Histological evaluation of ischemic alterations in donors after cardiac death: A useful tool to predict post-transplant renal function.

Kidneys retrieved from donors after cardiac death (DCD) pose significant challenges from a clinical and technical point of view, undergoing a variable degree of ischemia-reperfusion injury. At present, the utilization of kidneys is assessed according to the Karpinski score, which does not take into account the ischemic insult and does not predict the functional recovery of the organ once transplanted. Therefore, the correlation between biopsy results and post-transplant graft function is still debated. In this study we examined kidney biopsies from DCD donors; we calculated the Karpinski score and subsequently identified and quantified the ischemic lesions in the glomerular, interstitial, and tubular compartments. These same lesions were quantified in kidney biopsies from donors after brain death (DBD) in a case-control analysis. The collected data were correlated with the clinical data of the donors and the post-transplant follow-up. Proximal tubule alterations are crucial in ischemia-reperfusion damage, showing precise histological alterations, which are more frequent in DCD than in DBD donors and are statistically correlated with functional recovery of the organ. Quantification of ischemic tubular lesions in biopsies of kidneys from DCD donors is a useful tool for predicting post-transplant renal function and a valid parameter for assessing the quality of the graft.

The value of cystatin C in predicting perioperative and long-term prognosis of renal transplantation.

This study aimed to evaluate the value of cystatin C (Cys C) in predicting the perioperative and long-term prognosis of renal transplantation (RT). The clinical data of 198 RT recipients were collected. Blood samples were obtained daily until 7 d after transplantation and then discharge day to determine the serum levels of Cys C. The receiver-operating characteristic (ROC) analysis and the area under the curve (AUC) were used to determine the diagnostic accuracy of Cys C for delayed graft function (DGF). The presence of shrunken pore syndrome (SPS) with a cystatin C-based estimate of glomerular filtration rate less than 70% of a creatinine-based estimate, was also evaluated as a prognostic factor for the development of DGF. The serum Cys C levels of patients with DGF were higher than those of the non-DGF group. Cys C showed a higher AUC (0.928) in the ROC analysis than did sCr (0.862). Compared to the non-SPS group, there were more patients diagnosed with SPS in the DGF group (p < .05). The follow-up data showed that patients diagnosed with SPS had higher levels of sCr and Cys C compared to other patients, suggesting a poor long-term prognosis. Our findings suggest that Cys C is a sensitive indicator of renal function during the perioperative period. Cys C at a concentration of 4.9 mg/L had the highest sum of sensitivity and specificity for prediction of DGF, with a sensitivity of 0.889 and a specificity of 0.8. SPS is associated with the development of DGF and the poor long-term prognosis of RT.

Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation.

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.03 1.682.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.45 2.093.02 ; PFNC = 1.67 2.403.46 ; PCC = 1.48 2.243.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.34 1.621.95 ) than CLDKT (aHR = 1.96 2.292.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

Risk factors and outcomes for delayed kidney graft function in simultaneous heart and kidney transplant recipients: A UNOS/OPTN database analysis.

There are no prior studies assessing the risk factors and outcomes for kidney delayed graft function (K-DGF) in simultaneous heart and kidney (SHK) transplant recipients. Using the OPTN/UNOS database, we sought to identify risk factors associated with the development of K-DGF in this unique population, as well as outcomes associated with K-DGF. A total of 1161 SHK transplanted between 1998 and 2018 were included in the analysis, of which 311 (27%) were in the K-DGF (+) group and 850 in the K-DGF (-) group. In the multivariable analysis, history of pretransplant dialysis (OR: 3.95; 95% CI: 2.94 to 5.29; p < .001) was significantly associated with the development of K-DGF, as was donor death from cerebrovascular accident and longer cold ischemia time of either organ. SHK recipients with K-DGF had increased mortality (HR: 1.99; 95% CI: 1.52 to 2.60; p < .001) and death censored kidney graft failure (HR: 3.51; 95% CI: 2.29 to 5.36; p < .001) in the multivariable analysis. Similar outcomes were obtained when limiting our study to 2008-2018. Similar to kidney-only recipients, K-DGF in SHK recipients is associated with worse outcomes. Careful matching of recipients and donors, as well as peri-operative management, may help reduce the risk of K-DGF and the associated detrimental effects.

