3. Chronic Kidney Disease after Vascularized Composite Allotransplantation

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Introduction: Chronic kidney disease (CKD) is a significant complication in nonrenal transplant recipients (NRT), including vascularized composite allotransplantation (VCA) recipients who require lifelong immunosuppression. This study investigated renal function in an international cohort of VCA patients from 17 centers over a follow-up period of 1-10 years (median: 8 years). Methods: The study included 70 patients: 59 recipients of upper extremity allotransplantation (UET: 38 bilateral, 14 right and 7 left cases), 10 recipients of face and 1 of penis transplantation. Demographic data, immunosuppressive regimens, and serum creatinine values were collected pre- and post-transplantation to calculate eGFR using CKD-EPI 2021. Key outcomes included a ≥50% eGFR decline at consecutive follow-up points, eGFR <29 ml/min, and end-stage kidney disease (ESKD: dialysis or kidney transplantation). Results: Transplanted patients generally had few comorbidities before VCA transplantation, as illustrated in Table 1, presenting patient characteristics. Before transplantation, the median estimated glomerular filtration rate (eGFR) was 105.36 ml/min (range: 71.09–155.39), with 83% of patients classified as chronic kidney disease (CKD) stage 1 and 17% as stage 2. At three months post-transplantation, eGFR significantly declined (median: 78.42 ml/min, p=0.001). However, renal function stabilized thereafter, as illustrated in Figure 1, which depicts the trajectory of renal function both before transplantation and during follow-up in patients who experienced an initial decline in renal function in the early post-transplant period. Despite higher tacrolimus levels at 3 months, no correlation was found between its levels and eGFR at any time. Over the follow-up, 17.1% of patients experienced a ≥50% eGFR decline, 6.3% progressed to CKD stage 4, and 4.5% developed ESKD. All ESKD cases occurred in UET recipients. The current study’s limited sample size, comprising only 3 cases of end-stage kidney disease (ESKD) and 4 cases of CKD stage 4, unequivocally hindered our ability to demonstrate a significant correlation in a multivariate mixed model between the incidence of ESKD or a decline in eGFR of at least 50% and any risk factors. Conclusions: Renal function decline is evident in VCA recipients, but the incidence of severe outcomes, including ESKD, is lower compared to NRT recipients. While calcineurin inhibitors, particularly tacrolimus, are known to be nephrotoxic, this study could not establish a direct correlation between tacrolimus exposure and renal decline due to limited sample size and therapeutic regimen changes. Strategies to minimize calcineurin inhibitor exposure, especially early post-transplant, are recommended for preserving long-term renal function. Table 1 - Characteristics of the transplant recipients before transplantation Characteristic VCA recipientsn=70 Upper Extremityn=59 Face Txn=10 Urogenital tract Txn=1 Median Age (min-max) years 34 (19-69) 34 (21-69) 38 (19-59) 33 Gender (M/F) 58/12 49/10 8/2 1/0 Median BMI (min-max) 24.5 (15-68) 24.4 (15.5-68.5) 21.0 (18.4-30.0) 25.0 Hypertension 5 4 0 1 Diabetes 2 2 0 0 Smoking 9 6 3 0 History of acute renal failure 4 4 0 0 History of urinary tract infection 1 1 0 0 History of gout 2 1 1 0 History of kidney stone 3 3 0 0 Chronic use of NSAIDs 4 4 0 0 Figure 1.: Trajectory of renal function in patients who experienced eGFR below 60 ml/min

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