Search

Background: Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls., Methods: In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection., Results: We enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment., Conclusions: In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.)., (Copyright © 2024 Massachusetts Medical Society.)

Kidney transplant recipients require lifelong immunosuppression to prevent graft rejection. However, immunosuppression is associated with adverse effects. A minority of kidney transplant recipients can be weaned off immunosuppression and maintain their graft function, a situation referred to as "functional or operational tolerance". We describe a case of a 70-year-old man who received a haploidentical hematopoietic cell transplant for lymphoma 22 years before receiving a kidney transplant from the same donor and was weaned off all immunosuppression by four months post-transplant. Tolerance was present, and there has been no graft rejection or graft vs. host disease. This case demonstrates successful long-term hematopoietic chimerism and functional tolerance after receiving a kidney transplant from the same donor., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = 0.77 1.40 2.56 ,P = .3) and moderately (wIRR = 0.88 1.35 2.06 ,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = 1.33 2.22 3.72 ,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = 2.62 3.57 4.88 , P < .001) and death-censored graft loss (wHR = 1.15 4.01 13.95 ,P = .03). Post-KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients., (© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Desensitization protocols for HLA-incompatible living donor kidney transplantation (ILDKT) vary across centers. The impact of these, as well as other practice variations, on ILDKT outcomes remains unknown., Methods: We sought to quantify center-level variation in mortality and graft loss following ILDKT using a 25-center cohort of 1358 ILDKT recipients with linkage to Scientific Registry of Transplant Recipients for accurate outcome ascertainment. We used multilevel Cox regression with shared frailty to determine the variation in post-ILDKT outcomes attributable to between-center differences and to identify any center-level characteristics associated with improved post-ILDKT outcomes., Results: After adjusting for patient-level characteristics, only 6 centers (24%) had lower mortality and 1 (4%) had higher mortality than average. Similarly, only 5 centers (20%) had higher graft loss and 2 had lower graft loss than average. Only 4.7% of the differences in mortality (P < 0.01) and 4.4% of the differences in graft loss (P < 0.01) were attributable to between-center variation. These translated to a median hazard ratio of 1.36 for mortality and 1.34 of graft loss for similar candidates at different centers. Post-ILDKT outcomes were not associated with the following center-level characteristics: ILDKT volume and transplanting a higher proportion of highly sensitized, prior transplant, preemptive, or minority candidates., Conclusions: Unlike most aspects of transplantation in which center-level variation and volume impact outcomes, we did not find substantial evidence for this in ILDKT. Our findings support the continued practice of ILDKT across these diverse centers., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Infections remain a major threat to successful kidney transplantation (KT). To characterize the landscape and impact of post-KT infections in the modern era, we used United States Renal Data System (USRDS) data linked to the Scientific Registry of Transplant Recipients (SRTR) to study 141 661 Medicare-primary kidney transplant recipients from January 1, 1999 to December 31, 2014. Infection diagnoses were ascertained by International Classification of Diseases, Ninth Revision (ICD-9) codes. The cumulative incidence of a post-KT infection was 36.9% at 3 months, 53.7% at 1 year, and 78.0% at 5 years. The most common infections were urinary tract infection (UTI; 46.8%) and pneumonia (28.2%). Five-year mortality for kidney transplant recipients who developed an infection was 24.9% vs 7.9% for those who did not, and 5-year death-censored graft failure (DCGF) was 20.6% vs 10.1% (P < .001). This translated to a 2.22-fold higher mortality risk (adjusted hazard ratio [aHR]: 2.15 2.22 2.29 , P < .001) and 1.92-fold higher DCGF risk (aHR: 1.84 1.91 1.98 , P < .001) for kidney transplant recipients who developed an infection, although the magnitude of this higher risk varied across infection types (for example, 3.11-fold higher mortality risk for sepsis vs 1.62-fold for a UTI). Post-KT infections are common and substantially impact mortality and DCGF, even in the modern era. Kidney transplant recipients at high risk for infections might benefit from enhanced surveillance or follow-up to mitigate these risks., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Clinical decision-making in kidney transplant (KT) during the coronavirus disease 2019 (COVID-19) pandemic is understandably a conundrum: both candidates and recipients may face increased acquisition risks and case fatality rates (CFRs). Given our poor understanding of these risks, many centers have paused or reduced KT activity, yet data to inform such decisions are lacking. To quantify the benefit/harm of KT in this context, we conducted a simulation study of immediate-KT vs delay-until-after-pandemic for different patient phenotypes under a variety of potential COVID-19 scenarios. A calculator was implemented (http://www.transplantmodels.com/covid&#95;sim), and machine learning approaches were used to evaluate the important aspects of our modeling. Characteristics of the pandemic (acquisition risk, CFR) and length of delay (length of pandemic, waitlist priority when modeling deceased donor KT) had greatest influence on benefit/harm. In most scenarios of COVID-19 dynamics and patient characteristics, immediate KT provided survival benefit; KT only began showing evidence of harm in scenarios where CFRs were substantially higher for KT recipients (eg, ≥50% fatality) than for waitlist registrants. Our simulations suggest that KT could be beneficial in many centers if local resources allow, and our calculator can help identify patients who would benefit most. Furthermore, as the pandemic evolves, our calculator can update these predictions., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

