Renin-angiotensin system inhibitor use and cardio-renal outcomes in non-proteinuric chronic kidney disease: a post-hoc analysis of the Frontier of Renal Outcome Modification-Japan study

Patients with chronic kidney disease (CKD) frequently experience cardiovascular events, and as per current therapeutic guidelines, renin-angiotensin system inhibitors (RASi) can protect the cardiovascular system in those with proteinuric CKD. Effectiveness of RASi in treating non-proteinuric CKD is still unknown, yet. In order to evaluate the impact of RASi on cardiovascular morbidity and mortality in patients with non-proteinuric CKD, we performed a post-hoc analysis of the Frontier of Renal Outcome Modification-Japan study. A urine protein-to-creatinine ratio less than 0.15 g/g or negative/trace protein on urinalysis was considered as non-proteinuric CKD. Those who have undergone dialysis, kidney transplant recipients, and patients who refused to give their consent were excluded. A composite of cardiovascular events, initiation of renal replacement therapy, and all-cause mortality was studied as the primary outcome. Of 2379 patients with CKD, 630 met the criteria for non-proteinuric CKD. Among them, 490 used RASi, and 140 did not. Although the RASi group was considerably younger and had a higher prevalence of hypertension and calcium channel blocker use, baseline characteristics were comparable. 12.1% of the control group and 16.7% of the RASi group experienced the primary outcome during follow-up, with no significant difference (adjusted HR: 1.37; 95% CI: 0.81-2.31). Secondary outcomes and analyses of RASi use for the whole observation period did not show any significant differences (adjusted HR: 0.81; 95% CI: 0.43-1.56). These results imply that RASi was not linked to a decreased risk of mortality or long-term events in those with nonproteinuric CKD.