Acute Renal Failure Module

Resident Version

created by Dr. Chris Delong

Objectives:

By the end of this module, you should be able to: 1. Define acute renal failure (ARF) 2. Identify the main types of acute renal failure by whether they are prerenal, intrinsic renal (and subtypes) or postrenal. 3. Identify the typical laboratory tests used in working up renal failure and explain their utility. 4. Understand the Fractional Excretion of Sodium (FENa) equation and its utility in differentiating causes of ARF. 5. Understand the utility of urine microscopy in differentiating types of acute renal failure.

References:

1) Singri N, Ahya S, Levin M. Acute Renal Failure. JAMA, February 12, 2003; 289: 747-51.

2) Lameire N, Van Biesen W, Vanholder R. Acute Renal Failure. Lancet 2005;365: 417-30. Discussion Outline

FIRST STEP: Understanding the definition and types of renal failure

Acute renal failure is generally defined as an increase in serum creatinine of 0.5 mg/dL over 2 weeks or less when the baseline creatinine is less than 2.5. If the baseline creatinine is more than 2.5, it is defined as an increase of more than 20% over 2 weeks or less.

A general understanding of what can cause renal failure will assist you in clinical evaluation. What follows is a modified figure from the referenced Lancet article entitled “Acute Renal Failure” that concisely categorizes the major types of renal failure with their causes. - The most common causes of acute renal failure are acute tubular necrosis and prerenal azotemia.

SECOND STEP: History and examination

A thorough history and examination are essential in the assessment of acute renal failure. A modification of Table 2 from the referenced JAMA article on Acute Renal Failure follows:

Type of History questions Medications Physical Exam Renal Failure Prerenal Vomiting Diuretics Orthostatic Diarrhea Chemotherapy hypotension Bleeding Skin Turgor Fevers Buccal mucosa Recent operation Edema (hypotension) Heart or liver CHF findings disease Signs of chronic liver disease Intrarenal Pharyngitis or other URI Nephrotoxic Edema Sinusitis (Wegner’s) (NSAIDS, etc) Livedo Reticularis Hemoptysis (Wegner’s, Petechiae Goodpasture’s) IV contrast Palpable purpura Muscle trauma exposure Muscle tenderness Urine color Postrenal Decreased Urinary stream Diphenhydramine Bladder distension Nocturia Anticholinergics Prostate enlargement Anuria Abdominal or pelvic Increased frequency mass Flank pain THIRD STEP: Imaging and Laboratory studies Imaging studies: - A renal ultrasound is an extremely useful diagnostic tool to evaluate patients with ARF o Identifies obstruction if present o Size and echogenicity of kidneys

Laboratory tests: An initial assessment of renal function is an appropriate first step - Renal function evaluation o Serum Creatinine . BUN/Creatinine ratio: If >15-20:1 ratio, it is suggestive of kidney hypoperfusion  Keep in mind that patients with cirrhosis, low muscle mass may not have this finding in the setting of kidney hypoperfusion o Additional estimation of glomerular filtration rate (GFR), however these are more useful in patients with stable renal function . Cockcroft-Gault equation, Modification of Diet in Renal Disease (MDRD) - Urine studies o Volume . Oliguria <400 mL/day . Anuria <100 mL/day o Urinalysis and culture . Urinalysis specifics  Specific gravity (if high, consistent with prerenal etiology)  If infection may be underlying etiology (LCE, Nitrites)  Presence of blood (multiple etiologies including intrinsic renal and postrenal)  Elevated protein levels: o If present, obtain 24-hour urine protein to evaluate quantity o Urine Sodium and Creatinine . To assist in evaluation of Fractional Excretion of Sodium (FENa)  Equation: FENa percent = (Urine Na x Plasma xCr) 100 (Plasma Na x Urine Cr)  What is the utility of calculating the FENa? o Helps to distinguish prerenal (<1%) from renal etiology (>2%) . However a low FENa can also be seen in acute glomerulonephritis, vasculitis and obstruction o Urine Microscopy: Specific findings are helpful in establishing diagnosis . Eosinophils: May be suggestive of Acute Interstitial Nephritis (AIN); Though sensitivity and specificity of this finding for AIN are low. . Red blood cell casts: Consistent with glomerular pathology, nephritic syndrome . Dysmorphic red blood cells: Typically present with glomerular, nephritic diseases . Granular Casts: observed in numerous disorders, represent degenerating cellular casts or aggregated proteins; may be part of an “active sediment” or a non-specific finding . White blood cell casts: Typically present AIN, Pyelonephritis, or a nephritic syndrome . Muddy brown casts: Typically present with Acute Tubular Necrosis

