Test yourself: Renal insufficiency

The following cases and commentary, which address renal problems, are excerpted from ACP's Medical Knowledge Self-Assessment Program (MKSAP 15).

Case 1: Inflammatory arthritis and respiratory failure

A 57-year-old man is evaluated in the emergency department for the acute onset of rapidly worsening dyspnea. For the past 10 weeks, he has had pain and swelling in the small joints of the hands and in the knees; he was diagnosed with seronegative symmetric inflammatory polyarthritis 2 weeks ago and was started on low-dose methotrexate, a folic acid supplement, low-dose prednisone, and naproxen at that time. He also has a history of refractory otitis media and underwent bilateral tympanostomy tube placement 6 months ago.

He is in respiratory failure and is intubated, mechanically ventilated, and admitted to the hospital. Blood is noted when he is intubated. On physical examination on admission, temperature is 38.5°C (101.3°F), blood pressure is 135/95 mm Hg, pulse rate is 125/min, and respiration rate is 24/min. There is no bleeding from the gums. Pulmonary examination reveals diffuse crackles throughout all lung fields. The metacarpophalangeal and proximal interphalangeal joints are swollen, and both knees have medium-sized effusions. Palpable purpura is present on the calves.

Laboratory studies show: hemoglobin, 10 g/dL (100 g/L); leukocyte count, 12,500/µL (12.5 × 109/L) (80% neutrophils); serum creatinine, 2.6 mg/dL (198.4 µmol/L); rheumatoid factor, negative; antinuclear antibodies, negative; c-ANCA, positive; anti–cyclic citrullinated peptide antibodies, negative; antiproteinase-3 antibodies, positive; serologic test for HIV antibodies, negative; and urinalysis, 2+ protein, 1+ blood, 15 erythrocytes/hpf.

A chest radiograph shows normal heart size and diffuse alveolar infiltrates in both lung fields.

Ceftriaxone, azithromycin, and hydrocortisone are started. His previous medications are discontinued.

Which of the following is the most likely diagnosis?

A. Interstitial pneumonitis
B. Methotrexate-induced pneumonitis
C. Pneumocystis pneumonia
D. Wegener granulomatosis

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Case 2: History of seizures and alcohol abuse

A 50-year-old man is admitted to the hospital after having two generalized tonic-clonic seizures in a 24-hour period. He has had seizures in the past, which were always attributed to alcohol withdrawal. Ten years ago, he was in a major motor vehicle collision that was related to alcohol intoxication. He has end-stage liver disease secondary to alcoholic cirrhosis but has been sober for 2 years and is awaiting a liver transplant. His kidney function is normal. His current medications include nadolol, spironolactone, and furosemide.

On physical examination, the patient is awake and alert, is afebrile, and has a normal blood pressure and pulse rate. Neurologic examination findings are normal. The general physical examination reveals changes consistent with chronic liver disease, including jaundice and ascites.

Laboratory studies show a serum creatinine level of 0.6 mg/dL (45.8 µmol/L) and no blood ethanol. Serum electrolyte levels are normal.

An MRI of the brain shows an area of chronic encephalomalacia in the left frontotemporal head region, consistent with old trauma. An electroencephalogram shows left temporal sharp waves.

Which of the following is the best treatment for this patient?

A. Levetiracetam
B. Oxcarbazepine
C. Phenytoin
D. Valproic acid

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Case 3: Progressively increasing serum creatinine

A 75-year-old woman is evaluated for a progressively increasing serum creatinine level. She was admitted to the hospital 3 days ago for crampy abdominal pain; low-grade fever; and loose, mucus-streaked stools. She has a history of hypertension and chronic kidney disease; her serum creatinine level was 1.2 mg/dL (106.0 µmol/L) 1 month ago. Medications are enalapril, hydrochlorothiazide, and low-dose aspirin.

Colonoscopy showed areas of erythematous, eroded, friable, hemorrhagic, ulcerated mucosa with a decreased vascular pattern in the descending colon. Intravenous hydration is maintained and supplemented with oral intake.

On physical examination today, temperature is normal, blood pressure is 142/88 mm Hg, and pulse rate is 80/min without orthostatic changes. Respiration rate is 14/min. Skin turgor is normal. There is no rash or lymphadenopathy. Cardiopulmonary examination is normal. The abdomen is tender to palpation in the upper- and lower-left quadrants. There is trace bilateral pretibial edema.