In light of changes in donor/recipient case-mix and increased cold ischemia times under the Kidney Allocation System (KAS), there is some concern that cPRA 100% recipients might be doing poorly under KAS. We used granular, single-center data on 109 cPRA 100% deceased donor kidney transplant (DDKT) recipients to study post-KAS posttransplant outcomes not readily available in national registry data. We found that 3-year patient (96.4%) and death-censored graft survival (96.8%) was excellent. We also found that cPRA 100% recipients had a relatively low incidence of T cell-mediated rejection (9.2%) and antibody-mediated rejection (AMR) (13.8%). T cell-mediated rejection episodes tended to be relatively mild-50% (5 episodes) were grade 1, 50% (5 episodes) were grade 2, and none were grade 3. Only 1 episode was associated with graft loss, but this was in the context of a mixed rejection. Although only 15 recipients (13.8%) developed an AMR episode, 2 of these were associated with a graft loss. Despite the rejection episodes, the vast majority of recipients had excellent graft function 3 years posttransplant (median serum creatinine 1.5 mg/dL). In conclusion, cPRA 100% DDKT recipients are doing well under KAS, although every effort should be made to prevent AMR to ensure long-term outcomes remain excellent., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: One of the primary risks of HIV-positive to HIV-positive organ transplantation is loss of virological control because of donor-derived HIV superinfection, which occurs when an HIV-positive individual becomes infected with a new distinct HIV strain. In this study, as part of the larger HIV Organ Policy Equity pilot study, HIV-positive to HIV-positive kidney and liver transplant recipients in the USA were examined for evidence of sustained donor-derived HIV superinfection., Methods: In this multicentre, prospective, observational study, HIV-positive to HIV-positive kidney and liver transplant recipients were followed in three hospitals in the USA. Candidates with well controlled HIV infection on ART, no active opportunistic infections, and minimum CD4 T-cell counts (>100 cells per μL for liver and >200 cells per μL for kidney per federal guidelines) were eligible to receive a kidney or liver from deceased HIV-positive donors without active infections or neoplasm. Peripheral blood mononuclear cells were collected from donor-recipient pairs at the time of transplantation, and from recipients at several timepoints up to 3 years after transplantation. Donor samples were assessed for HIV RNA viral load, CD4 cell count, and antiretroviral drug-resistant mutations. Donor and recipient HIV proviral DNA, and viral RNA from the viraemic timepoint were sequenced using a site-directed next-generation sequencing assay for the reverse transcriptase and gp41 genes. Neighbour-joining phylogenetic trees and direct sequence comparison were used to detect the presence of HIV superinfection. This study is registered with ClinicalTrials.gov, NCT02602262., Findings: 14 HIV-positive to HIV-positive kidney and eight liver transplant recipients were followed from March, 2016, to July, 2019. 17 recipients had adequate viral sequences allowing for HIV superinfection assessment. Eight donors were suppressed (viral load <400 copies per mL), and none had multiclass drug-resistant mutations detected. None of the recipients examined had evidence of HIV superinfection. One recipient had a viraemic episode (viral load of 2 080 000 copies per mL) 3 years after transplantation as a result of non-adherence to ART. Only recipient viral sequences were detected during the viraemic episode, suggesting that the donor virus, if present, was not reactivated despite temporary withdrawal of ART., Interpretation: These findings suggest that loss of HIV suppression due to donor-derived HIV superinfection might not be a significant clinical concern in carefully monitored ART suppressed HIV-positive organ recipients., Funding: US National Institute of Allergy and Infectious Diseases and National Cancer Institute., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Stakeholders have expressed concerns regarding decreased deceased donor kidney transplant (DDKT) rates for pediatric candidates under the Kidney Allocation System (KAS). To better understand what might be driving this, we studied Scientific Registry of Transplant Recipients kidney offer data for 3642 pediatric (age <18 years) kidney-only transplant candidates between December 31, 2012 to December 3, 2014 (pre-KAS) and December 4, 2014 to January 6, 2017 (post-KAS). We used negative binomial regression and multilevel logistic regression to compare offer and acceptance rates pre- and post-KAS. We stratified by donor age (<18, 18-34, and 35+ years) and KDPI (<35% and ≥35%) to reflect differing allocation prioritization pre-KAS and post-KAS. As might be expected from prioritization changes, post-KAS candidates were less likely to receive offers for donors 18-34 years old with KDPI ≥ 35% (adjusted incidence rate ratio [aIRR]: 0.18 0.21 0.25 , P < .001), and more likely to receive offers for donors 18-34 years old and KDPI < 35% (aIRR: 1.12 1.20 1.29 , P < .001). However, offer acceptance practices also changed post-KAS: kidneys from donors 18-34 years old and KDPI < 35% were 23% less likely to be accepted post-KAS (adjusted odds ratio: 0.61 0.77 0.98 , P = .03). Using kidneys from donors 18-34 years old with KDPI < 35% post-KAS to the same extent they were used pre-KAS might be an effective strategy to mitigate any decrease in DDKT rates for pediatric candidates., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Prioritization of highly sensitized (HS) candidates under the kidney allocation system (KAS) and growth of large, multicenter kidney-paired donation (KPD) clearinghouses have broadened the transplant modalities available to HS candidates. To quantify temporal trends in utilization of these modalities, we used SRTR data from 2009 to 2017 to study 39 907 adult HS (cPRA ≥ 80%) waitlisted candidates and 19 003 recipients. We used competing risks regression to quantify temporal trends in likelihood of DDKT, KPD, and non-KPD LDKT for HS candidates (Era 1: January 1, 2009-December 31, 2011; Era 2: January 1, 2012-December 3, 2014; Era 3: December 4, 2014-December 31, 2017). Although the likelihood of DDKT and KPD increased over time for all HS candidates (adjusted subhazard ratio [aSHR] Era 3 vs 1 for DDKT: 1.74 1.85 1.97 , P < .001 and for KPD: 1.70 2.20 2.84 , P < .001), the likelihood of non-KPD LDKT decreased (aSHR: 0.69 0.82 0.97 , P = .02). However, these changes affected HS recipients differently based on cPRA. Among recipients, more cPRA 98%-99.9% and 99.9%+ recipients underwent DDKT (96.2% in Era 3% vs 59.1% in Era 1 for cPRA 99.9%+), whereas fewer underwent non-KPD LDKT (1.9% vs 30.9%) or KPD (2.0% vs 10.0%). Although KAS increased DDKT likelihood for the most HS candidates, it also decreased the use of non-KPD LDKT to transplant cPRA 98%+ candidates., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: There is concern in the transplant community that outcomes for the most highly sensitized recipients might be poor under Kidney Allocation System (KAS) high prioritization., Methods: To study this, we compared posttransplant outcomes of 525 pre-KAS (December 4, 2009, to December 3, 2014) calculated panel-reactive antibodies (cPRA)-100% recipients to 3026 post-KAS (December 4, 2014, to December 3, 2017) cPRA-100% recipients using SRTR data. We compared mortality and death-censored graft survival using Cox regression, acute rejection, and delayed graft function (DGF) using logistic regression, and length of stay (LOS) using negative binomial regression., Results: Compared with pre-KAS recipients, post-KAS recipients were allocated kidneys with lower Kidney Donor Profile Index (median 30% versus 35%, P < 0.001) but longer cold ischemic time (CIT) (median 21.0 h versus 18.6 h, P < 0.001). Compared with pre-KAS cPRA-100% recipients, those post-KAS had higher 3-year patient survival (93.6% versus 91.4%, P = 0.04) and 3-year death-censored graft survival (93.7% versus 90.6%, P = 0.005). The incidence of DGF (29.3% versus 29.2%, P = 0.9), acute rejection (11.2% versus 11.7%, P = 0.8), and median LOS (5 d versus 5d, P = 0.2) were similar between pre-KAS and post-KAS recipients. After accounting for secular trends and adjusting for recipient characteristics, post-KAS recipients had no difference in mortality (adjusted hazard ratio [aHR]: 0.861.623.06, P = 0.1), death-censored graft failure (aHR: 0.521.001.91, P > 0.9), DGF (adjusted odds ratio [aOR]: 0.580.861.27, P = 0.4), acute rejection (aOR: 0.610.941.43, P = 0.8), and LOS (adjusted LOS ratio: 0.981.161.36, P = 0.08)., Conclusions: We did not find any statistically significant worsening of outcomes for cPRA-100% recipients under KAS, although longer-term monitoring of posttransplant mortality is warranted.

