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Year : 2022  |  Volume : 16  |  Issue : 3  |  Page : 340-342

Tacrolimus-induced nonischemic dilated cardiomyopathy in a postrenal transplant recipient - A case report

Department of Nephrology, Ramkrishan Care Hospital, Raipur, Chhattisgarh, India

Date of Submission25-Feb-2021
Date of Acceptance03-Nov-2021
Date of Web Publication30-Sep-2022

Correspondence Address:
Dr. Prawash Kumar Chowdhary
Department of Nephrology, Ramkrishan Care Hospital, Raipur, Chhattisgarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijot.ijot_20_21

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We describe a case of nonischemic reversible dilated cardiomyopathy (DCM) due to tacrolimus in patient of live-related renal transplantation. Very few cases due to tacrolimus associated DCM has been reported in the literature, especially in the renal transplant recipient. With the growing use of tacrolimus in transplant medicine, this case report expands the literature of tacrolimus cardiotoxicity and can be useful for clinicians to evaluate and manage the case of DCM in the postrenal transplant recipient.

Keywords: Cardiomyopathy, nonischemic, postrenal transplant, tacrolimus

How to cite this article:
Chowdhary PK, Kale SA, Kumar S, Patel M. Tacrolimus-induced nonischemic dilated cardiomyopathy in a postrenal transplant recipient - A case report. Indian J Transplant 2022;16:340-2

How to cite this URL:
Chowdhary PK, Kale SA, Kumar S, Patel M. Tacrolimus-induced nonischemic dilated cardiomyopathy in a postrenal transplant recipient - A case report. Indian J Transplant [serial online] 2022 [cited 2022 Nov 27];16:340-2. Available from: https://www.ijtonline.in/text.asp?2022/16/3/340/357605

  Introduction Top

Tacrolimus is a calcineurin inhibitor used in renal transplantation as a potent immunosuppressive agent that has showed good graft and patient survival with fewer rejection episodes.[1] It inactivates the T-lymphocytes by inhibiting calcineurin after forming complex with FK-binding protein. It is suspected that calcineurin binding protein is also found in nervous, skeletal, and cardiac tissue, allowing for the possibility of adverse systemic effects. It is suspected that calcineurin inhibition can alter sympathetic activation or potentially influence calcium release channels, contributing to toxicity.[2] Nervous and renal toxicity has been discussed in the literature. Few literature regarding toxic effects on the heart is been discussed.[3],[4],[5] Concentric increase in the left ventricular posterior wall and interventricular septum thickness can occur with tacrolimus in 0.1% of patients.[6] This condition is reversible after dosage reduction or discontinuation of the drug. Very few cases are being reported of tacrolimus-associated nonischemic dilated cardiomyopathy (DCM) with severely reduced systolic function in a renal transplant patient. DCM is mostly an idiopathic disease with a progressive and irreversible course. It carries a poor prognosis and outcome. Rarely, a reversible etiology that is amenable to specific therapy as in our case due to tacrolimus is identified.

We report a case of reversible Tacrolimus associated nonischemic DCM in a postrenal transplant recipient after converting to sirolimus.

  Case Report Top

A 52-year-old male with type-2 diabetes mellitus and hypertension for 11 years was on maintenance hemodialysis for 1 year. He underwent a renal transplant workup with his sister as donor. Pretransplant echocardiogram showed left ventricular ejection fraction (LVEF) of 68% with mild left ventricular thickness. Pretransplant coronary angiogram showed normal coronary arteries. Patients underwent live-related renal transplantation roughly 3 months after workup, without complication. His immunosuppressive therapy constituted induction with methylprednisolone (500 mg, 250 mg, 250 mg) for 3 days and rabbit-antithymocyte globulin (1.5 mg/kg two dose) along with calcineurin inhibitor-based triple immunosuppression (tacrolimus, enteric-coated mycophenolate, prednisolone) for maintenance therapy. All patients received prophylaxis against CMV, fungal and Pneumocystis jiroveci pneumonia infection. Immediately, posttransplant had brisk diuresis with rapid normalization of serum creatinine. Subsequent echocardiograms after renal transplant continued to show normal LVEF. After normalization of blood sugar, he was discharged on the 10th postoperative day with serum creatinine of 1.1 mg/dl. On discharge, his maintenance immunosuppresants were tacrolimus (2.5 mg twice a day), enteric-coated mycophenolate (720 mg twice a day) and Prednisolone (20 mg once a day). Tacrolimus trough level at the time of discharge was 6.4 ng/ml. During posttransplant follow-up patients' renal function remained stable, with a serum creatinine at his baseline of 0.8 mg/dl. Posttransplant monitoring of tacrolimus trough levels was done and the dose of it was adjusted accordingly.

