Efficiency of dyslipidemia therapy using inclisiran in a series of clinical observations of kidney transplant patients
Relevance. Dyslipidemia is a risk factor for cardiovascular diseases leading to death in the late period after kidney transplantation.Kordonova O.O., Gubarev K.K., Voskanyan S.E., Praskurnichy E.A., Svetlakova D.S., Rudakov V.S., Frolova N.F., Vinogradov V.E., Usatyuk S.S.
Objective. Evaluation of the efficacy and safety of combination therapy for dyslipidemia with inclisiran in a group of patients with a transplanted kidney.
Material and methods. A single-center observational uncontrolled cohort study of the efficacy and safety of lipid-lowering therapy (LLT) using inclisiran in a group of patients with dyslipidemia after kidney transplantation was conducted. Data on 10 patients are presented: 8 (80%) women, mean age 39.8±10.5 years. At stage I, basic LLT was prescribed, at stage II, inclisiran was added to the treatment on days 1, 90, and 270. Follow-up period at stage I was 102 days, at stage II – 301 days. Efficacy and safety were assessed at 7 control points. Therapy efficacy was assessed by reducing low-density lipoprotein (LDL) levels, achieving blood LDL level ≤1.4 mmol/L, and the duration of maintaining the achieved effect (days). Blood levels of lipoprotein (a) – Lp(a), triglycerides (TG), and high-density lipoprotein (HDL) were also studied. Safety was assessed based on complaints, general examination and injection site data, alanine aminotransferase (ALT), aspartate aminotransferase (AST), glomerular filtration rate (GFR), blood immunosuppressant drug concentrations, daily proteinuria, and renal ultrasound results.
Results. A decrease in LDL levels by an average of >50% was revealed 30 days after each injection in 6 (60%) patients, and from 8.6 to 46% - in 4 (40%). The dynamics of HDL and TG levels were multidirectional. In 3 patients with elevated Lp(a) levels, a decrease in its level by 5.1–7.4% was revealed. At stage I, basic LLT therapy was ineffective. At stage II, LDL levels ≤1.4 mmol/l were achieved by 2 (20%) patients at points 2 and 3, 5 (50%) patients – at point 4, 3 (30%) – at point 5, 1 (10%) patient – at point 6, and 2 (20%) patients at point 7. A total of 7 patients achieved LDL levels ≤1.4 mmol/l with a median of 47 [IQR: 3; 90] (1; 112) days. LDL levels ≤1.8 mmol/l were achieved in 8 patients with a median of 98.5 [IQR: 61; 236.7] (42; 255) days. In 5 (50%) patients, a decrease in GFR by an average of “minus” 13.6±13.9% (-36.4; -0.1%) was detected. In the remaining 5 (50%) patients, the mean GFR value increased by 15.1±17.3% (1.7%; 42.6%). In all 10 patients, the level of daily proteinuria decreased by an average of 50.4±16.9% (25.6%; 76.9%).
Conclusion. The efficacy of the basic LLT (n=8) in reducing the LDL level compared to the baseline was on average 23.5±10.5% (1.9%; 39.6%) [95% CI 8.9–26.3%], the efficacy of the drug inclisiran was 48.9±20.4% (8.6%; 70.9%) [95% CI 34.3–63.5%]. The efficacy of all applied LLT in all patients was on average 59.9±22.5% (8%; 81.1%) [95% CI 43.8–76.0%]. The median of days with the LDL level ≤1.4 mmol/L in 7 patients was 47 [IQR: 3; 90] (1; 112) days, which amounted to a median share of 15.6% [IQR: 1%; 29.9%] (0.3%; 37.2%) of the total follow-up period (301 days). No side effects indicating poor tolerability of the drug were detected during the use of inclisiran.
Keywords
inclisiran
kidney transplantation
dyslipidemia
risk factors for cardiovascular events
lipid-lowering therapy
About the Authors
Olga O. Kordonova – Therapist of the Surgical Department № 2, Center for Surgery and Transplantology, State Research Center of the Federal Medical Biophysical Center named after A.I. Burnazyan of the Federal Medical and Biological Agency of Russia. Address: 23 Marshal Novikov st., Moscow, Russia, 123098.ORCID: https://orcid.org/0009-0003-9173-4535.
Konstantin K. Gubarev – Dr.Sci. (Med.), Head of the Surgical Department of Coordination of Organ and (or) Human Tissue Donation, State Research Center of the Federal Medical Biophysical Center named after A.I. Burnazyan of the Federal Medical and Biological Agency of Russia. Address: 23 Marshal Novikov st., Moscow, Russia, 123098.; e-mail: kkgubarev@gmail.com. ORCID: https://orcid.org/0000-0001-9006-163X.
Sergey E. Voskanyan – Dr.Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences, Deputy Chief Physician for Surgical Care, Head of the Center for Surgery and Transplantology, State Research Center of the Federal Medical Biophysical Center named after A.I. Burnazyan of the Federal Medical and Biological Agency of Russia. Address: 23 Marshal Novikov st., Moscow, Russia, 123098. ORCID: https://orcid.org/0000-0001-5691-5398.
Evgeny A. Praskurnichy – Dr.Sci. (Med.), Head of the Department of Therapy, MBU ICE, Federal Medical Biophysical Center named after A.I. Burnazyan of the Federal Medical and Biological Agency of Russia. Address: 23 Marshal Novikov st., Moscow, Russia, 123098. ORCID: 0000-0002-9523-5966.
Daria S. Svetlakova – Surgeon, Surgical Department for Coordination of Organ and (or) Tissue Donation, State Research Center of the Federal Medical Biophysical Center named after A.I. Burnazyan of the Federal Medical and Biological Agency of Russia. Address: 23 Marshal Novikov st., Moscow, Russia, 123098.
ORCID: https://orcid.org/0000-0002-2274-6204.
Vladimir S. Rudakov – Surgeon, Surgical Department for Coordination of Organ and (or) Tissue Donation, State Research Center of the Federal Medical Biophysical Center named after A.I. Burnazyan of the Federal Medical and Biological Agency of Russia. Address: 23 Marshal Novikov st., Moscow, Russia, 123098.
ORCID: https://orcid.org/0000-0002-3171-6621.
Nadiya F. Frolova – Cand.Sci. (Med.), Associate Professor, Department of Nephrology, Faculty of Continuous Professional Education, Russian University of Medicine; Deputy Chief Physician for Nephrology, Moscow Clinical Research Scientific Center «Clinic №52 of the Moscow Healthcare Department». Address: 3 Pekhotnaya St., Moscow, 123182. ORCID: https://orcid.org/0000-0003-3234-8266.
Vladimir E. Vinogradov – Head of the Consultative and Diagnostic Nephrology Department, Moscow Clinical Research Scientific Center «Clinic №52 of the Moscow Healthcare Department». Address: 3 Pekhotnaya St., Moscow, 123182. ORCID: 0000-0002-2499-4770.
Sergey S. Usatyuk – Head of the Nephrology Department № 2, Moscow Clinical Research Scientific Center «Clinic №52of the Moscow Healthcare Department». Address: 3 Pekhotnaya St., Moscow, 123182. ORCID: https://orcid.org/0000-0002-8742-3860
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