MKSAP quiz on acute kidney injury

The following cases and commentary, which focus on diagnosing acute kidney injury, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 16).

Case 1: Acute kidney injury after foreign travel

A 19-year-old woman is hospitalized for acute kidney injury (AKI) associated with bloody diarrhea that developed after she returned from a trip to South America. She also has nausea, vomiting, abdominal pain, fever, chills, and decreased urine output. Medical history is otherwise unremarkable, and she takes no medications.

On physical examination, temperature is 37.8°C (100.0°F), blood pressure is 135/90 mm Hg, and pulse rate is 110/min. The oral mucosa is dry. There is diffuse abdominal pain with guarding. The remainder of the physical examination is normal.

Laboratory studies show haptoglobin 8 mg/dL (80 mg/L), hemoglobin 5.2 g/dL (52 g/L), leukocyte count 20,000/µL (20 × 109/L), platelet count 36,000/µL (36 × 109/L), reticulocyte count 7.8%, serum creatinine 5.7 mg/dL (504 µmol/L) and lactate dehydrogenase 2396 units/L. Peripheral blood smear showed many schistocytes and urinalysis many erythrocytes and erythrocyte casts. Urine protein creatinine ratio is 0.5 mg/mg.

Which of the following is the most likely cause of this patient's acute kidney injury?

A. Acute tubular necrosis
B. Hemolytic uremic syndrome
C. Postinfectious glomerulonephritis
D. Scleroderma renal crisis

View correct answer for Case 1

Case 2: Cellulitis and reduced blood pressure

A 74-year-old man was hospitalized 3 days ago for extensive, nonpurulent cellulitis of the right lower extremity and is now being evaluated for acute kidney injury. He has hypertension, hyperlipidemia, and peripheral vascular disease. His hypertension has been poorly controlled; his last office blood pressure measurement was 165/92 mm Hg. Medications are lisinopril, metoprolol, hydrochlorothiazide, amlodipine, pravastatin, and aspirin. On admission, cefazolin was initiated.

The patient is now afebrile, and his blood pressure has not exceeded 118/60 mm Hg since admission. There is no evidence of orthostasis. The cellulitis has improved since admission.

Since admission, his serum creatinine level has progressively increased from 1.5 mg/dL (133 µmol/L) to 2.7 mg/dL (239 µmol/L).

Other laboratory studies show urine sodium 45 mEq/L (45 mmol/L) (normal range for men, 18-301 mEq/L [18-301 mmol/L]), fractional excretion of sodium 2.3% and fractional excretion of urea 51%. Urinalysis shows specific gravity 1.015, trace protein, no erythrocytes or leukocytes, occasional granular casts. Kidney ultrasound is normal.

Which of the following is the most likely cause of this patient's acute kidney injury?

A. Acute interstitial nephritis
B. Cholesterol emboli
C. Normotensive ischemic acute kidney injury
D. Prerenal azotemia

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Case 3: Pneumonia patient with rising creatinine

A 67-year-old man is evaluated in the hospital for an increasing serum creatinine level. He was hospitalized for pneumonia 2 days ago and is improving on levofloxacin therapy. He has experienced no episodes of hypotension during the hospitalization. His only other medication is prazosin for benign prostatic hyperplasia.

On physical examination, blood pressure is 144/75 mm Hg, and pulse rate is 64/min. BMI is 34. Cardiac and pulmonary examinations are normal. The abdomen is nontender, with normal bowel sounds and some suprapubic fullness. Urine output was 1200 mL in the past 24 hours.

Laboratory studies show serum creatinine 1.9 mg/dL (168 µmol/L) (1.2 mg/dL [106 µmol/L] on admission) and potassium 5.7 mEq/L (5.7 mmol/L) (4.5 mEq/L [4.5 mmol/L] on admission). Urinalysis shows specific gravity 1.011, pH 6.0, trace leukocyte esterase, 0-3 erythrocytes/hpf and 0-5 leukocytes/hpf.

Which of the following is the most appropriate diagnostic test to perform next?

A. Fractional excretion of sodium
B. Kidney biopsy
C. Kidney ultrasonography
D. Serum creatine kinase level measurement

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Case 4: Postoperative acute kidney injury

A 66-year-old woman is evaluated in the hospital for acute kidney injury 4 days following a partial colectomy for perforated diverticulitis. She had no intraoperative hypotension but has required a total of 15 L of intravenous fluids to maintain her blood pressure. Urine output has gradually diminished, and she is now oliguric with an indwelling bladder catheter in place. She received one dose of tobramycin postoperatively; additional medications are vancomycin and imipenem.

