Excellent clinical outcomes of renal transplant from pediatric deceased donors with acute kidney injury

Patient cohort and clinical data

This was a retrospective, single-center cohort study of patients who received deceased donor kidney transplants between January 2018 and December 2020. All study data were obtained from the China Scientific Registry of Kidney Transplantation (CSRKT) and the China Organ Transplant Response System (COTRS). The study was performed in accordance with the Declaration of Helsinki, Istanbul declaration standards, and the principles of Good Clinical Practice. All cases of organ donation and transplantation met the Chinese standards for human organ donation [19]. The study procedures were reviewed and approved by the Ethics Committee of the Second Xiangya Hospital of the Central South University.

All recipients were divided into four groups according to donor age (pediatric, < 18 years; adult, ≥ 18 years) and donor AKI status (with or without AKI). AKI was defined using the Kidney Disease: Improving Global Outcomes (KIDGO) criteria [20, 21]: an increase in SCr of 0.3 mg/dL (divided by 88.4 µmol/L to convert SCr level to micromoles per liter) within 48 h or an increase in SCr level to 1.5 times the baseline within the prior 7 days, irrespective of the urine output, as it was not available in the data set. AKI stage was defined using the KDIGO SCr level criteria as follows [20]: stage 1 (0.3 mg/dL or 50% increase from admission to the terminal SCr level), stage 2 (100% increase from admission to the terminal SCr level), and stage 3 (> 4.0 mg/dL or 200% increase from admission to the terminal SCr level), irrespective of urine output or dialysis initiation, as these data were not available. The exclusion criteria were ABO incompatibility, re-transplant recipients, or patients who underwent double kidney transplantation (including en-bloc or separate double kidney transplants).

All recipients received mycophenolate mofetil (MMF; 1 g) and intravenous methylprednisolone (500 mg) before transplantation. Basiliximab (more in non-AKI group) or antithymocyte globulin was used as induction therapy, and tacrolimus, MMF, and methylprednisolone were administered after kidney transplantation. The minimum concentration of tacrolimus was maintained at 7–10 ng/mL during the first 3 months and at 6–8 ng/mL during the first year post-transplantation. MMF was administered at an oral dose of 0.75 g twice daily, and the MMF area under the curve was maintained at 30–60 mg·h/L. Following intravenous methylprednisolone (1.5 g), oral methylprednisolone was administered at an initial dose of 64 mg/day, which was reduced to 8 mg/day and was eventually maintained at 4–8 mg/day.

We collected the baseline data of the donors, including age, sex, body mass index (BMI), history of diabetes, hypertension, cause of death, SCr level, and estimated glomerular filtration rate (eGFR) at admission and before procurement. We also collected the following baseline data of the recipients: age, sex, BMI, history of diabetes and hypertension, cause of ESRD, duration of dialysis, cold ischemia time (CIT), warm ischemia time (WIT), panel-reactive antibody (PRA) ≥ 20%, number of human leukocyte antigen (HLA) mismatches, induction therapy, and clinical outcomes. pre-transplant biopsy is not regularly performed for all AKI donor kidneys in our center. It is only being done as a last resort when the preoperative assessment of the deceased-donor kidney including surgeon appraisal, clinical parameters, and machine perfusion characteristics can not be determinative.

Clinical outcomes and statistical analysis

The primary endpoints of this study were patient and allograft survival and renal function at different time points (1 week, 1 month, 6 months, and 1 year after kidney transplant [KT]). The secondary endpoints included the development of DGF, which was defined as a serum creatinine ≥ 400 µmol/L or required dialysis in the first week after KT [3, 22]. In addition, we compared allograft outcomes, including DGF, acute rejection, renal function, and patient and graft survival rates between the AKI and non-AKI groups and the pediatric and adult groups. The Chronic Kidney Disease Epidemiology Collaboration equation or Modified Schwartz formula (for pediatric) was used to calculate the eGFR [23, 24].

Continuous variables are presented as median (interquartile range [IQR]) or the mean ± SD and were compared using the Mann–Whitney U test/Kruskal–Wallis H test (for non-normally distributed variables) or Student’s t-test. Frequencies (percentages) were used for categorical data and were compared using chi-square tests or Fisher's exact test. Graft survival was estimated using the Kaplan–Meier method and compared among groups using the log-rank test. Logistic regression analysis was performed to predicting DGF. Cox proportional hazard regression analysis of risk factors for death-censored graft survival and patient survival. The multivariate analysis included variables that were statistically significant (p < 0.05) in Univariate Analysis and other clinically significant factors. For the inference testing, a two-sided p-value < 0.05 was considered statistically significant. Analyses were conducted using SPSS, version 26.0 (IBM Corp, Armonk, NY, USA).

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