The Nephrotic Syndrome

Nephrotic syndrome encompasses a diverse group of conditions that share the common denominator of massive loss of protein in the urine. Progress in identifying the cause and pathogenesis of each of these conditions has been slow. The current identification of various forms of nephrotic syndrome is based primarily on histologic findings, which are not always pathognomonic. Treatment has and still depends on drugs that lack specificity and have numerous, often serious, adverse effects. The following conclusions are worth remembering: • Most children who have nephrotic syndrome have MCNS, which is responsive to prednisone therapy. • Response to steroid therapy is the best prognostic indicator. • Most (∼60%) of children who have MCNS relapse, some of them frequently. Cyclophosphamide and cyclosporine decrease the incidence of relapses. • Compelling evidence suggests that renal biopsy should be performed at onset only in children who, in addition to proteinuria, have macroscopic hematuria, hypertension, persistent renal insufficiency, or low C3 complement values. Another indication is failure to respond to steroid therapy (proteinuria still present at the end of 4 weeks of daily prednisone therapy). • Most children who have nephrotic syndrome and fail to respond to steroids have FSGS. Most alkylating agents are ineffective. Cyclosporine has been reported, in uncontrolled studies, to induce remission in 20% to 50% of patients who failed to respond to steroids. The drug requires monitoring of serum values and has serious adverse effects. Proteinuria recurs in most patients as soon as the treatment is discontinued. • Several genetic forms of FSGS, due to mutations that encode proteins at the level of the podocytes, have been identified. They account for a small minority of patients who have nephrotic syndrome, and none responds to treatment. • Dialysis and transplantation have improved the longterm prognosis of patients who reach end-stage renal disease, even infants who have CNS. • Some glomerulopathies, such as FSGS, MPGN, and possibly CNS, may recur in renal transplants. Treatment with immunosuppressive agents and plasmapheresis is effective in about 30% of such patients.