehta M. (2014). Diagnosis and management of urinary tract infection in older adults. Infectious Disease Clinics of North America. Vol. 28, p. 76–89. 66. Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. (2015). Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nat Rev Microbiol.; 13(5):269–84. 67. Castañeda DA, León K, Martín R, López L, Pérez H, Lozano E. (2013). Urinary Tract Infection and Kidney Transplantation: A Review of Diagnosis, Causes, and Current Clinical Approach. TPS.; 45:15901592. 68. McLellan LK, Hunstad DA. (2016). Urinary Tract Infection: Pathogenesis and Outlook. Trends in Molecular Medicine. Vol. 22, p. 946–57. 69. Saint S, Gaies E, Fowler KE, Harrod M, Krein SL. (2014). Introducing a catheter-associated urinary tract infection (CAUTI) prevention guide to patient safety (GPS). Am J Infect Control.; 42(5):548–50. 70. NICE. (2013). Urinary tract infection (lower) - women [Internet]. National Institute for Health and Care Excellence - Clinical Knowledge Summaries. Available from: http://cks.nice.org.uk/urinary-tract- infection-lower-women#!backgroundsub:3 71. Purvis S, Gion T, Kennedy G, Rees S, Safdar N, VanDenBergh S, et al. (2014). Catheter-Associated Urinary Tract Infection. J Nurs Care Qual.; 29(2):141–8. 72. Kauffman CA. (2014). Diagnosis and management of fungal urinary tract infection. Infectious Disease Clinics of North America. Vol. 28, p. 61–74.

51 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 73. Keren R, Shaikh N, Pohl H, Gravens-Mueller L, Ivanova A, Zaoutis L, et al. (2015). Risk Factors for Recurrent Urinary Tract Infection and Renal Scarring. Pediatrics.; 136(1):e13-21. 74. A.D. S, I.I. R, J.S. W, D. S, R. M. (2014). Ommaya reservoir-related infections: Clinical manifestations and treatment outcomes. Journal of Infection. Vol. 68, p. 216–24. 75. Lech M, Anders H-J. (2013). The Pathogenesis of Lupus Nephritis. J Am Soc Nephrol.; 24(9):1357–66. 76. Joyce E, Glasner P, Ranganathan S, Swiatecka-Urban A. (2017). Tubulointerstitial nephritis: diagnosis, treatment, and monitoring. Pediatr Nephrol.; 32(4):577–87. 77. Kiremitci S, Ensari A. (2014). Classifying lupus nephritis: An ongoing story. Scientific World Journal. 78. Porter CC, Avner ED. (2016). Chapter 532 - Tubulointerstitial Nephritis. Nelson Textb Pediatr; 2-Volume Set: 2535–2537. 79. Ali A, Al-Windawi S. (2013). Tubulointerstitial lupus nephritis. J Nephropathol.; 2(1):75–80. 80. Lim S, Alam MG. (2003). Ciprofloxacin-induced acute interstitial nephritis and autoimmune hemolytic anemia. Ren Fail.; 25(4):647–51. 81. Shah S, Carter-Monroe N, Atta MG. (2015). Granulomatous interstitial nephritis. Clin Kidney J.; 8(5):516–23. 82. Levinson RD. (2016). Tubulointerstitial nephritis and uveitis syndrome. Intraocular Inflammation. p. 873–9. 83. Park BS, Park S, Jin K, Choi G, Park KM, Jo KM, et al. (2014). Nephrotic syndrome complicated with portal, splenic, and superior mesenteric vein thrombosis. Kidney Res Clin Pract.; 33(3):161–4. 84. Liebeskind DS. (2014). Nephrotic syndrome. Handb Clin Neurol.; 119:405–15. 85. Cohen EP. (2015). Nephrotic syndrome. Medscape. 86. Jalanko H, Holmberg C. (2015). Congenital nephrotic syndrome. Pediatric Nephrology, Seventh Edition. p. 753–76. 87. Zhou H-T, Wang B, Che X-Y. (2014). Nephrotic syndrome in hand, foot and mouth disease caused by coxsackievirus A16: a case report. Int J Infect Dis.; 28:1–2. 88. Barbano B, Gigante A, Amoroso A, Cianci R. (2013). Thrombosis in nephrotic syndrome. Semin Thromb Hemost.; 39(5):469–76. 89. Mubarak M, Kazi J. (2013). Study of nephrotic syndrome in children: Importance of light, immunoflourescence and electron microscopic observations to a correct classification of glomerulopathies. Nefrologia; 33(2):237–42. 90. Glassock RJ, Fervenza FC, Hebert L, Cameron JS. (2015). Nephrotic syndrome redux. Nephrol Dial Transplant; 30(1):12–7. 91. Fanni C, Loddo C, Faa G, Ottonello G, Puddu M, Fanos V. (2014). Congenital nephrotic syndrome. J Pediatr Neonatal Individ Med;

