Pre-implantation Kidney Biopsy Research Articles

The Puzzle of Preimplantation Kidney Biopsy Decision-Making Process: The Pathologist Perspective.

Kidney transplantation is the best treatment for end-stage renal disease since it offers the greatest survival benefit compared to dialysis. The gap between the number of renal transplants performed and the number of patients awaiting renal transplants leads to a steadily increasing pressure on the scientific community. Kidney preimplantation biopsy is used as a component of the evaluation of organ quality before acceptance for transplantation. However, the reliability and predictive value of biopsy data are controversial. Most of the previously proposed predictive models were not associated with graft survival, but what has to be reaffirmed is that histologic examination of kidney tissue can provide an objective window on the state of the organ that cannot be deduced from clinical records and renal functional studies. The balance of evidence indicates that reliable decisions about donor suitability must be made based on the overall picture. This work discusses recent trends that can reduce diagnostic timing and variability among players in the decision-making process that lead to kidney transplants, from the pathologist's perspective.

European Society for Organ Transplantation (ESOT)-TLJ 3.0 Consensus on Histopathological Analysis of Pre-Implantation Donor Kidney Biopsy: Redefining the Role in the Process of Graft Assessment.

The ESOT TLJ 3.0. consensus conference brought together leading experts in transplantation to develop evidence-based guidance on the standardization and clinical utility of pre-implantation kidney biopsy in the assessment of grafts from Expanded Criteria Donors (ECD). Seven themes were selected and underwent in-depth analysis after formulation of PICO (patient/population, intervention, comparison, outcomes) questions. After literature search, the statements for each key question were produced, rated according the GRADE approach [Quality of evidence: High (A), Moderate (B), Low (C); Strength of Recommendation: Strong (1), Weak (2)]. The statements were subsequently presented in-person at the Prague kick-off meeting, discussed and voted. After two rounds of discussion and voting, all 7 statements reached an overall agreement of 100% on the following issues: needle core/wedge/punch technique representatively [B,1], frozen/paraffin embedded section reliability [B,2], experienced/non-experienced on-call renal pathologist reproducibility/accuracy of the histological report [A,1], glomerulosclerosis/other parameters reproducibility [C,2], digital pathology/light microscopy in the measurement of histological variables [A,1], special stainings/Haematoxylin and Eosin alone comparison [A,1], glomerulosclerosis reliability versus other histological parameters to predict the graft survival, graft function, primary non-function [B,1]. This methodology has allowed to reach a full consensus among European experts on important technical topics regarding pre-implantation biopsy in the ECD graft assessment.

Kidney Donation after circulatory death: The Veneto Region experience in Italy

Donation after circulatory death (DCD) is a promising strategy for increasing organ supply worldwide. The Italian current legislative framework has represented a major barrier to the implementation of such program, given the 20-minute no-touch period required for donor death declaration.In this study, we describe DCD reporting activity in Veneto, number of procurements and kidney transplants performed from DCD donors since the beginning of its application, in 2017. We considered donor characteristics (DCD Maastricht category, age, sex) and number of kidney grafts retrieved and transplanted for each donor.All the procured kidney grafts underwent ex situ hypothermic perfusion and pre-implantation kidney biopsy according to Karpinski-Remuzzi score. Perfusion parameters were monitored in order to predict functional recovery after transplantation and the histological evaluation focused on evaluating the extension of the ischemic injury. In the Veneto experience, histological data and hypothermic perfusion have proven to be very useful tools to make a decision concerning whether a kidney is suitable for transplantation.Considering logistical, clinical, ethical and technical issues related to DCD donor program in Italy, many resources had to be dedicated in Veneto to build adequate technical expertise and to develop dedicated care pathways. The Veneto Region Transplant Coordination has encouraged and supported the development of DCD activity, increasing kidney transplantation from DCD donors.

