Novel Therapeutic Strategies for Dyslipidemia: First Report of Inclisiran Therapy in a Kidney Transplanted Patient

Abstract

partly because there are incompatibilities and interactions between statins and immunosuppressive drugs i.e., ciclosporin A that limit adequate statin therapy and ezetimibe administration [3,4]. Therefore, novel and highly efficient therapies such as inclisiran (SmPC Leqvio, Novartis, Germany) may contribute to better LDLC management in this patient population. Inclisiran is a small interference-RNA against protein convertase subtilisin/kexin type 9 (PCSK9), preventing LDL receptor degradation [5]. It is injected subcutaneously at month 0 and 3 and every 6 months thereafter and results in ~50% LDLC reduction [6]. Inclisiran was first approved in the European Union in December 2020 for the treatment of primary hypercholesterolemia or mixed dyslipidemia in combination with a statin or other lipid-lowering therapies in patients who do not achieve LDLC goals with the maximum tolerable statin dose, or alone or in combination with other lipid-lowering therapies in patients with statin intolerance or for whom a statin is contraindicated.To our knowledge, there is no data about the use of inclisiran in kidney transplant recipients yet. Therefore, we present for the first time a case of a patient treated with inclisiran after renal transplantation.Our 79-year-old patient received a deceased donor kidney transplant 12 years prior to the first inclisiran administration. End-stage renal disease was caused by right-sided nephrectomy due to renal cell carcinoma and unspecified nephrosclerosis of the left kidney. The immunosuppressive regimen at the time reported consisted of everolimus and prednisolone.Serum creatinine was 2.44 mg/dl with an estimated GFR of 24 ml/min/m² (CKD4A2T, CKD EPI).The patient had mixed dyslipidemia and progressive peripheral artery disease (Fontaine IIB).On therapy with atorvastatin 80 mg and ezetimibe 10 mg serum lipids were insufficiently controlled (total cholesterol 200 mg/dl, LDLC 95 mg/dl, HDLC 82 mg/dl and triglycerides 158 mg/dl). For our very high-risk patient, the 2019 ESC/EAS guidelines on the treatment of dyslipidaemia recommend a target LDLC of ˂ 55 mg/dl and an LDLC reduction > 50% from baseline values [7]. Therapeutic options were discussed with the patient and the patient opted for inclisiran therapy for convenience and optimal therapy adherence.Inclisiran was administered at 0 and 3 months and then every 6 months. LDLC was significantly lowered to 40 mg/dl, 44 mg/dl and 51 mg/dl after 6, 9 and 12 months, respectively (figure 1).During the one-year follow-up, renal function was stable after 12 months (serum creatinine 2.39 mg/dl, eGFR 25 ml/min/m²; figure 1). We did not observe relevant side effects, or increase in proteinuria or change in everolimus level.The case presented demonstrates that inclisiran can be safely and conveniently administered with a profound effect on LDLC levels after renal transplantation. Further research needs to be conducted to demonstrate efficacy on cardiovascular death in transplanted patients.The authors have declared no conflicts of interest.Funding: The APC was funded by the Open Access Fund of the University of Münster.

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