Improved short-term outcomes of kidney transplants in controlled donation after the circulatory determination of death with the use of normothermic regional perfusion.

Normothermic regional perfusion (NRP) allows the in situ perfusion of organs with oxygenated blood in donation after the circulatory determination of death (DCDD). We aimed at evaluating the impact of NRP on the short-term outcomes of kidney transplants in controlled DCDD (cDCDD). This is a multicenter, nationwide, retrospective study comparing cDCDD kidneys obtained with NRP versus the standard rapid recovery (RR) technique. During 2012-2018, 2302 cDCDD adult kidney transplants were performed in Spain using NRP (n = 865) or RR (n = 1437). The study groups differed in donor and recipient age, warm, and cold ischemic time and use of ex situ machine perfusion. Transplants in the NRP group were more frequently performed in high-volume centers (≥90 transplants/year). Through matching by propensity score, two cohorts with a total of 770 patients were obtained. After the matching, no statistically significant differences were observed between the groups in terms of primary nonfunction (p = .261) and mortality at 1 year (p =  .111). However, the RR of kidneys was associated with a significantly increased odds of delayed graft function (OR 1.97 [95% CI 1.43-2.72]; p < .001) and 1-year graft loss (OR 1.77 [95% CI 1.01-3.17]; p = .034). In conclusion, compared with RR, NRP appears to improve the short-term outcomes of cDCDD kidney transplants.

Viability assessment and utilization of declined donor kidneys with rhabdomyolysis using ex vivo normothermic perfusion without preimplantation biopsy.

The role of ex vivo normothermic perfusion (EVNP) in both organ viability assessment and reconditioning is increasingly being demonstrated. We report the use of this emerging technology to facilitate the transplantation of a pair of donor kidneys with severe acute kidney injury (AKI) secondary to rhabdomyolysis. Donor creatinine was 10.18 mg/dl with protein (30 mg/dl) present in urinalysis. Both kidneys were declined by all other transplantation units and subsequently accepted by our unit. The first kidney was perfused with red cell-based perfusate at 37°C for 75 min, mean renal blood flow was 110 ml/min/100 g and produced 85 ml of urine. Having demonstrated favorable macroscopic appearance and urine output, the kidney was transplanted into a 61-year-old peritoneal dialysis dependent without complication. Given the reassuring information from the first kidney provided by EVNP, the second kidney was not perfused with EVNP and was directly implanted to a 64-year-old patient. The first kidney achieved primary function and the second functioned well after delayed graft function. Recipient eGFR have stabilized at 88.5 and 55.3, respectively (ml/min/1.73 m2 ), at 2 months posttransplant.

Effect of delayed graft function on longer-term outcomes after kidney transplantation from donation after circulatory death donors in the United Kingdom: A national cohort study.

Kidneys from donation after circulatory death (DCD) donors are utilized variably worldwide, in part due to high rates of delayed graft function (DGF) and putative associations with adverse longer-term outcomes. We aimed to determine whether the presence of DGF and its duration were associated with poor longer-term outcomes after kidney transplantation from DCD donors. Using the UK transplant registry, we identified 4714 kidney-only transplants from controlled DCD donors to adult recipients between 2006 and 2016; 2832 recipients (60·1%) had immediate graft function and 1882 (39·9%) had DGF. Of the 1847 recipients with DGF duration recorded, 926 (50·1%) had DGF < 7 days, 576 (31·2%) had DGF 7-14 days, and 345 (18·7%) had DGF >14 days. After risk adjustment, the presence of DGF was not associated with inferior long-term graft or patient survivals. However, DGF duration of >14 days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p = ·001) and recipient death (hazard ratio 1·8, p < ·001) compared to grafts with immediate function. This study suggests that shorter periods of DGF have no adverse influence on graft or patient survival after DCD donor kidney transplantation and that DGF >14 days is a novel early biomarker for significantly worse longer-term outcomes.

Cytokine absorption during human kidney perfusion reduces delayed graft function-associated inflammatory gene signature.