Table of Urinalysis and Chemistry findings in different types of renal failure

Urine Test Prerenal Acute Acute Glomerulonephritis Obstruction Tubular Interstitial Necrosis Nephritis Sediment Bland Muddy White blood Dysmorphic red Bland or red Brown cells, blood cells, red blood cells Casts eosinophils, blood cell casts cellular casts Protein None or None or Minimal, Increased, >100 Low low low may be mg/dL increased with NSAIDs Urine <20 >30 >30 <20 Acute <20 Sodium in After days mEq/L >40 FENa in <1 >1 Variable <1 Acute <1 percent After days >1

Adapted from cited JAMA article entitled “Acute Renal Failure” FOURTH STEP: Additional tests, indications and their meaning In what circumstances are more tests indicated? - Typically if there is an “active sediment,” meaning dysmorphic red blood cells or red blood cell casts, additional tests are indicated to determine the underlying etiology as treatments differ based on the diagnosis - Nephritic syndromes: Tests to obtain o Complements: If low, consistent with lupus, immune complex disease o Anti-GMB antibody: If positive, consistent with diagnosis of Goodpasture’s syndrome o ANCA . C-ANCA/PR3: If positive, consistent with diagnosis of Wegner’s . P-ANCA/MPO: If positive, consistent with Microscopic Polyangitis . P-ANCA (non-MPO/PR3): Polyarteritis Nodosa o Biopsy: Indicated in following cases . Isolated glomerular hematuria with proteinuria . Nephrotic syndrome . Acute nephritic syndrome . Unexplained acute or subacute renal failure

FIFTH STEP: Treatment - The treatment of renal failure will depend on many variables, among which are the etiology and severity of the condition. If the etiology is prerenal, establishing effective renal perfusion is a reasonable first approach. - however, this can be very difficult to do in patients with underlying heart or liver dysfunction - If the etiology is determined to be autoimmune, immunosuppression will likely be indicated. - If the etiology is infectious, antibiotics should be initiated. If postrenal, correction of obstruction should be the primary initial therapeutic goal. In all cases, following daily fluid input and output is essential. In addition, searching for and treating acute complications, specifically electrolyte abnormalities (Sodium, potassium, acidosis, hyperphosphatemia) is an important aspect to managing ARF. - Avoiding nephrotoxic agents such as NSAIDs, IV contrast and certain antibiotics is indicated in patients with ARF. Also, adjust renally-cleared medications based on the patient’s GFR. - Dialysis may be necessary, particularly in cases where patient’s renal function deteriorates. - indications for acute dialysis include o Severe acidosis not responsive to other treatment o Severe electrolyte abnormalities, particularly elevated potassium with cardiac conduction effects o Severe fluid overload unresponsive to diuresis o Uremia with end-organ effects such as pericardial rubs Case: HPI: A 52 year old man presents to you in clinic complaining of “red urine” for the past week. He has never had this problem before. He has not noted any changes in his urinary frequency and reports no difficulty with starting a urine stream or incomplete evacuation. He also states that he recently had a runny nose, sore throat and cough which resolved about 3 weeks ago. He did not take any antibiotics for this illness. On further review of systems he reports progressive shortness of breath over the past 6 months primarily with exertion. He denies any chest pain, rashes, swelling of his extremities or neurological symptoms.

PMH: 1. Hepatitis C confirmed by PCR, for which patient has not received treatment 2. Hypertension 3. Chronic allergies with sinusitis 4. Osteoarthritis

Medications: 1) Ibuprofen as needed for osteoarthritis pain (approximately 800-1600 mg daily 2) Hydrochlorothiazide 25 mg daily 3) Fluticasone nasal spray, 2 sprays in each nostril daily

FH: Father with MI at age 45, Mother with numerous blood clots and miscarriages SH: Pt quit smoking 10 years ago, drinks alcohol occasionally and stopped using IV drugs approximately 10 years ago

PE: VS: Temperature 36.9 C BP 140/85 HR 95 RR 16 O2 91% on room air HEENT: Pupils equally round, reactive to light; mucous membranes moist; no nasal abnormalities; bilateral maxillary sinus tenderness present; no lymphadenopathy or thyromegaly Lungs: Bilateral fine crackles throughout both lung fields CV: Regular rate and rhythm, no m/g/r Abd: Normal bowel sounds, no tenderness to palpation, no notable bladder distension Rectal: Normal rectal tone with normally sized prostate, no nodules; guaiac negative stool Neuro: Non-focal Extremities: No cyanosis, edema or clubbing

