PCSK9-Targeted Therapy and Kidney Function in Chronic Kidney Disease: A Systematic Review and Narrative Synthesis

Chronic kidney disease (CKD) increases cardiovascular risk, but renal impairment, proteinuria, dialysis, and transplantation complicate interpretation of lipid-lowering therapy. This systematic review evaluated renal tolerability, kidney-related clinical and biological evidence, and unresolved renal-outcome gaps for proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeted therapies in CKD.

PubMed/MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials were searched from inception and most recently updated on September 19, 2026; ClinicalTrials.gov was additionally searched on September 19, 2026. Eligible evidence included clinical trials and CKD subgroup analyses, renal-impairment pharmacology, observational cohorts, dialysis and transplant reports, pharmacovigilance, case-based evidence, and kidney-specific experimental studies. Two reviewers independently screened, extracted, and appraised reports. Findings were synthesized narratively without quantitative pooling. The protocol was prospectively registered in PROSPERO (CRD420261402376).

One hundred five reports representing 116 underlying studies were included. Evolocumab, alirocumab, and inclisiran consistently lowered low-density lipoprotein cholesterol without a clear short- to medium-term signal for deterioration in creatinine-based kidney function across the CKD strata studied. Evidence for reduced albuminuria or proteinuria was limited to small uncontrolled studies, and mechanistic findings did not establish clinical evidence of renoprotection. Most renal tolerability evidence came from cardiovascular or lipid-efficacy trials dominated by mild-to-moderate non-dialysis CKD; advanced CKD, dialysis, and kidney transplantation were excluded or sparsely represented.

Current evidence supports lipid-lowering efficacy in mild-to-moderate non-dialysis CKD but does not establish renoprotection or an antiproteinuric effect. Kidney-centered studies are needed in advanced CKD, dialysis, and transplantation.