Pam Harrison

June 12, 2015

LONDON, United Kingdom — In patients with IgA nephropathy, the optimization of supportive care minimizes renal function loss and can eliminate the need for immunosuppressive therapy in the great majority of patients, new research suggests.

"The value of immunosuppression is very controversial in IgA nephropathy," said Jürgen Floege, MD, from the University of Aachen in Germany.

"In the United Kingdom they don't do it, in Italy they do, and in Japan it's a must. This tells you that we don't know what the right approach is," Dr Floege said during a news conference here at the European Renal Association–European Dialysis and Transplant Association 52nd Congress.

"But by simply optimizing supportive care — getting blood pressure and proteinuria down to optimal levels and doing a lot of things we can do to help preserve kidney function conservatively — we saved patients from the need for immunosuppression," Dr Floege reported. "This is very much in contrast to what has been published so far."

He presented results from STOP-IgAN, the largest prospective randomized study of IgA nephropathy conducted to date.

Dr Floege's team screened 379 patients with biopsy-proven IgA nephropathy treated at 32 centers in Germany.

Supportive therapy was optimized in a 6-month run-in phase, during which physicians focused on the maximal use of antihypertensive and antiproteinuric agents to preserve kidney function.

Of the 309 patients who completed the run-in phase, 94 patients were categorized as low risk, defined as less than 0.75 g/day of protein in the urine, and were therefore excluded from the analysis. In addition, 38 patients dropped out during the run-in phase, and 15 refused to be randomized.

The remaining 162 patients with persistent proteinuria, defined as more than 0.75 g/day of protein in the urine, were randomized to supportive therapy alone or to supportive therapy plus immunosuppression for 3 years.

Depending on renal function, patients received either corticosteroids alone or in combination with other immunosuppressive agents, such as cyclophosphamide and azathioprine.

"The annual loss in the estimated glomerular filtration rate [eGFR] in patients randomized to either arm was 1.5 mL/min per 1.73 m² a year, which is what you and I lose when we are over the age of 60," said Dr Floege.

 
This study raises a major question about the use of immunosuppression in IgA nephropathy.
 

"Unlike in previously published studies, our supportive care group did just as well as the immunosuppressive group, so this study raises a major question about the use of immunosuppression in IgA nephropathy," he reported.

However, immunosuppression induced more full clinical remissions in particular in patients with lower levels of proteinuria.

Therefore, if proteinuria persists, immunosuppression might be considered an option in patients with early-stage disease whose proteinuria levels do not exceed 1.5 g/day, said Dr Floege. In patients with more advanced-stage disease, immunosuppression should be avoided.

Full clinical remission in this study was not accompanied by any detectable effect on functional loss, as indicated by eGFR, he added.

"Furthermore, we saw some very severe side effects from immunosuppression," said Dr Floege, including treatment-induced diabetes.

In addition, 20% of patients receiving immunosuppressive agents gained more than 5 kg, and there was one death from sepsis in the immunosuppressive group.

"Whether the higher number of patients achieving full clinical remission might translate into very long-term benefits is currently unknown," Dr Floege said.

"We hope our findings will lead to a much more cautious approach to the use of immunosuppression in IgA nephropathy," he added.

Immunosuppresives Not Needed in Most

It is very important for physicians to know that they do not have to use immunosuppressive drugs in the vast majority of patients with IgA nephropathy, said session cochair Johannes Mann, MD, from the University of Erlangen–Nuremberg in Germany.

"These drugs have a lot of side effects that affect quality of life for patients," Dr Mann told Medscape Medical News.

Furthermore, these results indicate that in previous studies, some of which date back more than 15 years, patients were not treated with conservative measures very well before treatment with immunosuppressive agents was initiated.

In STOP-IgAN, "over 90% of patients achieved blood pressure levels within the normal range — 125/75 mm Hg," Dr Mann said.

In previous studies, "ACE inhibitors were widely used to reduce proteinuria." (About 40% of STOP-IgAN patients received a combination of ACE inhibitors and angiotensin receptor blockers, Dr Floege noted.)

There was surprisingly little progression of renal disease in STOP-IgAN; however, Dr Mann said he would still consider immunosuppression for patients who show progressive and substantial decreases in eGFR over time.

This study was funded by the German government. Dr Floege and Dr Mann have disclosed no relevant financial relationships.

European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) 52nd Congress: Abstract LBA-3591. Presented May 29, 2015.

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