Board Review: Nephrology

Wednesday, August 19

Question 1
A 60-year-old woman with a history of type 1 diabetes mellitus and stage 4 chronic kidney disease comes for a routine followup examination. She asks about modalities of renal replacement therapy.

Which of the following is the best option for this patient? A. 0-Antigen-mismatched deceased donor kidney transplantation B. Peritoneal dialysis C. Hemodialysis D. Living donor kidney transplantation after a course of dialysis E. Preemptive living donor kidney transplantation

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

E. Preemptive living donor kidney transplantation

 Preemptive kidney transplantation is associated with improved mortality compared with transplantation performed after a course of dialysis. The reasons for this fact are not entirely clear, but accelerated cardiovascular disease associated with dialysis therapy most likely accounts for a portion of the excess mortality seen in patients treated with dialysis before transplantation. Timely referral of patients with chronic kidney disease to a nephrologist facilitates preemptive transplantation.

 Outcomes of living donor renal transplantations are equivalent to or better than those of wellmatched deceased donor transplantations. Mortality rates of patients treated with hemodialysis and peritoneal dialysis in the United States are roughly equivalent except for women with diabetes >65 years of age, in whom peritoneal dialysis has been reportedly associated with a higher mortality rate in some centers.

Question 2
A 62-year-old woman with type 2 diabetes mellitus, cerebrovascular disease, and chronic kidney disease develops nonoliguric acute renal failure after a left femoral popliteal bypass. During the surgery, intra- or postoperative hypotension did not develop. Preoperatively, she began cefazolin therapy for wound prophylaxis. For the first 48 hours postoperatively, she received hydration with dextran 40, followed by half-normal saline (0.45%). Over the first 3 days of hospitalization, her creatinine level increased to 5.4 mg/dL (477.47 mol/L); her creatinine level had been between 1.6 mg/dL (141.47 mol/L) and 1.8 mg/dL (159.16 mol/L) over the past year. Regular medications are ramipril; atenolol; and clopidogrel, which was discontinued 5 days preoperatively and has not been reinitiated. On physical examination, temperature is 36.7 (98.1 pulse rate is 86/min, and C F), blood pressure is 132/80 mm Hg. Cardiac examination is unremarkable except for a murmur of aortic sclerosis. The lungs are clear to auscultation. There is trace pretibial edema bilaterally. The operative site shows no erythema or drainage. Complete blood count is normal without peripheral eosinophilia. C3 and C4 levels are normal. Urinalysis shows 1+ protein, many monomorphic erythrocytes, and no cellular casts. Ultrasound shows symmetric echogenic kidneys without hydronephrosis.

Which of the following is the most likely diagnosis?

A. Osmotic tubular injury B. Ischemic tubular epithelial cell injury C. Angiotensin-converting enzyme inhibitorinduced acute renal failure D. Thrombotic microangiopathy

Which of the following is the most likely diagnosis?

A. Osmotic tubular injury

 This patient has osmotic tubular injury due to dextran 40 use. This condition can present as oliguric or nonoliguric acute renal failure and also has been reported in patients treated with mannitol or sucrose-containing preparations of intravenous immune globulin. Patients with preexisting renal insufficiency are at increased risk for developing this disorder. There are no clearly defined diagnostic urinary or laboratory findings associated with this condition, and renal biopsy is needed for definitive diagnosis. Treatment of osmotic tubular injury generally is supportive, but patients with oliguria and sustained increases in plasma osmolality may benefit from plasma exchange to remove retained dextran 40 and thereby limit further renal injury.

 This patient's urinary sediment findings show no muddy brown casts to support a diagnosis of acute tubular necrosis. The absence of hypotension and tachycardia on physical examination and during the surgery is not consistent with prerenal azotemia. Chronic angiotensin-converting enzyme inhibitor therapy is unlikely to cause acute renal failure. Thrombotic microangiopathy is unlikely in the absence of thrombocytopenia and hemolytic anemia. However, because of this patient's recent use of clopidogrel therapy, this diagnosis should be considered. Preliminary evidence shows that IgG inhibitors of the von Willebrand factorcleaving protease ADAMTS13 mediate clopidogrel-induced thrombotic thrombocytopenic purpura.