Transplantation is the optimal treatment for most patients with end-stage kidney disease but organ shortage is a major challenge. Normothermic machine perfusion (NMP) has been used to recondition marginal organs; however, mechanisms by which NMP might benefit organs are not well understood. Using pairs of human kidneys obtained from the same donor, we compared the effect of NMP with that of cold storage on the global kidney transcriptome. We found that cold storage led to a global reduction in gene expression, including inflammatory pathway genes and those required for energy generation processes, such as oxidative phosphorylation (OXPHOS). In contrast, during NMP, there was marked upregulation OXPHOS genes, but also of a number of immune and inflammatory pathway genes. Using biopsies from kidneys undergoing NMP that were subsequently transplanted, we found that higher inflammatory gene expression occurred in organs with prolonged delayed graft function (DGF). Therefore, we used a hemoadsorber (HA) to remove pro-inflammatory cytokines. This attenuated inflammatory gene expression increased OXPHOS pathway genes and had potentially clinically important effects in reducing the expression of a DGF-associated gene signature. Together, our data suggest that adsorption of pro-inflammatory mediators from the perfusate represents a potential intervention which may improve organ viability.

Recipient Obesity and Kidney Transplant Outcomes: A Mate-Kidney Analysis.

RATIONALE & OBJECTIVE: The impact of extreme recipient obesity on long-term kidney transplant outcomes has been controversial. This study sought to evaluate the association of various levels of recipient obesity on kidney transplantation outcomes by comparing mate-kidney recipient pairs to address possible confounding effects of donor characteristics on posttransplant outcomes. STUDY DESIGN: Nationwide observational cohort study using mate-kidney models. SETTING & PARTICIPANTS: In analysis based on the Organ Procurement and Transplant Network/United Network of Organ Sharing database, 44,560 adult recipients of first-time deceased-donor kidney transplants from 2001 through 2016 were paired by donor. PREDICTORS: Recipient body mass index (BMI) categorized as 18-25 (n = 12,446), >25-30 (n = 15,477), >30-35 (n = 11,144; obese), and >35 (n = 5,493; extreme obesity) kg/m2. OUTCOMES: Outcomes included patient survival, graft survival, death-censored graft survival, delayed graft function (DGF), and hospital length of stay. ANALYTICAL APPROACH: Conditional logistic regression and stratified proportional hazards models were used to compare outcomes as odds ratios and hazard ratios (HRs), adjusted for recipient and transplant factors, using recipients with a BMI >35 kg/m2 as a reference. RESULTS: At a median follow-up of 3.9 years, adjusted odds ratios for DGF were 0.42 (95% CI, 0.36-0.48), 0.55 (95% CI, 0.48-0.62), and 0.73 (95% CI, 0.64-0.83) for BMI 18-25, >25-30, and >30-35 kg/m2, respectively (P < 0.001 for all). Death-censored graft failure was less frequent for BMI ≤25 and >25-30 kg/m2 (HRs of 0.66 [95% CI, 0.59-0.74] and 0.79 [95% CI, 0.70-0.88], respectively; P < 0.001 for both), but not for BMI >30-35 kg/m2 (HR, 0.91 [95% CI, 0.81-1.02]; P = 0.09). Length of stay and patient survival did not differ by recipient BMI. LIMITATIONS: Observational study with limited detail regarding potential confounders. CONCLUSIONS: Despite an increased risk of DGF likely unrelated to donor organ quality, long-term transplant outcomes among recipients with a BMI >35 kg/m2 are similar to those among recipients with a BMI >30-35 kg/m2, supporting a flexible approach to kidney transplantation candidacy in candidates with extreme obesity.

Peritransplant eculizumab does not prevent delayed graft function in deceased donor kidney transplant recipients: Results of two randomized controlled pilot trials.