52 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 3(2):1–8. 92. Saleem MA. (2013). New developments in steroid-resistant nephrotic syndrome. Pediatric Nephrology. Vol. 28, p. 699–709. 93. Yee J. (2014). Treatment of nephrotic syndrome: Retrospection. Advances in Chronic Kidney Disease; 21(2):115–8. 94. Tullu M, Agarwal S, Deshmukh C, Divecha C. (2014). A rare case of nephrotic syndrome: ′Nailed′ the diagnosis. J Postgrad Med. 60(2):179. 95. Nishi S, Ubara Y, Utsunomiya Y, Okada K, Obata Y, Kai H, et al. (2014). Evidence-based clinical practice guidelines for nephrotic syndrome. Clinical and Experimental Nephrology. Vol. 20, p. 342–70. 96. Kang HG, Cheong H Il. (2015). Nephrotic syndrome: What’s new, what’s hot? Korean Journal of Pediatrics. Vol. 58, p. 275–82. 97. Pal A, Kaskel F. (2016). History of Nephrotic Syndrome and Evolution of its Treatment. Front Pediatr; 4(May):56. 98. Christiansen CF, Onega T, Sværke C, Körmendiné Farkas D, Jespersen B, Baron JA, et al. (2014). Risk and prognosis of cancer in patients with nephrotic syndrome. Am J Med; 127(9):871–877.e1. 99. Andolino TP, Reid-Adam J. (2015). Nephrotic syndrome. Pediatr Rev; 36(3):117-25, 129. 100. Holmberg C, Jalanko H. (2014). Congenital nephrotic syndrome and recurrence of proteinuria after renal transplantation. Pediatr Nephrol; 29(12):2309–17. 101. Gilbert RD, Hind E, Vadgama B. (2017). Diabetes and nephrotic syndrome: Answers. Pediatr Nephrol; 32(10):1887–9. 102. Zolotas E, Krishnan RG. (2016). Nephrotic syndrome. Paediatr Child Health (Oxford); 26(8):349–52. 103. Safder O, El-Desoky SM, Bockenhauer D, Sabire N, Kari JA. (2014). Steroid-resistant nephrotic syndrome in a child with dysmorphic features: Questions. Pediatr Nephrol; 29(5):837–8. 104. Andolino TP, Reid-Adam J. (2015). Nephrotic Syndrome. Pediatr Rev; 36(3):117–26. 105. Malaga-Dieguez L, Susztak K. (2013). ADCK4 “reenergizes” nephrotic syndrome. Journal of Clinical Investigation. Vol. 123, p. 4996–9. 106. Gansevoort RT, Correa-Rotter R, Hemmelgarn BR, Jafar TH, Heerspink HJL, Mann JF, et al. (2013). Chronic kidney disease and cardiovascular risk: Epidemiology, mechanisms, and prevention. Lancet; 382(9889):339–52. 107. Methods: Chronic kidney disease. Am J Kidney Dis. 2014;63(1 SUPPL.). 108. Ecder T. (2013). Early diagnosis saves lives: focus on patients with chronic kidney disease. Kidney Int Suppl; 3(4):335–6. 109. Kidney Health Australia. (2014). YOUR HEART AND CHRONIC KIDNEY DISEASE (CKD [Internet]. YOUR HEART AND CHRONIC KIDNEY DISEASE (CKD. Available from: http://www.kidney.org.au/ForPatients/Management/YourheartandCKD/

53 nursece4less.com nursece4less.com nursece4less.com nursece4less.com tabid/749/Default.aspx 110. Inagi R. (2015). The gut-kidney connection in advanced chronic kidney disease. Kidney Research and Clinical Practice; 34(4):191–3. 111. Ingelfinger JR, Chawla LS, Eggers PW, Star RA, Kimmel PL. (2014). Acute Kidney Injury and Chronic Kidney Disease as Interconnected Syndromes. N Engl J Med; 371:58–66. 112. Tonelli M, Riella MC. (2014). Chronic kidney disease and the aging population. Kidney Int; 85(2):487–91. 