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. 2020 Aug;7(4):1842-1849.
doi: 10.1002/ehf2.12749. Epub 2020 May 23.

Impact of tacrolimus versus cyclosporin A on renal function during the first year after heart transplant

Yasuyuki Shiraishi  1   2 , Eisuke Amiya  1   3 , Masaru Hatano  1   3 , Toshiomi Katsuki  2 , Chie Bujo  1 , Masaki Tsuji  1 , Daisuke Nitta  1 , Hisataka Maki  1 , Junichi Ishida  1 , Yukie Kagami  4 , Miyoko Endo  4 , Mitsutoshi Kimura  5 , Masahiko Ando  5 , Shogo Shimada  5 , Osamu Kinoshita  5 , Minoru Ono  5 , Issei Komuro  1
Affiliations

Impact of tacrolimus versus cyclosporin A on renal function during the first year after heart transplant

Yasuyuki Shiraishi et al. ESC Heart Fail. 2020 Aug.

Abstract

Aims: Nephrotoxicity of calcineurin inhibitors (CNIs) is associated with adverse events in patients undergoing heart transplant (HTx), although studies directly comparing tacrolimus (TAC) versus cyclosporin A (CsA), especially in combination with everolimus and low-dose CNIs approach, are limited. Thus, we sought to investigate the associations of TAC and CsA with clinical outcomes in HTx recipients, with specific focus on renal function.

Methods and results: From August 2007 to February 2017, 72 consecutive patients (39 treated with TAC vs. 33 with CsA) receiving de novo HTx in a single transplant centre were retrospectively evaluated. We used the instrumental variable method to account for unmeasured confounding. The study outcomes were percentage change in estimated glomerular filtration rates (eGFR) (safety endpoint) and biopsy-proven acute rejection (efficacy endpoint) within the first year after HTx. The enrolled patients (median age 40 years) were predominantly men (68%). There were no significant differences in baseline characteristics, including eGFR (64.8 [45.7-96.4] mL/min/1.73 m2 in TAC vs. 65.6 [57.9-83.0] mL/min/1.73 m2 for CsA; P = 0.48), other than sex (male, 49% for TAC vs. 91% for CsA; P < 0.001) between the two groups. Within the first year after HTx, 23 (59%) in the TAC group switched mycophenolate mofetil to everolimus, whereas 16 (48%) in the CsA group (P = 0.52). At 12 months, the rates of mortality and end-stage renal disease requiring renal replacement therapies were both 0%. In the instrumental variable analysis, no differences in renal function as well as graft rejection for 1 year after HTx existed between the TAC and CsA groups. These results were similar when taking into account of everolimus use.

Conclusions: Irrespective of everolimus use with low-dose CNIs, our analysis using the instrumental variable method showed no differences in renal function as well as graft rejection during the first year after HTx between HTx recipients who received TAC or CsA.

Keywords: Calcineurin inhibitor; Graft rejection; Heart transplant; Instrumental variable; Renal dysfunction.

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Conflict of interest statement

Dr Shiraishi has received an honorarium from Otsuka Pharmaceutical Co. Ltd. Dr Amiya and Dr Hatano belong to the Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, University of Tokyo, which is endowed by Actelion Pharmaceuticals Japan Ltd., Otsuka Pharmaceutical, NIPRO CORPORATION, Terumo Corp., Senko Medical Instrument Mfg., Century Medical Inc., Kinetic Concepts Inc., St. Jude Medical, and has received honoraria from Takeda Pharmaceutical Co. Ltd., Bayer Yakuhin. Ltd., Otsuka Pharmaceutical Co. Ltd. Other authors have no conflicts of interest to disclose. There are no patents, products in development, or marketed products to declare.

Figures

Figure 1
Figure 1
Distribution of normalized change in estimated glomerular filtration rate (eGFR) by calcineurin inhibitors. There was a significant difference in normalized change in eGFR between the two groups (P = 0.019). Normalized change in eGFR was calculated as the following equation: (eGFR at 1 year after heart transplant − eGFR at baseline) / (eGFR at baseline) × 100. eGFR, estimated glomerular filtration rate.
Figure 2
Figure 2
Frequencies of biopsy‐proven acute rejection by calcineurin inhibitors. There was no difference in frequencies of biopsy‐proven acute rejection between the two groups (P = 0.91).
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