Question 3
A 60-year-old man with a 10-year history of hypertension is hospitalized for shortness of breath. Two weeks before admission, he developed headache and dyspnea on exertion. Medications include metoprolol and hydrochlorothiazide. Physical examination on admission reveals a blood pressure of 180/120 mm Hg. Laboratory studies at that time showed a potassium level of 4.2 meq/L (4.2 mmol/L) and a creatinine level of 1.5 mg/dL (132.63 mol/L).

Question 3
Over the next 2 weeks, the blood pressure gradually normalizes after enalapril, 5 mg once daily, and amlodipine, 5 mg once daily, are added to his regimen. On follow-up examination, his blood pressure is 132/76 mm Hg. Funduscopic examination shows arteriolar tortuosity. The point of maximal impulse is laterally displaced. He has a right femoral systolic bruit. Distal pulses are 1+ bilaterally, and there is no peripheral edema.

Laboratory Studies Blood urea nitrogen Creatinine Sodium Potassium Chloride Bicarbonate Urinalysis 45 mg/dL (16.07 mmol/L) 3.5 mg/dL (309.47 mol/L) 140 meq/L (140 mmol/L) 5.1 meq/L (5.1 mmol/L) 105 meq/L (105 mmol/L) 20 meq/L (20 mmol/L) Trace protein; several hyaline casts/hpf

Which of the following is the most appropriate initial step in this patient's management? A. Perform renal biopsy B. Decrease the enalapril dose to 2.5 mg/d C. Perform magnetic resonance angiography of the renal arteries D. Discontinue enalapril E. Switch enalapril to losartan

Which of the following is the most appropriate initial step in this patient's management?

D. Discontinue enalapril

 This patient most likely has angiotensin-converting enzyme (ACE) inhibitorinduced prerenal acute renal failure. Therefore, the most appropriate initial step in this patient's management is discontinuing enalapril. Generally, an increase in the creatinine level up to 30% is acceptable after initiation of ACE inhibitors or angiotensin receptor blockers. A recent study demonstrated that continued ACE inhibitor therapy was associated with sustained renoprotective benefit in patients with stage III and IV chronic kidney disease. Therefore, continuation of ACE inhibitor therapy in patients with chronic kidney disease is indicated when possible. disease.

 Once-daily administration of lower doses of these agents is initially indicated, as is measurement of the potassium and creatinine levels 7 to 10 days after initiation of therapy and then every 2 to 3 months. However, this patient demonstrated a >100% increase in the creatinine level, which should raise suspicion for bilateral renal artery stenosis or advanced intrarenal small-vessel disease. The glomerular filtration rate (GFR) in patients with bilateral renal artery stenosis is maintained to a great extent by an angiotensin II induced vasoconstriction at the efferent arteriole. Both ACE inhibitors and angiotensin receptor blockers cause loss of efferent arteriolar vasoconstriction with a resultant decrease in the glomerular capillary pressure and GFR.

 This patient's urine sediment is not sufficiently active to warrant a renal biopsy. Discontinuation of enalapril would be favored over a dose reduction because of this patient's marked decline in GFR and the risk for subsequent ischemic renal injury. Magnetic resonance angiography of the renal arteries would document the status of the renal arteries after discontinuing enalapril. However, percutaneous angioplasty for renal artery stenosis generally is reserved for patients who remain hypertensive despite aggressive pharmacologic therapy. Prospective randomized clinical trials have yet to definitively establish indications for intervening to preserve renal function or decrease cardiovascular complications. Losartan, an angiotensin receptor antagonist, would be as likely as enalapril to cause a decrease in GFR.