On physical examination, the patient is intubated and sedated. Temperature is 37.2°C (98.9;°F), blood pressure is 91/52 mm Hg, pulse rate is 108/min, and respiration rate on ventilation is 14/min. BMI is 35. Cardiac examination is notable for tachycardia, with a regular rate and no murmur. Pulmonary examination is normal. Abdominal examination reveals a tense and distended abdomen, with hypoactive bowel sounds. The abdominal wall is edematous. There is pitting edema of the legs.

Laboratory studies show blood urea nitrogen 45 mg/dL (16.1 mmol/L), serum creatinine preoperative: 0.9 mg/dL (79.6 µmol/L) and postoperative day 4: 2.9 mg/dL (256 µmol/L) and fractional excretion of sodium 1.5%. Urinalysis shows specific gravity 1.011, pH 6.0, trace erythrocytes/hpf, 1-2 leukocytes/hpf and occasional granular casts. Kidney ultrasound reveals normal-sized kidneys and no hydronephrosis.

Which of the following is the most likely cause of this patient's kidney failure?

A. Abdominal compartment syndrome
B. Aminoglycoside nephrotoxicity
C. Prerenal acute kidney injury
D. Urinary obstruction

View correct answer for Case 4

Case 5: Diabetic foot ulcer and hypertension

A 59-year-old man is evaluated for worsening kidney function. He was hospitalized 24 hours ago with a diabetic foot ulcer and associated cellulitis of 4 weeks' duration. He also has chronic diabetic kidney disease, hypertension, and type 2 diabetes mellitus. Medications are metformin, insulin glargine, lisinopril, and piperacillin-tazobactam.

On physical examination, blood pressure is 160/100 mm Hg (3 months ago: 130/78 mm Hg); other vital signs are normal. BMI is 30. An area of erythema extends about 3 cm around a 3- × 3-mm ulcer on the right heel. The involved area is tender and warm. There is 2+ pedal edema.

Laboratory studies show albumin 2.4 g/dL (24 g/L), complement (C3 and C4) decreased and serum creatinine 4.1 mg/dL (362 µmol/L) (2 weeks ago: 1.4 mg/dL [124 µmol/L]). Urine studies show urine sodium 15 mEq/L (15 mmol/L) (normal range for men, 18-301 mEq/L [18-301 mmol/L]), urinalysis 25 erythrocytes/hpf and 1-2 erythrocyte casts/hpf, and urine albumin creatinine ratio 1500 mg/g.

Which of the following is the most likely cause of this patient's acute kidney injury?

A. Diabetic nephropathy
B. IgA nephropathy
C. Postinfectious glomerulonephritis
D. Primary membranous glomerulopathy

View correct answer for Case 5

Answers and Commentary

Case 1

Correct answer: B. Hemolytic uremic syndrome.

The most likely cause of this patient's acute kidney injury (AKI) is hemolytic uremic syndrome (HUS), which is caused by some strains of Escherichia coli, including the O157:H7 strain that produces Shiga-like toxin (also known as verotoxin). Shiga-like toxin is effective against small blood vessels such as those found in the digestive tract and the kidneys; one specific target for the toxin is the vascular endothelium of the glomerulus, causing cell death, breakdown of the endothelium, hemorrhage, and activation of platelets and inflammatory pathways resulting in intravascular thrombosis and hemolysis. In developing countries, enteric pathogen infections usually develop after ingesting contaminated food or water. This patient manifests the classic triad of microangiopathic hemolytic anemia (anemia, elevated reticulocyte count and lactate dehydrogenase level, low haptoglobin level, and schistocytes on the peripheral blood smear), thrombocytopenia, and AKI in the setting of dysentery caused by an enteric pathogen.

Acute tubular necrosis is an unlikely diagnosis in a patient with microangiopathic hemolytic anemia, thrombocytopenia, and evidence of glomerular damage (erythrocyte casts in the urine). Patients with acute tubular necrosis are more likely to present with muddy brown casts.

Postinfectious glomerulonephritis more commonly occurs after streptococcal and staphylococcal infections and characteristically has a latency period of 7 to 120 days before the onset of AKI. Postinfectious glomerulonephritis is not associated with microangiopathic hemolytic anemia.