Animal models and observational human data indicate that complement, including C5a, pathogenically participates in ischemia reperfusion (IR) injury that manifests as delayed graft function (DGF) following deceased donor kidney transplantation. We report on the safety/efficacy of anti-C5 monoclonal antibody eculizumab (Ecu) administered in the operating room prior to reperfusion, to prevent DGF in recipients of deceased donor kidney transplants in two related, investigator-sponsored, randomized controlled trials. Eight recipients from a single center were enrolled in a pilot study that led to a 19-subject multicenter trial. Together, 27 deceased donor kidney transplant recipients, 16 Ecu-treated and 11 controls, were treated with rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil with or without glucocorticoids, and followed for 6 months. Data analysis showed no epidemiological or transplant-related differences between study arms. Ecu was well tolerated with a similar severe adverse event incidence between groups. The DGF rate did not differ between Ecu-treated (44%) and control (45%, P = 1.0) subjects. Serum creatinine reduction in the first week after transplantation, and graft function up to 180-days post-transplant, were also similar. Ecu administration was safe but did not reduce the rate of DGF in a high-risk population of deceased donor recipients.

First-in-human use of a marine oxygen carrier (M101) for organ preservation: A safety and proof-of-principle study.

The medical device M101 is an extracellular hemoglobin featuring high oxygen-carrying capabilities. Preclinical studies demonstrated its safety as an additive to organ preservation solutions and its beneficial effect on ischemia/reperfusion injuries. OXYgen carrier for Organ Preservation (OXYOP) is a multicenter open-label study evaluating for the first time the safety of M101 added (1 g/L) to the preservation solution of one of two kidneys from the same donor. All adverse events (AEs) were analyzed by an independent data and safety monitoring board. Among the 58 donors, 38% were extended criteria donors. Grafts were preserved in cold storage (64%) or machine perfusion (36%) with a mean cold ischemia time (CIT) of 740 minutes. At 3 months, 490 AEs (41 serious) were reported, including two graft losses and two acute rejections (3.4%). No immunological, allergic, or prothrombotic effects were reported. Preimplantation and 3-month biopsies did not show thrombosis or altered microcirculation. Secondary efficacy end points showed less delayed graft function (DGF) and better renal function in the M101 group than in the contralateral kidneys. In the subgroup of grafts preserved in cold storage, Kaplan-Meier survival and Cox regression analysis showed beneficial effects on DGF independent of CIT (P = .048). This study confirms that M101 is safe and shows promising efficacy data.

Effect of preservation solutions for static cold storage on kidney transplantation outcomes: A National Registry Study.

This study aimed to evaluate how 5 preservation solutions for static cold storage affected kidney transplant outcomes. It included all first single kidney transplants during 2010-2014 from donations after brain death in the French national transplant registry, excluding preemptive transplants and transplants of kidneys preserved with a hypothermic perfusion machine. The effects of each preservation solution on delayed graft function (DGF) and 1-year transplant failure were evaluated with hierarchical multivariable logistic regression models. The study finally included 7640 transplanted kidneys: 3473 (45.5%) preserved with Institut Georges Lopez-1 solution (IGL-1), 773 (10.1%) with University of Wisconsin solution, 731 (9.6%) with Solution de Conservation des Organes et Tissus (SCOT, organ and tissue preservation solution), 2215 (29.0%) with Celsior, and 448 (5.9%) with histidine-tryptophan-ketoglutarate. Primary nonfunction rates did not differ by solution. After adjustment for donor, recipient, and transplant characteristics, the DGF risk was significantly lower with IGL-1 than with all other solutions (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.48-0.64). Conversely, SCOT was associated with a DGF risk significantly higher than the other solutions (OR 2.69, 95% CI 2.21-3.27) and triple that of IGL-1 (OR 3.37, 95% CI 2.72-4.16). One year after transplantation, the transplant failure rate did not differ significantly by preservation solution. The difference between the groups for 1-year mean creatinine clearance was not clinically relevant.

Targeted donor complement blockade after brain death prevents delayed graft function in a nonhuman primate model of kidney transplantation.