Question 4
A 75-year-old man with a 6-month history of the nephrotic syndrome is evaluated for the sudden onset of flank pain and hematuria of 18 hours' duration. Three months ago, his creatinine level was 1 mg/dL (88.42 mol/L) and 24hour urinary protein excretion was 3 g/24 h. At that time, he began treatment with an angiotensin-converting enzyme inhibitor to decrease his proteinuria. His loop diuretic dose also was increased to treat worsening peripheral edema. On physical examination, his blood pressure is 170/90 mm Hg with no orthostatic drop. Cardiac examination reveals an S4 and a normal S1 to S2 with a systolic murmur at the base. The lungs are clear to auscultation and percussion. Ophthalmologic examination reveals hypertensive retinopathy. The abdomen is soft with no masses.

Laboratory Studies Blood urea nitrogen Creatinine Cholesterol Urinalysis 38 mg/dL (13.57 mmol/L) 2.0 mg/dL (176.84 mol/L) 300 mg/dL (7.76 mmol/L) 5 erythrocytes and numerous oval fat bodies/hpf; no leukocytes 15 g /24 h

24-Hour urinary protein excretion

Which of the following most likely precipitated this patient's renal insufficiency? A. Overaggressive diuresis B. Renal artery stenosis C. Renal vein thrombosis D. Kidney stones

Which of the following most likely precipitated this patient's renal insufficiency?

C. Renal vein thrombosis

 In the setting of the nephrotic syndrome, deteriorating renal function and a urinary protein excretion that markedly increases over the course of 6 months accompanied by worsening peripheral edema raises the suspicion for renal vein thrombosis. The loss of several inhibitors of the clotting system, such as angiotensin III, into the urine predisposes patients with the nephrotic syndrome to the development of deep venous and renal vein thrombosis.

 Overaggressive diuresis can cause kidney dysfunction, but this presentation would be accompanied by findings associated with volume depletion, including elevated total bicarbonate and blood urea nitrogen levels. In addition, this condition does not cause an increase in proteinuria. Renal stones can cause flank pain. However, a rise in the creatinine level indicates the presence of bilateral obstructive stones, which would present with leukocyturia, not an increase in proteinuria.

Question 5
A 66-year-old woman is evaluated for fatigue, decreased exercise tolerance of 1 month's duration, and new-onset dyspnea on exertion. Therapy with over-the-counter ibuprofen was unsuccessful, and she discontinued its use. She has a history of hypertension and was diagnosed with type 2 diabetes mellitus that is controlled by diet 2 years ago. Medications are lisinopril, 20 mg/d, and hydrochlorothiazide, 25 mg/d. On physical examination, pulse rate is 74/min and blood pressure is 148/86 mm Hg. The conjunctivae are pale. Cardiac examination reveals a grade 2/6 systolic ejection murmur. There is 1+ lower-extremity edema.

Laboratory Studies Hemoglobin Leukocyte count Platelet count Blood urea nitrogen Creatinine Sodium Potassium Chloride Bicarbonate Glucose Albumin Calcium Phosphorus Urinalysis Urinary proteincreatinine ratio 7.2 g/dL 7100/ L 125,000/ L 64 mg/dL 5.2 mg/dL 133 meq/L 4.1 meq/L 110 meq/L 19 meq/L 142 mg/dL 4.0 mg/dL 11.0 mg/dL 5.4 mg/dL pH 5.0, specific gravity 1.015, no blood, 1+ protein, 510 leukocytes/hpf 2.5 mg/g

Which of the following is the most likely cause of this patient's renal failure? A. Chronic interstitial nephritis B. Hypertensive nephrosclerosis C. Acute interstitial nephritis D. Myeloma kidney E. Diabetic nephropathy

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

D. Myeloma kidney

 Myeloma kidney is most likely causing this patient's renal failure. Abnormalities in renal function are common in multiple myeloma, and nearly 50% of patients with this condition have an elevated creatinine level at the time of diagnosis. Myeloma kidney is characterized by an intratubular obstruction with light-chain casts that results in kidney failure. Classically, hypercalcemia, severe anemia, and a low anion gap due to an increase in unmeasured cations such as calcium and immunoglobulins in the setting of kidney disease should raise suspicion for myeloma-related kidney disease. In addition, myeloma kidney is associated with a discrepancy in proteinuria detection between the dipstick urinalysis and timed urine collection in which dipstick urinalysis reveals only albumin and not light chains. However, the addition of sulfosalicylic acid to the urine specimen precipitates all proteins, including light chains. Urine protein electrophoresis also confirms the presence and type of light chains excreted in the urine.

