Minimal Change Disease

MINIMAL CHANGE DISEASE

Minimal change disease (MCD), or nil disease, is the most common cause of nephrotic syndrome in children under age 10. It accounts for about 90 percent of cases in children and about 10–15 percent in adult cases. Patients usually present with heavy proteinuria (>3 g/day), hypoalbuminemia, dyslipidemia, and anasarca. Urine sedi-ment is benign. Diagnosis rests on kidney biopsy. Under light microscopy, the glom-eruli appear normal. There is absence of immune deposits by immunofluorescence. Electron microscopic findings show efface-ment of the epithelial foot processes. Inves-tigators believe that MCD is a T-lymphocyte disease because of its sensitive response to steroids and cyclosporine. It is strongly associated with Hodgkin’s lymphoma, a hematologic malignancy. Proteinuria appears to disappear when the malignancy goes into remission. A glomerular perme-ability factor (GPF) derived from a T-cell hybridoma has been identified to cause fusion of the foot processes and protein-uria, when injected into experimental rats. The T-cell hybridoma was made from T cells harvested from a patient with minimal change disease. It is thought that this GPF has TNF-like activity. In addition, epithe-lial damage causes loss of polyanions like heparin sulfate. This loss of charge selectiv-ity allows macromolecules like albumin to pass through the filtration barrier and leak into the urine.

In children with idiopathic nephrotic syndrome, treatment with steroids produces immediate results with about 50 percent of cases going into remission in two weeks, and almost all within eight weeks of treatment. Clinical response in adults tends to be slower, but the majority will achieve remission after twelve to six-teen weeks of treatment. Cytotoxic agents, which include cyclophosphamide, chlo-rambucil, azathioprine, mycophenolate mofetil, and cyclosporine are reserved for relapsers and steroid-resistant cases.