Proteinuria and focal segmental glomerulosclerosis in severely obese adolescents

Objective: To describe the clinical and laboratory features of obesity associated proteinuria and focal segmental glomerulosclerosis. Study design: The patients were seen over a 12-year period at two large children's hospitals. Renal biopsies, performed for the diagnosis of unexplained heavy proteinuria and prepared for light, immunofluorescent, and electron microscopy, were read independently by two pediatric pathologists. Blood pressure, body mass index, serum levels of creatinine, albumin, and cholesterol, and 24-hour urinary protein were measured. Results: Seven African American adolescents were identified with obesity-associated proteinuria, which was characterized by severe obesity (120 +/- 30 kg), markedly elevated body mass index (46 +/- 11), mild hypertension (134/74 +/- 10/18 mm Hg), slightly low to normal serum albumin levels (3.6 +/- 0.2 g/dL), moderately elevated serum cholesterol levels (196 +/- 60 mg/dL), and elevated 24-hour protein excretion (3.1 +/- 1.3 g/dL). Calculated creatinine clearance was normal in 6 patients and decreased in one. Typical renal histologic features included glomerular hypertrophy, focal segmental glomerulosclerosis, increased mesangial matrix and cellularity, relative preservation of foot process morphology, and absence of evidence of inflammatory or immune-mediated pathogenesis. One patient showed a dramatic reduction in proteinuria in response to weight reduction. Three patients who were given angiotensin-converting enzyme inhibitors had reduced urinary protein losses from 2.9 g to 0.7 g per day One patient developed end-stage renal disease. Conclusion: Obese adolescents should be monitored for proteinuria, which has distinct clinical and pathologic features and may be associated with significant renal seguelae. Such proteinuria may respond to weight reduction and/or treatment with angiotensin-converting enzyme inhibitors.