MKSAP quiz on acute kidney injury

The following cases and commentary, which focus on acute kidney injury, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 17), which released Part A on July 31.

Case 1: Alcoholic cirrhosis and altered mental status

A 49-year-old woman is hospitalized for altered mental status. She has alcoholic cirrhosis complicated by ascites. She has not had fever, focal infection symptoms, hematemesis, hematochezia, or melena. She takes lactulose, but she is now having four to five loose stools per day. She also takes furosemide and spironolactone.

On physical examination, temperature is 36.4 °C (97.5 °F), blood pressure is 102/74 mm Hg, pulse rate is 78/min, and respiration rate is 16/min; BMI is 24. She is disoriented to time and date. Scleral icterus, spider angiomata, and asterixis are noted. The mucous membranes are dry. Ascites is present.

Laboratory studies show INR 1.3 (normal range, 0.8-1.2), albumin 2.6 g/dL (26 g/L), total bilirubin 3.5 mg/dL (59.9 μmol/L), blood urea nitrogen 38 mg/dL (13.6 mmol/L), creatinine 2.5 mg/dL (221 μmol/L), and urinalysis is normal.

Blood culture results are pending. Her diuretics and lactulose are discontinued.

Which of the following is the most appropriate treatment for acute kidney injury in this patient?

A. Midodrine
B. Midodrine and octreotide
C. Norepinephrine
D. 25% albumin

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Case 2: Medication management with AKI

A 65-year-old woman is admitted to the hospital for evaluation of acute kidney injury secondary to dehydration after an episode of severe gastroenteritis. She has type 1 diabetes mellitus, secondary progressive multiple sclerosis, and osteopenia. Medications are irbesartan, insulin glargine, insulin lispro, glatiramer acetate, dalfampridine, baclofen, vitamin D, and calcium.

On physical examination, temperature is normal, blood pressure is 110/60 mm Hg, pulse rate is 108/min, and respiration rate is 14/min. She appears weak and tired. Neck veins are flat. The remainder of the physical examination is normal.

Results of laboratory studies show a serum creatinine level of 3.9 mg/dL (345 μmol/L), which is increased from her baseline level of 1.4 mg/dL (124 μmol/L).

Intravenous fluids are initiated.

In addition to irbesartan, which of the following medications must be discontinued?

A. Baclofen
B. Dalfampridine
C. Glatiramer acetate
D. Vitamin D

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Case 3: Systemic sclerosis and reduced kidney function

A 31-year-old woman is evaluated in the hospital for headache, blurred vision, and nausea occurring for the past 12 hours. She has a 2-year history of diffuse cutaneous systemic sclerosis with recent worsening of Raynaud phenomenon that is treated with nifedipine.

On physical examination, the patient is alert but is somnolent and has altered sensorium.

Temperature is normal, blood pressure is 150/92 mm Hg, pulse rate is 104/min, and respiration rate is 16/min. BMI is 22. Oxygen saturation is 95% on ambient air. Cardiopulmonary examination is normal. Examination of the skin reveals diffuse skin thickening of the face, anterior chest, and distal extremities; sclerodactyly; and multiple healed digital pits. Neurologic examination is nonfocal.

Laboratory studies show a normal complete blood count, albumin 3.0 g/dL (30 g/L), bicarbonate 32 mEq/L (32 mmol/L), creatinine 4.2 mg/dL (371.3 μmol/L) from a baseline of 0.8 mg/dL (70.7 μmol/L). Urinalysis shows 2+ protein, 3 erythrocytes/hpf, 5 leukocytes/hpf, few granular casts, and the urine protein-creatinine ratio is 1,200 mg/g.

Chest radiograph is normal. Noncontrast CT of the head is normal. MRI of the brain shows bilateral parietal lobe white matter prominence.

Which of the following is the most appropriate treatment?