Background: With growing transplant wait times, clinical trials are evaluating the safety and efficacy of transplanting HCV-infected donor (HCV+) organs into HCV-noninfected recipients (HCV D+/R-). Such transplants raise ethical questions about safety, consent, and access to organs. Methods: We interviewed eight of the ten total HCV D+/R- transplant recipients enrolled in a pilot clinical trial examining the safety and feasibility of these novel transplants regarding their experiences in the trial, including their decision-making and perceptions of the informed consent process. Results : All interviewees reported positive experiences and expressed confidence regarding their decision to participate. Participants accepted an HCV + organ based on their assessments of the risks and potential benefits of HCV D+/R- transplants. For many, the risks of HCV were minimal compared to the risks of not receiving a transplant. All participants recalled providing informed consent, reporting that the process was thorough and that all their questions were addressed. Participants did not regret receiving an HCV D+/R- transplant and did not report experiencing stigma. However, given their understanding of HCV cure rates in the general population and the survival benefit associated with kidney transplantation, participants may have conflated research regarding HCV D+/R- transplantation with clinical care, suggesting a potential therapeutic misconception. Conclusions: Recipients of experimental HCV D+/R- transplants generally seemed to recognize the risks and benefits of these novel transplants and did not regret participating. Such salutary reported experiences are important in assessing the appropriateness of further research into the feasibility of HCV D+/R- transplants.

