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Review
. 2025 May;241(5):e70047.
doi: 10.1111/apha.70047.

Calcineurin Inhibitor Associated Nephrotoxicity in Kidney Transplantation-A Transplant Nephrologist's Perspective

Carla M Hansen  1 , Sebastian Bachmann  1 , Mingzhen Su  1 , Klemens Budde  1 , Mira Choi  1
Affiliations
Review

Calcineurin Inhibitor Associated Nephrotoxicity in Kidney Transplantation-A Transplant Nephrologist's Perspective

Carla M Hansen et al. Acta Physiol (Oxf). 2025 May.

Abstract

Aim: Calcineurin inhibitors (CNIs) have revolutionized transplant medicine, improving allograft survival but posing challenges like calcineurin inhibitor-induced nephrotoxicity (CNT). Acute CNT, often dose-dependent, leads to vasoconstriction and acute kidney injury, with treatment focusing on CNI exposure reduction. Chronic CNT manifests as progressive allograft function decline, with challenges in distinguishing it from nonspecific allograft nephropathy.

Methods: This narrative review provides a concise overview of the clinical management of CNT, covering acute and chronic CNT. We reviewed original articles, landmark papers, and meta-analyses on CNT mitigation strategies, including CNI-sparing approaches.

Results: Preventive measures include co-medications, CNI exposure monitoring, and CNI sparing strategies, such as reducing target trough levels and converting to mTOR inhibitors (mTORi) or belatacept. Despite improvements in graft function, challenges persist in demonstrating significant differences in allograft survival with CNI-sparing regimens. The paradigm shift from chronic CNT as the main cause of chronic allograft nephropathy toward rather immunologic triggered injuries and/or comorbidities as relevant contributors to allograft deterioration over time must be kept in mind.

Conclusion: CNIs have significantly improved kidney transplant outcomes, but their associated nephrotoxicity necessitates mitigation strategies. The decision to implement such regimens is always an individual choice balancing against the risk of immunologic injuries. Further long-term studies are needed to optimize immunosuppressive approaches and refine CNT management.

Keywords: calcineurin inhibitor; kidney transplantation; toxicity.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Histopathology of CNT in human kidney biopsies from cyclosporine and tacrolimus‐based treatment regimens. (A, B) Interstitial fibrosis/tubular atrophy; note hyaline tubular casts in (A). (C–E) Arteriolar wall changes. Media hypertrophy and hyalinosis in Cyclosporine (C, D), luminal narrowing and perivascular inflammation in tacrolimus‐based treatment regimen (E). (F) Tubular vacuolization in proximal tubule. (G) Focal segmental glomerulosclerosis with focal adhesions to capsule. PAS staining (A–E, G), hematoxylin eosin (F); bars indicate magnification. Courtesy of Kerstin Amann, Marie‐Christine Heinrich.
See this image and copyright information in PMC

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