Associations between Deceased-Donor Urine MCP-1 and Kidney Transplant Outcomes.
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ABSTRACT: Introduction
Existing methods to predict recipient allograft function during deceased-donor kidney procurement are imprecise. Understanding the potential renal reparative role for monocyte chemoattractant protein-1 (MCP-1), a cytokine involved in macrophage recruitment after injury, might help predict allograft outcomes.Methods
We conducted a sub-study of the multicenter prospective Deceased Donor Study cohort, which evaluated deceased kidney donors from five organ procurement organizations from May 2010 to December 2013. We measured urine MCP-1 (uMCP-1) concentrations from donor samples collected at nephrectomy to determine associations with donor acute kidney injury (AKI), recipient delayed graft function (DGF), 6-month estimated GFR (eGFR), and graft failure. We also assessed perfusate MCP-1 concentrations from pumped kidneys for associations with DGF and 6-month eGFR.Results
AKI occurred in 111 (9%) donors. Median (interquartile range) uMCP-1 concentration was higher in donors with AKI compared to donors without AKI (1.35 [0.41-3.93] ng/ml vs. 0.32 [0.11-0.80] ng/ml, p<0.001). DGF occurred in 756 (31%) recipients, but uMCP-1 was not independently associated with DGF. Higher donor uMCP-1 concentrations were independently associated with higher 6-month eGFR in those without DGF [0.77 (0.10, 1.45) ml/min/1.73m2 per doubling of uMCP1]. However, there were no independent associations between uMCP-1 and graft failure over a median follow-up of about 2 years. Lastly, perfusate MCP-1 concentrations significantly increased during pump perfusion but were not associated with DGF or 6-month eGFR.Conclusion
Donor uMCP-1 concentrations were modestly associated with higher recipient 6-month eGFR in those without DGF. However, the results suggest that donor uMCP-1 has minimal clinical utility given no associations with graft failure.
SUBMITTER: Mansour SG
PROVIDER: S-EPMC5512592 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
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Project description:ImportanceIn the United States, substantial disparities in access to kidney transplant exist for wait-listed candidates with end-stage renal disease. The implications of transplant centers' willingness to accept kidney offers for access to transplant and mortality outcomes are unknown.ObjectiveTo determine the outcomes for wait-listed kidney transplant candidates after the transplant center's refusal of a deceased donor kidney offer.Design, setting, and participantsThis cohort study obtained data from the United Network for Organ Sharing Potential Transplant Recipient data set on all deceased donor kidney offers in the United States made between January 1, 2008, and December 31, 2015. The final study cohort included adult patients who were wait-listed for kidney transplant and received at least 1 allograft offer during the study period (N?=?280?041). Data analysis was conducted from June 1, 2018, to March 30, 2019.ExposureCandidate state of residence.Main outcomes and measuresWaiting list outcome event groups included received deceased donor allograft, received living donor allograft, died while on the waiting list, removed from the waiting list without a transplant, or still on the waiting list at the end of follow-up.ResultsAmong the 280?041 kidney transplant candidates included in the study, the mean (SD) age at wait-listing was 51.1 (13.1) years, and male patients were predominant (171 517 [61.2%]). In this cohort, 81 750 candidates (29.2%) received a deceased donor kidney allograft, 30 870 (11.0%) received a living donor allograft, 25 967 (9.3%) died while on the waiting list, and 59 359 (21.2%) were removed from the waiting list. Overall, 10 candidates with at least 1 previous allograft offer died each day during the study period. Time to first offer was similar for candidates who received deceased donor kidney allograft compared with those who died while waiting (median [interquartile range {IQR}] time, 79 [16-426] days vs 78 [17-401] days, respectively). Deceased donor allograft recipients had a median of 17 offers (IQR, 6-44) over 422 days (IQR, 106-909 days), whereas candidates who died while waiting received a median of 16 offers (IQR, 6-41) over 651 days (IQR, 304-1117 days). Most kidneys (84%) were declined on behalf of at least 1 candidate before being accepted for transplant. As reported by centers, organ or donor quality concerns accounted for 8 416 474 (92.6%) of all declined offers, whereas offers were infrequently refused because of patient-related factors (232 193 [2.6%]), logistical limitations (49 492 [0.5%]), or other concerns. The odds of death after an offer and the median number of offers received prior to death varied considerably by state.Conclusions and relevanceThis study found that transplant candidates appeared to receive a large number of viable deceased donor kidney offers that were refused on their behalf by transplant centers, potentially exacerbating the detrimental consequences of the organ shortage; increased transparency in organ allocation process and decisions may improve patient-centered care and access to kidney transplant.