Approximately 3 months after transplant, the patient was readmitted with complaint of gradual swelling of the body which later on became generalized leading to mild breathing difficulties. An echocardiogram was performed, showed global hypokinesia, a decreased ejection fraction to 25%, and mild mitral and tricuspid regurgitation [Figure 1]. There was no pericardial effusion. Electrocardiography showed sinus tachycardia with left ventricular with left bundle branch block. Cardiac enzymes were not elevated. His routine blood investigations including complete blood count, serum electrolytes, liver function test, and renal function (serum creatinine 1.2 mg/dl) were normal. Thyroid function was normal. His chest X-ray showed cardiomegaly with bilateral moderate pleural effusion. Infectious workup including cytomegalovirus, Epstein–Barr virus, Parvovirus, and hepatitis B and C were negative. He was not alcoholic. He was put on digoxin, sacubitril valsartan and diuretics. Once his general condition improved coronary angiogram done which showed mild coronary artery disease [Figure 2]. Tacrolimus trough level was 9.2 ng/ml. Tacrolimus was stopped and sirolimus was started. He was discharged on Sirolimus, Mycophenolate mofetil, Wysolone, Diuretics, Sacubitril Valsartan, and insulin.
Figure 1: ECHO of patients. (a) Left ventricular ejection fraction 25% at time of admission. (b) Left ventricular ejection fraction 60% after 3 months of admission

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Figure 2: Coronary angiography. (a) At the time of pretransplant work up. (b) At the time of admission

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He was in regular follow-up with local physician. On 3 months follow-up, his repeat echocardiogram showed improved left ventricular ejection function to 50%. His diuretics and Sacubitril Valsartan was stopped. His serum creatinine was 0.9 mg/dl. He continued to remain on sirolimus, Mycophenolate mofetil, and wysolone. On the 5th month follow-up, his echocardiogram showed LVEF of 60% showing complete recovery of cardiac function.

  Discussion Top

The cardiotoxic effect of tacrolimus immunosuppression has been described in literature. Most of the studies and case reports have described hypertrophic not DCM association with tacrolimus. Atkison et al.[4] described a pattern of concentric hypertrophy in pediatric patients on imaging, which resolved or showed improvement after tacrolimus was discontinued. Similarly, Uemoto et al.[5] presented an abstract at the 15th Annual Meeting of the American Society of Transplant Physicians, described a cohort of pediatric liver transplant recipients on tacrolimus therapy who developed reversible cardiac wall thickening within the left ventricle and interventricular septum by 1–2 weeks posttransplant. Roberts et al.[7] on autopsy finding of adult and pediatrics orthotopic liver transplantation patient found cardiac septal hypertrophy who even do not have identified risk factor before transplant.

Very few cases of tacrolimus associated DCM has been reported in literature, especially among renal transplant recipient. Proposed mechanisms responsible for causing DCM are coronary artery arteritis, cardiac tissue calcification, and tacrolimus-induced hypertension from sympathetic activation.[8] This usually occurs shortly after treatment is begun and is dose related. Usually, lowering the dose or stopping the medication temporarily will cause the symptoms to abate. If symptoms persist, switching to cyclosporine or sirolimus is suggested. Studies on this subject have been conflicting. Emre et al. examined 388 liver transplant patients who originally started on tacrolimus for immunosuppression. Seventy patients (18%) required conversion. Three of the patients converted to cyclosporine because of the development of tacrolimus-induced cardiomyopathy.[9] All three patients' symptoms resolved after changing to cyclosporine.

Kakhi et al. have described a case of new-onset severe DCM after renal transplantation. Reversal of heart failure was observed after tacrolimus discontinuation and switching to mammalian target of rapamycin inhibitor, sirolimus.[10] Bowman et al. also describe a case of tacrolimus-induced cardiomyopathy in an adult renal transplant recipient. He demonstrates prompt and complete reversal of tacrolimus-induced cardiomyopathy after complete tacrolimus discontinuation and switching to belatacept.[11] Our patients'cardiac function improved after converting from tacrolimus to sirolimus.

