El Mokadem M, Abd El Hady Y, Aziz A: A Personalized Update on IgA Nephropathy: A Prospective Single-Blind Randomized Trial of Ramipril, Eplerenone and Their Combination in Type 2 Diabetic Nephropathy. Cardiorenal Medicine DOI 10.1159/000508670
The benefits of renin-angiotensin system (RAS) inhibition for slowing the progress of diabetes-related CKD with overt proteinuria is well established. The utility (efficacy and safety) of adding mineralocorticoid receptor (MR) antagonists to RAS inhibitor therapy in this population of patients is less well understood.
El Mokadem and colleagues conducted a small single-blinded randomized clinical trial in adult subjects with type 2 diabetes mellitus (T2DM) and moderate albuminuria (urinary albumin to creatinine ratio [uACR] of 30-300 mg/g) who had mild hypertension but were naïve to both RAS inhibition and MR antagonism treatment. The subjects were randomized (1:1:1) to receive ramipril (R) 10mg/day (n = 25), eplerenone (E) 50 mg/day (n = 25), or R 10 mg/day plus E 50 mg/day (n = 25) and followed for 24 weeks. The primary endpoint was the percentage change in uACR from baseline.
Systolic blood pressure (SBP) fell in all three groups, most evidently in the R + E group. uACR also decreased in all 3 groups, again more evidently in the R + E group, and correlated with the decline in SBP, but both the reduction in SBP and treatment group assignment were independent predictors of a decline in uACR. Hyperkalemia (>5.5 mEq/L) was not a major clinical problem in any group (<4% prevalence), but was seen more frequently in patients with reduced eGFR at baseline.
These findings are largely confirmatory of the short-term effects of combinations of R and E on SBP and uACR. The short-term design, the inclusion of patients with only moderate albuminuria, and its small size precludes any interpretation of a renoprotective effect of the combined regimen and the absence of sodium-glucose transporter-2 inhibitor therapy as a comparison arm renders the trial rather non-informative in connection with contemporary management of T2DM with moderate albuminuria. Nevertheless, the improved SBP control and the effects on albuminuria of the combined regimen would likely predict longer-term benefits on CKD progression and cardiovascular disease (such as heart failure and strokes).