To the Editor: The shortage of deceased donor (DD) kidneys for transplantation remains a persistent concern. Despite the potential reversibility of acute kidney injury (AKI) lesions, kidneys from pediatric donors with AKI are often underutilized, especially in the context of pediatric transplantation. By implementing single kidney transplantation (SKT) from pediatric donors to pediatric recipients (PTP), we can optimize the utilization of available kidneys and increase the number of pediatric recipients. Previous studies have demonstrated promising outcomes of the transplantation of kidneys from donors with AKI in various scenarios, including adult donor to adult recipient (ATA) transplants, adult donor to pediatric recipient (ATP) transplants, and pediatric donor to adult recipient (PTA) transplants.[1,2] Thus, we designed this study to assess whether pediatric recipients who received single AKI kidneys from pediatric donors could achieve outcomes comparable to those of other PTP patients. This study was approved by the ethics committee of The First Affiliated Hospital, Sun Yat-sen University (No. 2022-162). All organs included in the study were recovered with prior informed consent and approval for organ donation from the respective organ procurement organizations. The entire study adhered to the ethical standards outlined in the Declaration of Helsinki 2000 and the Declaration of Istanbul 2018. This study included all pediatric recipients (<18 years old) who underwent SKT using kidneys from pediatric DDs at the Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, during the period from January 2012 to December 2020. Patients who had undergone en bloc kidney transplantation or multi-organ transplantation or were followed up for less than 90 days post-transplantation were excluded from the study. The diagnosis and staging of AKI in the donor were determined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria.[3] This included an increase in serum creatinine (SCr) levels of 0.3 mg/dL or more within 48 h, an increase in SCr to ≥1.5 times the baseline value within seven days, or a urine output rate less than 0.5 mL·kg−1·h−1 for six hours. The baseline SCr level was defined as the lowest SCr recorded during hospitalization or was based on the age- and sex-standardized SCr reference value for the Chinese population. Urine output was not considered due to the lack of data. The process used to recover the pediatric donor kidneys, the back-table preparation method, and the transplant procedures were described in a previous study.[4]En bloc kidney transplantation was exclusively considered for donors with a body weight less than 5 kg. Graft loss was defined as the irreversible failure of the transplanted kidney, indicated by the need for long-term dialysis, addition to the list for a subsequent kidney transplant, or retransplantation. The outcomes of interest included death-censored graft survival (DCGS), patient mortality, the occurrence of primary non-function (PNF) and delayed graft function (DGF), graft function, biopsy-proven acute rejection (BPAR), vascular complications, and pulmonary infection. Baseline characteristics are presented as the means and standard deviations for normally distributed data, medians and ranges for skewed data, or numbers and percentages for categorical data. Comparisons of continuous variables were performed with t-tests or Mann–Whitney U tests, as appropriate. For categorical variables, the χ2 test or Fisher's exact test was employed as appropriate. Kaplan–Meier curves and the log-rank test were used to assess DCGS and the cumulative incidence of complications. All analyses were performed using STATA 15.0 (College Station, TX, USA). A P value <0.05 denoted significance. This study included 197 pediatric kidney transplants from 139 DDs, and 58 (41.7%) of the donors had AKI. Among the