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Relapsing Nephrotic Syndrome Quiz 1
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Relapsing Nephrotic Syndrome Quiz 2
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Relapsing Nephrotic Syndrome Quiz 3
A 19-year-old man presented to a nephrology clinic. Two years previously, he had presented to a pediatric nephrologist with lower extremity edema, foamy urine, and nephrotic range proteinuria. He was started on prednisone 60 mg per day and had reduction of proteinuria to less than half a gram per day within a month. Over the course of the following 2 years he has had multiple relapses that have in part been related to medication noncompliance. He had received further courses of steroids with slow taper and was eventually started on maintenance cyclosporine.
At the time of his current encounter, he complained of a recent 20-pound weight gain and increased leg edema. He has no known family history of kidney disease or proteinuria. He does not take illicit drugs. Medications include enalapril and cyclosporine, though he admits to occasionally missing doses. His blood pressure was 142/84 mm Hg. He had decreased basilar lung sound and 2+ leg edema to the thighs. No rash or synovitis was noted.
His serum creatinine was 0.8 mg/dL, potassium was 5.3 mEq/L, and hemoglobin was 16 g/dL. Urine showed 600 protein. Negative serology included anti-nuclear antibody, anti-double stranded DNA antibody, hepatitis B surface antigen, hepatitis C antibody, and HIV antibody. His complement 3 and 4 levels were within normal limits. Random urine protein to creatinine ratios ranged from 5–13 grams.
A renal biopsy was eventually performed and representative micrographs are shown (including immunofluorescence for IgM and electron micrograph). The biopsy contained over 20 similarly appearing glomeruli. On the basis of IgM staining, the patient was diagnosed with minimal change disease.
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His biopsy contained over 20 glomeruli without focal sclerosis. There was positive IgM and negative for C1q by immunofluorescence. The light micrographs were essentially unremarkable. Electron micrographs did show diffuse podocyte foot process effacement. A diagnosis of minimal change disease with IgM staining was given.
Variants of minimal change nephropathy include entities known as diffuse mesangial proliferative glomerulonephritis, IgM nephropathy, and C1q nephropathy. Some feel these diseases lie on a spectrum contiguous with FSGS. In our case, the absence of any evidence of focal sclerosis in a sample of over 20 glomeruli would preclude an FSGS diagnosis at this time.
The IgM nephropathy variant was first described over 30 years ago. It is notable for more pronounced IgM mesangial staining in the absence of C1q and usually IgG. IgM variant minimal change patients tend to have more relapses and to require agents other than steroids. In some cases these patients were more likely to require agents such as cyclosporine or even Cytoxan to achieve a remission.
Generally speaking, minimal change patients with frequent relapses, similar to difficult cases with other glomerulonephritidies, tend to have a higher incidence of life-long hypertension and osteoporosis.
References
Border WA. Distinguishing minimal-change disease from mesangial disorders. Kidney Int 1988;34:419-434.
Swartz SJ, Eldin KW, Hicks MJ, Feig DI. Minimal change disease with IgM+ immunofluorescence a subtype of nephrotic syndrome. Pediatr Nephrol 2009;24:1187-1192.
Myllymäki J, Saha H, Mustonen J, Helin H, Pasternack A. IgM nephropathy: clinical picture and long-term prognosis. Am J Kidney Dis 2003;41:343-350.
Cohen AH, Border WA, Glassock RJ. Nehprotic syndrome with glomerular mesangial IgM deposits. Lab Invest 1978;38:610-619.
Kyrieleis HA, Löwik MM, Pronk I, et al. Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. Clin J Am Soc Nephrol 2009;4:1593-1600.
This case was prepared by Kevin T. Harley, MD, Assistant Clinical Professor of Medicine, Division of Nephrology & Hypertension, at the University of California in Irvine.
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