HLA eplet mismatch load has been suggested as an improvement to HLA antigen mismatch determination for organ selection. Given that eplet mismatches are determined based on amino acid sequence difference among HLA alleles, and that the frequency of HLA alleles varies between racial groups, we investigated the correlation between eplet mismatch load and allograft outcomes in 110 pediatric kidney transplant recipients who received their first organ from a donor of the same race (SRT) versus a donor of a different race (DRT). Adjusted modified Poisson regression was used to assess the interaction between eplet mismatch load and race mismatch and its effect on outcome. Caucasians and living donor recipients had lower eplet mismatched loads against their donors compared with non-Caucasian and deceased donor recipients. Overall, for the entire population, the risk of de novo HLA-DSA development was significantly increased with higher eplet loads (p < 0.001). Compared with the SRT group, the DRT group had higher eplet loads when compared with their donor, for HLA class I but not HLA class II molecules; however, there was no significant difference in the incidence of de novo HLA-DSA between the 2 groups. The risk of rejection increased significantly for DRT compared with SRT, only when class I eplet load was ≥ 70 (p = 0.04). Together this data show that eplet mismatch load analysis is an effective tool for alloimmune risk assessment. If considered for donor selection, acceptable eplet mismatch loads determined from studies in homogenous populations may restrict transplantation across racially diverse donor and patient groups with no evidence of poor outcome. Therefore, an acceptable eplet mismatch load threshold must consider the heterogeneity of the transplant population.

Background: Kidneys from infectious risk donors (IRD) confer substantial survival benefit in adults, yet the benefit of IRD kidneys to pediatric candidates remains unclear in the context of high waitlist prioritization., Methods: Using 2010-2016 Scientific Registry of Transplant Recipients data, we studied 2417 pediatric candidates (age <18 y) who were offered an IRD kidney that was eventually used for transplantation. We followed candidates from the date of first IRD kidney offer until the date of death or censorship and used Cox regression to estimate mortality risk associated with IRD kidney acceptance versus decline, adjusting for age, sex, race, diagnosis, and dialysis time., Results: Over the study period, 2250 (93.1%) pediatric candidates declined and 286 (11.8%) accepted an IRD kidney offer; 119 (41.6%) of the 286 had previously declined a different IRD kidney. Cumulative survival among those who accepted versus declined the IRD kidney was 99.6% versus 99.4% and 96.3% versus 97.8% 1 and 6 years post decision, respectively (P = 0.1). Unlike the substantial survival benefit seen in adults (hazard ratio = 0.52), among pediatric candidates, we did not detect a survival benefit associated with accepting an IRD kidney (adjusted hazard ratio: 0.791.723.73, P = 0.2). However, those who declined IRD kidneys waited a median 9.6 months for a non-IRD kidney transplant (11.2 mo among those <6 y, 8.8 mo among those on dialysis). Kidney donor profile index (KDPI) of the eventually accepted non-IRD kidneys (median = 13, interquartile range = 6-23) was similar to KDPI of the declined IRD kidneys (median = 16, interquartile range = 9-28)., Conclusions: Unlike in adults, IRD kidneys conferred no survival benefit to pediatric candidates, although they did reduce waiting times. The decision to accept IRD kidneys should balance the advantage of faster transplantation against the risk of infectious transmission.

The limited effectiveness of rituximab plus intravenous immunoglobulin (IVIG) in desensitization may be due to incomplete B cell depletion. Obinutuzumab is a type 2 anti-CD20 antibody that induces increased B cell depletion relative to rituximab and may therefore be more effective for desensitization. This open-label phase 1b study assessed the safety, pharmacokinetics, and pharmacodynamics of obinutuzumab in highly sensitized patients with end-stage renal disease. Patients received 1 (day 1, n = 5) or 2 (days 1 and 15; n = 20) infusions of 1000-mg obinutuzumab followed by 2 doses of IVIG on days 22 and 43. Eleven patients received additional obinutuzumab doses at the time of transplant and/or at week 24. The median follow-up duration was 9.4 months. Obinutuzumab was well tolerated, and most adverse events were grade 1-2 in severity. There were 11 serious adverse events (SAEs) in 9 patients (36%); 10 of these SAEs were infections and 4 occurred after kidney transplant. Obinutuzumab plus IVIG resulted in profound peripheral B cell depletion and appeared to reduce B cells in retroperitoneal lymph nodes. Reductions in anti-HLA antibodies, number of unacceptable antigens, and the calculated panel reactive antibody score as centrally assessed using single-antigen bead assay were limited and not clinically meaningful for most patients (NCT02586051)., (© 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