| S-EPMC6724162 | biostudies-literature
Project description:BackgroundAccurate and reliable assessment of kidney quality before transplantation is needed to predict recipient outcomes and to optimize management and allocation of the allograft. The aim of this study was to systematically review the published literature on biomarkers in two mediums (the perfusate from deceased-donor kidneys receiving machine perfusion and deceased-donor urine) that were evaluated for their possible association with outcomes after kidney transplantation.MethodsWe searched the Ovid Medline and Scopus databases using broad keywords related to deceased-donor biomarkers in kidney transplantation (limited to humans and the English language). Studies were included if they involved deceased-donor kidneys, measured perfusate or urine biomarkers and studied a possible relationship between biomarker concentrations and kidney allograft outcomes. Each included article was assessed for methodological quality.ResultsOf 1430 abstracts screened, 29 studies met the inclusion criteria. Of these, 23 were studies of perfusate (16 biomarkers examined) and 6 were studies of urine (18 biomarkers examined). Only 3 studies (two perfusate) met the criteria of 'good' quality and only 12 were published since 2000. Perfusate lactate dehydrogenase, glutathione-S-transferase (GST) and aspartate transaminase were all found to be significantly associated with delayed graft function in a majority of their respective studies (6/9, 4/6 and 2/2 studies, respectively). Urine neutrophil gelatinase-associated lipocalin, GST, Trolox-equivalent antioxidant capacity and kidney injury molecule-1 were found to be significantly associated with allograft outcomes in single studies that examined diverse end points.ConclusionHigher quality studies are needed to investigate modern kidney injury biomarkers, to validate novel biomarkers in larger donor populations and to determine the incremental predictive value of biomarkers over traditional clinical variables.
| S-EPMC3716303 | biostudies-literature
Project description:Background and objectivesIn kidney transplantation, the relative contribution of donor versus other factors on clinical outcomes is unknown. We sought to quantify overall donor effects on transplant outcomes for kidney donations from deceased donors.Design, setting, participants, & measurementsFor paired donations from deceased donors resulting in transplants to different recipients, the magnitude of donor effects can be quantified by examining the excess of concordant outcomes within kidney pairs beyond chance concordance. Using data from the Organ Procurement and Transplantation Network between the years 2013 and 2017, we examined concordance measures for delayed graft function, death-censored 1-year graft failure, and death-censored 3-year graft failure. The concordance measures were excess relative risk, excess absolute risk, and the fixation index (where zero is no concordance and one is perfect concordance). We further examined concordance in strata of kidneys with similar values of the Kidney Donor Profile Index, a common metric of organ quality.ResultsIf the transplant of the kidney mate resulted in delayed graft function, risk for delayed graft function was 19% higher (95% confidence interval [95% CI], 18% to 20%), or 1.76-fold higher (95% CI, 1.73- to 1.80-fold), than baseline. If a kidney graft failed within 1 year, then the kidney mate's risk of failure was 6% higher (95% CI, 4% to 9%), or 2.85-fold higher (95% CI, 2.25- to 3.48-fold), than baseline. For 3-year graft failure, the excess absolute risk was 7% (95% CI, 4% to 10%) but excess relative risk was smaller, 1.91-fold (95% CI, 1.56- to 2.28-fold). Fixation indices were 0.25 for delayed graft function (95% CI, 0.24 to 0.27), 0.07 for 1-year graft failure (95% CI, 0.04 to 0.09), and 0.07 for 3-year graft failure (95% CI, 0.04 to 0.10). Results were similar in strata of kidneys with a similar Kidney Donor Profile Index.ConclusionsOverall results indicated that the donor constitution has small or moderate effect on post-transplant clinical outcomes.