Labs: CBC: WBC 9.0 (70% PMNs, 20% Lymphocytes, 7% Monos, 2% Eosinophils), HCT 42, PLT 200 Chemistries: Sodium 135, Potassium 4.6, Chloride 105, Bicarbonate 18, BUN 20, Creatinine 2.5 (baseline 1.2), Glucose 96, Calcium 8.2, Phosphorus 3.2, Magnesium 2.5 LFTs: Significant for an AST of 90, ALT 100 Coags: Normal UA: Specific gravity 1.010 (normal), positive leukocyte esterase, negative nitrites, 3+ RBCs, 2+ protein Urine microscopy: RBC and WBC casts, dysmorphic RBCs ; no crystals

Imaging: CXR: Bilateral interstitial abnormalities Kidney Ultrasound: no hydronephrosis or stranding, kidneys are normal in size and echogenicity

Case Questions:

1. What is the etiology of this patient’s renal failure: Prerenal, Intrinsic Renal or Postrenal?

2. What is on your differential?

3. Which additional lab studies would you perform?

4. How does this test change your differential diagnosis?

5. What further tests would you perform to narrow your diagnosis?

6. Now what is your most likely diagnosis?

7. How would you typically confirm this diagnosis prior to instituting therapy? Review Questions

1. An otherwise healthy 54-year-old man presents to your office with the complaints of joint pain and swelling of his legs for one week. On exam, his blood pressure is elevated to 165/95. Other significant findings include bibasilar pulmonary crackles and 2+ bilateral lower extremity edema. You order a urine microscopy in which you find dysmorphic red blood cells, red blood cell casts and white blood cell casts. You suspect a rapidly progressive glomerulonephritis and order complement levels.

If they are low, which etiology is least likely? A. Glomerulonephritis related to SLE B. Wegener’s granulomatosis C. Post-infectious glomerulonephropathy D. Glomerulonephritis related to Hepatitis C (mixed essential cryoglobulinemia)

2. You are called to evaluate a 42 year-old man in the Intensive Care Unit for evaluation of acute renal failure. The patient was admitted 4 days previously for multilobar pneumonia that was severe enough to require intubation. In reviewing his records, you see that he was hypotensive to 85/45 on the day of admission, which improved to 105/52 with fluid boluses and pressor therapy. Upon evaluation, the patient is intubated and unable to answer questions. His most recent blood pressure is 140/90, with a heart rate of 90, oxygen saturation of 93% on his current ventilator settings and he has been afebrile for the past 48 hours. His last chemistry panel shows a Sodium on 140, potassium on 5.2, BUN of 30 and creatinine of 2.5 (baseline on admission was 1.3).

Which of the following results of urinalysis would be consistent with his clinical history? A. Moderate number of hyaline and granular casts B. Presence of moderate protein, dysmorphic red blood cells and red blood cell casts C. Dirty brown granular casts with granular epithelial cells D. Large amount of white blood cells with bacteria 3. A 48-year-old man is brought into the emergency department by his wife. She states that he began complaining of arthralgias and fevers about 2 weeks ago, which he attributed to the “flu.” Within the past 2 days the patient has become confused and has developed a rash and swelling in his legs. On physical exam, his Temperature is 37.0, Heart Rate is 89, and Blood pressure is 160/90. He is oriented to time but not to place. His exam reveals palpable purpuric lesions on his bilateral lower extremities with trace edema. Labs reveal an elevated white blood cell count to 19,000 with Neutrophil predominance, a hematocrit of 33 and platelets of 500. His BUN is elevated to 80 and his creatinine is 3.8. You obtain further tests which show Red blood cell and white blood cell casts in the urine with a moderate amount of protein. Complement levels are normal and a p-ANCA is positive with antimyeloperoxidase specificity.

Which of the following conditions is most likely responsible for his condition? A. Polyarteritis nodosa B. Wegener granulomatosis C. IgA Nephropathy D. Henoch Schonlein Purpura E. Microscopic Polyangiitis

4. A 40-year-old diabetic woman presents to your office with the complaint of “bloody urine” that started 2 days after the onset of an upper respiratory infection, from which she had symptoms of a sore throat, cough and nasal congestion. Her brother has a childhood history of a similar condition after he had strep throat. What is the most likely explanation for her hematuria? A. Poststreptococcal glomerulonephritis B. Polyarteritis nodosa C. IgA Nephropathy D. Glomerulosclerosis Post Module Evaluation

Please place completed evaluation in an interdepartmental mail envelope and address to Dr. Wendy Gerstein, Department of Medicine, VAMC (111).

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