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 0.54 0.83 , P = .005) but no statistically significant differences in mortality (HR: 0.29 0.72 1.83 , P = .5), DGF (odds ratio: 0.93 1.32 1.93 , P = .2), and LOS (LOS ratio: 0.96 1.06 1.19 , P = .4). After adjusting for donor-recipient characteristics, there were no statistically significant post-KAS differences in mortality (adjusted HR: 0.37 1.04 2.92 , P = .9), DGF (adjusted odds ratio: 0.94 1.41 2.13 , P = .1), or LOS (adjusted LOS ratio: 0.93 1.04 1.16 , P = .5). However, post-KAS pDDKT recipients still had less graft loss (adjusted HR: 0.38 0.59 0.91 , 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., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Several single-center reports of using HCV-viremic organs for HCV-uninfected (HCV-) recipients were recently published. We sought to characterize national utilization of HCV-exposed donors for HCV- recipients (HCV D+/R-) in kidney transplantation (KT) and liver transplantation (LT). Using SRTR data (April 1, 2015-December 2, 2018) and Gini coefficients, we studied center-level clustering of 1193 HCV D+/R- KTs and LTs. HCV-viremic (NAT+) D+/R- KTs increased from 1/month in 2015 to 22/month in 2018 (LTs: 0/month to 12/month). HCV-aviremic (Ab+/NAT-) D+/R- KTs increased from < 1/month in 2015 to 26/month in 2018 (LTs: <1/month to 8/month). HCV- recipients of viremic and aviremic kidneys spent a median (interquartile range [IQR]) of 0.7 (0.2-1.6) and 1.6 (0.4-3.5) years on the waitlist versus 1.8 (0.5-4.0) among HCV D-/R-. HCV- recipients of viremic and aviremic livers had median (IQR) MELD scores of 24 (21-30) and 25 (21-32) at transplantation versus 29 (23-36) among HCV D-/R-. 12 KT and 14 LT centers performed 81% and 76% of all viremic HCV D+/R- transplants; 11 KT and 13 LT centers performed 76% and 69% of all aviremic HCV D+/R- transplants. There have been marked increases in HCV D+/R- transplantation, although few centers are driving this practice; centers should continue to weigh the risks and benefits of HCV D+/R- transplantation., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Allocation for pediatric deceased-donor kidney transplantation (pDDKT) in the United States now de-emphasizes HLA matching to improve equality in access to transplantation, but other national systems still consider HLA matching due to concerns about graft survival. We hypothesized that the impact of HLA mismatching has decreased over time due to advances including improved immunosuppression., Methods: Using Scientific Registry of Transplant Recipient data, we analyzed whether the association between the number of HLA mismatches and outcomes of first-time pDDKTs changed between 2 eras: 1995 to 2004 (N = 2854) and 2005 to 2014 (N = 4643)., Results: Between eras, the median number of mismatches increased from 4 to 5 (P < 0.001). Overall graft failure risk was higher among HLA-mismatched versus HLA-matched transplants (adjusted hazard ratio 1.211.431.69 for 3-6 versus 0-2 mismatches; P < 0.001), and this association was similar pre-2005 and post-2005 (Pinteraction = 0.5). Median panel-reactive antibody change at relisting increased from 79 to 85 (P = 0.01), but the association between number of HLA mismatches and panel-reactive antibody change was similar between eras (Pinteraction = 0.6)., Conclusions: Our finding that increased HLA mismatching continues to impact graft survival, with 43% higher risk of graft failure, highlights the tradeoff between transplant access equity and outcomes and calls into question the deemphasis on HLA matching in pDDKT allocation in the United States.

Deceased donor kidney transplantation (DDKT) rates for highly sensitized (HS) candidates increased early after implementation of the Kidney Allocation System (KAS) in 2014. However, this may represent a bolus effect, and a granular investigation of the current state of DDKT for HS candidates remains lacking. We studied 270 722 DDKT candidates from the SRTR from 12/4/2011 to 12/3/2014 ("pre-KAS") and 12/4/2014 to 12/3/2017 ("post-KAS"), analyzing DDKT rates for HS candidates using adjusted negative binomial regression. Post-KAS, candidates with the highest levels of sensitization had an increased DDKT rate compared with pre-KAS (cPRA 98% adjusted incidence rate ratio [aIRR]: 1.27 1.77 2.46 P = .001, cPRA 99% aIRR: 3.18 4.36 5.98 P < .001, cPRA 99.5-99.9% aIRR: 16.91 24.29 34.89 P < .001, and cPRA 99.9%+ aIRR: 8.79 11.58 15.26 P < .001). To determine whether these changes produced more equitable access to DDKT, we compared DDKT rates of HS to non-HS candidates (cPRA 0-79%). Post-KAS, cPRA, 98% candidates had an equivalent DDKT rate (aIRR: 0.65 0.94 1.36 , P = .8) to non-HS candidates, whereas 99% candidates had a higher DDKT rate (aIRR: 1.19 1.68 2.38 , P = .02). Although cPRA 99.5-99.9% candidates had an increased DDKT rate (aIRR: 2.46 3.50 4.98 , P < .001) compared to non-HS candidates, cPRA 99.9%+ candidates had a significantly lower DDKT rate (aIRR: 0.29 0.40 0.56 , P < .001). KAS has improved access to DDKT for HS candidates, although substantial imbalance exists between cPRA 99.5-99.9% and 99.9%+ candidates., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Prehabilitation is the process of enhancing preoperative functional capacity to improve tolerance for the upcoming stressor; it was associated with improved postoperative outcomes in a handful of studies, but never evaluated in transplantation. Kidney transplant (KT) candidates may be uniquely suited for prehabilitation because they experience a profound loss of functional capacity while waiting years on dialysis. To better understand the feasibility and effectiveness of prehabilitation in KT, we conducted a pilot study of center-based prehabilitation for candidates; this intervention consisted of weekly physical therapy sessions at an outpatient center with at-home exercises. We enrolled 24 participants; 18 participated in prehabilitation (75% of enrolled; 17% of eligible). 61% were male, 72% were African American, and mean age = 52 (SD = 12.9); 71% of participants had lower-extremity impairment, and 31% were frail. By 2 months of prehabilitation, participants improved their physical activity by 64% (P = 0.004) based on accelerometry. Participants reported high satisfaction. Among 5 prehabilitation participants who received KT during the study, length of stay was shorter than for age-, sex-, and race-matched control (5 vs 10 days; RR = 0.69; 95% CI:0.50-0.94; P = 0.02). These pilot study findings suggest that prehabilitation is feasible in pretransplant patients and may potentially be a strategy to improve post-KT outcomes., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The availability of direct-acting antiviral (DAA) therapy might have impacted use of hepatitis C virus (HCV)-infected (HCV+) deceased donor kidneys for transplantation., Methods: We used 2005 to 2018 Scientific Registry of Transplant Recipients data to identify 18 936 candidates willing to accept HCV+ kidneys and 3348 HCV+ recipients of HCV+ kidneys. We compared willingness to accept, utilization, discard, and posttransplant outcomes associated with HCV+ kidneys between 2 treatment eras (interferon [IFN] era, January 1, 2005 to December 5, 2013 vs DAA era, December 6, 2013 to August 2, 2018). Models were adjusted for candidate, recipient, and donor factors where appropriate., Results: In the DAA era, candidates were 2.2 times more likely to list as willing to accept HCV+ kidneys (adjusted odds ratio, 2.072.232.41; P < 0.001), and HCV+ recipients were 1.95 times more likely to have received an HCV+ kidney (adjusted odds ratio, 1.761.952.16; P < 0.001). Median Kidney Donor Profile Index of HCV+ kidneys decreased from 77 (interquartile range [IQR], 59-90) in 2005 to 53 (IQR, 40-67) in 2017. Kidney Donor Profile Index of HCV- kidneys remained unchanged from 45 (IQR, 21-74) to 47 (IQR, 24-73). After adjustment, HCV+ kidneys were 3.7 times more likely to be discarded than HCV- kidneys in the DAA era (adjusted relative rate, 3.363.674.02; P < 0.001); an increase from the IFN era (adjusted relative rate, 2.783.023.27; P < 0.001). HCV+ kidney use was concentrated within a subset of centers; 22.5% of centers performed 75% of all HCV+ kidney transplants in the DAA era. Mortality risk associated with HCV+ kidneys remained unchanged (aHR, 1.071.191.32 in both eras)., Conclusions: Given the elevated risk of death on dialysis facing HCV+ candidates, improving quality of HCV+ kidneys, and DAA availability, broader utilization of HCV+ kidneys is warranted to improve access in this era of organ shortage.