| S-EPMC6895487 | biostudies-literature
Project description:Background and objectivesData reported to the Organ Procurement and Transplantation Network (OPTN) are used in kidney transplant research, policy development, and assessment of center quality, but the accuracy of early post-transplant outcome measures is unknown.Design, setting, participants, & measurementsThe Deceased Donor Study (DDS) is a prospective cohort study at five transplant centers. Research coordinators manually abstracted data from electronic records for 557 adults who underwent deceased donor kidney transplantation between April of 2010 and November of 2013. We compared the post-transplant outcomes of delayed graft function (DGF; defined as dialysis in the first post-transplant week), acute rejection, and post-transplant serum creatinine reported to the OPTN with data collected for the DDS.ResultsMedian kidney donor risk index was 1.22 (interquartile range [IQR], 0.97-1.53). Median recipient age was 55 (IQR, 46-63) years old, 63% were men, and 47% were black; 93% had received dialysis before transplant. Using DDS data as the gold standard, we found that pretransplant dialysis was not reported to the OPTN in only 11 (2%) instances. DGF in OPTN data had a sensitivity of 89% (95% confidence interval [95% CI], 84% to 93%) and specificity of 98% (95% CI, 96% to 99%). Surprisingly, the OPTN data accurately identified acute allograft rejection in only 20 of 47 instances (n=488; sensitivity of 43%; 95% CI, 17% to 73%). Across participating centers, sensitivity of acute rejection varied widely from 23% to 100%, whereas specificity was uniformly high (92%-100%). Six-month serum creatinine values in DDS and OPTN data had high concordance (n=490; Lin concordance correlation =0.90; 95% CI, 0.88 to 0.92).ConclusionsOPTN outcomes for recipients of deceased donor kidney transplants have high validity for DGF and 6-month allograft function but lack sensitivity in detecting rejection. Future studies using OPTN data may consider focusing on allograft function at 6 months as a useful outcome.
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Project description:BackgroundDeceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes.MethodsPrimary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages.ResultsDoubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted β coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF.ConclusionsUMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation.
| S-EPMC8805736 | biostudies-literature
Project description:BackgroundAfrican American (AA) recipients of deceased-donor (DD) kidney transplants (KT) have shorter allograft survival than recipients of other ethnic groups. Reasons for this disparity encompass complex interactions between donors and recipients characteristics.MethodsOutcomes from 3872 AA and 19,719 European American (EA) DDs who had one kidney transplanted in an AA recipient and one in an EA recipient were analyzed. Four donor/recipient pair groups (DRP) were studied, AA/AA, AA/EA, EA/AA, and EA/EA. Survival random forests and Cox proportional hazard models were fitted to rank and evaluate modifying effects of DRP on variables associated with allograft survival. These analyses sought to identify factors contributing to the observed disparities in transplant outcomes among AA and EA DDKT recipients.ResultsTransplant era, discharge serum creatinine, delayed graft function, and DRP were among the top predictors of allograft survival and mortality among DDKT recipients. Interaction effects between DRP with the kidney donor risk index and transplant era showed significant improvement in allograft survival over time in EA recipients. However, AA recipients appeared to have similar or poorer outcomes for DDKT performed after 2010 versus before 2001; allograft survival hazard ratios (95% CI) were 1.15 (0.74, 1.76) and 1.07 (0.8, 1.45) for AA/AA and EA/AA, compared to 0.62 (0.54, 0.71) and 0.5 (0.41, 0.62) for EA/EA and AA/EA DRP, respectively. Recipient mortality improved over time among all DRP, except unemployed AA/AAs. Relative to DDKT performed pre-2001, employed AA/AAs had HR = 0.37 (0.2, 0.69) versus 0.59 (0.31, 1.11) for unemployed AA/AA after 2010.ConclusionRelative to DDKT performed before 2001, similar or worse overall DCAS was observed among AA/AAs, while EA/EAs experienced considerable improvement regardless of employment status, KDRI, and EPTS. AA recipients of an AA DDKT, especially if unemployed, had worse allograft survival and mortality and did not appear to benefit from advances in care over the past 20 years.