113. Bakris, G. and Forman, J. (2017). Secondary factors and progression of chronic kidney disease. UpToDate. Available from https://www.uptodate.com/contents/secondary-factors-and- progression-of-chronic-kidney- disease?source=search_result&search=progressive%20chronic%20kidn ey%20disease&selectedTitle=3~150 114. James I. McMillan M. (2015). Chronic Kidney Disease. Merck Man; 1–7. 115. McFarlane P, Gilbert RE, MacCallum L, Senior P. (2013). Chronic Kidney Disease in Diabetes. Can J Diabetes; 37(SUPPL.1). 116. Pyram R, Kansara A, Banerji MA, Loney-Hutchinson L. Chronic kidney disease and diabetes. Maturitas. Vol. 71, p. 94–103. 117. Zhao Y-Y. (2013). Metabolomics in chronic kidney disease. Clin Chim Acta; 422:59–69. 118. Johansen KL, Lee C. (2015). Body composition in chronic kidney disease. Curr Opin Nephrol Hypertens; 1. 119. Sise ME, Courtwright AM, Channick RN. (2013). Pulmonary hypertension in patients with chronic and end-stage kidney disease. Kidney Int; 84(4):682–92. 120. Lewis R. (2013). An overview of chronic kidney disease in older people. Nurs Older People; 25(10):31–8. 121. Eckardt KU, Coresh J, Devuyst O, Johnson RJ, Köttgen A, Levey AS, et al. (2013). Evolving importance of kidney disease: From subspecialty to global health burden. Lancet; 382(9887):158–69. 122. Khan Z, Pandey M. (2014). Role of kidney biomarkers of chronic kidney disease: An update. Saudi Journal of Biological Sciences. Vol. 21, p. 294–9. 123. De Nicola L, Zoccali C. (2016). Chronic kidney disease prevalence in the general population: Heterogeneity and concerns. Nephrology Dialysis Transplantation; Vol. 31, p. 331–5. 124. Kalamas AG, Niemann CU. (2013). Patients with chronic kidney disease. Medical Clinics of North America. Vol. 97, p. 1109–22. 125. Koushik NS, McArthur SF, Baird AD. (2010). Adult chronic kidney disease: neurocognition in chronic renal failure. Neuropsychol Rev;20:33–51. 126. Dageforde LA, Cavanaugh KL. (2013). Health Literacy: Emerging Evidence and Applications in Kidney Disease Care. Advances in Chronic

54 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Kidney Disease; Vol. 20: p. 311–9. 127. Jha V, Garcia-garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. (2013). Global Kidney Disease 3 Chronic kidney disease: global dimension and perspectives. Lancet; 382(9888):260–72. 128. Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B, et al. (2013). Chronic kidney disease: global dimension and perspectives. Lancet; 382:260–72. 129. Drawz P, Rahman M. (2015). Chronic Kidney Disease. Ann Intern Med; 162(11):ITC1. 130. Vassalotti JA, Centor R, Turner BJ, Greer RC, Choi M, Sequist TD. (2016). Practical Approach to Detection and Management of Chronic Kidney Disease for the Primary Care Clinician. Am J Med; 129(2):153– 162.e7. 131. Kurts C. (2013). A crystal-clear mechanism of chronic kidney disease. Kidney Int.; 84(5):859–61. 132. Yerramilli M, Farace G, Quinn J, Yerramilli M. (2016). Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury. Vet Clin North Am Small Anim Pract; 46(6):1–33. 133. Savige J, Gregory M, Gross O, Kashtan C, Ding J, Flinter F. (2013). Expert Guidelines for the Management of Alport Syndrome and Thin Basement Membrane Nephropathy. J Am Soc Nephrol; 24(3):364–75. 134. Nakanishi K, Yoshikawa N. (2015). Alport syndrome. Nihon Jinzo Gakkai Shi; 57(4):736–42. 135. C.E. K. (2014). Genetics and biological therapies for Alport syndrome. Expert Opin Orphan Drugs; 2(10):1037–47. 136. Kashtan C. (2017). Alport syndrome: facts and opinions. F1000Research; 6:50. 137. Fogo AB, Lusco MA, Najafian B, Alpers CE. (2016). AJKD Atlas of Renal Pathology: Alport Syndrome. Am J Kidney Dis; 68(4):e15–6. 