Background: The process for evaluating kidney transplant candidates and applicable centers is distinct for patients with Veterans Administration (VA) coverage. We compared transplant rates between candidates on the kidney waiting list with VA coverage and those with other primary insurance., Methods: Using the Scientific Registry of Transplant Recipients database, we obtained data for all adult patients in the United States listed for a primary solitary kidney transplant between January 2004 and August 2016. Of 302,457 patients analyzed, 3663 had VA primary insurance coverage., Results: VA patients had a much greater median distance to their transplant center than those with other insurance had (282 versus 22 miles). In an adjusted Cox model, compared with private pay and Medicare patients, VA patients had a hazard ratio (95% confidence interval) for time to transplant of 0.72 (0.68 to 0.76) and 0.85 (0.81 to 0.90), respectively, and lower rates for living and deceased donor transplants. In a model comparing VA transplant rates with rates from four local non-VA competing centers in the same donor service areas, lower transplant rates for VA patients than for privately insured patients persisted (hazard ratio, 0.72; 95% confidence interval, 0.65 to 0.79) despite similar adjusted mortality rates. Transplant rates for VA patients were similar to those of Medicare patients locally, although Medicare patients were more likely to die or be delisted after waitlist placement., Conclusions: After successful listing, VA kidney transplant candidates appear to have persistent barriers to transplant. Further contemporary analyses are needed to account for variables that contribute to such differential transplant rates., (Copyright © 2018 by the American Society of Nephrology.)

Background: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage renal disease with a high rate of recurrence after kidney transplantation. Several factors, such as white race, rapid progression, and previous allograft failure due to recurrence, were found to be risks of recurrence. Data are limited on the benefits of rituximab and/or therapeutic plasma exchange (TPE) in preventing recurrence. In this study, we sought to assess the efficacy of rituximab and TPE for the prevention and treatment of recurrent FSGS after kidney transplantation., Methods: We enrolled 66 patients with FSGS in this prospective observational study and followed their outcomes. Patients with high risk for recurrence received preventative therapy with TPE and/or rituximab., Results: Twenty-three (62%) of the 37 patients who received preventative therapy developed recurrence compared with 14 (51%) recurrences of the 27 patients who did not receive any therapy (P = 0.21). There was a trend for less relapse when rituximab was used as a therapy for recurrent FSGS (6/22 vs 9/18, P = 0.066). We used a clinical score of 5 values to assess the prediction of FSGS recurrence. A score of 3 or more had a predictive receiver operating characteristic curve of 0.72. Treatment with TPE and/or rituximab resulted in better allograft survival than historical studies. Allograft failure because of recurrent FSGS occurred in only 6 (9%) patients., Conclusions: Preventative therapies do not decrease the recurrence rate of recurrent FSGS. However, prompt treatment of recurrence with these therapies may result in improved outcomes.

