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

Kidney transplantation is the preferred choice for patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), owing to improvements in long-term survival and quality of life when compared with maintenance dialysis [1, 2]. However, the limited supply of high-quality deceased donor kidneys has long been unable to meet the rising demand for kidney transplantations [3, 4]. As a result, it has led to increased use of marginal kidneys, including kidneys with acute kidney injury (AKI) to expand the donor pool [5, 6].

AKI is a syndrome characterized by the rapid loss of renal excretory function and can be diagnosed by decreased urine output and/or the accumulation of end products of nitrogen metabolism [7, 8]. AKI is thought to be associated with CKD [9, 10] and is often considered a reversible functional renal impairment, which is mainly characterized by acute tubular necrosis (ATN) [8, 11]. Previous multicenter reviews based on deceased donor kidney transplant cohort studies have found that donors with AKI and other known risk factors are not associated with long-term all-cause graft failure [12, 13]. Nonetheless, debate has continued regarding the use of deceased donors with AKI. Several studies have reported worse clinical outcomes when deceased donor kidneys with AKI were used [14, 15]. When considering donors, AKI can activate body repair processes and initiate ischemic preconditioning, which can be beneficial for graft function repair in the recipient [4, 16], and the kidneys procured from pediatric deceased donors may have greater repair potential because the donors are younger, with fewer underlying disease or comorbidities [17, 18]. However, there are scant data and allocation practices on the results of pediatric AKI deceased donor kidney transplantation, and the reliability of pediatric donors with AKI remains controversial [17, 18]. Therefore, in this study, we aimed to evaluate the safety and effectiveness of early post-transplantation outcomes in pediatric deceased donors with AKI under various circumstances.

The presence of AKI in organ donors appears to impact the willingness to accept and transplant donor kidneys in China [25]. The incidence rate of AKI ranges from 25 to 52% within pediatric intensive care units [26, 27], and to augment the donor pool with systematic analysis of kidney transplants from pediatric donors with AKI, we found that although the incidence of DGF was higher in recipients of allografts with AKI, deceased donor AKI status itself did not affect death-censored graft and recipient survival. Patients with kidney transplants from a pediatric AKI donor had a superior recovery of allograft function. This result may help decrease the number of discarded pediatric AKI kidneys and utilize this donor pool to minimize waiting-list-related mortality.

AKI is usually secondary to prerenal factors (e.g., hypovolemia, cardiac insufficiency), neurohormonal mechanisms, rhabdomyolysis, or the use of nephrotoxic agents in critically ill patients [7, 11]. The cause of AKI has long been debated, and no specific therapies have emerged that can expedite recovery or attenuate AKI [7, 28]. AKI is often considered a reversible functional renal impairment and is mainly characterized by acute tubular necrosis (ATN) [3, 29].

The literature on AKI recovery patterns, according to the Acute Disease Quality Initiative (ADQI) definition, has found a high rate of early recovery and transient AKI. The cumulative incidence of renal recovery increased progressively from 25% on day 5 to 41% on day 10. However, up to 40% of patients with AKI do not recover by day 7, and 38% of AKI cases persistent beyond 7 days can be defined as acute kidney disease [30]. Some hypothesized that AKI and CKD may have interconnections [31] and can be weakened in the renal recipients’ internal environments, especially considering that kidneys procured from pediatric deceased donors may have greater repair potential because the donors are younger and have fewer underlying diseases or comorbidities, donor AKI can activate body repair processes and initiate ischemic preconditioning, and complete perioperative management can be beneficial for graft function repair in the recipient [4, 16].