cohort, 85 (43.1%) patients received kidneys from donors with AKI in various terminal AKI stages: stage 1 (35, 17.8%), stage 2 (33, 16.8%), and stage 3 (17, 8.6%). None of the donors needed dialysis during the course of AKI. Table 1 presents the donor and recipient characteristics. Donors with AKI had a lower terminal median estimated glomerular filtration rate (eGFR) (61.4 mL·min−1·1.73 m−2vs. 130.5 mL·min−1·1.73 m−2, P <0.001) than those without AKI. Male and donor/recipient sex-matched recipients were relatively more common in the AKI group. No other significant differences in donor or recipient characteristics were noted between the two groups. Table 1 - Clinical characteristics of SKT donors and recipients. Variables Overall Non-AKI AKI P value Donors n 139 81 58 – Age (months) 30.7 (12.0, 78.2) 30.7 (12.0, 78.0) 30.1 (12.0, 79.0) 0.680 Gender Male 81 (58.3) 46 (56.8) 35 (60.3) 0.675 Female 58 (41.7) 35 (43.2) 23 (39.7) Height (cm) 90 (76.0, 120.0) 90 (76.5, 120.0) 89 (75.0, 120.9) 0.964 Body weight (kg) 12.5 (10.0, 20.0) 13.0 (10.0, 20.0) 12.0 (9.9, 20.3) 0.652 eGFR (mL·min–1·1.73m–2) 106.5 (64.1, 170.3) 130.5 (102.1, 194.7) 61.4 (40.2, 84.4) <0.001 Donor type DBD 97 (69.8) 58 (71.6) 39 (67.2) 0.581 DCD* 42 (30.2) 23 (28.4) 19 (32.8) CIT (h) 10.0 (7.5, 14.0) 10.0 (7.8, 14.0) 9.5 (7.0, 14.1) 0.718 Recipient n 197 112 85 – Age at Tx (years) 10.5 ± 4.0 10.2 ± 3.9 10.8 ± 4.1 0.335 Gender Male 95 (48.2) 45 (40.2) 50 (58.8) 0.009 Female 102 (51.8) 67 (59.8) 35 (41.2) Height (cm) 130.0 ± 23.4 128.6 ± 22.6 131.8 ± 24.3 0.342 Body weight (kg) 27.6 ± 11.8 26.7 ± 10.9 28.7 ± 12.9 0.256 Prior Tx 12 (6.1) 7 (6.3) 5 (5.9) 0.915 HLA mismatch 5 (4, 6) 5 (4, 6) 5 (5, 6) 0.197 Pre-Tx PRA ≥10% 7 (3.6) 5 (4.5) 2 (2.4) 0.701 Sex-matched 99 (50.3) 46 (41.1) 53 (62.4) 0.003 Follow-up time (months) 44.8 (35.8, 57.8) 44.7 (36.2, 53.0) 45.6 (35.1, 63.1) 0.415 Data were presented as median (IQR), n (%), or mean ± standard deviation. *Including 8 (5.8%), 5 (6.2%), and 3 (5.2%) DBCD, respectively. AKI: Acute kidney injury; CIT: Cold ischemia time; DBCD: Donation after brain death followed by circulatory death; DBD: Donation after brain death; DCD: Donation after circulatory death; eGFR: Estimated glomerular filtration rate; HLA: Human leukocyte antigen; IQR: Interquartile range; PRA: Panel reactive antibody; SKT: Single kidney transplantation SKT; Tx: Transplant; –: Not applicable. During a median follow-up of 3.7 years, there were 24 graft losses (12 in each group). In the AKI group, two deaths occurred due to pulmonary infection and respiratory failure at nine months and 14 months post-transplant, respectively. The one-year DCGS rates were 92.9% (AKI group) and 94.6% (non-AKI group), while the three-year rates were 87.7% and 90.8%, respectively (log-rank test, P = 0.493). Additionally, the three-year DCGS rates (85.2%, 87.5%, and 94.1% for AKI stages 1–3, respectively) were not significantly different (log-rank test, P = 0.691). No PNF was observed in either group. DGF occurred in 20.0% of the patients in the AKI group, compared to 11.6% in the non-AKI group (P = 0.104). The DGF rates were 20.0%, 15.2%, and 29.4% for patients with transplants from donors with AKI stages 1–3, respectively (P = 0.467). Renal allograft function, assessed by SCr and eGFR, was not significantly different between the AKI and non-AKI groups at one month (median eGFR: 59.1 mL·min−1·1.73 m−2 [AKI] vs. 63.1 mL·min−1·1.73 m−2 [non-AKI], P = 0.117) and three years post-transplant (median eGFR: 83.6 mL·min−1·1.73 m−2 [AKI] vs. 86.4 mL·min−1·1.73 m−2 [non-AKI], P = 0.653). The median three-year eGFR for recipients in the AKI group was 86.3, 92.2, and 64.6 mL·min−1·1.73 m−2 (P = 0.193) for those receiving transplants from donors with AKI stages 1–3, respectively. Neither the incidence (12.9% [AKI] vs. 9.8% [non-AKI], P = 0.491) nor the timing (log-rank test, P = 