MKSAP: 69-year-old woman with new-onset dependent edema

Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 69-year-old woman is evaluated in the emergency department for new-onset dependent edema that began 3 weeks ago. She says it is difficult to walk, and she has gained 4.5 kg (10 lb) of fluid weight. History is significant for obesity and hypertension. Her only medication is lisinopril.

On physical examination, vital signs are normal. BMI is 32. There is no rash. There is 3-mm bilateral dependent edema stopping just below the abdomen; it is equal on both sides. The remainder of the examination is unremarkable.

Laboratory studies:

Albumin 2.1 g/dL (21 g/L)
Creatinine 1.3 mg/dL (114.9 µmol/L)
Urine protein-creatinine ratio 8700 mg/g

Kidney biopsy findings are consistent with a diagnosis of minimal change glomerulopathy with superimposed acute tubular necrosis.

In addition to initiating diuretic therapy, which of the following is the most appropriate treatment?

A. Cyclosporine
B. High-dose oral prednisone
C. Rituximab
D. No additional treatment

MKSAP Answer and Critique

The correct answer is B. High-dose oral prednisone.

Diuretics plus high-dose prednisone is the most appropriate treatment for this patient with minimal change glomerulopathy (MCG; also known as minimal change disease). MCG is the most common cause of the nephrotic syndrome in children and accounts for approximately 10% to 15% of cases in adults. Immunosuppressive therapy is indicated for treatment of primary MCG, which invariably presents with the full nephrotic syndrome. The concomitant acute tubular necrosis makes treatment even more imperative in this case, because primary MCG with acute kidney injury has been shown to be a treatment-responsive lesion if treated in a timely manner. First-line therapy is prednisone at a dose of 1 mg/kg per day or 2 mg/kg every other day for 8 to 12 weeks, followed by a taper. Patients typically respond to glucocorticoids within 8 to 16 weeks. However, relapse is common, and in a substantial percentage of patients, the course of MCG is one of remission followed by relapse. For frequently relapsing or glucocorticoid-dependent disease, treatment options include cyclophosphamide, calcineurin inhibitors (tacrolimus or cyclosporine), mycophenolate mofetil, and rituximab. In addition to immunosuppression, patients should receive standard therapy for the nephrotic syndrome, including an ACE inhibitor or angiotensin receptor blocker (this patient is already taking lisinopril, with well-controlled blood pressure), diuretics for edema management, and cholesterol-lowering medication if total cholesterol >200 mg/dL (5.1 mmol/L). In rare cases of MCG secondary to malignancies (Hodgkin lymphoma, non-Hodgkin lymphoma, thymoma), medications (NSAIDs, lithium), infections (strongyloides, syphilis, mycoplasma, ehrlichiosis), and atopy (pollen, dairy products), treatment of the underlying condition without immunosuppression may be sufficient.

Cyclosporine and rituximab are generally reserved for glucocorticoid-resistant or glucocorticoid-dependent cases of MCG and, except for a clear contraindication to glucocorticoids, should not be used as first-line therapy.

Diuretics alone are not sufficient to manage this patient and prevent progressive kidney disease; immunosuppressive therapy is therefore indicated.

Key Point

  • Glucocorticoids are first-line therapy for primary minimal change glomerulopathy; standard treatment of the nephrotic syndrome (ACE inhibitor or angiotensin receptor blocker, diuretics for edema, and cholesterol-lowering medication if total cholesterol >200 mg/dL [5.1 mmol/L]) is also indicated as needed.

This content is excerpted from MKSAP 18 with permission from the American College of Physicians (ACP). Use is restricted in the same manner as that defined in the MKSAP 18 Digital license agreement. This material should never be used as a substitute for clinical judgment and does not represent an official position of ACP. All content is licensed to on an “AS IS” basis without any warranty of any nature. The publisher, ACP, shall no3t be liable for any damage or loss of any kind arising out of or resulting from use of content, regardless of whether such liability is based in tort, contract or otherwise.

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