Prior research on the utilization of pediatric deceased donors with AKI was limited. Jiang et al. [25] found that transplants procured from pediatric AKI donors have a comparable renal function and an excellent patient and graft survival rate, but they found a similar incidence of DGF, which is different from our study. In contrast, our study consists with another study includes very small (≤ 15 kg) pediatric donors with AKI and found that AKI can impact early post-transplant kidney graft function (e.g., the rate of DGF), but it did not increase the risk of early graft loss or decreased renal function in the long term [18]. A national study of pediatric KT recipients from a donor with AKI found that donor AKI status or increased peak and terminal creatinine levels do not affect the rate of DGF in pediatric KT recipients [17]. They also demonstrated that younger donors can be a protective factor for renal recovery, which is consistent with our finding that pediatric AKI donors have a superior recovery of allograft function.

In the adult cohort, the incidence of DGF was higher in recipients of allografts with AKI than in those without AKI (38.5% vs. 17.4%, p < 0.01) and tended to increase with the AKI stage, which is consistent with previous studies [6, 32]. Lui et al. [3] and Kwon et al. [33] reported that deceased donor AKI status did not affect death-censored graft survival and patient survival in an adult study cohort with a similar survival rates, and it can provide favorable graft functions for the later enginery, which is consistent with our study, but they did not analyze the trend of SCr postoperatively. In this study, we found that the downward trend in SCr was slower in the AKI group than in the non-AKI group, but after one year, there was no statistically significant difference in SCr levels between the two groups.

Denic et al. [34] analyzed both non-sclerotic glomeruli (NSG) and globally sclerotic glomeruli (GSG) using computed tomography scans and pathological biopsy before transplantation in living kidney donors and found that the number of NSG decreases with age, while GSG and the missing glomeruli increase with age, which is approximately proportional to the decline in GFR. In autopsy series [35, 36], the number of nephrons that decline with age is consistently evident. Considering that kidneys procured from pediatric deceased donors may have greater repair potential because the donors are younger with more NGS, fewer underlying diseases, or comorbidities [17, 18], and previous studies have demonstrated that younger donors can be a protective factor for renal recovery, even in pediatric AKI donors [17], pediatric AKI renal transplantation had a comparable clinical outcome and superior recovery of allograft function, tending to be superior to adult deceased donors with or without AKI. Therefore, the transplant community should obtain a new perspective on this type of organ pool and its potential use.

Our study has several strengths. This was a large-scale clinical cohort study. Previous research [18, 25] has been limited by less observation time or small sample sizes, particularly for the number of pediatric deceased donors with stage 2 and 3 AKI. Second, we confirmed our research by comparing early clinical outcomes between the pediatric and adult cohorts in detail. Several limitations of our study should be considered, including its retrospective, single-institution cohort nature, and within the period of this research there are very few death-censored graft loss or death events, so the censored data and selection bias were inevitable due to the evolution of the reliability and validity of the analysis process. Second, organ procurement decisions are multifactorial, but we have not analyzed the reason for the AKI-associated discard rate or many other factors involved in KT decisions. Third, the mean follow-up time of this study was 11.44 ± 1.68 months, and further prospective studies with long-term kidney allograft outcomes and larger study cohorts are required to strengthen this conclusion.

Kidney transplantation from deceased donors with AKI remains controversial. Prior research on the utilization of donors with pediatric AKI was limited. Compared with non-AKI pediatric donor kidneys, we found that AKI pediatric donor kidneys not only have similar excellent clinical outcomes but also show a comparable recovery speed, which indicates the superior recovery of allograft function of pediatric kidneys. However, in the adult cohort of our study, the downward trend in SCr level was substantially slower in the AKI group than that in the non-AKI group. However, at 1 year post-transplant, there was no statistically significant difference in the graft survival rate, patient survival, and AR between the adult AKI and non-AKI groups. The transplant community should utilize this donor pool, but further long-term prospective studies with larger cohorts are required to strengthen this conclusion. Our data showed that deceased donor AKI status had a negative effect on the DGF rate; it did not affect death-censored graft survival and recipient survival. Therefore, the transplant community should utilize this donor pool to minimize waiting-list-related mortalities. Future prospective studies with long-term kidney allograft outcomes and larger study cohorts are warranted if pediatric deceased donors with AKI are widely adopted.