PIRCHE-II Is Related to Graft Failure after Kidney Transplantation.
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ABSTRACT:
SUBMITTER: Geneugelijk K
PROVIDER: S-EPMC5844930 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ABSTRACT Background There is a lack of information regarding which is the best dialysis technique after kidney transplant (KT) failure. The aim of this study is to compare the effect of kidney replacement therapy modality-peritoneal dialysis (TX-PD-TX), haemodialysis (TX-HD-TX) and preemptive deceased donor retransplantation (TX-TX) on patient survival and second KT outcomes. Methods A retrospective observational study from the Catalan Renal Registry was carried out. We included adult patients with failing of their first KT from 2000 to 2018. Results Among 2045 patients, 1829 started on HD (89.4%), 168 on PD (8.2%) and 48 (2.4%) received a preemptive KT. Non-inclusion on the KT waiting list and HD were associated with worse patient survival. For patients included on the waiting list, the probability of human leucocyte antigens (HLA) sensitization and to receive a second KT was similar in HD and PD. A total of 776 patients received a second KT (38%), 656 in TX-HD-TX, 72 in TX-PD-TX and 48 in TX-TX groups. Adjusted mortality after second KT was higher in TX-HD-TX patients compared with TX-TX and TX-PD-TX groups, without differences between TX-TX and TX-PD-TX groups. Death-censored second graft survival was similar in all three groups. Conclusions Our results suggest that after first KT failure, PD is superior to HD in reducing mortality in candidates for a second KT without options for preemptive retransplantation.
| S-EPMC9613432 | biostudies-literature
Project description:Background and objectivesHypophosphatemia is common in the first year after kidney transplantation, but its clinical implications are unclear. We investigated the relationship between the severity of post-transplant hypophosphatemia and mortality or death-censored graft failure in a large cohort of renal transplant recipients with long-term follow-up.Design, setting, participants, & measurementsWe performed a longitudinal cohort study in 957 renal transplant recipients who were transplanted between 1993 and 2008 at a single center. We used a large real-life dataset containing 28,178 phosphate measurements (median of 27; first to third quartiles, 23-34) serial measurements per patient) and selected the lowest intraindividual phosphate level during the first year after transplantation. The primary outcomes were all-cause mortality, cardiovascular mortality, and death-censored graft failure.ResultsThe median (interquartile range) intraindividual lowest phosphate level was 1.58 (1.30-1.95) mg/dl, and it was reached at 33 (21-51) days post-transplant. eGFR was the main correlate of the lowest serum phosphate level (model R2 =0.32). During 9 (5-12) years of follow-up, 181 (19%) patients developed graft failure, and 295 (35%) patients died, of which 94 (32%) deaths were due to cardiovascular disease. In multivariable Cox regression analysis, more severe hypophosphatemia was associated with a lower risk of death-censored graft failure (fully adjusted hazard ratio, 0.61; 95% confidence interval, 0.43 to 0.88 per 1 mg/dl lower serum phosphate) and cardiovascular mortality (fully adjusted hazard ratio, 0.37; 95% confidence interval, 0.22 to 0.62) but not noncardiovascular mortality (fully adjusted hazard ratio, 1.33; 95% confidence interval, 0.9 to 1.96) or all-cause mortality (fully adjusted hazard ratio, 1.15; 95% confidence interval, 0.81 to 1.61).ConclusionsPost-transplant hypophosphatemia develops early after transplantation. These data connect post-transplant hypophosphatemia with favorable long-term graft and patient outcomes.
| S-EPMC5544514 | biostudies-literature
Project description:Relationships between renal function and medical costs for deceased donor kidney transplant recipients are not fully quantified post-transplant. We describe these relationships with renal function measured by estimated glomerular filtration rate (eGFR) and graft failure. The United States Renal Data System identified adults receiving single-organ deceased donor kidneys 2012-2015. Inpatient, outpatient, other facility costs and eGFRs at discharge, 6 and 12 months were included. A time-history of costs was constructed for graft failures and monthly costs in the first year post-transplant were compared to those without failure. The cohort of 24,021 deceased donor recipients had a 2.4% graft failure rate in the first year. Total medical costs exhibit strong trends with eGFR. Recipients with 6-month eGFRs of 30-59 ml/min/1.73m2 have total costs 48% lower than those <30 ml/min/1.73m2. For recipients with graft failure monthly costs begin to rise 3-4 months prior to failure, with incremental costs of over $38,000 during the month of failure. Mean annual total incremental costs of graft failure are over $150,000. Total costs post-transplant are strongly correlated with eGFR. Graft failure in the first year is an expensive, months-long process. Further reductions in early graft failures could yield significant human and economic benefits.
