Inclisiran in advanced chronic kidney disease (stage G4-G5 non-dialysis): sustained LDL-C reduction and favorable safety profile at 1-year follow-up in a real-world case series.

BACKGROUND AND AIMS: Advanced chronic kidney disease (CKD; stages G4-G5 not on dialysis) is associated with very high cardiovascular risk, and lipid control is particularly challenging due to reduced statin efficacy and frequent intolerance. Inclisiran, a small interfering RNA (siRNA) that inhibits hepatic PCSK9 synthesis, has demonstrated sustained LDL-C reductions in clinical trials, though data in advanced CKD remain scarce.

MATERIALS AND

METHODS

An observational, retrospective case series was conducted at a tertiary care hospital, including 10 patients with stage G4-G5 non-dialysis CKD and elevated LDL-C despite optimized therapy or with statin intolerance. Inclisiran was administered following the standard regimen (day 0, day 90, and every 6 months thereafter). Lipid profile, renal function, and albuminuria were assessed at baseline, 3-6 months, and 12 months.

RESULTS

Patients had a mean age of 75 ± 5 years with high cardiovascular comorbidity. Baseline LDL-C was 131.6 ± 22.1 mg/dl, falling to 46.1 ± 26.5 mg/dl at 1 year (mean reduction 65.6%). All patients responded to treatment; 80% achieved LDL-C < 70 mg/dl and 60% achieved < 55 mg/dl. Renal function remained stable (eGFR 22.7 vs. 23.7 ml/min/1.73 m2). A 27.4% reduction in median albuminuria was observed; however, all patients were receiving maximized nephroprotective therapy concurrently, and this finding should not be attributed to inclisiran. No adverse events or major cardiovascular events were recorded.

CONCLUSIONS

Inclisiran demonstrates a marked and sustained LDL-C reduction in patients with advanced CKD, with an excellent safety profile and preserved renal function, supporting its use in this high-risk population.