Pre-Implantation Kidney Biopsies in Extended Criteria Donors: From On Call to Expert Pathologist, from Conventional Microscope to Digital Pathology

The number of patients awaiting a kidney transplant is constantly rising but lack of organs leads kidneys from extended criteria donors (ECD) to be used to increase the donor pool. Pre-transplant biopsies are routinely evaluated through the Karpinski-Remuzzi score but consensus on its correlation with graft survival is controversial. This study aims to test a new diagnostic model relying on digital pathology to evaluate pre-transplant biopsies and to correlate it with graft outcomes. Pre-transplant biopsies from 78 ECD utilized as single kidney transplantation were scanned, converted to whole-slide images (WSIs), and reassessed by two expert nephropathologists using the Remuzzi-Karpinski score. The correlation between graft survival at 36 months median follow-up and parameters assigned by either WSI or glass slide score (GSL) by on-call pathologists was evaluated, as well as the agreement between the GSL and the WSIs score. No relation was found between the GSL assessed by on-call pathologists and graft survival (<i>P</i> = 0.413). Conversely, the WSI score assigned by the two nephropathologists strongly correlated with graft loss probability, as confirmed by the ROC curves analysis (DeLong test <i>P</i> = 0.046). Digital pathology allows to share expertise in the transplant urgent setting, ensuring higher accuracy and favoring standardization of the process. Its employment may significantly increase the predictive capability of the pre-transplant biopsy evaluation for ECD, improving the quality of allocation and patient safety.

Distinct global DNA methylation and NF-κB expression profile of preimplantation biopsies from ideal and non-ideal kidneys.

Epigenetic mechanisms may affect the ideal and non-ideal kidneys selected for transplantationand their inflammatory gene expression profile differently and may contribute to poor clinical outcomes. Study the Global DNA methylation and the expression profiles of the DNA methyltransferases (DNMTs) and nuclear factor kappa B (NF-κB) in preimplantation kidney biopsies from ideal and non-ideal kidneys (expanded criteria donor (ECD) and with KDPI > 85%). In a sample consistingof45 consecutive pre-implantation biopsies,global DNA methylation levels were detected by LINE-1 repeated elements using bisulfite pyrosequencing. DNMT gene expression was assessed by real-time quantitative polymerase chain reaction, and NF-κB protein expression by immunofluorescence. ECD kidneys displayed increased methylation levels in LINE-1, and DNMT1 and DNMT3B expression was upregulated when comparing ECD to standard criteria donor kidneys. Similarly, kidneys with KDPI > 85% exhibited increased LINE-1 methylation and DNMT1 upregulation when compared to a KDPI ≤ 85%. NF-κB protein expression levels were greatly increased in both types of non-ideal kidneys compared to ideal kidneys. Moreover, hypermethylation of LINE-1 was associated with cold ischemia time > 20h and ECD kidney classification. This study shows that global DNA hypermethylation and high expression of NF-κB occurred in both types of non-ideal kidneys and were associated with prolonged cold ischemia time. Global DNA methylation can be a useful tool to assess non-ideal kidneys and hence, could be used to expand the pool of kidneys donors.

P2.11: Distinct Global DNA Methylation and NF-κB Expression Profile of Preimplantation Biopsies From Ideal and Non-ideal Kidneys

Background: Epigenetic mechanisms may differently affect the ideal and non-ideal kidneys and their inflammatory gene expression profile and may contribute to poor clinical outcomes. Objective: To identify the Global DNA methylation was evaluated, as well as the expression profiles of the DNA methyltransferases (DNMTs) and nuclear factor kappa B (NF-κB) in preimplantation kidney biopsies from ideal and non-ideal kidneys (extended criteria donor-ECD and with KDPI>85%). Methods: Global DNA methylation was estimated by LINE-1 repeated elements methylation using bisulfite pyrosequencing, DNMTs expression was assessed by q-PCR and NF-κB protein expression by immunofluorescence. Results: ECD kidneys displayed increased methylation levels in LINE-1, and DNMT1 and DNMT3B expression were upregulated when comparing ECD to standard criteria donor kidneys. Similarly, kidneys with KDPI > 85% exhibited increased LINE-1 hypermethylation and DNMT1 upregulation vs. kidneys with a KDPI ≤ 85%. NF-κB protein expression levels were greatly increased in both types of non-ideal kidneys compared to ideal kidneys. Moreover, hypermethylation of LINE-1 was associated with cold ischemia time > 20 h and ECD kidney classification. Conclusions: This study shows that global DNA hypermethylation and high expression of NF-κB occurred in both types of non-ideal kidneys and were associated with prolonged cold ischemia time. Global DNA methylation can be a useful tool to assess suboptimal kidneys and hence, could be used to increase the use of these kidneys to expand the donor pool. This study was supported by São Paulo State Research Foundation (FAPESP – Fundação de Amparo à Pesquisa do Estado de São Paulo) grant number 2016/08301-8.