 Chronic tubulointerstitial disease secondary to analgesic use is unlikely in a patient with no history of chronic analgesic use. Acute interstitial nephritis due to nonsteroidal antiinflammatory drug use has developed in patients with minimal exposure to these agents. However, this condition is uncommon in the absence of skin rash, sterile pyuria, or peripheral eosinophilia. Diabetic nephropathy is the most common cause of chronic kidney disease but is unlikely to cause a discrepancy concerning the presence of proteinuria between the urinalysis and the timed urine collection. Diabetes mellitus also would not cause this patient's low anion gap or hypercalcemia.

Question 6
A 60-year-old woman with hypertension, type 2 diabetes mellitus, obesity, and chronic kidney disease comes for a routine office visit. She follows a renal diet. Medications are glipizide, 10 mg twice daily; pioglitazone, 30 mg/d; atenolol, 100 mg/d; benazepril, 80 mg/d; furosemide, 40 mg twice daily; simvastatin, 40 mg/d; and aspirin, 81 mg/d.

Laboratory Studies Creatinine Sodium Potassium Chloride Bicarbonate Calcium Phosphorus Albumin 2.3 mg/dL 140 meq/L 5.0 meq/L 106 meq/L 23 meq/L 9.7 mg/dL 6.9 mg/dL 4 g/dL

Which of the following should be started to most appropriately treat this patient? A. Aluminum hydroxide B. Sevelamer C. Vitamin D D. Hemodialysis

Which of the following should be started to most appropriately treat this patient?

B. Sevelamer

 Sevelamer should be added to this patient's regimen. Hyperphosphatemia contributes to renal osteodystrophy by stimulating parathyroid hormone secretion and may be an important cardiovascular risk factor in patients with chronic kidney disease. Oral calcium-free phosphate binders such as sevelamer or calcium-containing phosphate binders should be used to lower phosphorus levels and decrease parathyroid hormone secretion in chronic kidney disease.

 Aluminum hydroxide is the most potent phosphate binder available. However, this agent is not recommended because its chronic use is associated with aluminum retention and erythropoietin-resistant microscopic anemia, dementia, and severe osteomalacia. With a progressive decrease in the glomerular filtration rate, 1,25-dihydroxyvitamin D synthesis (calcitriol, the active metabolite of vitamin D) decreases, which results in increased parathyroid hormone secretion by removing the direct inhibitory effect of calcitriol on the parathyroid gland and by decreasing the serum calcium level. Calcitriol or newer generations of vitamin D analogs should be considered in chronic kidney disease to prevent renal osteodystrophy but only after hyperphosphatemia is controlled.

Question 7
A 49-year-old woman with end-stage renal disease is evaluated for painful ulcers involving both legs. Approximately 6 months ago, she noted nodular lesions on the right thigh and then the left. These lesions became progressively more painful and developed into ulcerative lesions over several months. She also has type 2 diabetes mellitus, atrial fibrillation, and hypertension. She has been maintained on chronic in-center hemodialysis for the past 6 years. Medications are warfarin; aspirin, 81 mg/d; enalapril; metoprolol; atorvastatin; calcium carbonate; calcitriol; and erythropoietin.

Question 7
On physical examination, pulse rate is 86/min and irregular and blood pressure is 140/90 mm Hg. She is obese. There are necrotic ulcers covering most of the thighs bilaterally. Cardiac examination shows an irregularly irregular rhythm. The lungs are clear to auscultation. Abdominal examination is unremarkable. There is no peripheral edema.

Laboratory Studies Hemoglobin Leukocyte count Platelet count INR Sodium Potassium Chloride Bicarbonate Calcium Phosphorus 11.6 g/dL 15,000/L 326,000/L 2.6 136 meq/L 5.3 meq/L 105 meq/L 19 meq/L 10.1 mg/dL 8.8 mg/dL

Which of the following is the most likely diagnosis? A. Calcinosis cutis B. Necrobiosis lipoidica diabetoricum C. Calcific uremic arteriolopathy D. Venous stasis ulcers E. Warfarin-induced skin necrosis

Which of the following is the most likely diagnosis?

