PCSK9 Inhibitors and Kidney Function
PCSK9 inhibitors do not adversely affect kidney function and are safe to use in patients with chronic kidney disease, including those with moderate to severe renal impairment (eGFR ≥20 mL/min/1.73 m²). In fact, emerging evidence suggests they may reduce proteinuria and preserve renal function.
Safety Profile in CKD
PCSK9 inhibitors maintain the same efficacy and safety profile in CKD patients as in those with normal kidney function, with no dose adjustment required for renal impairment 1, 2.
Clinical trials have included CKD patients with eGFR down to 20 mL/min/1.73 m², demonstrating consistent LDL-cholesterol reduction (approximately 50-60%) regardless of baseline kidney function 1, 2.
No increase in adverse events—including muscle symptoms, liver enzyme elevation, or cognitive effects—has been observed in CKD patients treated with PCSK9 inhibitors 3.
Potential Renal Benefits
A real-world multicentric study demonstrated that PCSK9 inhibitors significantly reduced proteinuria in CKD patients, with median proteinuria decreasing from 57 mg/g to 30 mg/g (p=0.021) over one year of treatment 4.
eGFR remained stable throughout follow-up in CKD patients treated with PCSK9 inhibitors, with no deterioration in kidney function 4.
The proteinuria-lowering effect may be mediated through reduced lipid nephrotoxicity, though this mechanism requires further investigation 4.
Clinical Indications in CKD
The American College of Cardiology recommends adding PCSK9 inhibitors to maximally tolerated statin therapy in high-risk CKD patients with atherosclerotic cardiovascular disease when <50% LDL-cholesterol reduction has been achieved 3.
The KDIGO 2024 guideline suggests considering PCSK9 inhibitors in CKD patients who have an indication for their use, particularly those at high cardiovascular risk 3.
PCSK9 inhibitors are particularly valuable in CKD patients with nephrotic syndrome, where they effectively address the severe dyslipidemia that is often refractory to statins alone 2, 5.
Knowledge Gaps
The 2018 ESC/EAS Task Force explicitly identifies the impact of PCSK9 inhibition in CKD patients (not requiring dialysis) as a major gap in knowledge 3.
Patients with severely impaired kidney function (eGFR <20 mL/min/1.73 m²) and those on dialysis have been excluded from major cardiovascular outcome trials, limiting evidence in this highest-risk population 3, 2.
The KDIGO Controversies Conference on peripheral arterial disease recommends future studies to evaluate the treatment role of PCSK9 inhibitors in reducing onset or progression of PAD among CKD patients 3.
Practical Considerations
No dose adjustment is required for PCSK9 inhibitors based on kidney function, making them straightforward to prescribe in CKD 1, 2.
PCSK9 inhibitors can be safely combined with statins and ezetimibe in CKD patients without increased risk of adverse effects 3, 1.
Plasma PCSK9 levels are not influenced by eGFR or albuminuria stage, but are elevated in patients on lipid-lowering therapy (particularly fibrate/statin combinations) 6.
The proteinuria-lowering effect observed in real-world studies suggests potential disease-modifying benefits beyond cardiovascular risk reduction, though long-term renal outcomes require dedicated trials 4.