The Relationship between Timing of Pretransplant Kidney Biopsy, Graft Loss, and Survival in Kidney Transplantation: An Italian Cohort Study

Introduction: Kidney biopsy is performed to assess if an extended criteria graft can be used for transplantation. It may be performed before or after cross-clamping during organ procurement. This study aims to evaluate whether the timing of biopsy may modify cold ischemia times (CIT) and/or graft outcomes. Methods: Kidney transplants performed in our center from January 2007 to December 2017 were analyzed. Grafts with preimplantation kidney biopsy were included. Biopsies were performed during surgical back table (ex situ kidney biopsy [ESKB]) until 2012 and since then before the aortic cross-clamping (in situ kidney biopsy [ISKB]). To overcome biases owing to different distributions, a propensity score model was developed. The study population consists in 322 patients, 115 ESKB, and 207 ISKB. Results: CIT was significantly lower for ISKB (730 min ISKB vs. 840 min ESKB, p value = 0.001). In both crude (OR 0.27; 95% confidence interval, 95% CI 0.12–0.60; p value = 0.002) and adjusted analyses (OR 0.37; 95% CI 0.14–0.94; p value = 0.039), ISKB was associated with a reduced odd of graft loss when compared to ESKB. Discussion/Conclusion: Performing preimplantation kidney biopsy during the recovery, prior to the aortic cross-clamping, may be a strategy to reduce CIT and improve transplant outcomes.

Tubular Cell Dropout in Preimplantation Deceased Donor Biopsies as a Predictor of Delayed Graft Function.

Delayed graft function (DGF) affects over 25% of deceased donor kidney transplants (DDKTs) and is associated with increased cost, worsened graft outcomes, and mortality. While approaches to preventing DGF have focused on minimizing cold ischemia, donor factors such as acute tubular injury can influence risk. There are currently no pharmacologic therapies to modify DGF risk or promote repair, in part due to our incomplete understanding of the biology of preimplantation tubular injury. We collected intraoperative, preimplantation kidney biopsies from 11 high-risk deceased donors and 10 living donors and followed transplant recipients for graft function. We performed quantitative high-dimensional histopathologic analysis using imaging mass cytometry to determine the cellular signatures that distinguished deceased and living donor biopsies as well as deceased donor biopsies which either did or did not progress to DGF. We noted decreased tubular cells (P < 0.0001) and increased macrophage infiltration (P = 0.0037) in high-risk DDKT compared with living donor biopsies. For those high-risk DDKTs that developed postimplant DGF (n = 6), quantitative imaging mass cytometry analysis showed a trend toward reduced tubular cells (P = 0.02) and increased stromal cells (P = 0.04) versus those that did not (n = 5). Notably, these differences were not identified by conventional histopathologic evaluation. The current study identifies donor tubular cell loss as a precursor of DGF pathogenesis and highlights an area for further investigation and potential therapeutic intervention.

MO089HISTOMORPHOMETRIC ANALYSIS OF GLOMERULI AND CAPILLARIES DENSITY IN THE INTERSTITIUM IN PREIMPLANTATION NEEDLE BIOPSIES OF PAIRED KIDNEYS HARVESTED FROM ADULT CADAVERIC DONORS

