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Immunosuppressive agents for treating IgA nephropathy

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Abstract

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Background

IgA nephropathy (IgAN) is a world‐wide disease and the cause of end‐stage renal failure (ESRF) in 15 to 20% of patients within 10 years and in 30 to 40% of individuals within 20 years from the apparent onset of disease. No specific treatment has yet been established but many approaches have been investigated.

Objectives

To assess the benefits and harms of immunosuppressive treatment for IgAN.

Search methods

We searched The Cochrane Renal Group's specialized register (May 2003), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2002) MEDLINE (1966 ‐ September 2002), EMBASE (1988 ‐ September 2002) and handsearched reference lists of retrieved articles and conference proceedings.

Selection criteria

Randomized controlled trials (RCTs) and quasi‐RCTs comparing treatment of IgAN with immunosuppressive agents against placebo, no treatment, other immunosuppressive or non‐immunosuppressive agents.

Data collection and analysis

Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals (CI).

Main results

Thirteen eligible RCTs involving 623 patients were identified. All identified RCTs had a placebo, no treatment or warfarin/dipyridamole control group. Seven trials used steroids, three used alkylating agents/cyclosporin and three used combinations of steroids and alkylating agents/cyclosporin. No trial directly compared steroids versus alkylating agents/cyclosporin. Quality was sub‐optimal. Steroids were associated with a lower risk of progression to ESRF (RR 0.44, 95% CI 0.25 to 0.80) and lower urinary protein excretion (WMD ‐0.49 g/24h, 95% CI ‐0.72 to ‐0.12). Urinary protein excretion was lower for patients treated with alkylating agents/cyclosporin compared to placebo/no treatment (WMD ‐0.94 g/24h, 95% CI ‐1.43 to ‐0.46). There was no significant reduction of urinary protein excretion with combination treatment of steroids and alkylating agents compared with placebo/no treatment.

Authors' conclusions

The optimal management of IgAN remains uncertain. The RCTs identified were small, of sub‐optimal methodological quality and tended to only report favorable and surrogate outcomes without a thorough reporting of treatment harms. All outcomes favor the use of immunosuppressive interventions, with steroids appearing to be the most promising. Further study, in the form of RCTs, is necessary to ascertain which patients would benefit from these interventions, whether they are the ones with early signs of renal dysfunction or those with more advanced renal impairment.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

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People with IgA nephropathy might have a better chance of avoiding kidney failure if they use immunosuppressive drugs (including steroids), but more research is needed

IgA nephropathy is a common kidney disease that progresses very slowly. It often leads to decreased kidney function and ultimately to kidney failure. The cause of this disease is not known, although most people with the disease have abnormalities in their immune system. The review found that if people with IgA nephropathy take immunosuppressive drugs, such as steroids, they may be less likely to develop kidney failure. However, more research is needed to be certain, to identify which people might benefit most from the treatment, and to study adverse effects.