Podcast: Immunosuppressive agents for treating IgA nephropathy

IgA nephropathy is a kidney condition, leading to kidney failure for many of those who are affected. About 10-20% of patients require dialysis or a kidney transplant within 10 years, and 30-40% within 20 years, from their disease onset. This long time between diagnosis and kidney failure makes it difficult to establish the most effective and safest treatment. In August 2015, Marinella Ruospo and her colleagues from Bari, Italy updated their Cochrane Review of immunosuppressive therapies and she tells us what they have found in this podcast.

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John: IgA nephropathy is a kidney condition, leading to kidney failure for many of those who are affected. About 10-20% of patients require dialysis or a kidney transplant within 10 years, and 30-40% within 20 years, from their disease onset. This long time between diagnosis and kidney failure makes it difficult to establish the most effective and safest treatment. In August 2015, Marinella Ruospo and her colleagues from Bari, Italy updated their Cochrane Review of immunosuppressive therapies and she tells us what they have found in this Evidence pod.

Marinella: A wide range of treatments that act on the immune system have been tested as possible treatments for IgA nephropathy, and corticosteroid therapy in addition to blood pressure control is the most commonly used therapy. However, as IgA nephropathy progresses very slowly, taking decades for patients to reach important clinical outcomes, it has been difficult to establish whether corticosteroids or other immunosuppressive drugs can prevent kidney failure without having unacceptable side-effects.
We tried to tackle this uncertainty by reviewing the randomized trials in both adults and children. Our 2003 version of this Cochrane Review included thirteen studies involving about 600 participants. We found a lower risk of kidney failure with steroid therapy, although the available research lacked information about treatment harms and the fact that the studies were small and had limitations in their methods resulted in considerable uncertainty in the results. Whether other immunosuppressive treatments were safe and prevented end-stage kidney disease while allowing patients with IgA nephropathy to minimize their exposure to steroid therapy was not clear from the evidence available then.
Twelve years on, we were able to update the review by combining the earlier studies with nineteen new studies. The 32 included studies now involve about 1800 adults and children. Treatment lasted for between 4 and 24 months on average, and patients were followed up for clinical outcomes for between 1 and 6 years. Unfortunately, though, the available studies continue to have marked methodological limitations, which gives us low confidence in their results.
Six studies investigated corticosteroid therapy, among 300 adults and children. These showed that prednisone therapy prevented end-stage kidney disease and doubling of the serum creatinine, a surrogate marker of kidney failure. Steroids given together with blood pressure lowering treatment prevented end-stage kidney disease when compared against blood pressure treatment alone, and mycophenolate mofetil reduced the chances of end-stage kidney disease when given with blood pressure care.
When looking for the possible side-effects of therapies, we found that the studies did not provide much detail on harms. Therefore, despite the addition of many more studies since 2003, there was very still limited information about the toxicities of treatment, particularly about the chances of important infections and cancer.
To sum up, adults and children with IgA nephropathy who receive steroids for between 6 and 24 months may be less likely to suffer kidney failure and need dialysis, but there is little information about the impact of treatment on death, cancer and major infections. There is an ongoing need for studies to focus on treatment toxicities in the short and longer term and to identify which patients are most likely to benefit from this treatment.

John: If you’d like to read more about the review, you can find full details in the Cochrane Library. Simply go online to Cochrane library dot com, and search for ‘immunosuppression and nephropathy'.

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