Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome : Workshop recommendations

Abstract

Management of idiopathic glomerular disease associated with nephrotic syndrome (INS) remains controversial and one of the most complex areas relates to utilization of the drug cyclosporin. This is despite its demonstrated effectiveness in several histologic types of the INS in randomized controlled trials. Cyclosporin is effective in inducing remission of proteinuria in approximately 80% of steroid-sensitive cases of minimal change disease (MCD). Cyclosporin is also effective in both the induction of remission and long-term preservation of renal function in steroid-dependent/-resistant MCD and steroid-resistant focal segmental glomerulosclerosis (FSGS). The overall response rate in FSGS is lower than in MCD, and long-term therapy (>12 months) may be required to both achieve remission and sustain it. Cyclosporin therapy is also of benefit in reducing proteinuria in 70-80% of patients with steroid-resistant membranous nephropathy (MGN). In MGN, the maximum benefit is often delayed compared to MCD (>12 weeks). Cyclosporin is generally well tolerated and safe. The major concern remains the nephrotoxicity, but with careful monitoring of the patient's renal function; minimizing the maintenance dose and utilizing repeat renal biopsy in those receiving long-term therapy, this risk can be minimized. The algorithms have been developed derived from the best evidence in the literature in each of the histologic types to help provide a guide to the integration of cyclosporin into the management of INS for the practicing nephrologist.

Two-Year Follow-Up of a Prospective Clinical Trial of Cyclosporine for Frequently Relapsing Nephrotic Syndrome in Children

“…Cyclosporine nephrotoxicity was detected in only 8.6% of patients who underwent renal biopsy after 2 years of treatment. Nevertheless, an important limitation of this treatment is cyclosporine dependency, namely the frequent relapse of nephrosis after discontinuation (9)(10)(11)(12). Most studies of relapse after cyclosporine to date have been retrospective, however, and no prospective evaluation in these patients has been reported.…”

Glomerulonephritis, Pathogenetic Mechanisms and Therapeutic Options: An Overview

“…Thus, the antiproteinuric effect of this medication may also be unrelated to the immunosuppressive effects on T lymphocytes. These findings may provide a rationale for the use in proteinuric non-immune-mediated diseases, such as focal segmental glomerulosclerosis and Alport's disease, in which is used the drug [1,42]. Cyclosporin is very dreaded for its side effects, even if the doses used in the course of the glomerulus nephritis are quite low.…”

Dystroglycan in the Diagnosis of FSGS

“…In adults (Ͼ16 yr of age), complete remission was defined as reduction of proteinuria to Յ0.20 g/d and serum albumin Ͼ3.5 mg/dl. Partial remission was defined as reduction of proteinuria to between 0.21 and 3.4 g/d and/or decrease in proteinuria of Ն50% from baseline (19). Renal insufficiency was defined as serum creatinine Ն1.2 mg/dl.…”