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
- Diabetic Kidney Disease: Clinical - II
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
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-# | Age | Gender | Pre UP/Cr gm/gm | Post-UP/Cr gm/gm | >90% Red | >75% Red | >50% Red | % Patiro | eGFR-24Mths | #ESRD | Death | |
| Total Patients | 32 | 62.3 | 56.2%M | 3.71+0.5 | 2.21+0.5 | 14.2% | 28.1% | 34.2% | 37.5% | 34.3 mls/min | 8 | 3 |
| Spironolactone | 14 | 61.3 | 62.5%M | 3.96+7 | 1.87+0.7* | 14.2% | 42.8% | 50.9% | 57.1% | 39.4 mls/min | 2 | 1 |
| RAAS-Control | 18 | 63.0 | 47.1%M | 3.10+0.7 | 2.49+0.6 | 0.0% | 21.4% | 21.4% | 22.2% | 28.6 mls/min* vs. Baseline | 6 | 2 |
*=Significance P value <0.05,
Funding
- Commercial Support – Vifor Pharmaceuticals