Dollinger et al.[12] wanted to examine adults on tacrolimus for signs of cardiotoxicity. They studied 12 patients, and the only patient who developed cardiomyopathy was the only patients who received intravenous instead of oral tacrolimus. Intravenous dosing is no longer the route of administration at most centers. The authors could not find any other significant correlation with tacrolimus use. Our patients were on oral tacrolimus dose and develop acute dilated cardiomyopathy which showed improvement after stopping it.

The patient discussed underwent live-related renal transplantation for end-stage renal disease secondary to diabetic nephropathy. He had uneventful surgeries and did well initially. Later on, after 3 months, he develops heart failure and acute DCM. We looked for all explainable causes including myocardial ischemia, infection, and drug reaction or toxicity including immunosuppression regimens. The patients showed no signs of sepsis or acute respiratory distress syndrome and all laboratories work was unrevealing. The degree and speed at which cardiac malfunction occurred and which improved after stopping tacrolimus immunosuppression suggest the nonischemic DCM was probably due to tacrolimus.

  Conclusion Top

With the growing use of tacrolimus in transplant medicine, more attention is needed to understand its full range of adverse effects. The described case contributes to the literature of tacrolimus cardiotoxicity and brings attention to the need for careful evaluation of patients exposed to this form of immunosuppression. Clearly, more research is needed in this area to prove the definite correlation between tacrolimus immunosuppression and DCM.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Busuttil RW, Holt CD. Tacrolimus (FK506) is superior to cyclosporine in liver transplantation. Transplant Proc 1997;29:534-8.  Back to cited text no. 1
Bechstein WO. Neurotoxicity of calcineurin inhibitors: Impact and clinical management. Transpl Int 2000;13:313-26.  Back to cited text no. 2
Japanese FK 506 Study Group. Study of FK506 on kidney transplantation: Results of an early phase II study. Transplant Proc 1991;23:3071-4.  Back to cited text no. 3
Atkison P, Joubert G, Barron A, Grant D, Paradis K, Seidman E, et al. Hypertrophic cardiomyopathy associated with tacrolimus in paediatric transplant patients. Lancet 1995;345:894-6.  Back to cited text no. 4
Uemoto S, Inomata Y, Egawa H. Effects of Tacrolimus on Cardiac Function after Living Related Liver Transplantation in Paediatric Patients. Paper Presented at: 15th Annual Meeting of the American Society of Transplant Physicians, Dallas TX; May 26-30, 1996.  Back to cited text no. 5
Coley KC, Verrico MM, McNamara DM, Park SC, Cressman MD, Branch RA. Lack of tacrolimus-induced cardiomyopathy. Ann Pharmacother 2001;35:985-9.  Back to cited text no. 6
Roberts CA, Stern DL, Radio SJ. Asymmetric cardiac hypertrophy at autopsy in patients who received FK506 (tacrolimus) or cyclosporine A after liver transplant. Transplantation 2002;74:817-21.  Back to cited text no. 7
Baruch Y, Weitzman E, Markiewicz W, Eisenman A, Eid A, Enat R. Anasarca and hypertrophic cardiomyopathy in a liver transplant patient on FK506: Relieved after a switch to neoral. Transplant Proc 1996;28:2250-1.  Back to cited text no. 8
Emre S, Genyk Y, Schluger LK, Fishbein TM, Guy SR, Sheiner PA, et al. Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients. Transpl Int 2000;13:73-8.  Back to cited text no. 9
Kakhi S, Phanish MK, Anderson L. Dilated cardiomyopathy in an adult renal transplant recipient: Recovery upon tacrolimus to sirolimus switch: A case report. Transplant Proc 2020;52:2758-61.  Back to cited text no. 10
Bowman LJ, Brennan DC, Delos-Santos R, LaRue SJ, Anwar S, Klein CL. Tacrolimus-induced cardiomyopathy in an adult renal transplant recipient. Pharmacotherapy 2015;35:1109-16.  Back to cited text no. 11
Dollinger MM, Plevris JN, Chauhan A, MacGilchrist AJ, Finlayson ND, Hayes PC. Tacrolimus and cardiotoxicity in adult liver transplant recipients. Lancet 1995;346:507.  Back to cited text no. 12


  [Figure 1], [Figure 2]


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