Scleroderma renal crisis (SRC) occurs almost exclusively in patients with early diffuse cutaneous systemic sclerosis. This condition is characterized by the acute onset of severe hypertension, kidney failure, and microangiopathic hemolytic anemia. SRC is not associated with bloody diarrhea, and the absence of skin findings makes this diagnosis unlikely.

Key Points

  • Patients with hemolytic uremic syndrome typically present with the classic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury.

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Case 2

Correct answer: C. Normotensive ischemic acute kidney injury.

This patient most likely has normotensive ischemic acute kidney injury (AKI), which results when a patient with vascular risk factors and hypertension attains a blood pressure lower than usual measurements. If the new blood pressure is lower than the patient's range of renal autoregulation, an increased serum creatinine level due to renal hypoperfusion may result. This patient's medical history suggests underlying chronic kidney and vascular disease, which increase his risk for a normotensive ischemic insult. His lower blood pressure in the hospital may be the result of his infection, better adherence to medications, and/or diet. The findings of an elevated fractional excretion of sodium, fractional excretion of urea, granular casts on urinalysis, and normal kidney ultrasound are all consistent with this diagnosis.

Acute interstitial nephritis, which is most often caused by a hypersensitivity reaction to a medication, usually occurs after 1 week of exposure to the offending agent. This patient's lack of rash, fever, and leukocytes or erythrocytes on urinalysis also argues against this diagnosis.

Cholesterol crystal embolization may cause AKI in patients with aortic atherosclerotic plaques. This condition may occur spontaneously but most often develops after coronary or kidney angiography or aortic surgery. Anticoagulation with heparin, warfarin, or thrombolytic agents is believed to help incite this condition. It is associated with cutaneous and extrarenal manifestations and a bland urine sediment. Although this patient likely has underlying vascular disease, he has not had an invasive procedure or anticoagulation and lacks any of the associated skin or extrarenal manifestations of the syndrome, making this diagnosis less likely.

Patients with prerenal azotemia may have a history of fluid losses and decreased fluid intake accompanied by physical examination findings consistent with extracellular fluid volume depletion. Two findings make prerenal azotemia unlikely in this patient: fractional excretion of sodium above 2% and fractional excretion of urea above 50% (more reliable than fractional excretion of sodium for patients on diuretics). These findings are more consistent with acute tubular necrosis.

Key Points

  • Normotensive ischemic acute kidney injury can occur when patients with vascular risk factors and hypertension attain a blood pressure lower than their usual measurements.

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Case 3

Correct answer: C. Kidney ultrasonography.

Kidney ultrasonography is indicated for this patient with acute kidney injury (AKI) most likely caused by urinary obstruction. Because relief of obstruction can reverse kidney injury and prevent chronic damage, timely diagnosis is essential. Urinary obstruction can be asymptomatic and can be associated with no noted change in urine output. Because of the lack of definitive symptoms on presentation, kidney imaging, typically ultrasonography, should be considered in all patients with AKI, particularly when risk factors for obstruction are present. Medical history findings, including pelvic tumors or irradiation, congenital urinary abnormalities, kidney stones, genitourinary infections, procedures or surgeries, and prostatic enlargement, should increase suspicion for obstruction. Bladder ultrasonography can be done as a quick bedside procedure and may also diagnosis bladder obstruction; however, it will not reveal hydronephrosis or kidney anatomy.

In obstruction, the urinalysis is bland. Urine electrolytes are variable; in early obstruction, the urine sodium and fractional excretion of sodium (FENa) may be low, but in late obstruction, the urine sodium and FENa may be high, indicative of tubular damage. Because of impaired kidney excretion of potassium, acid, and water, hyperkalemic metabolic acidosis and hyponatremia can be present. The FENa is not helpful in obstruction, and the clinical information provided does not suggest a prerenal etiology of AKI should be entertained.

Kidney biopsy is performed to evaluate for kidney injury of unknown cause. In this patient with a history suggestive of obstruction, imaging to exclude obstruction should be done first.

Rhabdomyolysis is associated with an increased serum creatine kinase level and can cause elevated serum creatinine and potassium levels; however, the patient has no risk factors for rhabdomyolysis (crush injury, muscle pain, or medications known to cause rhabdomyolysis).

Key Points

  • Kidney imaging, typically ultrasonography, should be considered in all patients with acute kidney injury, particularly when risk factors for obstruction are present.

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Case 4

Correct answer: A. Abdominal compartment syndrome.