C. Calcific uremic arteriolopathy

 The location and clinical presentation of this patient's esions are most characteristic of calcific uremic arteriolopathy, often termed calciphylaxis. These lesions typically present as painful violaceous nodules on the trunk, proximal extremities, and buttocks. Risk factors for development of this syndrome include use of warfarin, vitamin D analogues, and calcium-based phosphate binders; an elevated calciumphosphorus product; protein S or C deficiency; obesity; and female sex.

 Calcinosis cutis presents with painless calcified subcutaneous nodules that do not ulcerate. Necrobiosis lipidoca diabeticorum usually is asymptomatic, and the lesions associated with this condition typically appear as oval to irregularly shaped plaques on the shins of patients with diabetes. Venous stasis ulcers are shallow, red-based ulcers typically located medially in the lower leg. Warfarininduced skin necrosis typically occurs early in the course of warfarin therapy, and lesions associated with this condition present as erythematous macules but progress to ulcers within hours.

 The role of parathyroid hormone in the pathogenesis of calcific uremic arteriolopathy remains uncertain. Therapy for this condition includes avoidance of vitamin D analogues and calcium-based phosphate binders, control of the phosphorus level with noncalcium-based phosphate binders, aggressive wound care, and treatment of secondary infection. Parathyroidectomy is reserved for affected patients whose serum calcium and phosphorus levels cannot be controlled with phosphate binders and other medical interventions such as cinacalcet.

Question 8
A 44-year-old man diagnosed with cryptogenic cirrhosis 2 years ago is hospitalized for a fractured left hip sustained after a car accident. He is asymptomatic except for pain in his hip. He has felt well recently and is currently on the liver transplant list. He smokes 1 pack of cigarettes daily and does not drink alcoholic beverages or use illicit drugs. Medications are spironolactone, 50 mg twice daily; lactulose, 30 mL twice daily; oral propranolol, 20 mg twice daily; and furosemide, 20 mg twice daily.

Question 8
On physical examination, temperature is 36 pulse C, rate is 72/min, respiratory rate is 18/min, and blood pressure is 98/55 mm Hg. He is cachectic. There is scleral icterus. He has normal mentation, and no asterixis is noted. Cardiac examination reveals no murmurs or rubs, and his lungs are clear to auscultation. The abdomen is distended but nontender. There is 2+ peripheral edema and palmar erythema.

Laboratory Studies Glucose Blood urea nitrogen Creatinine Sodium Potassium Chloride Bicarbonate Albumin Arterial blood gas studies pH PCO PO
2 2

88 mg/dL 14 mg/dL 0.9 mg/dL 130 meq/L 3.3 meq/L 107 meq/L 18 meq/L 2.6 g/dL

7.48 25 mm Hg 92 mm Hg

Which of the following is the most likely cause of this patient's acidbase disorder? A. Renal tubular acidosis B. Impaired hepatic conversion of lactate C. Lactulose-induced diarrhea D. Reduced acid buffering capacity of the blood E. Increased minute ventilation

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

E. Increased minute ventilation

 Increased minute ventilation is the most likely cause of this patient's acidbase disorder. The acidbase disturbance in this patient is a respiratory alkalosis, which commonly develops in end-stage liver disease. If the serum pH is not measured, this disturbance can be misdiagnosed as metabolic acidosis in patients with end-stage liver disease. The liver helps to metabolize circulating steroid hormones. Elevated levels of progestins in end-stage liver disease lead to stimulation of the respiratory drive, which causes a primary respiratory alkalosis. In severe liver disease, decreased clearance of lactate from the circulation can lead to lactic acidosis. However, the absence of an anion gap in this patient excludes this condition.

 Renal tubular acidosis would lead to a metabolic acidosis. However, this patient's pH is alkaline, indicating that an alkalosis is the primary disorder or that another acidbase disorder is present. Reduced conversion of lactate would be associated with an anion gap metabolic acidosis (lactic acidosis), which is not present in this patient. Diarrhea would cause a metabolic acidosis, not respiratory alkalosis. Cirrhosis is not associated with a decreased buffering capacity of the blood.