138. Savige J. (2014). Alport syndrome: its effects on the glomerular filtration barrier and implications for future treatment. J Physiol; 592(18):4013–23. 139. Miner JH. (2014). Pathology vs. molecular genetics: (re)defining the spectrum of Alport syndrome. Kidney Int; 86(6):1081–3. 140. Rosado C, Bueno E, Felipe C, Valverde S, González-Sarmiento R. (2015). Study of the true clinical progression of autosomal dominant alport syndrome in a European population. Kidney Blood Press Res; 40(4):435–42. 141. Bellini LP, Brum GS. (2016). Cataract surgery in patients with Alport syndrome. European Journal of Ophthalmology. Vol. 26, p. e85. 142. Zhang Y, Ding J. (2017). Renal, auricular, and ocular outcomes of Alport syndrome and their current management. Pediatric Nephrology; 1–8. 143. Ahmed F, Kamae KK, Jones DJ, DeAngelis MM, Hageman GS, Gregory

55 nursece4less.com nursece4less.com nursece4less.com nursece4less.com MC, et al. (2013). Temporal Macular Thinning Associated With X-Linked Alport Syndrome. JAMA Ophthalmol.; 131(6):777. 144. J.H. M, C. B, F. F, O. G, P. J, C.E. K, et al. (2014). The 2014 international workshop on alport syndrome. Kidney International. Vol. 86, p. 679–84. 145. Mencarelli MA, Heidet L, Storey H, van Geel M, Knebelmann B, Fallerini C, et al. (2015). Evidence of digenic inheritance in Alport syndrome. J Med Genet.; 52(3):163–74. 146. Gross O, Perin L, Deltas C. (2014). Alport syndrome from bench to bedside: The potential of current treatment beyond RAAS blockade and the horizon of future therapies. Nephrology Dialysis Transplantation. Vol. 29, p. iv124-iv130. 147. Kashtan CE. (2017). Clinical manifestations, diagnosis and treatment of hereditary nephritis (Alport syndrome) [Internet]. UpToDate. Available from: http://www.uptodate.com/contents/clinical-manifestations- diagnosis-and-treatment-of-hereditary-nephritis-alport- syndrome?source=search_result&search=doença+de+alport&selectedT itle=1~37 148. Żurawski J, Burchardt P, Seget M, Moczko J, Woźniak A, Grochowalski M, et al. (2016). Difficulties in differentiating thin basement membrane disease from Alport syndrome. Polish J Pathol.; 67(4):357–63. 149. Savige J, Colville D, Rheault M, Gear S, Lennon R, Lagas S, et al. (2016). Alport Syndrome in Women and Girls. Clin J Am Soc Nephrol.; 11(9):1713–20. 150. Mallett A, Tang W, Clayton PA, Stevenson S, McDonald SP, Hawley CM, et al. (2014). End-stage kidney disease due to alport syndrome: Outcomes in 296 consecutive Australia and New Zealand dialysis and transplant registry cases. Nephrol Dial Transplant.; 29(12):2277–86. 151. Ghosh S, Singh M, Sahoo R, Rao S. (2014). Alport syndrome: A rare cause of uraemia. BMJ Case Rep. 152. Katayama K, Nomura S, Tryggvason K, Ito M. (2014). Searching for a treatment for Alport syndrome using mouse models. World J Nephrol.; 3(4):230–6. 153. Noone D, Licht C. (2013). An update on the pathomechanisms and future therapies of Alport syndrome. Pediatric Nephrology. Vol. 28, p. 1025–36. 154. Omachi K, Miyakita R, Fukuda R, Kai Y, Suico MA, Yokota T, et al. (2017). Long-term treatment with EGFR inhibitor erlotinib attenuates renal inflammatory cytokines but not nephropathy in Alport syndrome mouse model. Clinical and Experimental Nephrology.; 1–9. 155. Savva I, Pierides A, Deltas C. (2016). RAAS inhibition and the course of Alport syndrome. Pharmacological Research. Vol. 107, p. 205–10. 156. Neves C, Cordinhã C, Ferreira C, Gomes C, Correia AJ. (2014). Alport syndrome - A rare presentation. Pediatr Nephrol.; 29(9):1836.

