Despite adverse events, corticosteroids may benefit patients with IgA nephropathy

1. In this multicenter, double blind study, IgA nephropathy patients had improved kidney function with corticosteroid treatment compared to those treated with placebo.

2. Unfortunately, patients receiving corticosteroids had high rates of serious adverse events, primarily infections, and recruitment for the trial was stopped early.

Evidence Rating Level: 1 (Excellent)

Study Rundown: IgA nephropathy is the most common primary glomerular disease, with highest prevalence in the Asia-Pacific region. Though the disease is mediated by immunoglobulin deposits, validating the use of corticosteroids has been difficult. In this multicenter, double blind study, patients with high risk IgA nephropathy received either full-dose corticosteroids or placebo for 6-8 months and were followed every 3 months for the first year and every 12 months thereafter. After roughly 3 years, the study was discontinued due to a high rate of serious adverse effects—primarily infections—in the corticosteroid group. Though truncated, the study demonstrated that patients who received corticosteroids had better eGFR preservation, and reduced proteinuria compared to those who took placebo.

Though limited, this study adds evidence that high-dose corticosteroids may benefit patients with IgA nephropathy. However, the clear disadvantages of corticosteroid therapy reported in this study make the decision to use this therapy more difficult. Future clinical trials with prophylactic anti-microbials or increased monitoring for immunosuppression-related adverse effects should be undertaken to help physicians decide if and when this regimen should be used for patient with IgA nephropathy.

Click to read the study, published in JAMA

Relevant Reading: Early Change in Urine Protein as a Surrogate End Point in Studies of IgA Nephropathy: An Individual-Patient Meta-analysis

In-Depth [randomized controlled trial]: A total of 262 (86% completing treatment) IgA nephropathy patients with proteinuria >1g/d from China and Australia were randomized to receive full-dose methylprednisolone or placebo daily for 6-8 months and were followed every 3 months for the first year and every 12 months thereafter as part of the Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study. After about 3 years, the study was discontinued due to a statistically significant higher rate of serious adverse effects, primarily infections, in the corticosteroid group (relative risk 4.63 CI₉₅ 1.63 to 13.2). Most of these events occurred within the first 3 months of treatment. The primary endpoint was development of a “composite renal outcome,” which consisted of a first occurrence of a 40% decrease in eGFR, the development of ESKD, or death due to kidney disease. Patients who received corticosteroids had a lower rate of this primary renal outcome (Hazard Ratio 0.37; CI₉₅ 0.17 to 0.85). The mean annual rate of eGFR decline was less in the corticosteroid treated group (difference of 5.15 mL/min/1.73 m2 ; CI₉₅ 0.42 to 9.89 mL/min/1.73 m2. Mean proteinuria was also reduced in the corticosteroid treated group by 0.99 g/d (CI₉₅ −1.34 to −0.64 g/d).

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