Laboratory studies show: hemoglobin, 12.2 g/dL (122 g/L); leukocyte count, 18,200/µL (18.2 × 109/L); platelet count, 150,000/µL (150 × 109/L); phosphorus, 18.7 mg/dL (6.0 mmol/L); calcium, 8.3 mg/dL (2.0 mmol/L); serum creatinine, currently 2.3 mg/dL (203.3 µmol/L) and 1.3 mg/dL (114.9 µmol/L) three days ago; serum uric acid, 6 mg/dL (0.35 mmol/L); and urinalysis, specific gravity 1.011, pH 5.0, no blood, protein, or casts.

Peripheral blood smear shows no schistocytes. On kidney ultrasound, the right kidney is 11.6 cm and the left kidney is 11.8 cm. There is no hydronephrosis.

Which of the following is the most likely diagnosis?

A. Acute phosphate nephropathy
B. Acute urate nephropathy
C. Hemolytic uremic syndrome
D. Prerenal azotemia

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Case 4: Disorientation after subarachnoid hemorrhage

A 44-year-old man is evaluated in the hospital because of disorientation and hallucinations. He was admitted to the hospital 4 days ago for a subarachnoid hemorrhage that was repaired with surgical clipping. His medical history is otherwise unremarkable; before he was admitted to the hospital, he took no medications.

On physical examination, he is disoriented, confused, and hallucinating. Temperature is normal, blood pressure is 140/80 mm Hg, pulse rate is 90/min, and respiration rate is 16/min. Upon standing, his blood pressure is 120/60 mm Hg and pulse rate is 110/min. The remainder of the physical examination is normal.

Laboratory values were normal on admission.

Current laboratory studies show: sodium, 118 mEq/L (118 mmol/L); potassium, 4.1 mEq/L (4.1 mmol/L); chloride, 85 mEq/L (85 mmol/L); bicarbonate, 23 mEq/L (23 mmol/L); serum osmolality, 248 mosm/kg H2O (248 mmol/kg H2O); serum uric acid, 6.8 mg/dL (0.4 mmol/L); spot urine sodium, 105 mEq/L (105 mmol/L); spot urine potassium, 20 mEq/L (20 mmol/L); spot urine chloride, 90 mEq/L (90 mmol/L); and urine osmolality, 633 mosm/kg H2O (633 mmol/kg H2O).

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

A. Adrenal insufficiency
B. Cerebral salt wasting
C. Hypothyroidism
D. Syndrome of inappropriate antidiuretic hormone secretion

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Case 5: HIV and syphilis

A 45-year-old man with a 10-year history of HIV infection is evaluated in the hospital for an elevated serum creatinine level and abnormal urinalysis 5 days after admission for cytomegalovirus retinitis and latent syphilis. He has previously refused treatment with highly active antiretroviral therapy. Medications are ganciclovir, trimethoprim-sulfamethoxazole, metoprolol, intramuscular penicillin G benzathine, and low-molecular-weight heparin.

On physical examination, temperature is normal, blood pressure is 150/88 mm Hg, pulse rate is 88/min, and respiration rate is 16/min. BMI is 22. Funduscopic examination reveals yellow-white, fluffy retinal lesions adjacent to retinal vessels. Cardiopulmonary examination is normal. Cutaneous and neurologic examinations are normal. There is trace bilateral lower-extremity edema.

Laboratory studies show hemoglobin, 8.6 g/dL (86 g/L); leukocyte count, 4800/µL (4.8 × 109/L); platelet count, 168,000/µL (168 × 109/L); CD4 cell count, 60/µL; HIV RNA viral load, 147,300 copies/mL; positive VDRL; positive for antibodies to hepatitis C; C3, 71 mg/dL (710 mg/L); C4, 7 mg/dL (70 mg/L) (normal 13-38 mg/dL [130-380 mg/dL]); serum creatinine, 1.9 mg/dL (168 µmol/L).

Urinalysis shows 3+ protein, 1+ blood, 15 dysmorphic erythrocytes/hpf, 2-5 leukocytes/hpf, occasional erythrocyte casts and a urine protein-creatinine ratio of 2.3 mg/mg.

On kidney ultrasound, the right kidney is 11.6 cm and the left kidney is 11.8 cm. The echotexture of the renal parenchyma is diffusely increased. There is no hydronephrosis, and no calculi or solid masses are seen.

Which of the following is the most likely diagnosis?

A. Acute interstitial nephritis
B. Collapsing focal segmental glomerulosclerosis
C. Immune complex–mediated glomerular nephritis
D. Pigment nephropathy

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Answers and commentary

Case 1

Correct answer: D. Wegener granulomatosis.