| S-EPMC8722061 | biostudies-literature
Project description:Kidney transplantation is regarded as the best treatment option for patients with end-stage renal disease. However, living-donor recipients (LDRs) and deceased-donor recipients (DDRs) still face challenges in transplant-specific emotional adjustment post-transplantation. Research distinguishing emotional adjustment between transplant groups has been limited to Western settings, with little attention given to Asian populations. As such, documenting and comparing the emotional adjustment of LDRs and DDRs in an ethnically diverse Asian setting in Singapore and identifying factors associated with emotional adjustment are of interest. Methods:One hundred eighty-two kidney transplant patients (106 LDRs and 76 DDRs) completed measures of generic distress (Depression, Anxiety, Stress Scale-21) and transplantation-specific emotional and behavioral outcomes (Transplant Effects Questionnaire). Results:LDRs were significantly younger (P = 0.019) and had higher education levels (P = 0.007), higher personal income (P < 0.001), shorter dialysis vintage (P < .001), and higher estimated glomerular filtration rates (eGFRs) (P = 0.002) compared with DDRs. Generic symptoms of depression and stress were very low; however, 29.2% of LDRs and 19.7% of DDRs experienced moderate to severe symptoms of anxiety. Similarly, 83.0% of LDRs and 72.4% of DDRs reported high levels of transplant-specific worry. Multivariate models showed younger patients expressing greater generic distress, and transplant-specific worry (P < 0.01), despite higher eGFRs (P < 0.05). ANCOVA controlling for casemix differences showed that LDRs experienced higher feelings of guilt (P = 0.004) and greater willingness to disclosure (P = 0.041). Conclusions:Clinicians should be vigilant of younger kidney transplant patients who have greater risk of poorer emotional adjustment. Future interventions should target alleviating anxiety and transplant-specific worry.
| S-EPMC7004627 | biostudies-literature
Project description:BackgroundThe need for kidney transplantation drives efforts to expand organ donation. The decision to accept organs from donors with acute kidney injury (AKI) can result in a clinical dilemma in the context of conflicting reports from published literature.Material and methodsThis observational study included all deceased donor kidney transplants performed in Australia and New Zealand between 1997 and 2017. The association of donor-AKI, defined according to KDIGO criteria, with all-cause graft failure was evaluated by multivariable Cox regression. Secondary outcomes included death-censored graft failure, death, delayed graft function (DGF) and acute rejection.ResultsThe study included 10,101 recipients of kidneys from 5,774 deceased donors, of whom 1182 (12%) recipients received kidneys from 662 (11%) donors with AKI. There were 3,259 (32%) all-cause graft failures, which included 1,509 deaths with functioning graft. After adjustment for donor, recipient and transplant characteristics, donor AKI was not associated with all-cause graft failure (adjusted hazard ratio [HR] 1.11, 95% CI 0.99-1.26), death-censored graft failure (HR 1.09, 95% CI 0.92-1.28), death (HR 1.15, 95% CI 0.98-1.35) or graft failure when death was evaluated as a competing event (sub-distribution hazard ratio [sHR] 1.07, 95% CI 0.91-1.26). Donor AKI was not associated with acute rejection but was associated with DGF (adjusted odds ratio [OR] 2.27, 95% CI 1.92-2.68).ConclusionDonor AKI stage was not associated with any kidney transplant outcome, except DGF. Use of kidneys with AKI for transplantation appears to be justified.
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Project description:Unfavourable procurement biopsy findings are the most common reason for deceased donor kidney discard in the United States. We sought to assess the association between biopsy findings and post-transplant outcomes when donor characteristics are accounted for. We used registry data to identify 1566 deceased donors of 3132 transplanted kidneys (2015-2020) with discordant right/left procurement biopsy classification and performed time-to-event analyses to determine the association between optimal histology and hazard of death-censored graft failure or death. We then repeated all analyses using a local cohort of 147 donors of kidney pairs with detailed procurement histology data available (2006-2016). Among transplanted kidney pairs in the national cohort, there were no significant differences in incidence of delayed graft function or primary nonfunction. Time to death-censored graft failure was not significantly different between recipients of optimal versus suboptimal kidneys. Results were similar in analyses using the local cohort. Regarding recipient survival, analysis of the national, but not local, cohort showed optimal kidneys were associated with a lower hazard of death (adjusted HR 0.68, 95% CI 0.52-0.90, P = 0.006). In conclusion, in a large national cohort of deceased donor kidney pairs with discordant right/left procurement biopsy findings, we found no association between histology and death-censored graft survival.
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