This patient has abdominal compartment syndrome (ACS), which is defined by new organ dysfunction in the setting of a sustained, abnormal increase in the intra-abdominal pressure. Intra-abdominal pressure is normally between 0 and 5 mm Hg and is usually maintained in that range by the significant compliance of the abdominal wall. However, when a pathologic process (such as massive ascites, volume overload, or intra-abdominal or retroperitoneal hemorrhage) is present, the pressure may exceed the ability of the abdominal wall to compensate. Intra-abdominal hypertension is defined by sustained intra-abdominal pressures greater than 12 mm Hg; ACS occurs when the pressure exceeds 20 mm Hg and is accompanied by new organ dysfunction. The exact pathophysiology of ACS is uncertain, but high intra-abdominal pressure may adversely affect kidney function. Patients with a distended abdomen in the setting of aggressive fluid resuscitation and recent abdominal surgery should be evaluated for ACS. Measurement of the intravesicular pressure through a bladder catheter is the most common method for assessing the intra-abdominal pressure; although this value may not be identical to a directly measured intra-abdominal pressure, bladder pressure measurement appears to correlate adequately to be used in clinical decision making. Surgical decompression of the abdomen is often necessary to definitively treat ACS.

Aminoglycosides are well-known nephrotoxins. However, a single dose of tobramycin makes this a less likely cause of acute kidney injury (AKI), and aminoglycoside nephrotoxicity cannot account for this patient's increased intra-abdominal pressure.

Although kidney injury from ACS may appear prerenal because it is often associated with low blood pressures, the isosthenuric urine with a fractional excretion of sodium greater than 1% and the patient's unresponsiveness to fluids make this diagnosis less likely.

Although obstruction may have similar pathophysiology to ACS, the presence of an indwelling bladder catheter and lack of hydronephrosis on ultrasound suggest a different etiology of the AKI.

Key Points

  • Abdominal compartment syndrome occurs when intra-abdominal pressure exceeds 20 mm Hg and is accompanied by new organ dysfunction.

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Case 5

Correct answer: C. Postinfectious glomerulonephritis.

The most likely cause of this patient's acute kidney injury (AKI) is postinfectious glomerulonephritis (PIGN). PIGN presents with acute nephritic syndrome characterized by rapid onset of edema, hypertension, oliguria, and erythrocyte casts in the urine sediment. Less commonly, PIGN can manifest as rapidly progressive glomerulonephritis or as persistent nephritic-nephrotic syndrome that may progress to advanced chronic kidney disease (CKD). Diagnosis of PIGN is confirmed when at least three of the following criteria are fulfilled: clinical or laboratory evidence of infection preceding the onset of the disease; low serum complement levels; an exudative-proliferative glomerulonephritis pattern by light microscopy; C3-dominant or co-dominant glomerular staining by immunofluorescence microscopy; and subepithelial humps by electron microscopy. This patient had a documented stable baseline serum creatinine level of 1.4 mg/dL (123.8 micromoles/L) within the first 2 weeks of the infectious event onset before the onset of AKI 2 weeks later accompanied by hypocomplementemia due to activation of both the classic and alternative pathways. PIGN is confirmed by characteristic findings on kidney biopsy.

Diabetic nephropathy alone does not explain the onset of this patient's AKI. The natural history of progressive diabetic nephropathy in patients with type 2 diabetes mellitus is predictable, and decline of the glomerular filtration rate is no greater than 12 to 16 mL/min/1.73 m2 per year.

Patients with IgA nephropathy may present with an episode of AKI and macroscopic or gross hematuria concomitantly with an infectious episode. However, there is no latency period between the infection and the AKI in IgA nephropathy. IgA deposition can be seen in PIGN associated with staphylococcal infections in which enterotoxins can act as superantigens, initiating an immunologic response.

Adult patients with primary membranous glomerulopathy frequently present with the nephrotic syndrome: timed urine protein collection of more than 3.5 g/24 h, edema, hypoalbuminemia, and hyperlipidemia. Another 30% to 40% of patients present with asymptomatic proteinuria, usually in the subnephrotic range. The urine sediment can reveal erythrocytes and granular casts, but erythrocyte casts are not a feature. Furthermore, complement levels are always normal.

Key Points

  • The typical manifestation of postinfectious glomerulonephritis is a preceding infection associated with an acute nephritic syndrome, which is characterized by rapid onset of edema, hypertension, oliguria, and erythrocyte casts in the urine sediment.