PCSK9 Inhibition Lowers LDL-C in Patients With Kidney Disease

Two posters presented at the American Society of Nephrology (ASN) Kidney Week 2026 in Denver, Colorado, add early evidence that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition can lower cholesterol in patients with kidney disease. In this population, hypercholesterolemia is common, drives cardiovascular (CV) mortality, and often responds poorly to conventional lipid-lowering therapy. A small real-world cohort found that PCSK9-targeted therapy cut low-density lipoprotein cholesterol (LDL-C) by half within 3 months in patients receiving dialysis. A separate manufacturer-funded pharmacokinetic (PK) analysis concluded that the oral PCSK9 inhibitor enlicitide (Lipfendra; Merck) needs no dose adjustment for renal impairment.^1,2

Lipid Lowering in Patients on Dialysis

Investigators in Milan and Pesaro-Urbino, Italy, retrospectively evaluated 21 patients receiving dialysis who started PCSK9-targeted therapy: 16 with evolocumab (Repatha; Amgen) and 5 with inclisiran (Leqvio; Novartis). Sixteen were on hemodialysis, and 5 were on peritoneal dialysis. The mean age was about 65 years, and mean dialysis vintage was 4 years. Eight patients were reported to have a history of CV events and 17 peripheral artery disease.¹

The reasons for starting therapy mirror gaps pharmacists see in practice. Seven patients began PCSK9-targeted therapy because of statin intolerance with creatine phosphokinase elevation. The other 14 had it added to a statin or ezetimibe because cholesterol control remained inadequate.¹

Improvements came quickly. At 3 months, total cholesterol had fallen approximately 40% and LDL-C had fallen 50%. The effect held at 6 months, with reductions of 36% and 40%, respectively. Triglycerides did not change significantly, falling less than 10%. Lipid lowering was similar between hemodialysis and peritoneal dialysis (P = .9). Median follow-up was 8 months, and only 2 patients reached 1 year.¹

There were no adverse events, treatment discontinuations, or CV events that occurred during follow-up. One patient died of metastatic cancer after 7 months, and another was excluded after 4 months because of kidney transplantation. The authors called for larger prospective studies to confirm long-term safety and CV benefit, which this design cannot establish.¹

Oral Enlicitide Across Kidney Function

The FDA approved enlicitide in July 2026 as a 20-mg once-daily tablet. It is the first oral PCSK9 inhibitor; until then, the class was primarily available as injections.³ Nonclinical and human absorption, distribution, metabolism, and excretion data demonstrate that enlicitide is primarily eliminated intact through passive renal excretion, so kidney function is a natural question when it is dispensed.²

Merck investigators addressed this with noncompartmental and integrated population PK analyses. These drew on phase 1 studies in moderate and severe renal impairment and in end-stage renal disease (ESRD) on hemodialysis, plus phase 2 and phase 3 studies, including CORALreef Lipids (NCT05952856) and CORALreef HeFH (NCT05952869). At the 20-mg daily dose, steady-state exposure was approximately 5% higher in participants with mild renal impairment (n = 844) and 11% higher in those with moderate impairment (n = 191) than in participants with normal kidney function. Modeling predicted roughly 26% higher exposure in severe impairment. In the single-dose study, exposure was 17% higher in participants with ESRD when enlicitide was given before hemodialysis.²

The authors determined these increases are not clinically meaningful compared with the drug’s established safety profile at doses up to 300 mg once and 120 mg daily. They concluded that no dose adjustment is needed. The study was funded by Merck, and all authors are Merck employees.²

A separate pooled CORALreef analysis presented at the meeting looked at efficacy in patients with an estimated glomerular filtration rate below 60. It found a 65.9% placebo-adjusted LDL-C reduction at week 24, with safety comparable to placebo.⁴

Counseling Points for Pharmacists

For patients with chronic kidney disease who are candidates for oral therapy, counseling centers on administration. Enlicitide is taken first thing in the morning on an empty stomach, and patients should wait 30 minutes before eating. Pharmacists should also present it as an LDL-C–lowering therapy for now, because the ongoing CORALreef Outcomes (NCT06008756) trial has not yet shown whether it reduces CV morbidity and mortality.³

Questions remain for patients on dialysis. The PK abstract does not address when to take doses relative to dialysis sessions, beyond its single-dose ESRD data. Neither poster reports CV outcomes in patients on dialysis.^1,2

REFERENCES

1. Abinti M, Di Luca M, Castellano G, et al. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly reduce hypercholesterolemia in patients on dialysis. Poster presented at: ASN Kidney Week 2026; October 24, 2026. Abstract SA-PO0440. doi:10.1681/ASN.2026xxqg5s61

2. Johns D, Bajwa E, Banka P, et al. Renal impairment does not have a clinically meaningful effect on the pharmacokinetics of the oral PCSK9 inhibitor enlicitide. Poster presented at: ASN Kidney Week 2026; October 22, 2026. Abstract TH-PO0817. doi:10.1681/ASN.20263f2mwert

3. Antrim A, Halpern L. FDA approves enlicitide, the first oral PCSK9 inhibitor for high cholesterol. Pharmacy Times. Updated July 17, 2026. Accessed October 27, 2026. https://www.pharmacytimes.com/view/fda-approves-enlicitide-the-first-oral-pcsk9-inhibitor-for-high-cholesterol

4. Halpern L. Enlicitide cuts LDL-C regardless of kidney function. Pharmacy Times. October 23, 2026. Accessed October 27, 2026. https://www.pharmacytimes.com/view/enlicitide-cuts-ldl-c-regardless-of-kidney-function