Delayed graft function (DGF) in renal transplant is associated with reduced graft survival and increased immunogenicity. The complement-driven inflammatory response after brain death (BD) and posttransplant reperfusion injury play significant roles in the pathogenesis of DGF. In a nonhuman primate model, we tested complement-blockade in BD donors to prevent DGF and improve graft survival. BD donors were maintained for 20 hours; kidneys were procured and stored at 4°C for 43-48 hours prior to implantation into ABO-compatible, nonsensitized, MHC-mismatched recipients. Animals were divided into 3 donor-treatment groups: G1 - vehicle, G2 - rhC1INH+heparin, and G3 - heparin. G2 donors showed significant reduction in classical complement pathway activation and decreased levels of tumor necrosis factor α and monocyte chemoattractant protein 1. DGF was diagnosed in 4/6 (67%) G1 recipients, 3/3 (100%) G3 recipients, and 0/6 (0%) G2 recipients (P = .008). In addition, G2 recipients showed superior renal function, reduced sC5b-9, and reduced urinary neutrophil gelatinase-associated lipocalin in the first week posttransplant. We observed no differences in incidence or severity of graft rejection between groups. Collectively, the data indicate that donor-management targeting complement activation prevents the development of DGF. Our results suggest a pivotal role for complement activation in BD-induced renal injury and postulate complement blockade as a promising strategy for the prevention of DGF after transplantation.

Transplanting kidneys from donation after cardiac death donors with acute kidney injury.

Donation after cardiac death (DCD) and acute kidney injury (AKI) donors have historically been considered independent risk factors for delayed graft function (DGF), allograft failure, and inferior outcomes. With growing experience, updated analyses have shown good outcomes. There continues to be limited data, however, on outcomes specific to DCD donors who have AKI. Primary outcomes for this study were post-kidney transplant patient and allograft survival comparing two donor groups: DCD AKIN stage 2-3 and DBD AKIN stage 2-3. In comparing these groups, there were no short- or long-term differences in patient (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.54-1.93, P = .83) or allograft survival (HR 1.47, 95% CI 0.64-2.97, P = .32). In multivariate models, the DCD/DBD status had no significant impact on the estimated GFR (eGFR) at 1 (P = .38), 2 (P = .60), and 3 years (P = .52). DGF (57.9% vs 67.9%, P = .09), rejection (12.1% vs 13.9%, P = .12), and progression of interstitial fibrosis/tubular atrophy (IFTA) on protocol biopsy (P = .16) were similar between the two groups. With careful selection, good outcomes can be achieved utilizing severe AKI DCD kidneys. Historic concerns regarding primary nonfunction, DGF resulting in interstitial fibrosis and rejection, and inferior outcomes were not observed. Given the ongoing organ shortage, increased effort should be undertaken to further utilize these donors.

Microvasculature partial endothelial mesenchymal transition in early posttransplant biopsy with acute tubular necrosis identifies poor recovery renal allografts.

Acute tubular necrosis (ATN), a frequent histopathological feature in the early post-renal transplant biopsy, affects long-term graft function. Appropriate markers to identify patients at risk of no or incomplete recovery after delayed graft function are lacking. In this study, we first included 41 renal transplant patients whose biopsy for cause during the first month after transplantation showed ATN lesions. Using partial microvasculature endothelial (fascin, vimentin) and tubular epithelial (vimentin) to mesenchymal transition markers, detected by immunohistochemistry, we found a significant association between partial endothelial to mesenchymal transition and poor graft function recovery (Spearman's rho = -0.55, P = .0005). Transforming growth factor-ß1 was strongly expressed in these phenotypic changed endothelial cells. Extent of ATN was also correlated with short- and long-term graft dysfunction. However, the association of extensive ATN with long-term graft dysfunction (24 months posttransplant) was observed only in patients with partial endothelial to mesenchymal transition marker expression in their grafts (Spearman's rho = -0.64, P = .003), but not in those without. The association of partial endothelial to mesenchymal transition with worse renal graft outcome was confirmed on 34 other early biopsies with ATN from a second transplant center. Our results suggest that endothelial cell activation at the early phase of renal transplantation plays a detrimental role.

Outcomes From Right Versus Left Deceased-Donor Kidney Transplants: A US National Cohort Study.

