Compendium of urinalysis Urine test strips and microscopy Main disease indications Urinary Tract Infection Interesting facts Are you aware of that … • More than 500 million people – 10% • One in 20 deaths is caused by diabetes; of the world’s population – have some 8,700 deaths every day; six every min- form of kidney damage 1 ute 3 • Urinary tract infections are the sec- • By 2030, almost 23.6 million people will ond most common type of infection in die from cardiovascular disease, mainly the human body 2 heart disease and stroke 4 1 22 Content 1 Main disease indication Urinary tract infection 8 Kidney disease 10 Diabetes 14 2 From urine fortune telling to real time diagnosis History of urinalysis 18 Application areas for urine test strips 20 Pre-analytical treatment and test procedure 22 3 Characteristics of urine test strips from Roche Composition and benefit of the test strip 28 Parameters of urine test strips 32 Detection of microalbuminuria with micral-test 56 4 Drug interferences in urine Influencing factors 60 5 Automated urinalysis Urine test strip systems 64 6 Urine microscopy in differential diagnosis Microscope 70 7 Urine particles and formed elements Blood cells 74 White blood cells 74 Red blood cells 76 Epithelial cells 78 Squamous epithelial cells 78 Renal tubular cells 79 Transitional epithelial cells 80 Atypical cells 81 Casts 82 Hyaline casts 82 Granular casts 84 Pigmented casts 85 Waxy casts 86 Red blood cell casts 87 White blood cell casts 88 Epithelial cell casts 88 Fatty casts 89 Cylindroids 90 Rare casts 90 Pseudo casts 91 3 Pathogens 92 Trichomonads 92 Fungi 93 Bacteria 94 Crystals 96 Calcium oxalate 96 Uric acid 97 Amorphous urate 98 Amorphous phosphate 98 Calcium phosphate 99 Calcium carbonate 99 Magnesium ammonium phosphate 99 Rare crystal 100 Dicalcium phosphate 100 Dimagnesium phosphate 100 Tyrosine 101 Leucine 101 Hippuric acid 101 Cystine 102 Ammonium biurate 102 Drug crystals 104 Other constituents 106 Fat globules and cholesterol crystals 106 Spermatozoa 106 Contamination 107 Vaginal secretion 107 Skin 107 Feces 107 Clothing 107 Sample vessels 108 Air 108 Latex gloves 108 Glass splinters 108 8 Diagnostic Renal disease 112 Glomerulonephritis 112 Acute pyelonephritis 112 Endocarditis 112 Nephrotic syndrome 113 Acute tubular necrosis 113 Urogenital disease 114 Bacterial cystitis 114 Vaginitis/urethritis/balanitis 114 9 Appendix References 118 Storage, influence and interference factors 122 Color change in urine 124 Drug interference factors 126 Microscopic urine sediment figures 130 44 5 66 1 Main disease indications Urine is a key health barometer for many diseases, mainly UTIs, kidney disease and diabetes. The analysis of urine can reveal se- rious diseases, which do not show symptoms in their early but treatable stages and causes severe damage if they remain undetected. 7 Urinary tract infection (UTI) The urinary apparatus is made up of: What is a UTI? • Two kidneys Most UTIs are caused by bacteria entering • Two ureters the urinary tract (urethra) and multiplying • The urinary bladder rapidly. The origin of bacteria, especially • The urethra E. coli, is usually the intestines or anus. Each day, the human body filters 170 liters of • UTI can mean anything from a mild inflam- primary urine through the kidneys. Primary mation of the bladder to severe kidney in- urine consists of water, salt and dissolved fections, and should be treated as soon as low-molecular blood constituents. possible The water and all substances needed by the • Bacteria can spread and infect the bladder organism are largely reabsorbed. The re- and kidneys. The only way to stop this is early maining “worthless” substance is known as detection and the prescription of antibiotics urine. The amount of urine finally excreted through the urethra each day is approxi- mately 1.5 liters. Two kidneys Two ureters The urinary bladder The urethra Fig. 1: The urinary apparatus 88 Main disease indications Urinary tract infection Symptoms and causes of UTI Did you know? Symptoms can vary, and sometimes there may Research by the National Institutes of Health be none at all. However, the most common are suggests that recurrent UTIs may be caused as follows: by the ability of bacteria to attach to cells • A burning sensation when urinating lining the urinary tract. • A frequent urge to urinate, but only in small A growth of E. coli bacteria in the vagina amounts can also result from spermicidal foam on • The urine may be discolored or cloudy, condoms. strong or foul-smelling • Back or abdominal pain • General feelings of illness or fever Causes of UTI include: • Sexual intercourse • Poor hygiene • Genetic makeup e.g. the proximity of the anus to the urethra Risk groups • Women are much more likely to get a UTI • People with diabetes have a higher risk of developing a UTI due to changes in the im- mune system • Any other disorder