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17-01-2013 | Immunology | Article

Optimum therapy for idiopathic membranous nephropathy identified


Free abstract

medwireNews: A combination of prednisolone and chlorambucil is the most effective treatment approach for patients with idiopathic membranous nephropathy and declining renal function, according to findings from a recent trial.

In contrast, the nephrotoxicity seen with ciclosporin monotherapy make it a poor choice for this patient subset.

"Some physicians advocate the use of ciclosporin together with prednisolone, but we know of no good evidence that this combination reduces renal toxicity," say Peter Mathieson (Southmead Hospital and University of Bristol, UK) and colleagues, who studied 108 patients from 37 renal centers across the UK.

In this randomized controlled trial, patients who had a 20% or greater decline in excretory renal function prior to study entry benefited from prednisolone plus chlorambucil therapy for at least 3 years of follow-up.

Almost all (99) patients received supportive therapy with angiotensin-converting enzyme inhibitors throughout the study, with 33 also receiving prednisolone (0.5 mg/kg per day) and chlorambucil (0.15 mg/kg per day) on alternate months for 6 months, and 37 patients receiving ciclosporin (5mg/kg per day) for 12 months. Patients were followed up for a minimum of 3 years or until the primary endpoint of a further 20% reduction in renal function was reached.

As reported in The Lancet, the primary endpoint occurred at a significantly lower rate in the prednisolone plus chlorambucil group than in the supportive therapy group (58% versus 84%). Furthermore, the greatest decline in proteinuria over time was observed with prednisolone plus chlorambucil, which reduced 24-hour urinary protein by 2.2 g more than supportive therapy did. There was no signifcant difference in rates between the ciclosporin and supportive therapy group.

Overall, 10% of patients reached end-stage renal disease: 3% of the prednisolone plus chlorambucil group compared with 17% of the ciclosporin group and 11% of the supportive therapy group.

However, the proportion of patients with a serious adverse event after 1 year was significantly higher with prednisolone plus chlorambucil than with supportive therapy, at 52% verus 29%, while it did not differ significantly between ciclosporin and supportive therapy. And hematologic events were common in patients given prednisolone and chlorambucil, often necessitating dose reducions or interruption of therapy. In the ciclosporin group, nephrotoxicity was a substantial problem, with dose reductions, treatment interruptions, and reaching of the primary endpoint frequent in this group.

"Clearly, the preservation of renal function that can be achieved with prednisolone and chlorambucil comes at a price, and careful monitoring of the therapy is needed," say the researchers.

However, "until new treatments are available and have been properly tested, the evidence favors use of prednisolone and an alkylating agent in the most severely affected patients," they add.

"Our findings do not support the use of ciclosporin in this group-the adverse effects on renal function make it unsuitable once renal function has started to decline."

By Sally Robertson, medwireNews Reporter

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