Abstract Background and Aims Preimplantation needle biopsy of kidney allows more precise interpretation of subsequent kidney biopsies performed after transplantation and potentially also may predict kidney graft survival. It is unknown, whether it is justified to perform the biopsy of one kidney only and then to transmit obtained results also to the second kidney or biopsies of both kidneys are mandatory. The aim of the study was to assess differences regarding glomerular volume, glomerular density and capillary density in the interstitium of both kidneys harvested from the same deceased donor. Method The study involved 40 pairs of kidneys (all together 80 kidneys) in which preimplantation kidney biopsies were performed. Kidneys were harvested from 40 deceased donors (17 females and 23 males; mean age 42.3 [37.6-47.0] years old) died because of intracranial haemorrhage (17 donors) or cerebral trauma due to accident (23 donors). Histomorphometric analysis was performed using “Olympus BX51” microscope (Olympus, Tokyo, Japan) coupled with “Olympus BX50” camera and the “cellSens Standard” software (Olympus, Tokyo, Japan). Weibel-Gomez formula was adapted to calculate glomerular volume. Results No significant differences were found between mean kidneys length [115.8 (112.4-119.1) vs.115.5 (112.5-118.5) mm], glomerular volume [2.59 (2.24-2.93) vs 2.49 (2.15-2.84) μm3 x106 ], glomerular density [3.43 (3.07-3.80) vs 3.24 (2.87-3.61) n/mm2] and interstitial capillaries density [233.58 (211.26) vs 217.80 (199.45-236.47) n/mm2] of both kidneys harvested from the same deceased donor. Conclusions 1. Both kidneys harvested from the same deceased donor did not differ significantly in kidney length, glomerular volume, glomerular density and capillary density. 2. Our results justify to preimplantation biopsy of only one kidney and the results from the histomorphometric analysis may be used in the future also for assessment of the second kidney.

Advantages of Using a Web-based Digital Platform for Kidney Preimplantation Biopsies

Background: In the setting of kidney transplantation, histopathology of kidney biopsies is a key element in the organ assessment and allocation. Despite the broad diffusion of the Remuzzi-Karpinski score on preimplantation kidney biopsies, scientific evidence of its correlation to the transplantation outcome is controversial. The main issues affecting the prognostic value of histopathology are the referral to general on-call pathologists and the semiquantitative feature of the score, which can raise issues of interpretation. Digital pathology has shown very reliable and effective in the oncological diagnosis and treatment; however, the spread of such technologies is lagging behind in the field of transplantation. The aim of our study was to create a digital online platform where whole-slide images (WSI) of preimplantation kidney biopsies could be uploaded and stored. Methods: We included 210 kidney biopsies collected between January 2015 and December 2019 from the joint collaboration of the transplantation centers of Padua and Verona. The selected slides, stained with hematoxylin and eosin, were digitized and uploaded on a shared web platform. For each case, the on-call pathologists’ Remuzzi grades were obtained from the original report, together with the clinical data and the posttransplantation follow-up. Results: The storage of WSI of preimplantation kidney biopsies would have several clinical, scientific, and educational advantages. The clinical utility relies on the possibility to consult online expert pathologists and real-time quality checks of diagnosis. From the perspective of follow-up, the archived digitized biopsies can offer a useful comparison to posttransplantation biopsies. In addition, the digital online platform is a precious tool for multidisciplinary meetings aimed both at the clinical discussion and at the design of research projects. Furthermore, this archive of readily available WSI is an important educational resource for the training of professionals. Conclusions: Finally, the web platform lays the foundation for the introduction of artificial intelligence in the field of transplantation that would help create new diagnostic algorithms and tools with the final aim of increasing the precision of organ assessment and its predictive value for transplant outcome.

Donneurs très âgés en transplantation rénale : jusqu’où peut-on aller ?

In order to increase the pool of organ donors, kidney transplantation from very old-donors, notably aged more than 70, is increasing. Compared to the United States, where the use of these grafts does not reach 5%, in France it reaches over 20%. Kidney aging is determined by a progressive glomerusclerosis, interstitial fibrosis, and nephrosclerosis, responsible of a linear decrease of glomerular filtration rate with time. Aging in kidney transplantation goes along also with an increased immunogenicity and risk of ischemia-reperfusion injuries. Hence, the prognosis of these transplantations is worse than those from younger donors, even though it remains better than dialysis. Data is lacking on risk factors of graft loss in this specific population. Hypothermic perfusion machine, pre-implantation kidney biopsy, dual kidney transplantation and immunosuppressive strategies have been evaluated to improve the long-term prognosis of these grafts.

Pre-implantation kidney biopsy: value of the expertise in determining histological score and comparison with the whole organ on a series of discarded kidneys.