A. Captopril
B. Cyclophosphamide
C. Methylprednisolone
D. Sildenafil

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Case 4: Heart failure and acutely reduced kidney function

A 56-year-old man with heart failure is admitted to the hospital with a 2-week history of increasing exertional dyspnea and fatigue. He also has type 2 diabetes mellitus. Medications are metformin, lisinopril, carvedilol, furosemide, metolazone, and digoxin.

On physical examination, blood pressure is 88/60 mm Hg, pulse rate is 95/min, and respiration rate is 20/min. He is somewhat confused and inattentive. Jugular venous distention is present to the angle of the jaw while sitting. Cardiac examination reveals an S3. There are bibasilar crackles on pulmonary examination. He has edema to the midthighs. Extremities appear mottled and are cool to the touch.

Serum creatinine level is 3.1 mg/dL (274 μmol/L); baseline value was 1.1 mg/dL (97.2 μmol/L). Serum sodium level is 133 mEq/L (133 mmol/L). Electrocardiogram shows no evidence of ischemia. Chest radiograph shows cardiomegaly and vascular congestion.

In addition to intravenous diuresis, which of the following is the most appropriate management?

A. Dobutamine
B. Intra-aortic balloon pump
C. Milrinone
D. Right heart catheterization

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Case 5: Abdominal pain and purpuric lesions

A 65-year-old man is evaluated for severe abdominal pain, joint pain, and a rash. He states that he had an upper respiratory infection about 10 days ago. Three days ago he noted a rash on his lower extremities. One day later, he experienced pain in his knees and ankles, along with abdominal pain that worsened over the past two days. He reports no visual symptoms, numbness, weakness, or other symptoms.

On physical examination, the patient appears uncomfortable. The chest and cardiac examinations are unremarkable. Decreased bowel sounds and diffuse abdominal tenderness without rebound are noted. The knees and ankles are tender and mildly swollen. Palpable purpuric lesions are present on the lower extremities, including the soles of the feet. The remainder of the physical examination reveals no abnormalities.

Laboratory studies show a normal complete blood count, an erythrocyte sedimentation rate of 88 mm/h, a serum creatinine level of 1.7 mg/dL (150.3 μmol/L), and a urinalysis showing 3+ protein, 20-30 erythrocytes/hpf, 20-30 leukocytes/hpf, and mixed granular and cellular casts. A stool test is positive for occult blood.

An abdominal ultrasound reveals thickening and edema of the ileum. A biopsy of an affected skin lesion demonstrates the presence of small-vessel, leukocytoclastic vasculitis accompanied by deposition of IgA.

Which of the following is the most appropriate therapy at this time?

A. Cyclophosphamide
B. Dapsone
C. Ibuprofen
D. Prednisone

View correct answer for Case 5

Answers and commentary

Case 1

Correct answer: D. 25% albumin.

The most appropriate treatment for acute kidney injury in this patient is 25% albumin. This patient has acute kidney injury (AKI) and hepatic encephalopathy, most likely precipitated by dehydration from lactulose-induced diarrhea. AKI is common and occurs in approximately 20% of hospitalized patients with cirrhosis. In approximately 70% of patients with cirrhosis and AKI, the precipitant is prerenal, from sources such as infection, gastrointestinal bleeding, excessive diuresis, or diarrhea. This patient has dry mucous membranes, diarrhea, and no obvious signs of infection or bleeding and has been treated with diuretics. Approximately two thirds of patients with prerenal AKI are fluid responsive. After stopping diuretics and lactulose, the best initial treatment is intravenous colloid administration, usually in the form of 25% albumin, administered at 1 g/kg body weight per day in divided doses.

The other third of patients who are not fluid responsive generally have type 1 or type 2 hepatorenal syndrome (HRS). HRS diagnostic criteria consist of 1) an increase in the serum creatinine level to greater than 1.5 g/dL (132.6 μmol/L) over days to weeks, 2) lack of response to an albumin challenge of 1 g/kg/d for 2 days, and 3) the absence of shock, nephrotoxic drugs, active urine sediment, proteinuria greater than 500 mg/d, and ultrasound evidence of parenchymal kidney disease or obstruction. Although this patient could have evolving HRS, this cannot be diagnosed until fluid responsiveness has been evaluated. If she is not fluid responsive and does not have evidence of acute tubular necrosis on urinalysis, then treatment for type 1 HRS could begin. Norepinephrine with albumin infusion is effective for patients with type 1 HRS who are in the ICU. Midodrine, octreotide, and albumin are the appropriate treatments for type 1 HRS in patients outside of the ICU. Terlipressin is effective for type 1 HRS but is not available in the United States.