56 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 157. Mohamed N, Nasr SH. (2014). Renal Amyloidosis. Surgical Pathology Clinics. Vol. 7, p. 409–25. 158. Said SM, Sethi S, Valeri AM, Leung N, Cornell LD, Fidler ME, et al. (2013). Renal amyloidosis: Origin and clinicopathologic correlations of 474 recent cases. Clin J Am Soc Nephrol.; 8(9):1515–23. 159. Hazenberg BPC. (2013). Amyloidosis. Rheum Dis Clin North Am.; 39(2):323–45. 160. Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet. 2015;387(10038):2641–54. 161. Hazenberg BPC. (2013). Amyloidosis. A clinical overview. Vol. 39, Rheumatic Disease Clinics of North America. p. 323–45. 162. Abdallah E, Waked E. (2013). Incidence and clinical outcome of renal amyloidosis: a retrospective study. Saudi J Kidney Dis Transpl.; 24(5):950–8. 163. Abdallah E, Waked E. (2013). Incidence and clinical outcome of renal amyloidosis: a retrospective study. Saudi J Kidney Dis Transpl.; 24(5):950–8. 164. Sonneveld P, Jongen JLM. (2010). Dealing with neuropathy in plasma- cell dyscrasias. Hematology Am Soc Hematol Educ Program: p.423–30. 165. Mahmood S, Palladini G, Sanchorawala V, Wechalekar A. (2014). Update on treatment of light chain amyloidosis. Haematologica. Vol. 99; p. 209–21. 166. Fogo AB, Lusco MA, Najafian B, Alpers CE. (2015). AJKD atlas of renal pathology: AL amyloidosis. American Journal of Kidney Diseases. Vol. 66, p. e43–5. 167. Abdallah E, Waked E. (2013). Incidence and clinical outcome of renal amyloidosis: a retrospective study. Saudi J Kidney Dis Transpl.; 24(5):950–8. 168. Gonzalo-Garijo MA, et al. (2014). Renal amyloidosis in a patient with x- linked agammaglobulinemia (Bruton’s Disease) and bronchiectasis. J Clin Immunol.; 34(1):119–22. 169. Ando Y. (2015). Amyloidosis and neurological disorders: Treatable amyloidosis. Rinsho Shinkeigaku.; 55(11):797–803. 170. Mohamed N, Nasr SH. (2014). Renal Amyloidosis. Surg Pathol Clin.; 7(3):409–25. 171. Dispenzieri A. (2015). Renal risk and response in amyloidosis. Vol. 124, Blood. p. 2315–6. 172. Roy V. (2012). Autologous Stem Cell Transplant for AL Amyloidosis. Bone Marrow Research. p. 1–5. 173. Sethi S, Theis JD, Quint P, Maierhofer W, Kurtin PJ, Dogan A, et al. (2013). Renal amyloidosis associated with a novel sequence variant of gelsolin. Am J Kidney Dis.; 61(1):161–6. 174. Stoilova T, Colombo L, Forloni G, Tagliavini F, Salmona M. (2013). A new face for old antibiotics: tetracyclines in treatment of amyloidoses. J

57 nursece4less.com nursece4less.com nursece4less.com nursece4less.com Med Chem.; 56:5987–6006. 175. Wechalekar AD, Gillmore JD, Hawkins PN. (2016). Systemic amyloidosis. The Lancet; Vol. 387, p. 2641–54. 176. Misumi Y, Ando Y. (2014). Classification of amyloidosis. Brain and Nerve; 66(7):731–7. 177. Ilgen U, Çelebi ZK, Kuzu I, Kutlay S, Nergizoglu G, Ates K. (2013). Renal amyloidosis secondary to hidradenitis suppurativa. Clinical Kidney Journal. Vol. 6, p. 667–8. 178. Mollee P, Renaut P, Gottlieb D, Goodman H. (2014). How to diagnose amyloidosis. Internal Medicine Journal. Vol. 44, p. 7–17. 179. Tang W, McDonald SP, Hawley CM, Badve S V., Boudville N, Brown FG, et al. (2013). End-stage renal failure due to amyloidosis: Outcomes in 490 ANZDATA registry cases. Nephrol Dial Transplant.; 28(2):455–61. 180. Koscielska M, Shebani Z, Matuszkiewicz-Rowinska J. (2013). Renal amyloidosis. Przegl Lek.; 70(4):205–10. 181. Picken MM. (2015). Proteomics and mass spectrometry in the diagnosis of renal amyloidosis. Clinical Kidney Journal. Vol. 8, p. 665–72. 