This patient most likely has Wegener granulomatosis, a necrotizing vasculitis that typically affects the upper- and lower-respiratory tract and the kidneys. This patient's purpura is consistent with vasculitis. His diffuse pulmonary infiltrates (generally associated with alveolar hemorrhage), history of refractory otitis media, renal failure, and urinalysis findings that suggest glomerulonephritis particularly raise suspicion for Wegener granulomatosis.

Wegener granulomatosis may be associated with inflammatory arthritis involving the small and large joints and joint effusions. The presence of c-ANCA and antiproteinase-3 antibodies is approximately 90% specific for this condition. The presentation of Wegener granulomatosis is highly nonspecific and evolves slowly over a period of months; therefore, diagnosis of this condition is often delayed by several months.

Patients with severe, long-standing rheumatoid arthritis may develop interstitial pneumonitis, and this condition is particularly likely to develop in men. Radiographs of patients with this condition usually show bibasilar interstitial markings. Interstitial lung disease associated with rheumatoid arthritis most characteristically has an insidious onset and is associated with seropositive, erosive joint disease. In most patients, the lung disease appears 5 years or more after the diagnosis of rheumatoid arthritis.

Methotrexate-induced pneumonitis can occur at any time in the course of therapy with this agent, regardless of the dosage or duration of treatment. However, this condition would not explain this patient's entire clinical picture, including c-ANCA positivity, vasculitis, renal failure, and his urinalysis findings.

Pneumocystis pneumonia may manifest as fever, dyspnea, tachypnea, and crackles heard on pulmonary examination. However, dyspnea is typically progressive and not acute and would not result in rapid pulmonary failure. Chest radiography in patients with this condition may show diffuse infiltrates. Pneumocystis pneumonia also usually develops in patients who are significantly immunosuppressed, whereas this patient has received only a short course of low-dose methotrexate. Furthermore, Pneumocystis pneumonia would not explain this patient's additional findings.

Key Point

  • Wegener granulomatosis should be considered in patients with upper- and lower-airway manifestations, renal involvement, and inflammatory arthritis.

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Case 2

Correct answer: A. Levetiracetam.

Given his clinical history, MRI findings, and electroencephalographic findings, this patient is likely to have epilepsy. Treatment of epilepsy in a patient with an underlying hepatic disease requires careful selection and management of the antiepileptic medication. Levetiracetam, gabapentin, and pregabalin are the preferred choices in patients with significant liver disease because they do not undergo significant hepatic metabolism and have low protein binding. Therefore, levetiracetam is most appropriate for this patient.

For antiepileptic drugs that are hepatically metabolized or highly protein bound, alterations of hepatic enzymatic pathways and hypoalbuminemia can result in unexpected drug toxicity. For these reasons, oxcarbazepine, phenytoin, and valproic acid would be less favored options for this patient. Additionally, some antiepileptic drugs should be avoided because of their potential hepatoxicity, particularly valproic acid and felbamate.

In patients who have undergone or are expected to undergo organ transplantation, it is particularly important to consider potential drug interactions that might alter the effectiveness of their immunosuppression regimen. Cytochrome P450 enzyme inducers, including phenytoin and oxcarbazepine, and inhibitors, including valproic acid, can be problematic in this population. Highly protein-bound drugs, such as phenytoin, are also best avoided when possible. Levetiracetam, gabapentin, and pregabalin are preferred for these patients because of the lack of significant drug interactions. Because these three medications are renally excreted, the dosage may need to be lowered in the presence of renal insufficiency. Dosing should be based on clinical response rather than the serum drug level because the therapeutic range for these agents is quite broad.

Key Point

  • For patients who should avoid hepatically metabolized antiepileptic drugs, either because of drug interaction or underlying liver disease, levetiracetam, gabapentin, and pregabalin can be used.

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Case 3

Correct answer: A. Acute phosphate nephropathy.

This patient most likely has acute phosphate nephropathy. This condition typically develops within a few days of exposure to an oral sodium phosphate bowel preparation but often remains unrecognized until laboratory studies are performed at a later time. Manifestations of acute phosphate nephropathy may include hyperphosphatemia out of proportion to the degree of kidney failure and minimal abnormalities on urinalysis.

Because phosphate nephropathy may develop even in patients with normal kidney function, safer bowel-cleansing agents such as polyethylene glycol should be used instead of oral sodium phosphate.

Acute urate nephropathy is usually a component of the tumor lysis syndrome, which also may manifest as hypocalcemia and hyperphosphatemia. However, tumor lysis syndrome usually occurs in the presence of a tumor with a high cell-turnover rate, which is not suggested by this patient's clinical presentation.