Key Points

  • Acute kidney injury occurs in approximately 20% of hospitalized patients with cirrhosis; such patients should receive a fluid challenge (usually with 25% albumin) to evaluate fluid responsiveness before hepatorenal syndrome can be diagnosed.

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Case 2

Correct answer: B. Dalfampridine.

This patient's dalfampridine (4-aminopyridine) should be discontinued. Dalfampridine is a voltage-gated potassium channel antagonist that can potentiate action potentials along demyelinated axons and is used in patients with multiple sclerosis (MS) for potassium channel blockade. This medication can improve lower extremity function and walking speed and endurance. Because of its mechanism of action, seizures have been reported as a rare, dose-dependent adverse effect of this medication. Dalfampridine is excreted through the kidneys and thus is contraindicated in patients with kidney disease because its resultant decreased clearance would significantly increase the seizure risk. For this reason, this medication should be discontinued in this patient.

Baclofen can alleviate the spasticity often associated with MS. There is no reason to discontinue the drug in this patient with acute kidney injury because no specific adverse effects of this drug due to kidney toxicity or related to kidney clearance have been reported. Dosing may have to be modified in patients with severe kidney failure, however.

Glatiramer acetate is a disease-modifying medication used in the treatment of MS to impede disease activity and prevent relapses. This drug has no known adverse effects on the kidneys due to poor clearance or direct toxicity.

Vitamin D supplementation is now suggested for all patients with MS to reduce the accumulation of new lesions on MRI. No adverse effects on kidney function or kidney clearance have been reported.

Key Points

  • Dalfampridine is renally excreted and thus is contraindicated in patients with kidney disease.

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Case 3

Correct answer: A. Captopril.

The ACE inhibitor captopril is the most appropriate treatment for this patient who most likely has scleroderma renal crisis (SRC) in the setting of diffuse cutaneous systemic sclerosis (DcSSc). SRC occurs in 10% to 15% of patients with systemic sclerosis and is more frequent in DcSSc compared with limited cutaneous systemic sclerosis. Vascular involvement of afferent arterioles leads to glomerular ischemia and hyperreninemia. The typical presentation is acute onset of oliguric kidney disease and severe hypertension, mild proteinuria, urinalysis with few cells or casts, microangiopathic hemolytic anemia, and thrombocytopenia. Some patients develop pulmonary edema and hypertensive encephalopathy. Normal blood pressure may be present in up to 10%. This patient presents acutely with a rapid rise in serum creatinine consistent with acute kidney injury, with a bland urinalysis and non–nephrotic-range proteinuria as well as neurologic symptoms suggestive of encephalopathy. Although her blood pressure is almost normal, these findings are highly suggestive of SRC. Treatment with an ACE inhibitor is essential to restore kidney function and manage hypertension associated with SRC. Captopril is the preferred ACE inhibitor because it has been the most extensively studied agent in this clinical setting, and its short half-life allows rapid titration.

Cyclophosphamide is a potent immunosuppressant used to treat severe or life-threatening manifestations of certain diseases such as systemic lupus erythematosus or systemic vasculitis. It is ineffective in treating SRC, which is vascular and noninflammatory.

This patient does not have inflammatory end-organ involvement; therefore, methylprednisolone is not needed. Glucocorticoids are not useful in SRC, and intravenous glucocorticoids may cause worsening symptoms.

Sildenafil can be used to treat pulmonary hypertension or finger ulcerations but is not appropriate for SRC, which is primarily mediated through the renin-angiotensin axis.