182. Wechalekar AD, Gillmore JD, Bird J, Cavenagh J, Hawkins S, Kazmi M, et al. (2015). Guidelines on the management of AL amyloidosis. Br J Haematol.; 168(2):186–206. 183. Yilmaz M, Unsal A, Sokmen M, Kaptanogullari OH, Alkim C, Kabukcuoglu F, et al. (2013). Renal involvement in aa amyloidosis: Clinical outcomes and survival. Kidney Blood Press Res.; 37(1):33–42. 184. Greco A, Rizzo MI, De Virgilio A, Gallo A, Fusconi M, Pagliuca G, et al. (2015). Goodpasture’s syndrome: A clinical update. Autoimmunity Reviews. Vol. 14, p. 246–53. 185. Balke L, Both M, Arlt A, Rosenberg M, Bewig B. (2015). Severe adult respiratory distress syndrome from goodpasture syndrome: Survival using extracorporeal membrane oxygenation. Am J Respir Crit Care Med.; 191(2):228–9. 186. Salama AD, Pusey CD. (2013). Goodpasture syndrome and other antiglomerular basement membrane diseases. National Kidney Foundation’s Primer on Kidney Diseases, Sixth Edition. p. 193–197. 187. Seddiq N, Bella A. (2014). Goodpasture syndrome: First case from Saudi Arabia. Respirology.; 19:94. 188. V. J, A. V, A.A. R, J. J, J. W. (2014). Goodpasture’s syndrome with concomitant immune complex mixed membranous and proliferative glomerulonephritis. Clinical Nephrology. Vol. 81, p. 216–23. 189. Huart A, Josse AG, Chauveau D, Korach JM, Heshmati F, Bauvin E, et al. (2016). Outcomes of patients with Goodpasture syndrome: A nationwide cohort-based study from the French Society of Hemapheresis. J Autoimmun.; 73:24–9. 190. Mackintosh D, Mantha M, Oliver K. (2016). Goodpasture disease as a consequence of melioidosis. Intern Med J.; 46(12):1446–9.

58 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 191. E. A, M. F, M. B, H. M, M. A. (2014). Renal involvement as sole presentation of goodpasture’s syndrome. Journal of Investigative Medicine. Vol. 62, p. 426. 192. Stojkovikj J, Zejnel S, Gerasimovska B, Gerasimovska V, Stojkovic D, Trajkovski M, et al. (2016). Goodpasture syndrome diagnosed one year and a half after the appearance of the first symptoms. Maced J Med Sci.; 4(4):683–7. 193. Herbert DG, Buscher H, Nair P. (2014). Prolonged venovenous extracorporeal membrane oxygenation without anticoagulation: A case of goodpasture syndrome-related pulmonary haemorrhage. Crit Care Resusc.; 16(1):69–72. 194. Gado K, Szabo LZ, Csako L, Domjan G. Wegener’s granulomatosis. Orv Hetil. 2013;154(28):1083–95. 195. Dinic MZ, Sekulovic LK, Zolotarevski L, Zecevic RD. (2013). Fulminant Wegener’s granulomatosis: a case report. Vojnosanit Pregl.; 70:887– 90. 196. Falk, R. and Merkel, P. (2017). Maintenance immunosuppressive therapy in granulomatosis with polyangiitis and microscopic polyangiitis. UpToDate. Available from https://www.uptodate.com/contents/maintenance-immunosuppressive- therapy-in-granulomatosis-with-polyangiitis-and-microscopic- polyangiitis?source=search_result&search=wegeners&selectedTitle=3~ 150. 197. Merkel, P. (2017). Overview of and approach to the vasculitides in adults. UpToDate. Retrieved online at https://www.uptodate.com/contents/overview-of-and-approach-to-the- vasculitides-in- adults?source=search_result&search=wegeners&selectedTitle=5~150 198. Islam MA, Azad AK, Islam MS, Shazzad MN, Haq SA. (2013). Wegener’s granulomatosis - a case report. Mymensingh Med J.; 22(1):196–9. 199. Vervloet DMTF, De Backer T, Van Dorpe J. (2016). Granulomatosis with polyangiitis (Wegener’s) hidden in the aortic valve. Int J Cardiovasc Imaging.; 32(5):753–5. 200. Dammacco F, Cicco S, Ribatti D, Vacca A. (2016). Granulomatosis with polyangiitis (Wegener’s). Systemic Vasculitides: Current Status and Perspectives. p. 119–28. 201. Zycinska K, Wardyn K, Zielonka TM, Nitsch-Osuch A, Zarzycki S, Demkow U, et al. (2013). Subglottic and tracheal stenosis due to Wegener’s granulomatosis. Advances in Experimental Medicine and Biology. p. 221–4. 202. Yegin EG, Can M, Yilmaz N, Aydin SZ, Yavuz S, Tuglular S, et al. (2013). Activity and damage in granulomatosis with polyangiitis. Int J Rheum Dis.; 16(1):61–71. 203. Polachek A, Caspi D, Elkayam O. (2013). Granulomatosis and

