ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO271

Safety and Efficacy of Maximally Tolerated RAS Therapy Alone or in Combination With Spironolactone in Diabetic Kidney Disease: Effect on Proteinuria and eGFR in the MRA-ACE Trial

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Tumlin, James A., NephroNet Clinical Trials Consortium, Atlanta, Georgia, United States
  • Kopyt, Nelson P., NephroNet Clinical Trials Consortium, Atlanta, Georgia, United States
  • Wilson, Daniel J., NephroNet Clinical Trials Consortium, Atlanta, Georgia, United States

Group or Team Name

  • NephroNet Clinical Trials Consortium
Background

DKD is generally characterized by proteinuria and progressive of CKD. Although RAS inhibitors reduce proteinuria and slow the progression there is a high residual risk for ESRD at 8-10 years. Despite these benefits, few studies have examined the combination of mineralocorticoid receptor antagonists (MRA) with maximally tolerated RAS therapy (maxRAS). Herein we present the results of the MRA-ACE trial; a prospective, randomized, open labeled study investigating the safety/efficacy of spironolactone in combination with (maxRAS) therapy on proteinuria, delta eGFR and hyperkalemia (HK).

Methods

Thirty-two pts with T2D and DKD were randomized to (maxRAS) alone or in combination with spironolactone 25 mg/day (Spiro). Pts developing HK (K+ > 5.5 mmol/L) during therapy received patiromer 8.4 gm Q MWF and titrated as needed. Twenty-seven (85%) of the 32 pts had biopsies confirming DKD. At entry all patients were 1) receiving insulin or oral agents, 2) BP <140/90 mm/Hg on max tolerated ACE or ARB, 3) two consecutive, pre-study UP/Cr >500 mg/gm, 4) CKD-Epi eGFR >20 ml/min/1.73M2. The primary endpoint was reduction in proteinuria at 24 months. A complete response was as defined UP/Cr <500 mg/gm, while a partial response was >50% reduction from baseline. Mean follow-up was 29 months.

Results

Results appear in Table-1. Addition of Spiro to RAS reduced UP/Cr at 24 months (p<0.028). The rate of complete/partial response was significantly higher with Spiro (76.6%) vs. maxRAS (38.8%) (P<0.025). HK occurred in 22.2% maxRAS and 57.1% Spiro pts (p<0.027). There were no withdrawals due to HK. ESRD developed in 8 pts; maxRAS-(6) and Spiro-(2). There was 3 deaths; 2-controls and 1-Spriro group; none due to HK. All HK patients were successfully controlled with Patiromer.

Conclusion

Combination therapy with Spironolactone and max-RAS was more effective than max RAS alone in reducing nephrotic range proteinuria and slowing eGFR decline DKD, with a trend to fewer cases of ESRD. Patiromer was effective in management of HK in both groups, and enabled continuous therapy.

Table-1
 Pt-#AgeGenderPre UP/Cr gm/gmPost-UP/Cr gm/gm>90% Red>75% Red>50% Red% PatiroeGFR-24Mths#ESRDDeath
Total Patients3262.356.2%M3.71+0.52.21+0.514.2%28.1%34.2%37.5%34.3 mls/min83
Spironolactone1461.362.5%M3.96+71.87+0.7*14.2%42.8%50.9%57.1%39.4 mls/min21
RAAS-Control1863.047.1%M3.10+0.72.49+0.60.0%21.4%21.4%22.2%28.6 mls/min* vs. Baseline62

*=Significance P value <0.05,

Funding

  • Commercial Support