Hemolytic uremic syndrome (HUS) may develop after enteric infection with verotoxin-producing strains of Escherichia coli (VTEC), but only 6% to 12% of cases occur in adults. Within 1 to 2 days of toxin exposure, abdominal pain and watery diarrhea with subsequent bloody diarrhea develop. In addition to acute kidney injury, patients with HUS have thrombocytopenia and microangiopathic hemolytic anemia, which are absent in this patient. Furthermore, this patient's pattern of decreased vascularity seen on colonoscopy is more consistent with ischemic colitis than with infectious colitis.

This patient's absence of postural hypotension, tachycardia, and progressive azotemia despite ongoing hydration with normal saline argues against prerenal azotemia. This condition also is rarely associated with a serum phosphorus level above 13 mg/dL (4.2 mmol/L).

Key Point

  • The cathartic agent sodium phosphate may cause acute phosphate nephropathy resulting in acute kidney injury and hyperphosphatemia out of proportion to the degree of kidney failure.

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Case 4

Correct answer: B. Cerebral salt wasting.

Cerebral salt wasting (CSW) is a rare cause of hyponatremia. This condition typically occurs within a few days of a neurosurgical procedure or subarachnoid hemorrhage and is characterized by kidney salt wasting, hyponatremia, and hypotension. Laboratory findings may include a serum sodium level less than 135 mEq/L (135 mmol/L), low or low-normal plasma osmolality, elevated urine osmolality, and an elevated spot urine sodium level relative to the hyponatremia. CSW is distinguished from the syndrome of inappropriate antidiuretic hormone secretion (SIADH) by the presence of hypotension, which reflects the decreased intravascular volume associated with kidney salt wasting. The treatment of CSW is intravenous normal saline.

This patient's kidney salt wasting and volume depletion are consistent with adrenal insufficiency. However, this patient has no predisposing factors for hypoadrenalism, such as discontinuation of long-term corticosteroid therapy, sepsis, or autoimmune disease. Furthermore, hyperkalemia and a mild, non–anion gap metabolic acidosis are found in over 60% of patients with adrenal insufficiency but are absent in this patient.

Hypothyroidism can lead to hyponatremia but would not explain this patient's volume-depleted state. Furthermore, thyroid hormone deficiency leads to increased central release of antidiuretic hormone, and hypothyroidism-associated hyponatremia usually resembles SIADH and not CSW.

Patients with SIADH are euvolemic or slightly volume expanded, which is not consistent with this patient's presentation. In addition, patients with SIADH usually have extremely decreased serum uric acid levels, because volume expansion in this setting causes decreased uric acid absorption in the proximal nephron.

Key Point

  • Cerebral salt wasting may affect patients undergoing neurosurgery, particularly those with subarachnoid hemorrhage, and manifests as hyponatremia, increased urine sodium excretion, concentrated urine, and evidence of hypovolemia.

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Case 5

Correct answer: C. Immune complex–mediated glomerular nephritis.

Patients with HIV infection are at risk for numerous kidney-related diseases that often manifest as glomerular hematuria, proteinuria, and an elevated serum creatinine level. This patient's increased serum creatinine level accompanied by hypocomplementemia and dysmorphic erythrocytes and erythrocyte casts seen on urinalysis is most consistent with immune complex–mediated glomerular nephritis. Syphilis and hepatitis C virus infection also may be associated with this condition.

Acute interstitial nephritis may be associated with cytomegalovirus infection or use of trimethoprim-sulfamethoxazole. However, this condition is usually associated with leukocyte casts seen on urinalysis and may be accompanied by fever, rash, or eosinophilia.

HIV nephropathy is a form of collapsing focal segmental glomerulosclerosis (FSGS) that is found in 60% of kidney biopsies in patients with HIV infection and kidney disease. This condition typically develops in black patients with high HIV RNA viral loads and manifests as the nephrotic syndrome with normal serum complement levels and fatty casts and oval fat bodies in the urine sediment. This patient's hypocomplementemia and urinalysis findings are more consistent with immune complex–mediated glomerular nephritis than with collapsing FSGS.

Rhabdomyolysis and pigment nephropathy may occur in association with HIV infection. In this setting, the urine dipstick indicator for blood would be falsely positive because of the presence of myoglobin. The absence of pigmented or muddy brown casts on urinalysis also argues against a diagnosis of pigment nephropathy.

Key Point

  • Immune complex–mediated glomerular nephritis is characterized by hypocomplementemia and dysmorphic erythrocytes and erythrocyte casts seen on urinalysis.