Treatment options

Corticosteroids are now a mainstay of FSGS, a condition initially considered to be a steroid-resistant disease. Several studies have shown improved responsiveness to more prolonged courses of steroids. Partial or complete remission may be achieved in about 50% of adults with FSGS treated with long-term corticosteroid therapy (Semin Nephrol. 2000;20:309-317).

Cyclophosphamide has been used in the past as standard second-line therapy in patients with steroid-resistant FSGS, but complete response rates in adults are disappointing (Semin Nephrol. 2000;20:309-317). Higher response rates have been reported in pediatric patients with FSGS treated with cyclophosphamide. Cyclophosphamide may be useful in patients with FSGS who do not respond to other immunosuppressive therapies.
For patients with steroid-resistant or steroid-dependent FSGS, cyclosporine has shown efficacy in clinical trials. In a double-blind, randomized, controlled study of 49 patients with steroid-resistant FSGS randomized to 26 weeks of cyclosporine plus low-dose prednisone or placebo plus prednisone, complete or partial re-mission of proteinuria at 26 weeks was achieved in 70% of the treatment group and 4% of the placebo group (Kidney Int. 1999;56:2220-2226). Renal function was better preserved in the cyclosporine group than in the placebo group. A significant 50% reduction in baseline creatinine clearance was observed in 25% of the cyclosporine group and 52% of the placebo group.


Tacrolimus is an alternative immunosuppressive agent to cyclosporine. About 60% of patients with steroid-resistant FSGS treated with adjunctive tacrolimus achieve partial or complete remission. There are few differences between cyclosporine and tacrolimus in terms of partial and complete response rates and toxicity in patients with steroid-resistant FSGS. Tacrolimus may be useful in some cyclosporine-resistant patients with FSGS and in those who are intolerant of cyclosporine.

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Alkylating agents

Alkylating agents have been used in the treatment of idiopathic FSGS but are not widely re-commended as standard second-line therapy. A group of 57 patients with FSGS were randomized to receive steroids and cyclosporine or steroids and chlorambucil for six months (Am J Kidney Dis. 2004; 43:10-18). At four years there were no significant differences between the groups in terms of mean creatinine and proteinuria levels, the proportions of patients who achieved partial or complete remission, and in the number of patients who developed (ESRD).

Mycophenolate mofetil

Mycophenolate mofetil (MMF) appears safe for use in patients with steroid-resistant FSGS and lowers proteinuria in about 44% of patients after six months of treatment (Clin Nephrol. 2004;62:405-411). Relapses are common, suggesting more prolonged or combination therapy may be needed. In patients with primary glomerular disease, empiric treatment with MMF may provide stabilization of renal function and the ability to withdraw steroids and is generally well tolerated (Kidney Int. 2002; 61:1098-1114). Several studies examining the use of sirolimus in patients with steroid-resistant FSGS have yielded disappointing results.

About 50% of patients with refractory FSGS treated with sirolimus experienced acute renal failure with significant increases in serum creatinine level; decreases in glomerular filtration rate (GFR) and worsening proteinuria were also observed; however, in one prospective, open-label trial, 21 patients with idiopathic, steroid-resistant FSGS were treated with sirolimus (Clin J Am Soc Nephrol. 2006;1:109-116). After six months of treatment, four and eight patients achieved complete and partial remission, respectively. Among treatment responders, sirolimus decreased proteinuria and glomerular pore size and maintained GFR. Patients with complete remission had a higher GFR at the end of treatment compared with nonresponders. 


The prognosis of untreated patients with FSGS is poor, and about 50%-70% of untreated nephrotic patients with FSGS progress to ESRD. Although FSGS was considered to be a steroid-resistant disease, several stud-ies have shown improved responsiveness to more prolonged courses of steroids. In subnephrotic patients with FSGS, treatment with a combination of ACE inhibitors or angiotensin receptor-blockers, diuretics, and statins should be considered. Patients with classic idiopathic FSGS may benefit from treatment with prednisone administered daily with taper or every other day for six months.

Alternatives to steroids should be considered for first-line therapy in patients with FSGS who are obese or diabetic. For patients with steroid-resistant or steroid-dependent FSGS and in those with collapsing FSGS and markedly elevated serum creatinine levels, cyclosporine and cytotoxic agents have shown efficacy in clinical trials. The role of other agents used in patients with FSGS, including azathioprine, MMF, and tacrolimus, remains poorly defined.

Dr. Gerald Appel is director of clinical nephrology at the New York-Presbyterian Medical Center and professor of clinical medicine at the Columbia University College of Physicians and Surgeons in New York. Dr. Alice Appel is a senior research associate in the division of nephrology at Columbia University College of Physicians & Surgeons.