The following cases and commentary, which address acute kidney injury, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 15).
Case 1: Three-week history of nausea, vomiting and decreased oral intake
A 55-year-old woman is admitted to the hospital with a three-week history of nausea, vomiting and decreased oral intake. She was diagnosed with stage IIB cervical cancer three months ago. Six weeks ago, she completed primary radiotherapy with adjuvant weekly cisplatin. During a follow-up office visit one week ago, her serum creatinine level was 1.3 mg/dL (114.9 µmol/L) (baseline 0.8 mg/dL [70.7 µmol/L]). Intravenous saline was administered, but her symptoms did not improve. Her only current medication is ondansetron as needed.
On physical examination, she appears cachectic. She is afebrile, blood pressure is 118/68 mm Hg without orthostatic changes, pulse rate is 90 beats/min, and respiration rate is 18 breaths/min. BMI is 19.5. The bladder dome is not palpable. The remainder of the physical examination is normal.
Laboratory studies indicate the following:
- hemoglobin level of 10.2 g/dL (102 g/L)
- platelet count of 165,000/µL (165 × 109/L)
- sodium level of 140 meq/L (140 mmol/L)
- potassium level of 5.3 meq/L (5.3 mmol/L)
- chloride level of 112 meq/L (112 mmol/L)
- bicarbonate level of 18 meq/L (18 mmol/L)
- blood urea nitrogen level of 122 mg/dL (43.5 mmol/L)
- serum creatinine level of 5.1 mg/dL (450.8 µmol/L)
- urinalysis with pH 5.0, 1+ protein, 1+ blood, 0-5 erythrocytes/hpf, no bacteria and no glucose
Which of the following is the most likely diagnosis?
A. Cisplatin nephrotoxicity
C. Membranous nephropathy
D. Obstructive nephropathy
Case 2: Hypertension and proteinuria in a pregnant patient
A 27-year-old woman in the twelfth week of pregnancy is admitted to the hospital for hypertension and proteinuria. She has a two-year history of diffuse cutaneous systemic sclerosis associated with gastroesophageal reflux disease and Raynaud phenomenon. She had been taking omeprazole but discontinued this agent when she became pregnant. Her only current medications are over-the-counter calcium carbonate and prenatal vitamins.
On physical examination, temperature is 37.0°C (98.6°F), blood pressure is 194/104 mm Hg, pulse rate is 84 beats/min, and respiration rate is 17 breaths/min. Cardiopulmonary examination is normal except for an S4 gallop. There is skin thickening over the face, chest, abdomen, arms, hands and feet. Funduscopic examination is normal. Abdominal examination reveals a normal for pregnancy gravid uterus. Tendon friction rubs are present over the anterior lower extremities.
Laboratory studies indicate the following:
- hemoglobin level of 7.4 g/dL (74 g/L)
- leukocyte count of 8000/µL (8 × 109/L)
- platelet count of 66,000/µL (66 × 109/L)
- serum creatinine level of 2.4 mg/dL (183.1 µmol/L)
- alanine aminotransferase of 35 U/L
- aspartate aminotransferase of 32 U/L
- lactate dehydrogenase of 300 U/L
- urinalysis with 3+ protein, no leukocytes or erythrocytes/hpf.
A peripheral blood smear shows schistocytes.
Which of the following is the most appropriate management for this patient?
B. Immediate delivery of the fetus
D. Plasma exchange
Answers and Commentary
Correct answer: D. Obstructive nephropathy.
This patient most likely has obstructive nephropathy, which causes chronic tubulointerstitial disease and often manifests as hyperkalemic renal tubular acidosis. Cervical cancer is one of the most common causes of obstructive nephropathy in women. Kidney damage is typically irreversible if an obstruction is present for longer than 8 to 12 weeks; therefore, to ensure a prompt diagnosis, obstructive nephropathy must always be included in the differential diagnosis of a patient with acute kidney injury.
The presence of hydronephrosis and/or renal pelvis dilatation visible on kidney ultrasonography or noniodinated contrast CT is diagnostic of obstructive nephropathy. Relief of obstruction may lead to the reversal of acute kidney injury.