RATIONALE & OBJECTIVE: There may be important transplant-related differences between right and left kidneys, including logistical/surgical considerations about vessel length for the right compared to the left kidney from the same donor. Because US centers choose between the right and left kidney when their recipient is ranked higher on a "match-run," we sought to determine whether deceased-donor right kidneys have had worse posttransplantation outcomes than left kidneys. STUDY DESIGN: Paired Organ Procurement and Transplantation Network analysis. SETTING & PARTICIPANTS: Deceased-donor kidney pairs transplanted during 1990 to 2016. EXPOSURE: Right versus left kidney controlling for other significant factors. OUTCOMES: Delayed graft function (DGF), all-cause and death-censored graft failure, and mortality. ANALYTICAL APPROACH: Multivariable conditional logistic regression for DGF; proportional hazards models (conditional on same donor) for failure/mortality with right kidneys (operationalized as 6-month time-varying coefficients) adjusting for DGF and other confounders. RESULTS: 87,112 recipient pairs shared the following donor characteristics: mean age of 41 ± 14 years, 60% males, and 11% with cardiac death. Recipient characteristics were numerically similar by donor kidney side but with some statistical differences given the sample size. Right kidneys had slightly longer cold ischemia time. DGF occurred more often for right kidneys (28% vs 25.8%; P < 0.001; adjusted OR, 1.15 [95% CI, 1.12-1.17]). The adjusted hazard ratio (aHR) for all-cause graft failure with right kidneys within 6 months was 1.07 (95% CI, 1.03-1.11), and was 0.99 (95% CI, 0.97-1.01) thereafter. The aHRs for death-censored graft failure with right kidneys before and after 6 months were 1.11 (95% CI, 1.06-1.16) and 0.96 (95% CI, 0.93-0.99), respectively; the corresonding aHRs for mortality were 0.99 (95% CI, 0.93-1.04) and 1.00 (95% CI, 0.98-1.03), respectively. LIMITATIONS: Registry data, different transplant eras, reasons for kidney side unavailable. CONCLUSIONS: There is modest association for transplantation of right kidneys with DGF and graft loss within the first 6 months, which is lost beyond this time point. These findings do not support the use of laterality of deceased-donor kidneys as an important factor in organ acceptance decisions.

Pediatric deceased donor kidney transplant outcomes under the Kidney Allocation System.

The Kidney Allocation System (KAS) has resulted in fewer pediatric kidneys being allocated to pediatric deceased donor kidney transplant (pDDKT) recipients. This had prompted concerns that post-pDDKT outcomes may worsen. To study this, we used SRTR data to compare the outcomes of 953 pre-KAS pDDKT (age <18 years) recipients (December 4, 2012-December 3, 2014) with the outcomes of 934 post-KAS pDDKT recipients (December 4, 2014-December 3, 2016). We analyzed mortality and graft loss by using Cox regression, delayed graft function (DGF) by using logistic regression, and length of stay (LOS) by using negative binomial regression. Post-KAS recipients had longer pretransplant dialysis times (median 1.26 vs 1.07 years, P = .02) and were more often cPRA 100% (2.0% vs 0.1%, P = .001). Post-KAS recipients had less graft loss than pre-KAS recipients (hazard ratio [HR]: 0.35 0.540.83 , P = .005) but no statistically significant differences in mortality (HR: 0.29 0.721.83 , P = .5), DGF (odds ratio: 0.93 1.321.93 , P = .2), and LOS (LOS ratio: 0.96 1.061.19 , P = .4). After adjusting for donor-recipient characteristics, there were no statistically significant post-KAS differences in mortality (adjusted HR: 0.37 1.042.92 , P = .9), DGF (adjusted odds ratio: 0.94 1.412.13 , P = .1), or LOS (adjusted LOS ratio: 0.93 1.041.16 , P = .5). However, post-KAS pDDKT recipients still had less graft loss (adjusted HR: 0.38 0.590.91 , P = .02). KAS has had a mixed effect on short-term posttransplant outcomes for pDDKT recipients, although our results are limited by only 2 years of posttransplant follow-up.

Urinary metabolites predict prolonged duration of delayed graft function in DCD kidney transplant recipients.

