BackgroundMineralocorticoid receptor antagonists (MRAs) were shown to delay chronic kidney disease (CKD) progression in patients with hypertension and/or heart failure (HF) and proteinuria.ObjectiveWe conducted a systematic literature review on real-world evidence to identify the literature gaps related to the efficacy and safety outcomes of MRAs administered to CKD patients.ResultsA total of 751 records were identified of which, 23 studies (26 publications) were analyzed. Studies included heterogeneous populations, including the overall CKD, CKD and diabetes, CKD and HF, and CKD and a history of cardiovascular disease. Most of the studies were small and non-rigorous, resulting in a notable lack of evidence in these populations. In the overall CKD population, steroidal MRAs resulted in a significant or sustained eGFR reduction but no efficacy in delaying progression to end-stage kidney disease. No cardiovascular protection was found. Results for all-cause mortality and hospitalization for HF were inconsistent; however, the longest follow-up studies indicate similar or lower incidence for spironolactone non-users. Most results consistently reported a higher incidence of hyperkalemia among patients on steroidal MRAs in all CKD stages, and side effects led to high discontinuation rates in the real-world setting.ConclusionsDespite the limited availability of evidence on the effectiveness and safety of steroidal MRAs in CKD patients and subgroups with diabetes, HF or history of cardiovascular disease, MRAs were shown to have a limited effect on renal and cardiovascular outcomes. Gaps in the evidence regarding the efficacy and safety of MRAs are particularly relevant in diabetic CKD patients; therefore, further research is warranted.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40620-022-01492-w.