Cisplatin nephrotoxicity typically occurs within the first 2 weeks after drug administration and manifests as a Fanconi-like syndrome of glycosuria, phosphaturia, aminoaciduria, and renal wasting of magnesium and hypomagnesemia. Furthermore, cisplatin nephrotoxicity that develops weeks or months after beginning treatment is more commonly associated with thrombotic microangiopathy. These findings are absent in this patient.
Membranous nephropathy is associated with malignancies and may manifest as proteinuria. However, this condition is unlikely to develop after the malignancy has been treated and is usually associated with nephrotic-range proteinuria and a more slowly progressive decline in kidney function.
Hypovolemia is one of the most common causes of acute kidney injury in patients admitted to the hospital, and this patient's vomiting and decreased oral intake are suggestive of volume depletion. However, hypovolemia usually is associated with orthostasis. In addition, this patient's lack of response to saline infusion argues against this diagnosis.
- Obstructive nephropathy must always be included in the differential diagnosis of a patient with acute kidney injury to ensure prompt diagnosis and reversal of kidney injury
Correct answer: A. Captopril.
The most likely diagnosis is scleroderma renal crisis (SRC), and the most appropriate management for this patient is initiation of captopril. Patients with early diffuse systemic sclerosis have an increased risk for developing SRC.
The differential diagnosis of a pregnant patient with diffuse cutaneous systemic sclerosis who presents with acute kidney injury, proteinuria, thrombocytopenia, and a microangiopathic hemolytic anemia includes SRC and preeclampsia, eclampsia (preeclampsia with seizures), HELLP (hemolysis, elevated liver function tests, low platelets) syndrome, and thrombotic thrombocytopenic purpura (TTP). Differentiating among these conditions is often extremely difficult but critical. SRC occurs almost exclusively in patients with diffuse cutaneous systemic sclerosis, particularly those with skin fibrosis that develops within 3 years of disease onset. In this patient, the abrupt onset of the signs and symptoms of hypertension and renal failure in the presence of diffuse systemic sclerosis during early gestation supports the diagnosis of SRC and helps to exclude the other entities in the differential diagnosis. Angiotensin-converting enzyme inhibitor therapy with aggressive upward titration is indicated in patients with SRC to reduce mortality. Therefore, captopril must be used in this patient to preserve renal function, control blood pressure, and reduce mortality despite being associated with an increased risk to the fetus.
Preeclampsia is most commonly characterized by the gradual onset of hypertension, proteinuria and edema. Symptoms typically develop in the late third trimester and rarely as early as the late second trimester. Some patients experience the onset of symptoms after delivery, but the presence of signs and symptoms of this condition before 20 weeks of gestation is unusual and argues strongly against this diagnosis. HELLP syndrome develops only in women whose pregnancies are complicated by preeclampsia. Delivery of the fetus is curative for patients with preeclampsia, eclampsia, or HELLP syndrome. Because this patient is symptomatic during the twelfth week of pregnancy, preeclampsia, eclampsia, and the HELLP syndrome are unlikely and delivery of the fetus is not appropriate.
Methyldopa is an appropriate treatment for chronic hypertension in a pregnant patient, but chronic hypertension would not explain this patient's acute kidney injury and microangiopathic anemia. Methyldopa also does not alter outcome in patients with SRC and is therefore not indicated for this patient.
TTP is characterized by thrombocytopenia, microangiopathic hemolytic anemia, acute kidney injury, fever, and neurologic symptoms; however, hematologic and renal manifestations are usually predominant. TTP is a much more rare complication of pregnancy compared with preeclampsia and tends to present at midpregnancy or later.
Like preeclampsia, TTP before 20 weeks would be very unusual. In addition, the lactate dehydrogenase level is often markedly elevated in TTP secondary to both hemolysis and widespread tissue ischemia. The treatment of choice for TTP is plasma exchange. Because TTP is an unlikely diagnosis in this patient based upon the timing of the symptoms, treatment with plasma exchange would not be warranted.
- Therapy with an angiotensin-converting enzyme inhibitor is indicated for scleroderma renal crisis in pregnant patients despite being associated with an increased risk to the fetus.