Nephrotic Syndrome: Pathogenesis and Management

1. Karl S. Roth, MD* 2. Barbara H. Amaker, MD* 3. James C.M. Chan, MD† 1. *Departments of Pediatrics and Pathology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 2. †Department of Pediatrics, The Barbara Bush Children’s Hospital at Maine Medical Center, Portland, ME After completing this article, readers should be able to: 1. Describe the signs and symptoms of minimal-change nephrotic syndrome. 2. Characterize the laboratory findings in children who have minimal-change nephrotic syndrome. 3. Plan a treatment program for a young child who has an initial episode of minimal-change nephrosis. 4. Recognize the major complications of minimal-change nephrotic syndrome. The estimated annual incidence of nephrotic syndrome in healthy children is 2 to 7 new cases per 100,000 children younger than 18 years of age, making it a relatively common major disease in pediatrics. The peak age of onset occurs at 2 to 3 years except for the rare, congenital type of nephrosis. Approximately 50% of affected children are ages 1 to 4 years; 75% are younger than age 10 years. In addition, even the most benign form of the nephrotic syndrome is, by nature, a recurrent disorder, so each new-onset case likely will continue to manifest disease for some time. Nephrotic syndrome is one of the most frequent reasons for referral to a pediatric nephrologist for evaluation, although its insidious onset frequently causes delay in diagnosis. Careful examination of the anatomy of a nephron permits characterization of the glomerular basement membrane as the barrier between the circulation and the external environment. Thus, the glomerular membrane, which permits passage in an adult of approximately 180 L/d of fluid, is the final determinant of how much of the solute originally contained in this volume enters the tubular lumen. The normal glomerular membrane is remarkably selective for protein compared with other solutes (Table 1⇓). Once this selectivity is lost, the ensuing proteinuria defines not only the diagnosis of nephrotic syndrome, but many pathophysiologic consequences as well. It is the purpose of this article to discuss the definition, causes, pathophysiologic consequences, and management of nephrotic syndrome. The emphasis is …