Interventions for minimal change disease in adults with nephrotic syndrome

Nephrotic syndrome is a condition where the kidneys leak protein from the blood into the urine. Minimal change disease is the third most common primary kidney disease in adults with unexplained nephrotic syndrome (10% to 15%). Steroids have been used widely since the early 1970s for the treatment of adult-onset minimal change disease, however the optimal agent, dose and duration has not been determined. This review identified three small studies (68 participants) comparing: 1) intravenous plus oral steroid treatment versus oral sterids; 2) oral versus short-course intravenous steroid treatment; and 3) oral steroid treatment versus placebo. Only oral steroid treatment (compared to short-course intravenous steroid treatment) showed an increase in the number of patients who achieved complete remission. However, the lack of available studies leaves important treatment questions unanswered; what is the optimal dose and duration of steroid treatment in new-onset adult minimal change disease; how are relapses following steroid-induced remission prevented and treated; and what are the appropriate treatments for steroid-dependent or treatment-resistant minimal change disease?

Authors' conclusions: 

Further comparative studies are required to examine the efficacy of immunosuppressive agents for achievement of sustained remission of nephrotic syndrome caused by minimal change disease. Studies are also needed to evaluate treatments for adults with steroid-dependent or relapsing disease.

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Background: 

Steroids have been used widely since the early 1970s for the treatment of adult-onset minimal change disease. The response rates to immunosuppressive agents in adult minimal change disease, especially steroids, are more variable than in children. The optimal agent, dose, and duration of treatment for the first episode of nephrotic syndrome, or for disease relapse(s) has not been determined.

Objectives: 

To determine the benefits and harms of interventions for the nephrotic syndrome in adults caused by minimal change disease.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference articles and abstracts from conference proceedings, without language restriction.
Search date: January 2007.

Selection criteria: 

Randomised controlled trials (RCTs) and quasi-RCTs of any intervention for minimal change disease in adults over 18 years with the nephrotic syndrome were included. Studies comparing different routes, frequencies, and duration of immunosuppressive agents were selected. Studies comparing non-immunosuppressive agents were also assessed.

Data collection and analysis: 

Two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random effects model and results were expressed as a risk ratio (RR) for dichotomous outcomes, or mean difference (MD) for continuous data with 95% confidence intervals (CI).

Main results: 

Three RCTs (68 participants) were identified. All treatment comparisons contained only one study. No significant difference was found between prednisone compared with placebo for complete (RR 1.44, CI 0.95 to 2.19) and partial remission (RR 1.00, CI 0.07 to 14.45) of the nephrotic syndrome due to minimal change disease. There was no difference between intravenous methylprednisolone plus oral prednisone compared with oral prednisone alone for complete remission (RR 0.74, CI 0.50 to 1.08). Prednisone, compared with short-course intravenous methylprednisolone, increased the number of subjects who achieved complete remission (RR 4.95, CI 1.15 to 21.26). The lack of statistical evidence of efficacy associated with prednisone therapy was based on data derived from a single study that compared 'alternate-day prednisone' to no immunosuppression' with only a small number of participants in each group. No RCTs were identified comparing regimens in adults with a steroid-dependent or relapsing disease course or comparing treatments comprising alkylating agents, cyclosporine, tacrolimus, levamisole, or mycophenolate mofetil.

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