Evidence about the reliability of pre-implantation biopsy is still conflicting, depending on both biopsy type and pathologist's expertise. Aim of the study is to evaluate the agreement of general v specialist pathologists and to compare scores on biopsy and whole organs in a set of discarded kidneys. 46 discarded kidneys were identified with their corresponding biopsies. The biopsies were reviewed by three general and two specialist pathologists, blinded to the original report, according to Remuzzi score. The intraclass correlation coefficient (ICC) was calculated for both groups. Discarded kidneys were scored according to Remuzzi score by a single specialist pathologist. Biopsies and organs were compared by Wilcoxon signed rank test. Weighted κ coefficients between biopsy and organ scores were also calculated. Specialist pathologists achieved higher values of ICC, reaching excellent or good agreement in most of the parameters, while general pathologists values were mainly fair or good. On whole organs, scores were consistently lower than biopsies, with a significant difference in most of the parameters. Weighted κ coefficient was slight or fair for most of the parameters. Our data suggests that the creation of a pool of specialist pathologists would improve organ utilization. Moreover, biopsies are not representative of the whole organ. As the Remuzzi score on biopsy is a major reasons for discard, a quota of transplantable kidneys may be erroneously discarded. Refinement in Remuzzi cut-offs based on expert reporting and recognition of sampling error of biopsies in correlation with clinical outcome data should be undertaken.

P126 The combination of lowTMEM52B expression in preimplantation kidney biopsies and high donor last creatinine confers risk for the occurrence of delayed graft function

P126 The combination of lowTMEM52B expression in preimplantation kidney biopsies and high donor last creatinine confers risk for the occurrence of delayed graft function

Chronic histological changes in deceased donor kidneys at implantation do not predict graft survival: a single-centre retrospective analysis.

The use of preimplantation kidney biopsies (PIKBs) to aid deceased donor kidney utilization decisions is controversial. Outcomes of transplants that had been biopsied after the decision had been made to implant were analysed, in order to determine the association between chronic histological changes at implantation and graft outcomes. A retrospective analysis of transplants between the year range 2006-2015 was performed. Karpinski scores on biopsies were collected, and graft outcomes were analysed using univariate and multivariable techniques. Also, Karpinski scores from single and dual kidney transplants from older donors were examined to determine if knowledge of the score preoperatively would have altered utilization. Four hundred and eight single kidneys were transplanted. Although kidneys with scores >4 had lower 1- and 3-year median (IQR) estimated glomerular filtration rates (eGFRs) than those scoring 0-4 (51 (37-66) vs. 35 (26-52) ml/min/1.73m2 , P<0.001, and 52 (34-64) vs. 35 (24-52) ml/min/1.73m2 , P<0.001, respectively), there was no significant association between Karpinski score and death-censored graft survival on univariate or multivariable analyses. The utilization analysis (75 single and 25 dual kidney transplant recipients) suggested that systematic use of PIKBs would have resulted in 29% fewer patients being transplanted. This analysis does not support the systematic use of PIKBs to determine deceased donor kidney utilization.

PreImplantation Trial of Histopathology In renal Allografts (PITHIA): a stepped-wedge cluster randomised controlled trial protocol

IntroductionMost potential kidney transplant donors in the UK are aged over 60 years, yet increasing donor age is associated with poorer graft survival and function. Urgent preimplantation kidney biopsy can...

Histological analysis of pre-transplant deceased donor renal biopsies and its association with long-term graft survival and function

Background: Pre-implantation kidney biopsy is a diagnostic tool used for deciding whether to accept an expanded-criteria deceased donor graft. However, the study of histopathological lesions in renal compartments as prognostic factors for graft function and survival has led to conflicting results. Objectives: This study aimed to evaluate the presence of chronic lesions in pre-implantation kidney biopsies and correlate the findings with graft function and survival at 1, 3, and 5 years post-transplantation. Patients and Methods: Around 430 kidney biopsies from standard and expanded-criteria deceased donors were analyzed between 2006 and 2013 at the hospital Santa Casa de Porto Alegre. Lesions were graded according to the Banff criteria. The glomerular filtration rate (GFR) was calculated by the CKD-EPI equation. Graft survival was calculated by the Kaplan-Meier method. Clinical variables related to graft outcome were assessed by Cox regression analysis. Results: The decrease in graft survival and function at the analyzed periods was related to a greater degree of chronic lesions in renal compartments. Glomerulosclerosis (GS) was an independent risk factor for graft loss. Conclusions: Chronic lesions in any renal compartment should be taken into account in the clinical decision of accepting the kidney, but a greater weight should be given to GS. Kidney recipients with more than 25% GS had a less favorable outcome in our study

