Balancing Immunosuppression and Graft Preservation: Calcineurin Inhibitor Nephrotoxicity in Kidney Transplant Recipients

Abstract

Background: Immunosuppressive therapy after kidney transplantation is essential and a widely-used component is the use of calcineurin inhibitors (CNIs), such as tacrolimus and cyclosporine. While very effective for acute rejection prevention, chronic use of CNI can cause nephrotoxicity that can lead to chronic allograft dysfunction and loss of graft. To maximize the chances for a successful transplant, early diagnosis and treatment are important.

Objective: To Determine the incidence of calcineurin inhibitor nephrotoxicity, risk factors for it and its effect on graft function in kidney transplant recipients.

Methodology: A prospective study was conducted at Begum Akhtar Rukhsana Memorial Trust and Hospital, Rawalpindi, from June 2022 to November 2022. Fifty kidney transplant recipients receiving tacrolimus- or cyclosporine-based immunosuppressive therapy were enrolled. Demographic characteristics, clinical parameters, serum creatinine, estimated glomerular filtration rate (eGFR), calcineurin inhibitor trough levels, biopsy findings, and graft outcomes were recorded prospectively. Calcineurin inhibitor nephrotoxicity was diagnosed using clinical, laboratory, and histopathological criteria. Data were analyzed using SPSS version 26, and a p-value <0.05 was considered statistically significant.

Results: A total of 50 kidney transplant recipients were included in the analysis. The mean age of participants was 43.2 ± 11.4 years, and 33 (66.0%) were male. Calcineurin inhibitor nephrotoxicity was identified in 12 (24.0%) patients, while 38 (76.0%) had stable graft function without evidence of toxicity. Patients with nephrotoxicity were significantly older than those without nephrotoxicity (46.8 ± 10.2 versus 42.1 ± 11.7 years; p=0.041). Elevated calcineurin inhibitor trough levels were present in 8 (66.7%) affected patients compared with 8 (21.1%) unaffected recipients (p<0.001). Hypertension and diabetes mellitus were significantly more common among patients with nephrotoxicity. Mean eGFR was significantly lower among affected patients (43.5 ± 12.1 vs. 58.8 ± 13.9 mL/min/1.73 m²; p<0.001). Proteinuria was observed in 6 (50.0%) patients with nephrotoxicity and 7 (18.4%) patients without toxicity (p=0.001).

Conclusion: An important side effect of the kidney transplantation is the so called calcineurin inhibitor nephrotoxicity, which is positive with reduced graft function. To maintain long term allograft outcomes, it is important to schedule and receive therapeutic drug monitoring and tailored immunosuppressive therapy.