Immunosuppression may not change outcomes for patients with IgA nephropathy
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No differences in renal outcomes were observed after 10 years in patients with IgA nephropathy who had immunosuppression added to supportive care vs. supportive care alone, according to study results.
“IgA nephropathy (IgAN) is the most prevalent type of glomerulonephritis in the Western world and one of the most common reasons for younger adults to require a kidney transplantation,” Thomas Rauen, MD, of the division of nephrology and clinical immunology at RWTH Aachen University in Germany, and colleagues wrote. “Its pathogenesis is incompletely understood; consequently, therapy for IgAN has been largely empiric and centrally has relied on immunosuppression, in particular high-dose systemic corticosteroids.”
The researchers contended that The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for IgA nephropathy, which promote the use of systemic corticosteroids in patients with “preserved renal function and persistent proteinuria,” are based on randomized controlled trials published more than a decade ago when renin-angiotensin system (RAS) blockers were “inconsistently used.”
A previous study, known as the STOP-IgAN trial, found no differences between patients randomized to supportive care alone or supportive care plus additional immunosuppression after 3 years. However, the researchers wrote, that trial “has been criticized because of its relatively short duration which may have precluded the detection of a benefit from immunosuppression in a disease that frequently follows a slowly progressive course.”
Extending follow-up time to 10 years for this study, researchers considered the first occurrence of a composite of all-cause mortality, end-stage kidney disease and an eGFR decline of more than 40% from baseline in 149 patients randomized to supportive care alone (optimal therapy described here as care including the use of RAS blockers) or additional immunosuppression.
They found that the primary composite endpoint was reached by 50% of patients in supportive care vs. 45.5% in those with added immunosuppression, with no difference between groups in time-to-event analysis (HR = 1.20).
Researchers further observed that ESKD occurred in 17 of the patients with supportive care vs. 20 of the patients with additional immunosuppression, and that eGFR loss of more than 40% and annual eGFR loss did not differ between groups. Regarding mortality, two patients died with supportive care and three patients with additional immunosuppression died.
Despite noting the study may be limited by its inclusion of only Caucasian patients, the researchers suggested “the evidence that additional immunosuppression is not better than supportive care alone is supported by the analysis of changes in eGFR, data on adverse events and subgroup analyses.”
Further, they wrote that the findings demonstrate no indication that the choice of immunosuppression (whether it be corticosteroid monotherapy or combined immunosuppressive therapy) or patient characteristics (including low baseline GFR, high proteinuria) alter outcomes.
“It is frustrating to note that despite optimized supportive care with or without immunosuppression, almost half of our patients eventually reached the primary clinical endpoint, stressing the urgent need for even better supportive measures and/or more targeted therapies,” the researchers concluded. – by Melissa J. Webb
Disclosures: Rauen reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Rauen T, et al. Kidney Int. 2020;doi:10.1016/j.kint.2020.04.046.
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