Altered Expression of Inflammation Genes in Preimplantation Kidney Biopsies of Extended Criteria Donors

Background Changes to an organ can occur at the time of brain death and a series of inflammatory proteins are generated within the organ. It is not known whether this inflammatory similarly affects the kidneys from extended (ECD) and standard (SCD) criteria donors and because we have previously reported that preimplantation kidney biopsies from ECD donors have a heavier inflammatory profile when compared with SCD donors. In the present study we extended our results using great number of genes and seeking to identify some immunologic pathways involved in the mechanism of sterile inflammation. Methods Pretransplant kidney biopsies (Bx) were obtained from ECD (n=40) and SCD (n=40). Gene expression profile measured by Real Time qPCR Array representing expression levels of genes indicative of inflammation (IL-10, IL-1b, TNF-α, MCP-1, NFK-b, TLR-4, HMGB1, IFN-gamma, TGF-b, Myd-88), cytoprotection (HO-1, HIF-1a), apoptose (CASP-1) and intercellular adhesion (ICAM-1) and correlated with donor variables. Results ECD donors were older had more cerebrovascular accident, arterial hypertension and diabetes (p<0.01) and recipients of ECD kidneys had renal function and 24h proteinuria worst 1 year after transplantation (p<0.006). Genes IL-10, IL-1 β, TLR-4, HMGB-1, HIF-1 and CASP-1 were significantly more expressed in biopsies from ECD than SCD. Presence of DGF, acute rejection, was not associated with any individual transcript. Conclusions The present results confirm and expand our previous findings that ECD kidney is highly inflamed when compared with SCD and that a Myd-88 independent pathway of innate immunity may be activated. We appreciate the FAPESP (#2014/25831-5) for the financial support.

Effect of Prolonged Cold Ischemia on Intragraft Gene Expression Profiles

Background Deceased-donor (DD) kidneys are at higher risk for ischemia/reperfusion injury leading to increased inflammatory mediators and innate immune response. We aimed to investigate the effects of prolonged cold ischemia on intragraft molecular gene expression profiles of DD kidneys comparing to living-donors (LD) pre-implantation biopsies using microarrays. Methods There were 48 pre-implantation kidney biopsy samples (29 LD and 19 DD). The cold ischemia time (CIT) was < 16 hours in 10 and > 16 hours in 9 DD kidneys. The gene expression profiles were studied by Affymetrix HuGene 1.0 ST expression arrays. Results There were 198 differentially expressed genes when pre-implantation DD biopsies were compared to LD biopsies (Both False discovery rate p<0.05 and fold change >2). Pathogenesis based transcripts (PBT) showed increased transcripts associated with injury and response (IRIT), Constitutive Macrophage (CMAT), and Gamma Interferon (GRIT) in DD samples compared to pre-implantation LD biopsies. There was no difference in Cytotoxic T-cell (CAT), Natural-Killer cell (NKAT), B-cell (BAT), and Endothelial cell (ENDAT) associated gene transcripts between 2 groups. However, there was no statistically significant difference in expression of any PBTs studied when biopsies with CIT > 16 hours compared to biopsies with CIT < 16 hours. Gene Ontology analysis showed that DD preimplantation biopsies had increased expression of pathways related to acute inflammatory response, lymphocyte mediated immunity, innate and humoral immune response, complement activation and regulation of immune response and IL-6 activation. Conclusions Pre-implantation DD kidney biopsies showed increased expression of gene transcripts associated with inflammatory mediators, cytokines, macrophages, innate immune response and response to injury compared to LD kidneys. However, increased cold ischemia time does not change the intragraft gene expression profiles.