Objectives and Methods: The Furosemide Stress Test (FST) is a novel dynamic assessment of tubular function that has been shown in preliminary studies to predict patients who will progress to advanced stage acute kidney injury, including those who receive renal replacement therapy (RRT). The aim of this study is to investigate if the urinary response to a single intraoperative dose of intravenous furosemide predicts delayed graft function (DGF) in patients undergoing deceased donor kidney transplant., Results: On an adjusted multiple logistic regression, a single 100 mg dose of intraoperative furosemide after the anastomosis of the renal vessels (FST) predicted the need for RRT at 2 and 6 h post kidney transplantation (KT). Recipient urinary output was measured at 2 and 6 h post furosemide administration. In receiver-operating characteristic (ROC) analysis, the FST predicted DGF with an area-under-the curve of 0.85 at an optimal urinary output cut-off of <600 mls at 6 h with a sensitivity of and a specificity of 83% and 74%, respectively., Conclusions: The FST is a predictor of DGF post kidney transplant and has the potential to identify patients requiring RRT early after KT.

Background: Immunoglobulin (Ig)A nephropathy is the most common primary glomerulonephritis worldwide, with a high recurrence rate after kidney transplantation. The aim of this study was to assess allograft survival, impact of recurrence on allograft function, and risk factors for post-transplant IgA recurrence., Methods: We identified 104 patients with IgA nephropathy who underwent kidney transplantation at our center between 1993 and 2014. Fourteen patients underwent more than one allograft., Results: IgA recurrence was documented in 23 (19%) allografts. Median time to recurrence was 6.75 years (interquartile range, 1.4-9.2 years). Twelve of the 23 recurrences were from living related donors (P = .07), and those with younger age at transplantation (37.7 ± 2.3 vs 44 ± 1.3, P = .05) were at higher risk of recurrence. Mean allograft survival was reduced in those with recurrence (6.5 ± 5.1 years) compared with those without recurrence (10.4 ± 7.5 years). At 6 years after transplant, allograft failure was documented in 52% of the recurrence group compared with 10% in the non-recurrence group (P = .002)., Conclusions: IgA recurrence after transplant is an important cause of allograft loss. Living related donors and younger age at transplantation are associated with high recurrence rate. Close monitoring and treatment of recurrence are crucial., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Choosing between multiple living kidney donors, or evaluating offers in kidney paired donation, can be challenging because no metric currently exists for living donor quality. Furthermore, some deceased donor (DD) kidneys can result in better outcomes than some living donor kidneys, yet there is no way to compare them on the same scale. To better inform clinical decision-making, we created a living kidney donor profile index (LKDPI) on the same scale as the DD KDPI, using Cox regression and adjusting for recipient characteristics. Donor age over 50 (hazard ratio [HR] per 10 years = 1.15 1.241.33 ), elevated BMI (HR per 10 units = 1.01 1.091.16 ), African-American race (HR = 1.15 1.251.37 ), cigarette use (HR = 1.09 1.161.23 ), as well as ABO incompatibility (HR = 1.03 1.271.58 ), HLA B (HR = 1.03 1.081.14 ) mismatches, and DR (HR = 1.04 1.091.15 ) mismatches were associated with greater risk of graft loss after living donor transplantation (all p < 0.05). Median (interquartile range) LKDPI score was 13 (1-27); 24.2% of donors had LKDPI < 0 (less risk than any DD kidney), and 4.4% of donors had LKDPI > 50 (more risk than the median DD kidney). The LKDPI is a useful tool for comparing living donor kidneys to each other and to deceased donor kidneys., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Since March 26, 2012, the Kidney Donor Profile Index (KDPI) has been provided with all deceased-donor kidney offers, with the goal of improving the expanded criteria donor (ECD) indicator. Although an improved risk index may facilitate identification and transplantation of marginal yet viable kidneys, a granular percentile system may reduce provider-patient communication flexibility, paradoxically leading to more discards ("labeling effect"). We studied the discard rates of the kidneys recovered for transplantation between March 26, 2010 and March 25, 2012 ("ECD era," N = 28 636) and March 26, 2012 and March 25, 2014 ("KDPI era," N = 29 021) using Scientific Registry of Transplant Recipients (SRTR) data. There was no significant change in discard rate from ECD era (18.1%) to KDPI era (18.3%) among the entire population (adjusted odds ratio [aOR] = 0.97 1.041.10 , p = 0.3), or in any KDPI stratum. However, among kidneys in which ECD and KDPI indicators were discordant, "high risk" standard criteria donor (SCD) kidneys (with KDPI > 85) were at increased risk of discard in the KDPI era (aOR = 1.07 1.421.89 , p = 0.02). Yet, recipients of these kidneys were at much lower risk of death (adjusted Risk Ratio [aRR] = 0.56 0.770.94 at 2 years posttransplant) compared to those remaining on dialysis waiting for low-KDPI kidneys. Our findings suggest that there might be an unexpected, harmful labeling effect of reporting a high KDPI for SCD kidneys, without the expected advantage of providing a more granular risk index., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

