Management of Nephrotic Syndrome in Children

Renee F. Robinson, PharmD, MPH, Milap C. Nahata, PharmD, John D. Mahan, MD, Donald L. Batisky, MD


Pharmacotherapy. 2003;23(8) 

In This Article

Abstract and Introduction


Idiopathic childhood nephrotic syndrome generally has a favorable long-term prognosis. Prompt administration of and improved guidelines for monitoring therapy have decreased morbidity and mortality. The treatment goal is to induce prompt remission while minimizing complications and adverse events. Aggressive therapy induces remission and decreases the frequency of relapse in most patient populations; however, such treatment often results in unnecessary toxicity. We critically assessed the current clinical evidence that supports each pharmacologic therapy. For each drug regimen, the risks and monitoring parameters required to reduce complications and optimize therapy are discussed. Some of the treatments are the common corticosteroid approaches, cytotoxic therapies (chlorambucil, cyclophosphamide), cyclosporine, less frequently used drugs (e.g., levamisole), and experimental therapies. Further studies are needed to identify the most effective and least toxic therapeutic regimens for inducing and maintaining remission in children with nephrotic syndrome.


Over 80 years have passed since the identification of the distinct entity now known as nephrotic syndrome. This chronic disorder often requires pharmacologic therapy and hospitalization for acute relapses and complications. Its complications and subsequent mortality are often avoidable with appropriate management.[1] Although various etiologies and pathologic abnormalities have been associated with the disorder in children, the exact cause for idiopathic nephrotic syndrome and the risk factors for progression are unknown.

Before the 1940s, concurrent infections and complications of edema often resulted in dismal outcomes for children with nephrotic syndrome. In a remarkable development, the advent of antibiotic therapy and administration of the first synthetic corticosteroid, prednisolone, dramatically decreased morbidity and mortality.[2] Most patients, however, continued to relapse despite adequate treatment and in some cases aggressive corticosteroid therapy, a few progressing to end-stage renal disease.[3]

The advent of percutaneous biopsy technique in the 1950s and 1960s led to pathologic evaluation of the kidney and classification and treatment of nephrotic syndrome based on the extent of progression of sclerosis and hyalinization. The three pathologic types identified in the syndrome are minimal change disease, focal segmental glomerulosclerosis, and membranoproliferative glomerulonephritis.[4] Minimal change disease is the most common cause of nephrotic syndrome in children. Under a light microscope the glomeruli appear normal; however, under an electron microscope characteristic changes in the glomeruli can be seen, such as fusion of a portion of the epithelial layer. The cause is unknown, but the disease may be preceded by viral infection, allergic reactions, or recent immunizations. The second type of pathology is focal segmental glomerular sclerosis, which accounts for 10-15% of all cases of nephrotic syndrome of undetermined origin. Scar tissue and more prominent lesions are noted in some of the glomeruli on biopsy. Finally, membranoproliferative glomerulonephritis is a form of glomerulonephritis caused by an abnormal immune response, with deposits of antibodies in the kidneys. The result is structural glomerular membrane changes.

Patients not responding to corticosteroid therapy received cytotoxic therapy. This practice was soon replaced with treatment guided by disease responsiveness (resolution of proteinuria) to corticosteroids. The primary emphasis, however, was still to achieve remission, alleviate symptoms, and decrease risks associated with concurrent infection.

The lack of standards of care and variations in treatment goals continued to result in suboptimal treatment for many children. In the early 1970s, many complex and precise terms associated with nephrotic syndrome were defined ( Table 1 ), and recommendations for therapy were provided based on a series of prospective, cooperative, multicenter studies. Monitoring parameters were suggested, and prevention of relapse became the focus. Care was also shifted from the hospital to the home setting, with aggressive monitoring to detect disease activity early. Today, hospitalization is necessary only if debilitating edema or infection is present. Better standardization of care and monitoring allow for detection and prompt treatment of relapse.

Further study is necessary to determine the full effect of differences in population, ethnicity, age at onset, and underlying disease on treatment outcomes. We provide a brief review of idiopathic childhood nephrotic syndrome — in particular, minimal change disease — with a more detailed review on its pharmacotherapy.