RNA therapeutics
Lp(a) rises as kidney function declines, adding unaddressed cardiovascular risk in CKD, review (Cardiorenal Med 2026)
Original title: Lipoprotein(a) and Cardiovascular Risk: Emerging Therapeutic Perspectives with Implications for Chronic Kidney Disease
Review of lipoprotein(a) in chronic kidney disease (CKD), noting that Lp(a) is a genetically determined, likely causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis, largely inherited and only modestly modified by lifestyle or conventional lipid-lowering therapy. European and North American guidelines support at least one lifetime Lp(a) measurement for cardiovascular risk refinement. In CKD, Lp(a) levels may rise as renal function declines, contributing to excess cardiovascular burden and residual risk, including severe vascular calcification, that historical statin trials in end-stage renal disease left unaddressed, though Lp(a)'s causal role in CKD-related cardiovascular disease remains incompletely defined. Novel RNA-based and small-molecule therapies, including pelacarsen, olpasiran, lepodisiran, zerlasiran and muvalaplin, show marked Lp(a)-lowering effects, but definitive cardiovascular outcome data specific to CKD are still missing.
Original abstract
Background: Lipoprotein(a) (Lp(a)) is an low-density lipoprotein (LDL)-like particle containing apolipoprotein B100 covalently bound to apolipoprotein(a). Elevated Lp(a) is now recognized as a genetically determined, independent, and likely causal risk factor for atherosclerotic cardiovascular disease, calcific aortic valve stenosis, and residual cardiovascular risk despite optimal LDL cholesterol control. Current European and North American recommendations support measuring Lp(a) at least once in adulthood, particularly for cardiovascular risk refinement. Lp(a) levels are predominantly inherited and are only modestly influenced by lifestyle or conventional lipid-lowering therapies.
Summary: Chronic kidney disease (CKD) represents a clinically relevant setting in which Lp(a) levels may rise as renal function declines, contributing to the excess cardiovascular burden and residual risk (including severe vascular calcification) left unaddressed by historical statin trials in the end-stage renal disease population. However, the causal role of Lp(a) in CKD-related cardiovascular disease remains incompletely defined.
Key Messages: Novel RNA-based and small molecule therapies, including pelacarsen, olpasiran, lepodisiran, zerlasiran, and muvalaplin, have shown marked Lp(a)-lowering effects, but definitive cardiovascular outcome data are still missing.
oral inhibitionolpasiranpelacarsenRNA therapeutics
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.