Does Immunosuppression Improve Outcomes in IgA Nephropathy?

For high-risk patients with IgA nephropathy, adding immunosuppression to intensive supportive care doesn’t improve clinical outcomes—but does increase the rate of infections and other serious adverse effects, reports a trial in The New England Journal of Medicine.

The randomized, open-label trial included 337 patients with IgA nephropathy at 32 German nephrology centers. Three hundred nine patients completed a six-month run-in phase in which supportive care was adjusted according to proteinuria. In 94 patients, urinary protein excretion decreased to less than the target level of 0.75 g/d.

One hundred sixty-two patients with persistent proteinuria were randomly assigned to three years of supportive care alone or supportive care plus immunosuppressive therapy. Two primary endpoints were compared between groups: full clinical remission and at least a 15 mL/min/1.73 m2 decrease in estimated glomerular filtration rate.

At three years, full clinical remission occurred in five percent of patients with supportive care only and 17 percent with supportive care plus immunosuppressive therapy. This difference was entirely related to remission of proteinuria: nine patients in the supportive care group and 20 in the immunosuppression group. Rates of the threshold decrease in eGFR were 28 and 26 percent, respectively, with no significant decrease in the annual rate of eGFR decline.

Patients receiving immunosuppressive therapy had more adverse events, including severe infections, impaired glucose tolerance, and weight gain of more than 5 kg. There was one case of fatal sepsis in the immunosuppression group.

Some evidence supports the use of immunosuppressive therapy for patients with IgA nephropathy. This three-year trial finds no substantial kidney-related benefit of adding immunosuppression to intensive supportive care for high-risk IgA nephropathy. Immunosuppressive therapy also has significant adverse effects, including a risk of severe infections [Rauen T, et al. Intensive supportive care plus immunosuppression in IgA nephropathy. N Engl J Med. 2015; 373:2225–2236].