Acute Kidney Transplant Rejection After Administration of Nivolumab in a Dialysis Patient With a Failed Graft.
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ABSTRACT:
SUBMITTER: Duni A
PROVIDER: S-EPMC8116751 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In the present work, we have used whole genome expression profiling of peripheral blood samples from 51 patients with biopsy-proven acute kidney transplant rejection and 24 patients with excellent function and biopsy-proven normal transplant histology. The results demonstrate that there are 1738 probesets on the Affymetrix HG-U133 Plus 2.0 GeneChip representing 1472 unique genes which are differentially expressed in the peripheral blood during an acute kidney transplant rejection. By ranking these results we have identified minimal sets of 50 to 150 probesets with predictive classification accuracies for AR of greater than 90% established with several different prediction tools including DLDA and PAM. We have demonstrated that a subset of peripheral blood gene expression signatures can also diagnose four different subtypes of AR (Banff Borderline, IA, IB and IIA) and the top 100 ranked classifiers have greater than 89% predictive accuracy. Finally, we have demonstrated that there are gene signatures for early and late AR defined as less than or greater than one year post-transplant with greater than 86% predictive accuracies. We also confirmed that there are 439 time-independent gene classifiers for AR. Based on these results, we conclude that peripheral blood gene expression profiling can be used to diagnose AR at any time in the first 5 years post-transplant in the setting of acute kidney transplant dysfunction not caused by BK nephropathy, other infections, drug-induced nephrotoxicity or ureteral obstruction. Keywords: kidney transplantation, peripheral blood, DNA microarrays, acute kidney rejection, biomarkers
2014-03-01 | GSE15296 | GEO
Project description:In the present work, we have used whole genome expression profiling of peripheral blood samples from 51 patients with biopsy-proven acute kidney transplant rejection and 24 patients with excellent function and biopsy-proven normal transplant histology. The results demonstrate that there are 1738 probesets on the Affymetrix HG-U133 Plus 2.0 GeneChip representing 1472 unique genes which are differentially expressed in the peripheral blood during an acute kidney transplant rejection. By ranking these results we have identified minimal sets of 50 to 150 probesets with predictive classification accuracies for AR of greater than 90% established with several different prediction tools including DLDA and PAM. We have demonstrated that a subset of peripheral blood gene expression signatures can also diagnose four different subtypes of AR (Banff Borderline, IA, IB and IIA) and the top 100 ranked classifiers have greater than 89% predictive accuracy. Finally, we have demonstrated that there are gene signatures for early and late AR defined as less than or greater than one year post-transplant with greater than 86% predictive accuracies. We also confirmed that there are 439 time-independent gene classifiers for AR. Based on these results, we conclude that peripheral blood gene expression profiling can be used to diagnose AR at any time in the first 5 years post-transplant in the setting of acute kidney transplant dysfunction not caused by BK nephropathy, other infections, drug-induced nephrotoxicity or ureteral obstruction. Keywords: kidney transplantation, peripheral blood, DNA microarrays, acute kidney rejection, biomarkers Microarray profiles of peripheral blood from 51 biopsy-proven acute kidney rejection (AR) and 24 well-functioning kidney transplants were randomized and compared using class comparisons, network and biological function analyses.
2014-03-01 | E-GEOD-15296 | biostudies-arrayexpress
Project description:BACKGROUND:Suboptimal immunosuppression after kidney transplantation contributes to toxicity and loss of efficacy. Little is known regarding the impact of intra-patient variability of tacrolimus (TAC) doses and troughs in the early post-transplant period or the influence of genetic variants on variability. METHODS:Coefficients of variation (CV) of TAC troughs and doses of 1226 European American (EA) and 246 African American (AA) adult recipients enrolled in DeKAF Genomics were compared for association with acute rejection and graft failure. Additionally, the influence of recipients' number of CYP3A5 loss-of-function alleles was assessed. RESULTS:Acute rejection was associated with greater CV of dose in AA (P < 0.001) and EA recipients (P = 0.012). Graft failure was associated with a greater CV of dose (P = 0.022) and trough (P < 0.001) in AA, and higher CV of trough (P = 0.024) in EA recipients. In EA, CYP3A5 loss-of-function alleles were associated with decreased CV of trough (P = 0.0042) and increased CV of dose (P < 0.0001). CONCLUSION:CYP3A5 loss-of-function alleles influence intra-patient TAC trough and dose variability. High variability of TAC dose increases risk of acute rejection. High variability of TAC trough increases risk of graft failure. Early clinical recognition of TAC dose and trough variability may improve patient management and outcomes.