| S-EPMC9184448 | biostudies-literature
Project description:We analyzed in a cohort of 68,606 first deceased donor kidney transplantations reported to the Collaborative Transplant Study whether an epitope-based matching of donor-recipient pairs using the Predicted Indirectly ReCognizable HLA Epitopes algorithm (PIRCHE-II) is superior to currently applied HLA antigen matching. PIRCHE-II scores were calculated based on split antigen HLA-A, -B, -DRB1 typing and adjusted to the 0-6 range of HLA mismatches. PIRCHE-II scores correlated strongly with the number of HLA mismatches (Spearman ρ = 0.65, P < 0.001). In multivariable analyses both parameters were found to be significant predictors of 5-year death-censored graft loss with high prognostic power [hazard ratio (HR) per adjusted PIRCHE-II score = 1.102, per HLA mismatch = 1.095; z-value PIRCHE-II: 9.8, HLA: 11.2; P < 0.001 for both]. When PIRCHE-II scores and HLA mismatches were analyzed simultaneously, their predictive power decreased but remained significant (PIRCHE-II: P = 0.002; HLA: P < 0.001). Influence of PIRCHE-II was especially strong in presensitized and influence of HLA mismatches in non-sensitized recipients. If the level of HLA-incompatibility was low (0-3 mismatches), PIRCHE-II scores showed a low impact on graft survival (HR = 1.031) and PIRCHE-II matching did not have additional significant benefit (P = 0.10). However, if the level of HLA-incompatibility was high (4-6 mismatches), PIRCHE-II improved the positive impact of matching compared to applying the traditional HLA matching alone (HR = 1.097, P = 0.005). Our results suggest that the PIRCHE-II score is useful and can be included into kidney allocation algorithms in addition to HLA matching; however, at the resolution level of HLA typing that is currently used for allocation it cannot fully replace traditional HLA matching.
| S-EPMC7952296 | biostudies-literature
Project description:Although hyponatremia is related to poorer outcomes in several clinical settings, its significance remains unresolved in kidney transplantation. Data on 1,786 patients who received kidney transplantations between January 2000 and December 2011 were analyzed. The patients were divided into two groups according to the corrected sodium values for serum glucose 3 months after their transplantations (<135 mmol/L vs. ?135 mmol/L). Subsequently, the hazard ratios (HRs) for biopsy-proven acute rejection, graft failure, and all-cause mortality were calculated after adjustments for several immunological and non-immunological covariates. 4.0% of patients had hyponatremia. Patients with hyponatremia had higher risks for graft failure and all-cause mortality than did the counterpart normonatremia group; the adjusted HRs for graft failure and mortality were 3.21 (1.47-6.99) and 3.03 (1.21-7.54), respectively. These relationships remained consistent irrespective of heart function. However, hyponatremia was not associated with the risk of acute rejection. The present study addressed the association between hyponatremia and graft and patient outcomes in kidney transplant recipients. Based on the study results, our recommendation is to monitor serum sodium levels after kidney transplantations.
| S-EPMC4877062 | biostudies-literature
Project description:CD4+ T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4+ memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4+ memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome. In this study, the amount of T-cell epitopes shared between immunizing and donor HLA was used as a surrogate marker to evaluate the effect of donor-reactive CD4+ memory T-helper cells on the 10-year risk of death-censored kidney graft failure in 190 donor/recipient combinations using the PIRCHE-II algorithm. The T-cell epitopes of the initial theoretical immunizing HLA and the donor HLA were estimated and the number of shared PIRCHE-II epitopes was calculated. We show that the natural logarithm-transformed PIRCHE-II overlap score, or Shared T-cell EPitopes (STEP) score, significantly associates with the 10-year risk of death-censored kidney graft failure, suggesting that the presence of pre-transplant donor-reactive CD4+ memory T-helper cells might be a strong indicator for the risk of graft failure following kidney transplantation.
| S-EPMC8637278 | biostudies-literature
Project description:IntroductionAboriginal and Torres Strait Islander peoples (hereafter respectfully termed Indigenous Australians) experience a 3-fold increased risk of acute rejection after transplantation compared to non-Indigenous Australians. We investigated whether acute rejection explains the association between Indigenous status, infection-related deaths, and all-cause deaths after kidney transplantation, and whether acute rejection mediates the relationship between Indigenous status and overall graft loss.MethodsThis cohort study included all recipients who received their first kidney transplant between 2005 and 2018 in Australia, using data from the Australia and New Zealand Dialysis and Transplant registry. Multivariable Cox regression models determined the associations between Indigenous status, graft loss, infection-related deaths, and all-cause deaths. Mediation analyses examined if acute rejection mediated these relationships. Primary outcome was infection-related death. Secondary outcomes included all-cause death and overall graft loss.ResultsThere were 9993 patients (n = 390 (3.9%) Indigenous Australians) who received a kidney transplant between 2005 and 2018, and they were followed-up with for 56,876 patient-years. A total of 1165 died (12%) (211 infection-related deaths) and 1957 (20%) lost their allografts. Compared with non-Indigenous recipients, the adjusted hazard ratio (HR) (95% confidence interval [CI]) for graft loss, infection-related deaths and all-cause deaths among Indigenous Australians were 2.27 (1.90-2.71), 3.01 (1.90-4.77) and 2.36 (1.89-2.94), respectively. The mediation analysis showed the association between Indigenous status and graft loss (but not infection-related death or all-cause death) was partially mediated by acute rejection (1.06 [1.03-1.09]), and the proportion of effects mediated by acute rejection was 0.10.ConclusionIndigenous Australians experienced a higher risk of graft loss, a relationship mediated partially through acute rejection. The higher risk of infection-related death was independent of acute rejection.
