A case of rhabdomyolysis after atorvastatin therapy of a liver transplant recipient receiving immunosuppressive therapy with cyclosporine

Rationale. To date, liver transplantation is the most effective method of treating end-stage liver failure, and therefore this treatment has become widespread throughout the world. However, due to the improvement in the quality of transplant care and an increase in the long-term survival of patients, the development of concomitant pathology, which often requires medical treatment, is inevitably associated with a higher life expectancy of liver transplant recipients. Thus, in patients who underwent liver transplantation, there is. a significant increase in the incidence of dyslipidemia. However, a long-term immunosuppressive therapy in organ transplant patients can adversely modify the effect of the prescribed drugs, which requires careful monitoring and consideration of drug interactions.
Purpose. Using a clinical example to demonstrate the importance of taking drug interactions into account in the treatment of patients after organ transplantation receiving immunosuppressive drugs.
Material and methods. In the presented clinical case, a patient after orthotopic liver transplantation performed in 2005 underwent a staged treatment of cicatricial stricture of choledochal anastomosis in the S.P. Botkin City Clinical Hospital. During the following hospitalization, the patient complained of minor muscle pain when walking. At doctor's visit 3 weeks before hospitalization, a local physician prescribed therapy with atorvastatin 10 mg per day due to an increase in blood plasma cholesterol levels. The patient underwent removal of the self-expanding nitinol stent. During the follow-up examination, the patient had no evidence of an impaired bile outflow, however, muscle pain and weakness progressively increased, the rate of diuresis decreased, and in the biochemical analysis of blood there was an abrupt increase in the concentration of creatinine, aspartate aminotransferase, alanine aminotransferase. Atorvastatin was canceled, a diagnosis of acute non-traumatic rhabdomyolysis was established, treatment with hemodialysis and plasma exchange was started on 03/05/2020. The last session of renal replacement therapy was 03/30/20.
Results. With the restoration of the diuresis rate, there was a spontaneous decrease in the level of creatinine to 170 μmol/L. The patient was discharged with satisfactory renal and hepatic function. The pain syndrome completely resolved. Conclusion. Drug interactions between atorvastatin and cyclosporine have resulted in acute rhabdomyolysis with life-threatening consequences. This once again confirms the importance of taking drug interactions into account when managing patients after solid organ transplantation.

1. Gonikova ZZ, Nikolskaya AO, Kirsanova LA, Shagidulin M.Y, Onishchenko NA, Sevastyanov VI. Comparative analysis of regenerative activity of bone marrow cells and total RNA extracted from them in chronic fibrosing liver disease. Russian Journal of Transplantology and Artificial Organs. 2019;21(3):100–110. (In Russ.). https://doi.org/10.15825/1995-1191-2019-3-100-110

2. Halliday N, Westbrook RN. Liver transplantation; need, indications, patient selection and pre-transplant care. Br J Hosp Med (Lond). 2017;78(5):252-259 PMID: 28489446 https://doi.org/10.12968/hmed.2017.78.5.252

3. Gautier SV, Moy syuk YG, Poptsov VN, Kornilov MN, Yaroshenko EB, Pogrebnichenko IV, et al. Long-term outcomes of deceased donor liver transplantation. Russian Journal of Transplantology and Artificial Organs. 2014;16(3):45–53. (In Russ.). https://doi.org/10.15825/1995-1191-2014-3-45-53

4. Muñoz LE, Nañez H, Rositas F,Pérez E, Razo S, Cordero P, et al. Long-term complications and survival of patients after orthotopic liver transplantation. Transplant Proc. 2010;42(6):2381–2382. PMID: 20692485 https://doi.org/10.1016/j.transproceed.2010.05.007

5. Lucey MR, Terrault N, Ojo L, Hay JE, Neuberger J, Blumberg E, et al. Long term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transpl. 2013;19(1):3–26. PMID: 23281277 https://doi.org/10.1002/lt.23566

6. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. PMID: 31504418 https://doi.org/10.1093/eurheartj/ehz455

7. Dyadyk AI, Kugler TE, Suliman YV, Zborovskyy SR, Zdykhovskaya II. Statin adverse effects: mechanisms, diagno sis, prevention and management. The Russian Archives of Internal Medicine. 2018;8(4):266–276. (In Russ.). https://doi.org/10.20514/2226-6704-2018-8-4-266-276

8. Drapkina OM, Chernova EM. Myopathy as a side effect of statin therapy: mechanisms of development and prospects for treatment. Rational Pharmacotherapy in Cardiology. 2015;11(1):96–101. (In Russ.). https://doi.org/10.20996/1819-6446-2015-11-1-96-101

9. Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, et al. Statin-associated muscle symptoms: impact on statin therapy – Europe an Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015;36(17):1012–1022. PMID: 25694464 https://doi.org/10.1093/eurheartj/ehv043

10. Cervellin G, Comelli I, Lippi G. Rhabdomyolysis: historical background, clinical, diagnostic and therapeutic features. Clin Chem Lab Med. 2010;48(6):749–56. PMID: 20298139 https://doi.org/10.1515/CCLM.2010.151

11. European Association for the Study of the Liver. EASL Сlinical practice guidelines: liver transplantation. J Hepatology. 2016;64(2):433–485. https://doi.org/10.1016/j.jhep.2015.10.006

12. Huang CJ, Chen CL, Wang CS, Cheng KW, Chen KH, Wang CC. Rhabdomyolysis after liver transplantation: a case report. Transplant Proc. 2008;40(8):2821–2822. PMID: 18929870 https://doi.org/10.1016/j.transproceed.2008.07.032

13. Shahbazov R, Fox M, Alejo J, Anjum MA, Azari F, Doyle A, et al. A case of rhabdomyolysis after kidney transplantation successfully managed with intensive continuous dialysis. J Surg Case Rep. 2018(4):rjy078. PMID: 29765590 https://doi.org/10.1093/jscr/rjy078

14. Moiseenko AV, Polikarpov AA, Granov DA, Tarazov PG, Shapoval CV, Sheraliev AR, et al. The possibilities of interventional radiology before and after orthotopic liver transplantation. Russian Journal of Transplantology and Artificial Organs. 2018;20(3):75–79. (In Russ.). https://doi.org/10.15825/1995-1191-2018-3-75-79

15. Gautier SV, Khomyakov SM. Organ donation and transplantation in the Russian Federation in 2018. 11th report of the Registry of the Russian Transplant Society. Russian Journal of Transplantology and Artificial Organs. 2019;21(3):7–32. (In Russ.). https://doi.org/10.15825/1995-1191-2019-3-7-32

16. Yaremin BI, Parabina EV, Masliko va UV, Alexandrova VE. Acute episode of rhabdomyolysis associated with everolimus and cabergoline in a kidney recipient after childbirth. Transplantologiya. The Russian Journal of Transplantation. 2017;9(4)312–316. (In Russ.). https://doi.org/10.23873/2074-0506-2017-9-4-312-316