Preimplant histologic acute tubular necrosis and allograft outcomes

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

Utility of Applying Quality Assessment Tools for Kidneys With KDPI ≥80

BACKGROUND: Kidneys with “high” kidney donor profile index (KDPI) are often biopsied and pumped, yet frequently discarded. METHODS: In this multicenter study, we describe the characteristics and outcomes of kidneys with KDPI ≥80 that were procured from 338 deceased donors. We excluded donors with anatomical kidney abnormalities. RESULTS: 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 1(st) hour renal resistance. Kidney injury biomarker levels (NGAL, IL-18, and KIM-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 (eGFR) or graft failure between groups 1 and 2 (41.5±18 vs. 41.4±22 mL/min/1.73m(2); p=0.97 and 9% vs. 10%; p=0.76). CONCLUSIONS: Kidneys with KDPI ≥80 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 ≥80 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

The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans

Expression, genetic variation, and tissues Human genomes show extensive genetic variation across individuals, but we have only just started documenting the effects of this variation on the regulation of gene expression. Furthermore, only a few tissues have been examined per genetic variant. In order to examine how genetic expression varies among tissues within individuals, the Genotype-Tissue Expression (GTEx) Consortium collected 1641 postmortem samples covering 54 body sites from 175 individuals. They identified quantitative genetic traits that affect gene expression and determined which of these exhibit tissue-specific expression patterns. Melé et al. measured how transcription varies among tissues, and Rivas et al. looked at how truncated protein variants affect expression across tissues. Science , this issue p. 648 , p. 660 , p. 666 ; see also p. 640 </jats:p

Synchronized age-related gene expression changes across multiple tissues in human and the link to complex diseases

Aging is one of the most important biological processes and is a known risk factor for many age-related diseases in human. Studying age-related transcriptomic changes in tissues across the whole body can provide valuable information for a holistic understanding of this fundamental process. In this work, we catalogue age-related gene expression changes in nine tissues from nearly two hundred individuals collected by the Genotype-Tissue Expression (GTEx) project. In general, we find the aging gene expression signatures are very tissue specific. However, enrichment for some well-known aging components such as mitochondria biology is observed in many tissues. Different levels of cross-tissue synchronization of age-related gene expression changes are observed, and some essential tissues (e.g., heart and lung) show much stronger “co-aging” than other tissues based on a principal component analysis. The aging gene signatures and complex disease genes show a complex overlapping pattern and only in some cases, we see that they are significantly overlapped in the tissues affected by the corresponding diseases. In summary, our analyses provide novel insights to the co-regulation of age-related gene expression in multiple tissues; it also presents a tissue-specific view of the link between aging and age-related diseases.Version of Recor

Effect of predicted protein-truncating genetic variants on the human transcriptome

Expression, genetic variation, and tissues Human genomes show extensive genetic variation across individuals, but we have only just started documenting the effects of this variation on the regulation of gene expression. Furthermore, only a few tissues have been examined per genetic variant. In order to examine how genetic expression varies among tissues within individuals, the Genotype-Tissue Expression (GTEx) Consortium collected 1641 postmortem samples covering 54 body sites from 175 individuals. They identified quantitative genetic traits that affect gene expression and determined which of these exhibit tissue-specific expression patterns. Melé et al. measured how transcription varies among tissues, and Rivas et al. looked at how truncated protein variants affect expression across tissues. Science , this issue p. 648 , p. 660 , p. 666 ; see also p. 640 </jats:p