| S-EPMC9751678 | biostudies-literature
Project description:Uromodulin and microRNAs (miRNAs) have recently been investigated as potential biomarkers for kidney graft associated pathology and outcome, with a special focus on biomarkers indicating specific disease processes and kidney graft survival. The study's aim was to determine whether expression of serum uromodulin concentration and selected miRNAs might be related to renal function in kidney transplant recipients (KTRs). The uromodulin concentration and expression of six selected miRNAs (miR-29c, miR-126, miR-146a, miR-150, miR-155, and miR-223) were determined in the serum of 100 KTRs with stable graft function and chronic kidney disease of all five stages. Kidney graft function was estimated with routine parameters (creatinine, urea, cystatin C, and Chronic Kidney Disease Epidemiology Collaboration study equations) and precisely measured using chromium-51 labelled ethylenediaminetetraacetic-acid clearance. The selected miRNAs were shown to be independent of kidney graft function, indicating their potential as biomarkers of associated kidney graft disease processes. In contrast, the serum uromodulin level depended entirely on kidney graft function and thus reflected functioning tubules rather than any specific kidney graft injury. However, decreased concentrations of serum uromodulin can be observed in the early course of tubulointerstitial injury, thereby suggesting its useful role as an accurate, noninvasive biomarker of early (subclinical) kidney graft injury.
| S-EPMC7460670 | biostudies-literature
Project description:BackgroundImproving both patient and graft survival after kidney transplantation are major unmet needs. The goal of this study was to assess risk factors for specific causes of graft loss to determine to what extent patients who develop either death with a functioning graft (DWFG) or graft failure (GF) have similar baseline risk factors for graft loss.MethodsWe retrospectively studied all solitary renal transplants performed between January 1, 2006, and December 31, 2018, at 3 centers and determined the specific causes of DWFG and GF. We examined outcomes in different subgroups using competing risk estimates and cause-specific Cox models.ResultsOf the 5752 kidney transplants, graft loss occurred in 21.6% (1244) patients, including 12.0% (691) DWFG and 9.6% (553) GF. DWFG was most commonly due to malignancy (20.0%), infection (19.7%), cardiac disease (12.6%) with risk factors of older age and pretransplant dialysis, and diabetes as the cause of renal failure. For GF, alloimmunity (38.7%), glomerular diseases (18.6%), and tubular injury (13.9%) were the major causes. Competing risk incidence models identified diabetes and older recipients with higher rates of both DWFG and nonalloimmune GF.ConclusionsThese data suggest that at baseline, 2 distinct populations can be identified who are at high risk for renal allograft loss: a younger, nondiabetic patient group who develops GF due to alloimmunity and an older, more commonly diabetic population who develops DWFG and GF due to a mixture of causes-many nonalloimmune. Individualized management is needed to improve long-term renal allograft survival in the latter group.
| S-EPMC8759617 | biostudies-literature
Project description:Increased utilization of suboptimal organs in response to organ shortage has resulted in increased incidence of delayed graft function (DGF) after transplantation. Although presumed increased costs associated with DGF are a deterrent to the utilization of these organs, the financial burden of DGF has not been established. We used the Premier Healthcare Database to conduct a retrospective analysis of healthcare resource utilization and costs in kidney transplant patients (n = 12 097) between 1/1/2014 and 12/31/2018. We compared cost and hospital resource utilization for transplants in high-volume (n = 8715) vs low-volume hospitals (n = 3382), DGF (n = 3087) vs non-DGF (n = 9010), and recipients receiving 1 dialysis (n = 1485) vs multiple dialysis (n = 1602). High-volume hospitals costs were lower than low-volume hospitals ($103 946 vs $123 571, P < .0001). DGF was associated with approximately $18 000 (10%) increase in mean costs ($130 492 vs $112 598, P < .0001), 6 additional days of hospitalization (14.7 vs 8.7, P < .0001), and 2 additional ICU days (4.3 vs 2.1, P < .0001). Multiple dialysis sessions were associated with an additional $10 000 compared to those with only 1. In conclusion, DGF is associated with increased costs and length of stay for index kidney transplant hospitalizations and payment schemes taking this into account may reduce clinicians' reluctance to utilize less-than-ideal kidneys.
| S-EPMC8415124 | biostudies-literature