Does Assessing Preimplantation Kidney Biopsy and Pump Resistive Index Values Predict Kidney Allograft Survival?

Background The relationship between histological findings of preimplantation kidney biopsies and pump resistive index (RI) values during machine preservation and allograft survival remains unclear due to conflicting results between different studies. Objective To determine the association between histological findings of preimplantation kidney biopsies and pump resistive index values and short-term graft survival (up to 3 years post-transplant). Methods We performed a retrospective review of all patients who received a kidney-only transplant between January 1, 2009, and December 31, 2014, at our center and followed-up until December 1, 2016. Patients who died with a functioning allograft were excluded from analysis. Obsolete glomerulosclerosis was divided into 3 groups (< 10%, 10-20%, and > 20%), intimal arterial narrowing was divided into 3 groups (< 10%, 11-25% and > 25%) and RI was divided into 5 groups (0.00-0.09, 0.10-0.19, 0.20-0.29, 0.30-0.39 and 0.40=0.49). The log-rank test was used to test if there is a significant difference in different RI groups in terms of the probability of survival. Results A total of 662 patients received kidney-only transplants in our study period. 506 of 662 received deceased donor kidneys and were included in our analysis with 21% Caucasian, 47% African American, and 31% Hispanic. The median age was 53.6 (range, 21.1-79.2) and 58% were male. 57% of deceased donors were standard, 31% expanded and 12% donation after cardiac death donors with a median KDPI of 62. During a median follow-up time of 36 months (range, 23-94), 51 patients lost their allografts (death-censored graft survival 90%). There was no difference in terms of patients’ age, sex, race, etiology of kidney disease, type of induction agent, and cold ischemia time when graft loss patients are compared to patients with functioning allograft. The graft loss group had higher KDPI (71 vs. 61, p=0.03) and received more expanded criteria donor (49% vs. 29%, p=0.01). Percent of obsolete glomerulosclerosis and arterial intimal narrowing in preimplantation biopsies showed no association with short-term allograft failure at 1, 2, and 3 years. RI was a strong predictive factor for short-term allograft failure. Kidneys in different RI categories have significantly different survival experiences in 1, 2, and 3 years (p=0.030, p=0.001, p=0.008, respectively). RI > 0.4 performed worse than other RI groups as seen in Figure 1 (Figure 1 shows 3 year Kaplan-Meier graft survival).Conclusions Recipients of higher KDPI score and expanded criteria donor were at higher risk for allograft failure. Percent of obsolete glomerulus and arterial narrowing in preimplantation biopsies did not predict short-term allograft failure. However, RI was a strong predictive factor for short-term allograft failure.

Tubular Cell Senescence in the Donated Kidney Predicts Allograft Function, but Not Donor Remnant Kidney Function, in Living Donor Kidney Transplantation

Background: It is uncertain whether kidneys from marginal donors are suitable for live kidney transplantation. In deceased donor kidneys, tubular cell senescence affects allograft function. However, the degree of cell senescence in a living donor kidney with marginal factors has not been reported. In this study, we assessed the association of tubular cell senescence with allograft and remnant kidney function by a prospective observational clinical study. Methods: Thirty-eight living donor kidney transplantations were analyzed prospectively. Tissue sections obtained from preimplantation kidney biopsies were immunostained for p16^INK4a to indicate cell senescence. Various kidney biomarkers were analyzed in urine and blood samples. Results: Of the 38 donors, 21 had marginal factors. Severe tubular senescence was found in living donors with overlapping marginal criteria. Tubular senescence in living donor kidneys was significantly related to donor age and lower recipient kidney function at 1 year after transplantation independently of donor age (β = –0.281; p = 0.050) but did not affect remnant kidney function after donation. Pretransplantation donor pre-estimated glomerular filtration rate and hypertension did not show a significant area under the curve (AUC) for prediction of high tubular senescence. High plasma levels of soluble αKlotho were associated with a higher predictive value for low tubular cell senescence with an AUC of 0.78 (95% CI 0.62–0.93; p < 0.01). Conclusions: The nuclear p16-staining rate in donated kidney tubules is a predictor for allograft kidney function but not donor remnant kidney function. Detection of tubular cell senescence may facilitate selection of appropriate living donor candidates.