59 nursece4less.com nursece4less.com nursece4less.com nursece4less.com polyangiitis: The rituximab option. Isr Med Assoc J.; 15(3):193–4. 204. Lutalo PMK, D’Cruz DP. (2014). Diagnosis and classification of granulomatosis with polyangiitis (aka Wegener’s granulomatosis). J Autoimmun.; 48–49:94–8. 205. Comarmond C, Cacoub P. (2014). Granulomatosis with polyangiitis (Wegener): Clinical aspects and treatment. Autoimmunity Reviews. Vol. 13, p. 1121–5. 206. Tarzi RM, Pusey CD. (2014). Current and future prospects in the management of granulomatosis with polyangiitis (Wegener’s granulomatosis). Ther Clin Risk Manag.; 10:279–93. 207. Larkins N, Harris KC, Morishita K, Matsell DG. (2014). Chylous pericardial effusion in granulomatosis with polyangiitis. Nephrology. Vol. 19, p. 367–8. 208. Da Costa CF, Polanski JF. (2014). Wegener granulomatosis: Otologic manifestation as first symptom. Int Arch Otorhinolaryngol.; 19(3):266– 268. 209. Csernok E, Gross WL. (2013). Current understanding of the pathogenesis of granulomatosis with polyangiitis (Wegener’s). Expert Rev Clin Immunol.; 9(April):641–8. 210. Bohm M, Gonzalez Fernandez MI, Ozen S, Pistorio A, Dolezalova P, Brogan P, et al. (2014). Clinical features of childhood granulomatosis with polyangiitis (wegener’s granulomatosis). Pediatr Rheumatol Online J.; 12(1):18. 211. Hughes J, Barkhoudarian G, Ciarlini P, Laws ER, Mody E, Inzucchi SE, et al. (2013). Refractory pituitary granulomatosis with polyangiitis (Wegener’s) treated with rituximab. Endocr Pract.; 19(1):e1-7. 212. Wechsler ME, Akuthota P, Jayne D, Khoury P, Klion A, Langford CA, et al. (2017). Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis. N Engl J Med.; 376(20):1921–32. 213. Sharma A, Deshmukh S, Dabholkar J. (2013). ENT manifestations of Wegeners granulomatosis. Otolaryngol Pol.; 67(5):257–60. 214. Campainha S, Goncalves M, Tavares V, Casteloes P, Marinho A, Neves S. (2013). Granulomatosis with polyangiitis initially misdiagnosed as lung cancer. Rev Port Pneumol.; 19(1):45–8. 215. Næser E, Friis P, Hansen IT, Næser K. (2013). External dacryocystorhinostomy in Wegener’s granulomatosis. Acta Ophthalmol.; 91(8):776–8. 216. Vaszar LT, Orzechowski NM, Specks U, Ytterberg SR, Loftus E V., Mark EJ, et al. (2014). Coexistent Pulmonary Granulomatosis With Polyangiitis (Wegener Granulomatosis) and Crohn Disease. Am J Surg Pathol.; 38(3):354–9. 217. Hoyle P, Steele JC. (2014). Granulomatosis with polyangiitis. Oral Surg.; 7(S1):84–7. 218. Taylor SC, Clayburgh DR, Rosenbaum JT, Schindler JS. (2013). Clinical