0.458) of BPAR onset was significantly different between the two groups during the three years of follow-up. Additionally, the incidence of BPAR also did not significantly differ among patients who received transplants from donors with different stages of AKI (14.3% vs. 12.1% vs. 11.8% in the groups who received transplants from donors with AKI stages 1–3, respectively, P = 0.953). However, more than half of the BPAR cases occurred within six months post-transplant in the AKI group, unlike in the non-AKI group (7/11, 63.6% vs. 3/11, 27.3%). No significant difference was observed between the AKI and non-AKI groups in terms of the incidence (3.5% [AKI] vs. 3.6% [non-AKI], P = 0.837) or timing (log-rank test, P = 0.458) of vascular thrombotic events. The rates of artery stenosis (4.7% [AKI] vs. 3.6% [non-AKI], P = 0.728) and pulmonary infection (22.4% [AKI] vs. 13.4% [non-AKI], P = 0.099) were not significantly different between the two groups. Due to the national "pediatric to pediatric" matching policy, there has been a significant increase in pediatric kidney transplants in China.[5] Many potential pediatric DDs are admitted to pediatric intensive care units, where the incidence of AKI is reported to be as high as 25–39%. Organs from these pediatric DDs are prioritized for transplantation to pediatric recipients. Thus, it is crucial to evaluate the outcomes in recipients of organs from pediatric donors with AKI in the PTP transplant cohort, particularly considering whether the results are as satisfactory as those in the ATA, ATP, and PTA cohorts. In this retrospective longitudinal cohort study with a median follow-up of approximately four years, we found that utilizing pediatric AKI donor kidneys did not result in reduced short-term DCGS in pediatric kidney transplant recipients. Both groups demonstrated satisfactory renal allograft function, except for cases of early graft loss. However, due to the limitations of the retrospective study design, potential unmeasured confounding factors and selection bias toward low-risk AKI donor kidneys should be considered. In summary, this study demonstrates that the transplantation of single kidneys from pediatric AKI donors yields comparable outcomes to the transplantation of those from non-AKI pediatric donors when PTP transplantation is performed. The results support the use of organs from pediatric donors with AKI as a viable option for pediatric SKT. Further research and larger prospective studies are needed to validate these findings and provide a more comprehensive understanding of the outcomes associated with the use of kidneys from pediatric donors with AKI in the PTP transplant cohort. Acknowledgments We thank the study participants, as well as the medical team – especially Mingchuan Huang, Wenrui Wu, Liuting Ling, Mengling Chen, Jinghong Tan, Jianyi Li, Jianming Li, and Zebin Lin – at Organ Transplant Center and Department of Pediatric Surgery, The First Affiliated Hospital, Sun Yat-sen University, for their dedication to this study. Funding This work was supported by funding from the National Natural Science Foundation of China (Nos. 81870511, 82170770, and 82200848), Natural Science Foundation of Guangdong Province (No. 2023A1515010139), Science and Technology Planning Project of Guangzhou City (No. 202201011318), Key Clinical Technique of Guangzhou (No. 2023P-ZD15), Elite Talent Project of Guangdong Province (No. R09002), Guangdong Basic and Applied Basic Research Foundation (No. 2020A1515010884), Guangdong Provincial Key Laboratory on Organ Donation and Transplant Immunology (No. 2020B1212060026), Guangdong Provincial International Cooperation Base of Science and Technology (No. 2020A0505020003), and Science Research Cultivation Program of Stomatological Hospital, Southern Medical University (No. PY2021026).
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