| S-EPMC6317347 | biostudies-literature
Project description: Not available
| S-EPMC8596849 | biostudies-literature
Project description:Acute rejection is detrimental to most transplanted solid organs, but is considered to be less of a consequence for transplanted livers. We evaluated risk factors for and outcomes after biopsy-proven acute rejection (BPAR) based on an analysis of a more recent national sample of recipients of liver transplants from living and deceased donors.We analyzed data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) from 2003 through 2014 as the exploratory cohort and the Scientific Registry of Transplant Recipients (SRTR) from 2005 through 2013 as the validation cohort. We examined factors associated with time to first BPAR using multivariable Cox regression or discrete-survival analysis. Competing risks methods were used to compare causes of death and graft failure between recipients of living and deceased donors.At least 1 BPAR episode occurred in 239 of 890 recipients in A2ALL (26.9%) and 7066 of 45,423 recipients in SRTR (15.6%). In each database, risk of rejection was significantly lower when livers came from biologically related living donors (A2ALL hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.43-0.76; and SRTR HR, 0.78; 95% CI, 0.66-0.91) and higher in liver transplant recipients with primary biliary cirrhosis, of younger age, or with hepatitis C. In each database, BPAR was associated with significantly higher risks of graft failure and death. The risks were highest in the 12 month post-BPAR period in patients whose first episode occurred more than 1 year after liver transplantation: HRs for graft failure were 6.79 in A2ALL (95% CI, 2.64-17.45) and 4.41 in SRTR (95% CI, 3.71-5.23); HRs for death were 8.81 in A2ALL (95% CI, 3.37-23.04) and 3.94 in SRTR (95% CI, 3.22-4.83). In analyses of cause-specific mortality, associations were observed for liver-related (graft failure) causes of death but not for other causes.Contrary to previous data, acute rejection after liver transplant is associated with significantly increased risk of graft failure, all-cause mortality, and graft failure-related death, regardless of primary liver disease etiology. Living donor liver transplantation from a biologically related donor is associated with decreased risk of rejection.
| S-EPMC5326609 | biostudies-literature
Project description:PurposeThe influence of prior failed kidney transplants on outcomes of peritoneal dialysis (PD) is unclear. Thus, we conducted a systematic review and meta-analysis to compare the outcomes of patients initiating PD after a failed kidney transplant with those initiating PD without a prior history of kidney transplantation.MethodsWe searched PubMed, Embase, CENTRAL, and Google Scholar databases from inception until 25 November 2020. Our meta-analysis considered the absolute number of events of mortality, technical failures, and patients with peritonitis, and we also pooled multi-variable adjusted hazard ratios (HR).ResultsWe included 12 retrospective studies. For absolute number of events, our analysis indicated no statistically significant difference in technique failure [RR, 1.14; 95% CI, 0.80-1.61; I2=52%; p = 0.48], number of patients with peritonitis [RR, 1.13; 95% CI, 0.97-1.32; I2=5%; p = 0.11] and mortality [RR, 1.00; 95% CI, 0.67-1.50; I2=63%; p = 0.99] between the study groups. The pooled analysis of adjusted HRs indicated no statistically significant difference in the risk of technique failure [HR, 1.25; 95% CI, 0.88-1.78; I2=79%; p = 0.22], peritonitis [HR, 1.04; 95% CI, 0.72-1.50; I2=76%; p = 0.85] and mortality [HR, 1.24; 95% CI, 0.77-2.00; I2=66%; p = 0.38] between the study groups.ConclusionPatients with kidney transplant failure initiating PD do not have an increased risk of mortality, technique failure, or peritonitis as compared to transplant-naïve patients initiating PD. Further studies are needed to evaluate the impact of prior and ongoing immunosuppression on PD outcomes.
| S-EPMC8079072 | biostudies-literature
Project description: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.
| S-EPMC8016719 | biostudies-literature
Project description: Not available
| S-DIXA-D-1057 | biostudies-other
Project description:Outcomes after lung transplant lag behind those of other solid-organ transplants. A better understanding of the pathways that contribute to rejection and tolerance after lung transplant will be required to develop new therapeutic strategies that take into account the unique immunological features of lungs. Mechanistic immunological investigations in an orthotopic transplant model in the mouse have shed new light on immune responses after lung transplant. Here, we highlight that interactions between immune cells within pulmonary grafts shape their fate. These observations set lungs apart from other organs and help provide the conceptual framework for the development of lung-specific immunosuppression.
| S-EPMC5711341 | biostudies-other
Project description:BackgroundDeclining rates of acute rejection (AR) and the high rate of 1-year graft survival among patients with AR have prompted re-examination of AR as an outcome in the clinic and in trials. Yet AR and its treatment may directly or indirectly affect longer-term outcomes for kidney transplant recipients.MethodsTo understand the long-term effect of AR on outcomes, we analyzed data from the Australia and New Zealand Dialysis and Transplant Registry, including 13,614 recipients of a primary kidney-only transplant between 1997 and 2017 with at least 6 months of graft function. The associations between AR within 6 months post-transplant and subsequent cause-specific graft loss and death were determined using Cox models adjusted for baseline donor, recipient, and transplant characteristics.ResultsAR occurred in 2906 recipients (21.4%) and was associated with graft loss attributed to chronic allograft nephropathy (hazard ratio [HR], 1.39; 95% confidence interval [95% CI], 1.23 to 1.56) and recurrent AR beyond month 6 (HR, 1.85; 95% CI, 1.39 to 2.46). Early AR was also associated with death with a functioning graft (HR, 1.22; 95% CI, 1.08 to 1.36), and with death due to cardiovascular disease (HR, 1.30; 95% CI, 1.11 to 1.53) and cancer (HR, 1.35; 95% CI, 1.12 to 1.64). Sensitivity analyses restricted to subgroups with either biopsy-proven, antibody-mediated, or vascular rejection, or stratified by treatment response produced similar results.ConclusionsAR is associated with increased risks of longer-term graft failure and death, particularly death from cardiovascular disease and cancer. The results suggest AR remains an important short-term outcome to monitor in kidney transplantation and clinical trials.
| S-EPMC6727270 | biostudies-literature