60 nursece4less.com nursece4less.com nursece4less.com nursece4less.com manifestations and treatment of idiopathic and Wegener granulomatosis-associated subglottic stenosis. JAMA Otolaryngol Head Neck Surg.; 139(1):76–81. 219. Asakura K, Muto T. (2013). Neurological involvement in Wegener’s granulomatosis. Brain and Nerve.; 65(11):1311–7. 220. de Lima AM, Torraca P de FS, da Rocha SP, Santiago CMR, Paes-Ferraz FHR. (2015). Granulomatosis with polyangiitis, a new nomenclature for Wegener’s granulomatosis - Case report. An Bras Dermatol.; 90(3):S101–3. 221. Daar G, Cengiz AB, Kara A, Topaloğlu R, Yücel ÖT, Dursun İ. Wegener’s (2014). granulomatosis presenting with an isolated paranasal sinus involvement in a child. Arch Rheumatol.; 29(2):130–3. 222. Jiang B, Zhao Y, Wei S. (2013). Granulomatosis with Polyangiitis: The Relationship Between Ocular and Nasal Disease. Ocul Immunol Inflamm.; 21(2):115–8. 223. Christopher W. M, James O. B. (2014). Dialysis. BMJ.; 348. 224. Wilkie M. (2015). Peritoneal dialysis??? taking the lead to promote health literacy. Peritoneal Dialysis International.; 35(1):3. 225. Ronco C, Kellum JA, Bellomo R, Mehta RL. (2013). Acute dialysis quality initiative (ADQI). Contrib Nephrol.; 182:1–4. 226. Daugirdas JT. (2013). Dialysis time, survival, and dose-targeting bias. Kidney Int.; 83(1):9–13. 227. Azar AT, Grzegorzewska AE. (2013). Initiation of dialysis. Stud Comput Intell.; 404:3–43. 228. Johansen KL, Delgado C, Bao Y, Tamura MK. (2013). Frailty and Dialysis Initiation. Semin Dial.; 26(6):690–6. 229. St. Peter WL. (2015). Management of Polypharmacy in Dialysis Patients. Semin Dial.; 28(4):427–32. 230. Christie E, Pannu N. (2014). Dialysis and acute kidney injury: Current evidence. Semin Dial.; 27(2):154–9. 231. Brown EA. (2015). Peritoneal dialysis for the elderly. Dialysis in Older Adults: A Clinical Handbook. p. 57–65. 232. Karopadi AN, Mason G, Rettore E, Ronco C. (2013). Cost of peritoneal dialysis and haemodialysis across the world. Nephrol Dial Transplant.; 28(10):2553–69. 233. Hansson JH, Watnick S. (2016). Update on Peritoneal Dialysis: Core Curriculum. Am J Kidney Dis.; 67(1):151–64. 234. Wong G, Turner RM, Chapman JR, Howell M, Lim WH, Webster AC, et al. (2013). Time on dialysis and cancer risk after kidney transplantation. Transplantation.; 95(1):114–21. 235. Hamilton D. (2013). Kidney Transplantation: A History. Kidney Transplantation-Principles and Practice: Seventh Edition. p. 1–9. 236. Brennan DC. (2016). Introduction: Kidney Transplantation and Viral Infection. Seminars in Nephrology.; 36(5):343.

61 nursece4less.com nursece4less.com nursece4less.com nursece4less.com 237. Mahendran AO, Barlow AD. (2014). Kidney transplantation. Surg.; 32(7):364–70. 238. Wallace CJ, Kingsmore DB. (2006). Transplantation and immunosuppressive therapy. Anaesth Intensive Care Med.;7(6):196–9. 239. Jain S, Jani A. (2016). Biomarkers in Kidney Transplantation. Biomarkers of Kidney Disease. p. 335–419. 240. Tzvetanov I, Giulianotti PC, Bejarano-Pineda L, Jeon H, Garcia-Roca R, Bianco F, et al. (2013). Robotic-assisted kidney transplantation. Surgical Clinics of North America. Vol. 93, p. 1309–23. 241. Bansal T, Garg A, Snowden JA, McKane W. (2012). Defining the role of renal transplantation in the modern management of multiple myeloma and other plasma cell dyscrasias. Nephron - Clinical Practice. Vol. 120. 242. Lewis T, Kirby E, Kyle JA. (2014). Infection in kidney transplantation. US Pharm.; 39(8):HS10-HS16. 243. Boffa C, Barnes JC, Knight SR, Ploeg RJ. (2015). Protocol biopsies following kidney transplantation. Cochrane Database of Systematic Reviews. 244. Franquesa M, Flaquer M, Cruzado JM, Grinyó JM. (2013). Kidney regeneration and repair after transplantation. Curr Opin Organ Transplant.;18:191–6. 245. T. L, E. K. (2014). Infection in kidney transplantation. U.S. Pharmacist. Vol. 39, p. HS10-HS16. 246. Neild, G.H. (2017). Life expectancy with chronic kidney disease: an educational review. Pediatr Nephrol; 32(2): 243–248.

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