ERA-EDTA 2015: Immunosuppression for IgA Nephropathy

If and when to immunosuppress patients with the world’s commonest glomerular disease is a crucially important topic for Nephrologists. There is a large amount of therapeutic nihilism with IgA Nephropathy, at least in the countries where I have practiced. Jurgen Floege delivered 2 masterclass presentations at the congress on this issue. He started with some background data:

  1. KDIGO recommendation is for 3-6 months supportive therapy for all (not just limited to RAAS inhibition, but also consider lipid management, addition of spironolactone, NaHCO3 therapy, smoking cessation, allopurinol? and others).
  2. No immunosuppression is suggested for those with eGFR <30 mL/min or those with preserved function and only minor urinary abnormalities (they should be watched, however, as they may progress despite good early prognosticators).
  3. Those with an RPGN presentation are often treated as per vasculitis protocols but without any real data. They likely will do poorly.
  4. eGFR 30-50 mL/min have been excluded from studies so data is lacking. They could be considered for steroids if heavy proteinuric.
  5. eGFR >50mL/min: if <1g/day proteinuria, continue supportive management. If >1g/day proteinuria despite 6 months supportive care, then 6 months of corticosteroids should be considered. Old data was presented from Italy & China showing benefit of steroids plus ACEi compared to ACEi alone. (Manno et al).
  6. Evidence for a lack of efficacy with Azathioprine or MMF in addition to steroids, at least in white cohorts.
  7. An important point was made that previous studies have discontinued RAAS inhibition before recruitment, rendering patients proteinuric again and eligible for enrollment. Therefore, patients were potentially included who may have done very well with RAAS inhibition alone (if the trialists hadn’t meddled and stop the drug!).

The VALIGA study was mentioned which demonstrated a benefit with steroids, even extending to eGFR <50 mL/min, in this retrospective cohort.

Dr Floege then kept the audience in anticipation at the end of his first talk on the eagerly awaited STOP-IgA Nephropathy trial, which was still under embargo until the late-breaking session later in the morning. Here’s what we finally discovered:

– STOP-IgAN included adults with proteinuric disease and eGFR >30 mL/min. They all underwent an 6 month period of supportive care, as per real life, and only if they still had >0.75 g/day proteinuria were they randomized to steroids or continued supportive care. This cut-off was chosen largely for logistical reasons to ensure recruitment numbers it seems.

– In the run-in, 34% of patients did well leading to them not being randomized. This highlights the importance of ‘aggressive’ supportive care.

– Results demonstrated an overall higher number of complete remissions with immunosuppression at 3 years, apparently dominated by low proteinuria patients. However, there was no accompanying benefit from an eGFR point of view. There was an improvement in proteinuria but it appeared to be transient.

– Control group did better than expected, again showing what proper supportive management can achieve.

– There were significantly more adverse events, including severe infections, with immunosuppression.

The take home message was that appropriate supportive care blunted the effect of immunosuppression in proteinuric IgA Nephropathy patients. We will have to wait and see if the improvement in numbers achieving complete remissions will translate into overall better outcomes in the immunosuppression group. The investigators should be applauded for what seems to be an important and very well-conducted and presented study. After today, I certainly feel better educated to manage my IgA nephropathy patients but I don’t think I’ll be doing much different than I did before.

Post written by Dr. Paul Phelan, AJKD Blog Contributor.

Check out more AJKD Blog coverage of the 2015 ERA-EDTA Congress.

2 Comments on ERA-EDTA 2015: Immunosuppression for IgA Nephropathy

  1. Richard Glassock // May 29, 2015 at 11:20 am // Reply

    Why would anyone bother with combined immunosuppression in IgA N with such unimpressive and potentially toxic effects? We still need to clarify the role of corticosteroids in IgA N- when, how much, for how long. Hopefully, the TESTING study (in progress) will give us an answer.

    Richard Glassock, MD

    Sent from my iPhone

    >

  2. Paul Phelan // May 29, 2015 at 2:30 pm // Reply

    Thanks for commenting Richard. I should have specified the treatment arm in STOP-IgAN received either Pozzi regime steroids or Steroids plus CyP I believe (I’m unsure as to the decision process behind who got what but think it was eGFR based). Pozzi regime is certainly cumbersome and 6 months is arbitrary. We do need clarity however I think this trial gives us useful data. Agree that combination immunosuppression is certainly not warranted given current data

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