Key Points

  • In patients with scleroderma renal crisis, treatment with an ACE inhibitor is essential to restore kidney function and manage hypertension.

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Case 4

Correct answer: A. Dobutamine.

This patient should be started on dobutamine for probable cardiogenic shock. Cardiogenic shock is present when there is systemic hypotension and evidence for end-organ hypoperfusion, primarily due to inadequate cardiac output. Cardiogenic shock usually requires treatment with intravenous vasoactive medications and, in severe cases, device-based hemodynamic support. Manifestations of end-organ hypoperfusion may include acute kidney failure, elevated serum aminotransferase levels or hyperbilirubinemia, cool extremities, and decreased mental status. In this patient, initiating inotropic therapy is reasonable. Both dobutamine and milrinone are used to increase cardiac output; however, in the setting of kidney dysfunction, dobutamine would be the appropriate choice because milrinone is metabolized by the kidneys. Also, milrinone is a vasodilator, which could exacerbate his hypotension.

Mechanical therapy for cardiogenic shock should be considered in patients with end-organ dysfunction that does not rapidly show signs of improvement (within the first 12-24 hours) with intravenous vasoactive medications and correction of volume overload. Options for mechanical therapy include placement of an intra-aortic balloon pump and percutaneous or surgically implanted ventricular assist devices (VADs). An intra-aortic balloon pump is timed to inflate during diastole, augmenting coronary and systemic perfusion, and deflate during systole, reducing left ventricular afterload. It is premature to consider mechanical therapy for this patient.

Right heart catheterization can be helpful to guide therapy if volume status or cardiac output is uncertain. However, it has not been shown to improve outcomes in patients hospitalized with heart failure. This patient has clinical evidence of volume overload, including jugular venous distention, pulmonary crackles, edema to the mid thighs, pulmonary edema on chest radiography, and an S3. Additionally, he has evidence of low cardiac output (narrow pulse pressure, hypotension, acute kidney injury, mottled and cool extremities). Placement of a right heart catheter is not necessary prior to initiating inotropic therapy.

Key Points

  • Cardiogenic shock usually requires treatment with intravenous vasoactive medications and, in severe cases, device-based hemodynamic support.

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Case 5

Correct answer: D. Prednisone.

Prednisone is appropriate for this patient. His findings demonstrate the presence of a small-vessel vasculitis affecting the skin, joints, kidneys, and gastrointestinal tract. Deposition of IgA in the skin confirms the diagnosis of adult-onset Henoch-Schönlein purpura (HSP). In children, HSP is generally a benign, self-limited condition, and treatment is most commonly supportive pending spontaneous remission. HSP in adults is less common and typically is more severe. Although adult HSP also tends to run a self-limited course, adults with HSP are more likely to experience severe disease and to accumulate irreversible organ damage before the acute disease resolves. In this case, the involvement of multiple organ systems, including the gastrointestinal tract, probably warrants prednisone treatment based upon expert consensus recommendation.

Cyclophosphamide is an alkylating agent and potent immunosuppressant. It is commonly used for treatment of severe autoimmune disease such as systemic lupus erythematosus and ANCA-associated vasculitis. Its use in adult-onset HSP is less well established; although it is sometimes used in conjunction with prednisone for severe HSP nephritis, it would not be a first-choice therapy in the absence of prednisone use.

Dapsone is an antibiotic that has antileukocyte activity and is occasionally used to treat the leukocytoclastic vasculitides, including HSP. However, given the severity of this patient's condition, dapsone is less likely to be effective, and prednisone use is warranted.

Like all NSAIDs, ibuprofen may help alleviate joint pain and swelling and may have some modest effect on reducing the inflammation of small-vessel vasculitis. However, ibuprofen is unlikely to be adequately effective in a serious case such as this. Moreover, the nephrotoxic and antiplatelet effects of an NSAID would be undesirable in this patient who already has acute kidney injury and intestinal bleeding.

Key Points

  • Treatment with prednisone should be considered for patients who have severe Henoch-Schönlein purpura with involvement of multiple organ systems.