that suppresses the im- mune system raises the risk of a UTI 9 Kidney disease The kidneys are the most important excre- What does kidney disease imply? tion organ in the human organism. Every Kidney diseases are disorders that affect 24 hours around 1,500 liters of blood flow the kidneys. In many cases the tiny filtering through the kidneys. units (nephrons) are attacked and their abi- lity to filter properly is limited. Gradual loss If a UTI is not treated promptly, bacteria may of kidney function is called chronic kidney travel further up the ureters to multiply and disease (CKD), and people with CKD may infect the kidneys. develop permanent kidney failure as it pro- gresses. This may have fatal consequences Function of the kidneys: unless a dialysis machine is used or a kid- • Filter blood to excrete water, electrolytes ney transplant is performed. CKD occurs and metabolic end products (e.g. urea) gradually and is often silent, going unde- • Help to control blood pressure and blood tected for years. People with CKD may also pH have a high risk of suffering from a stroke or • Produce the important enzyme renin and heart attack. glycoprotein-hormone EPO • Help maintain healthy bones • Excrete blood constituents (e.g. glucose) • Maintain water and electrolyte balance • Regulate water content of intracellular and extracellular fluid Clean Blood with blood wastes Glomerulus Tubule Wastes (urine) to the bladder Nephron Fig. 2: Schematic illustration of a nephron 10 Main disease indications Kidney disease Nephrons – the trigger for CKD Also, substances such as protein may leak Each kidney has between one and three mil- into the urine rather than remaining within lion nephrons. Each nephron can be sub- the blood. divided further into glomerular and tubular sections. CKD can lead to kidney failure and trans- plantation without early detection and mo- In the nephron, a glomerulus – a tiny blood nitoring. vessel – intertwines with a tubule which collects urine. The glomerulus acts as a fil- Stages of CKD tering unit and determines which substan- CKD develops gradually over time and can ces are excreted as waste and which are be divided into five stages of increasing se- reabsorbed into the blood to nourish the verity: body’s cells, such as water, essential nut- rients, salts and minerals. Afterwards, the Stage 1: Slight kidney damage with normal tubules collect and concentrate waste and or decreased filtration excrete it into the urine. Stage 2: Mild decrease in kidney function Stage 3: Moderate decrease in kidney function Damaged nephrons can lead to CKD and Stage 4: Severe decrease in kidney function leave kidneys unable to remove wastes. The Stage 5: Kidney failure requiring dialysis or damage can occur slowly and over many transplantation to stay alive years. As blood filtering becomes impaired, urine production decreases and water and waste products accumulate in the blood. Stage 5 Stage 4 Stage 3 Stage 2 Stage 1 GFR <15mL/min GFR 15-29mL/min GFR 30-59mL/min GFR 60-89mL/min GFR ≥90mL/min Sensitive to serum creatinine Not sensitive to serum creatinine 12 Persistent albuminuria 884 10 707 8 530 6 mg/dL µmol/L 354 4 177 Standard value 2 Serum creatinine 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Glomerular filtration rate [mL/min] Replacement Preparation Evaluating, treating Estimating, slowing Diagnosis, treatment for replacement complications progression of comorbid conditions Fig. 3: Glomerular filtration rate in correlation with CKD stages 5, 6 11 Symptoms of CKD Did you know? Unfortunately, symptoms often occur very Kidney disease may also occur after a bacte- late or not at all. Abnormal urine or blood rial infection in another part of the body, such tests are often one of the earliest signs. as a streptococcus infection of the throat or skin or an infection inside the heart.7 Common symptoms are • Problems urinating: burning feeling or ab- Viruses, such as the HIV virus that leads to normal discharge during urination, or a AIDS, can also trigger kidney disease. 1 Kid- change in the frequency of urination, espe- ney disease requires prompt attention, and cially at night high-risk populations should be carefully • Urine that is foamy, bloody, red, brown monitored for abnormal kidney function. • Mid-back pain, below the ribs • High blood pressure (hypertension) Otherwise, testing for CKD only begins when • Lost of appetite or nausea and vomiting symptoms are present, which may be too late. • Swelling in hands, feet or eyes • Muscle cramps Diagnostic tests, such as simple urine tests, are the first line of defense in detecting kid- Risk groups ney problems and minimizing damage. • People with diabetes, hypertension or obe- sity, and older age groups 1212 Main disease indications Kidney disease 13 Diabetes Diabetes, even when controlled, is the most Common consequences common cause of CKD and kidney failure.