Assessment of deceased-donor organ quality is integral to transplant allocation practices, but tools to more precisely measure donor kidney injury and better predict outcomes are needed. In this ...study, we assessed associations between injury biomarkers in deceased-donor urine and the following outcomes: donor AKI (stage 2 or greater), recipient delayed graft function (defined as dialysis in first week post-transplant), and recipient 6-month eGFR. We measured urinary concentrations of microalbumin, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) from 1304 deceased donors at organ procurement, among whom 112 (9%) had AKI. Each biomarker strongly associated with AKI in adjusted analyses. Among 2441 kidney transplant recipients, 31% experienced delayed graft function, and mean±SD 6-month eGFR was 55.7±23.5 ml/min per 1.73 m(2) In analyses adjusted for donor and recipient characteristics, higher donor urinary NGAL concentrations associated with recipient delayed graft function (highest versus lowest NGAL tertile relative risk, 1.21; 95% confidence interval, 1.02 to 1.43). Linear regression analyses of 6-month recipient renal function demonstrated that higher urinary NGAL and L-FABP concentrations associated with slightly lower 6-month eGFR only among recipients without delayed graft function. In summary, donor urine injury biomarkers strongly associate with donor AKI but provide limited value in predicting delayed graft function or early allograft function after transplant.
Kidneys with "high" Kidney Donor Profile Index (KDPI) are often biopsied and pumped, yet frequently discarded.
In this multicenter study, we describe the characteristics and outcomes of kidneys with ...KDPI of 80 or greater that were procured from 338 deceased donors. We excluded donors with anatomical kidney abnormalities.
Donors were categorized by the number of kidneys discarded: (1) none (n = 154, 46%), (2) 1 discarded and 1 transplanted (n = 48, 14%), (3) both discarded (n = 136, 40%). Donors in group 3 were older, more often white, and had higher terminal creatinine and KDPI than group 1 (all P < 0.05). Biopsy was performed in 92% of all kidneys, and 47% were pumped. Discard was associated with biopsy findings and first hour renal resistance. Kidney injury biomarker levels (neutrophil gelatinase-associated lipocalin, IL-18, and kidney injury molecule-1 measured from donor urine at procurement and from perfusate soon after pump perfusion) were not different between groups. There was no significant difference in 1-year estimated glomerular filtration rate or graft failure between groups 1 and 2 (41.5 ± 18 vs 41.4 ± 22 mL/min per 1.73 m; P = 0.97 and 9% vs 10%; P = 0.76).
Kidneys with KDPI of 80 or greater comprise the most resource consuming fraction of our donor kidney pool and have the highest rates of discard. Our data suggest that some discarded kidneys with KDPI of 80 or greater are viable; however, current tools and urine and perfusate biomarkers to identify these viable kidneys are not satisfactory. We need better methods to assess viability of kidneys with high KDPI.
Deceased donor kidneys with acute kidney injury (AKI) are often discarded due to fear of poor outcomes. We performed a multicenter study to determine associations of AKI (increasing ...admission‐to‐terminal serum creatinine by AKI Network stages) with kidney discard, delayed graft function (DGF) and 6‐month estimated glomerular filtration rate (eGFR). In 1632 donors, kidney discard risk increased for AKI stages 1, 2 and 3 (compared to no AKI) with adjusted relative risks of 1.28 (1.08–1.52), 1.82 (1.45–2.30) and 2.74 (2.0–3.75), respectively. Adjusted relative risk for DGF also increased by donor AKI stage: 1.27 (1.09–1.49), 1.70 (1.37–2.12) and 2.25 (1.74–2.91), respectively. Six‐month eGFR, however, was similar across AKI categories but was lower for recipients with DGF (48 interquartile range: 31–61 vs. 58 45–75 ml/min/1.73m2 for no DGF, p < 0.001). There was significant favorable interaction between donor AKI and DGF such that 6‐month eGFR was progressively better for DGF kidneys with increasing donor AKI (46 29–60, 49 32–64, 52 36–59 and 58 39–71 ml/min/1.73m2 for no AKI, stage 1, 2 and 3, respectively; interaction p = 0.05). Donor AKI is associated with kidney discard and DGF, but given acceptable 6‐month allograft function, clinicians should consider cautious expansion into this donor pool.