Question 9
A 29-year-old man with a 10-year history of IgA glomerulonephritis is evaluated for persistent microscopic hematuria. He strictly maintains a sodium-restricted diet. His only medication is the maximal dose of an angiotensin-converting enzyme inhibitor. One year ago, the protein/creatinine ratio was 1 mg/g. On physical examination, the blood pressure is 138/85 mm Hg. The cardiac, pulmonary, and abdominal examinations are unremarkable. There is no peripheral edema or rash.

Laboratory Studies Creatinine Albumin Urinary protein creatinine ratio 1 mg/dL 3.8 g/dL 2 mg/g

Which of the following is the most appropriate next step in the management of this patient's IgA glomerulonephritis?

A. Tonsillectomy B. A diuretic C. Oral corticosteroids D. An angiotensin receptor blocker E. A calcium-channel blocker

Which of the following is the most appropriate next step in the management of this patient's IgA glomerulonephritis?

A. Tonsillectomy B. A diuretic C. Oral corticosteroids D. An angiotensin receptor blocker E. A calcium-channel blocker

 The most appropriate next step for this patient is the addition of angiotensin receptor blocker therapy. This patient's protein excretion has doubled over the course of a year, and his blood pressure is not optimally controlled at a level <130/80 mm Hg despite using a maximal dose of an angiotensin-converting enzyme inhibitor. Therefore, the addition of another antihypertensive agent is indicated. In the Combination Treatment of Angiotensin-II Receptor Blocker and Angiotensin-Converting Enzyme Inhibitor in Nondiabetic Renal Disease (COOPERATE) trial, which included many patients with IgA glomerulonephritis, combination therapy with an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker was associated with a decrease in proteinuria.

 There are no prospective data showing that tonsillectomy decreases morbidity in adult patients in this setting. Corticosteroid therapy has been shown to be effective in IgA glomerulonephritis when used with pulse methylprednisolone. However, therapy with corticosteroids alone has not been shown to be useful. Finally, the addition of a calcium-channel blocker or diuretics in a patient with IgA glomerulonephritis using an angiotensin-converting enzyme inhibitor has been shown to be less useful compared with the addition of an angiotensin receptor blocker.

Question 10
A 34-year-old asymptomatic black man is evaluated for peripheral edema of several months' duration. Medical history is unremarkable. On physical examination, pulse rate is 79/min and blood pressure is 140/90 mm Hg. He is in excellent health and appears muscular. There is 2+ lower-extremity edema. The remainder of the examination is normal.

Laboratory Studies Blood urea nitrogen Creatinine Albumin Urinalysis 5.1 mg/dL (1.82 mmol/L) 1.8 mg/dL (159.16 mol/L) 3.0 g/dL (30 g/L) 3+ proteinuria, several oval fat bodies/hpf

Urinary proteincreatinine ratio 3 mg/g

Which of the following is the most likely diagnosis?

A. Membranous nephropathy B. Focal segmental glomerulosclerosis C. Minimal change disease D. Membranoproliferative glomerulonephritis E. Focal proliferative lupus nephritis

Which of the following is the most likely diagnosis?

B. Focal segmental glomerulosclerosis

 This patient most likely has focal segmental glomerulosclerosis. This condition is the most common cause of the nephrotic syndrome in black patients, particularly those of younger age. Two other possible causes of the nephrotic syndrome, membranous nephropathy and minimal change disease, are much less likely. Minimal change disease primarily occurs in children, whereas membranous nephropathy usually affects older white patients.

 Membranoproliferative glomerulonephritis and focal proliferative lupus nephritis are both examples of the nephritic syndrome characterized by hypertension, hematuria, and renal insufficiency. Although this patient has hypertension and renal insufficiency, the absence of hematuria makes any form of the nephritic syndrome less likely. Moreover, membranoproliferative glomerulonephritis typically is associated with infectious diseases or systemic lupus erythematosus, of which this patient shows no signs.