Extending kidney donor criteria, including donation after circulatory death (DCD), has resulted in increased rates of delayed graft function (DGF) and primary nonfunction. Here, we used Nuclear Magnetic Resonance (NMR) spectroscopy to analyze the urinary metabolome of DCD transplant recipients at multiple time points (days 10, 42, 180, and 360 after transplantation). The aim was to identify markers that predict prolonged duration of functional DGF (fDGF). Forty-seven metabolites were quantified and their levels were evaluated in relation to fDGF. Samples obtained at day 10 had a different profile than samples obtained at the other time points. Furthermore, at day 10 there was a statistically significant increase in eight metabolites and a decrease in six metabolites in the group with fDGF (N = 53) vis-à-vis the group without fDGF (N = 22). In those with prolonged fDGF (≥21 days) (N = 17) urine lactate was significantly higher and pyroglutamate lower than in those with limited fDGF (<21 days) (N = 36). In order to further distinguish prolonged fDGF from limited fDGF, the ratios of all metabolites were analyzed. In a logistic regression analysis, the sum of branched-chain amino acids (BCAAs) over pyroglutamate and lactate over fumarate, predicted prolonged fDGF with an AUC of 0.85. In conclusion, kidney transplant recipients with fDGF can be identified based on their altered urinary metabolome. Furthermore, two ratios of urinary metabolites, lactate/fumarate and BCAAs/pyroglutamate, adequately predict prolonged duration of fDGF.

No impact of disseminated intravascular coagulation in kidney donors on long-term kidney transplantation outcome: A multicenter propensity-matched study.

The diagnosis of disseminated intravascular coagulation (DIC) is often considered to be a contraindication to organ donation. The aim of this study was to evaluate the impact of DIC+ donors on kidney recipient (KR) evolution. We identified 169 KRs with DIC+ donation after brain death donors between January 1996 and December 2012 in 6 French transplant centers. Individuals were matched using propensity scores to 338 recipients with DIC- donors according to donor age and sex, whether expanded criteria for the donor existed, graft year, and transplantation center. After kidney transplantation, delayed graft function was observed in 28.1% of DIC+ KRs and in 22.8% of DIC- KRs (NS). Renal allograft survival at 1, 5, and 10 years was 94.5%, 89.3%, and 73.9% and 96.2%, 90.8%, and 81.3% in DIC+ KRs and DIC- KRs, respectively (NS). The median estimated glomerular filtration rate (eGFR) was similar between DIC+ and DIC- KRs at 3 months, 1 year, and 10 years: 45.9 vs 48.1 mL/min, 42.1 vs 43.1 mL/min, and 33.9 vs 38.1 mL/min, respectively. Delayed calcineurin inhibitor introduction or induction had no impact on delayed graft function rate or eGFR evolution at 10 years after transplantation in DIC+ KRs. Donor DIC did not seem to affect initial outcome, long-term graft function, or allograft survival.

Accelerating kidney allocation: Simultaneously expiring offers.

Using nonideal kidneys for transplant quickly might reduce the discard rate of kidney transplants. We studied changing kidney allocation to eliminate sequential offers, instead making offers to multiple centers for all nonlocally allocated kidneys, so that multiple centers must accept or decline within the same 1 hour. If more than 1 center accepted an offer, the kidney would go to the highest-priority accepting candidate. Using 2010 Kidney-Pancreas Simulated Allocation Model-Scientific Registry for Transplant Recipients data, we simulated the allocation of 12 933 kidneys, excluding locally allocated and zero-mismatch kidneys. We assumed that each hour of delay decreased the probability of acceptance by 5% and that kidneys would be discarded after 20 hours of offers beyond the local level. We simulated offering kidneys simultaneously to small, medium-size, and large batches of centers. Increasing the batch size increased the percentage of kidneys accepted and shortened allocation times. Going from small to large batches increased the number of kidneys accepted from 10 085 (92%) to 10 802 (98%) for low-Kidney Donor Risk Index kidneys and from 1257 (65%) to 1737 (89%) for high-Kidney Donor Risk Index kidneys. The average number of offers that a center received each week was 10.1 for small batches and 16.8 for large batches. Simultaneously expiring offers might allow faster allocation and decrease the number of discards, while still maintaining an acceptable screening burden.