This multicenter cohort study shows that clinically defined acute kidney injury in deceased donors is associated with kidney discarding as well as delayed graft function, but that the transplanted kidneys tend to have acceptable 6‐month function.
The influence of deceased-donor AKI on post-transplant outcomes is poorly understood. The few published studies about deceased-donor preimplant biopsy have reported conflicting results regarding ...associations between AKI and recipient outcomes.
This multicenter study aimed to evaluate associations between deceased-donor biopsy reports of acute tubular necrosis (ATN) and delayed graft function (DGF), and secondarily for death-censored graft failure, first adjusting for the kidney donor risk index and then stratifying by donation after cardiac death (DCD) status.
Between March 2010 and April 2012, 651 kidneys (369 donors, 4 organ procurement organizations) were biopsied and subsequently transplanted, with ATN reported in 110 (17%). There were 262 recipients (40%) who experienced DGF and 38 (6%) who experienced graft failure. DGF occurred in 45% of kidneys with reported ATN compared with 39% without ATN (P=0.31) resulting in a relative risk (RR) of 1.13 (95% confidence interval 95% CI, 0.9 to 1.43) and a kidney donor risk index-adjusted RR of 1.11 (95% CI, 0.88 to 1.41). There was no significant difference in graft failure for kidneys with versus without ATN (8% versus 5%). In stratified analyses, the adjusted RR for DGF with ATN was 0.97 (95% CI, 0.7 to 1.34) for non-DCD kidneys and 1.59 (95% CI, 1.23 to 2.06) for DCD kidneys (P=0.02 for the interaction between ATN and DCD on the development of DGF).
Despite a modest association with DGF for DCD kidneys, this study reveals no significant associations overall between preimplant biopsy-reported ATN and the outcomes of DGF or graft failure. The potential benefit of more rigorous ATN reporting is unclear, but these findings provide little evidence to suggest that current ATN reports are useful for predicting graft outcomes or deciding to accept or reject allograft offers.
Kidney transplant from donors with hepatitis C virus (HCV) antibody has been limited to HCV viremic recipients only, due to concern of the HCV transmission. However, the new antiviral medications ...provide an opportunity to expand the utilization of these donors. To study the risk of HCV transmission in kidney transplantation, we used discarded donor kidneys and determined HCV RNA levels by quantitative real‐time PCR in bilateral (right and left) kidney biopsies and plasma from 14 HCV antibody‐positive donors (sensitivity: 15 international unit (IU)/mL plasma; 1.8 IU/50 nL kidney). In three NAT‐negative donors, HCV RNA was negative in plasma and kidney. In all 11 NAT‐positive donors, HCV RNA was positive in plasma (range: 5807‐19 134 177 IU/mL) but negative in six kidneys from four donors with plasma HCV RNA <1.5 million IU/μL. HCV RNA correlated between right and left kidneys (P = 0.75) and between kidney and plasma (r = 0.86). When normalized by volume, HCV RNA median (range) was 49 (0‐957) IU/50 nL plasma and 1.0 (0‐103) IU/50 nL kidney, significantly lower in kidney (P = 0.005) than in plasma (14‐fold). Plasma HCV RNA can be used to predict the kidney HCV load. Future studies are needed if plasma/kidney HCV levels can be used to stratify donors for transmission risk and recipients for post‐transplant management in extended utilization of HCV antibody‐positive donors.
Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multi‐center study was to determine the associations of the alpha and pi iso‐enzymes of ...glutathione S‐transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso‐enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha‐ and pi‐GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log‐unit increase in base and post pi‐GST were 1.14 (1.0–1.3) and 1.36 (1.1–1.8), respectively. Alpha‐GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We found pi‐GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions.
The authors show that kidney machine pump perfusate levels of the pi iso‐enzyme of glutathione S‐transferase are associated with delayed graft function but are no different between discarded and transplanted kidneys, whereas renal resistive indices are different and may be driving discard decisions.
West Nile virus (WNV) is the most common domestic arbovirus in the United States. During 2018, WNV was transmitted through solid organ transplantation to 2 recipients who had neuroinvasive disease ...develop. Because of increased illness and death in transplant recipients, organ procurement organizations should consider screening during region-specific WNV transmission months.
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