End-stage renal disease (ESRD) is associated with high rates of morbidity and mortality, and increased health care use. Optimal management of patients with ESRD requires close collaboration among primary care physicians, nephrology subspecialists, and other subspecialists. Critical issues for the family physician include helping patients transition from chronic kidney disease to ESRD, recognizing and managing common issues in patients receiving dialysis or after kidney transplantation, and understanding palliative care for patients with ESRD. Dialysis typically is initiated for patients with a glomerular filtration rate less than 15 mL/min/1.73 m(2) if they are symptomatic due to uremia or if medical management of metabolic conditions is unsuccessful. Kidney transplantation is the optimal form of renal replacement therapy in suitable patients. The choice between hemodialysis and peritoneal dialysis often is based on patient preference and coexisting conditions. Meticulous monitoring of volume status is necessary to achieve and maintain control of blood pressure. Sleep disorders and pruritus are common and can be managed by optimization of metabolic parameters, adequacy of dialysis, and drugs., (Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.)

Background: Mycophenolate mofetil (MMF) side effects often prompt dose reduction or discontinuation, and this MMF dose reduction (MDR) can lead to rejection and possibly graft loss. Unfortunately, little is known about what factors might cause or contribute to MDR. Frailty, a measure of physiologic reserve, is emerging as an important, novel domain of risk in kidney transplantation recipients. We hypothesized that frailty, an inflammatory phenotype, might be associated with MDR., Methods: We measured frailty (shrinking, weakness, exhaustion, low physical activity, and slowed walking speed), other patient and donor characteristics, longitudinal MMF doses, and graft loss in 525 kidney transplantation recipients. Time-to-MDR was quantified using an adjusted Cox proportional hazards model., Results: By 2 years after transplantation, 54% of frail recipients and 45% of nonfrail recipients experienced MDR; by 4 years, incidence was 67% and 51%. Frail recipients were 1.29 times (95% confidence interval [95% CI], 1.01-1.66; P = 0.04) more likely to experience MDR, as were deceased donor recipients (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.44-2.54, P < 0.001) and older adults (age ≥ 65 vs <65; aHR, 1.47; 95% CI, 1.10-1.96, P = 0.01). Mycophenolate mofetil dose reduction was independently associated with a substantially increased risk of death-censored graft loss (aHR, 5.24; 95% CI, 1.97-13.98, P = 0.001)., Conclusion: A better understanding of risk factors for MMF intolerance might help in planning alternate strategies to maintain adequate immunosuppression and prolong allograft survival.

We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post-KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single-center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single-center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respectively. Frailty was independently associated with a 2.17-fold (95% CI: 1.01-4.65, p = 0.047) higher risk of death. In conclusion, regardless of age, frailty is a strong, independent risk factor for post-KT mortality, even after carefully adjusting for many confounders using a novel, efficient statistical approach., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The Kidney Donor Profile Index (KDPI) has been introduced as an aid to evaluating deceased donor kidney offers, but the relative benefit of high-KDPI kidney transplantation (KT) versus the clinical alternative (remaining on the waitlist until receipt of a lower KDPI kidney) remains unknown. Using time-dependent Cox regression, we evaluated the mortality risk associated with high-KDPI KT (KDPI 71-80, 81-90 or 91-100) versus a conservative, lower KDPI approach (remain on waitlist until receipt of KT with KDPI 0-70, 0-80 or 0-90) in first-time adult registrants, adjusting for candidate characteristics. High-KDPI KT was associated with increased short-term but decreased long-term mortality risk. Recipients of KDPI 71-80 KT, KDPI 81-90 KT and KDPI 91-100 KT reached a "break-even point" of cumulative survival at 7.7, 18.0 and 19.8 months post-KT, respectively, and had a survival benefit thereafter. Cumulative survival at 5 years was better in all three high-KDPI groups than the conservative approach (p < 0.01 for each comparison). Benefit of high-KDPI KT was greatest in patients age >50 years and patients at centers with median wait time ≥33 months. Recipients of high-KDPI KT can enjoy better long-term survival; a high-KDPI score does not automatically constitute a reason to reject a deceased donor kidney., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Renal transplantation in patients with antiphospholipid antibodies has historically proven challenging due to increased risk for thrombosis and allograft failure. This is especially true for patients with antiphospholipid antibody syndrome (APS) and its rare subtype, the catastrophic antiphospholipid antibody syndrome (CAPS). Since a critical mechanism of thrombosis in APS/CAPS is one mediated by complement activation, we hypothesized that preemptive treatment with the terminal complement inhibitor, eculizumab, would reduce the extent of vascular injury and thrombosis, enabling renal transplantation for patients in whom it would otherwise be contraindicated. Three patients with APS, two with a history of CAPS, were treated with continuous systemic anticoagulation together with eculizumab prior to and following live donor renal transplantation. Two patients were also sensitized to human leukocyte antigens (HLA) and required plasmapheresis for reduction of donor-specific antibodies. After follow-up ranging from 4 months to 4 years, all patients have functioning renal allografts. No systemic thrombotic events or early graft losses were observed. While the appropriate duration of treatment remains to be determined, this case series suggests that complement inhibitors such as eculizumab may prove to be effective in preventing the recurrence of APS after renal transplantation., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

We recently elucidated risk factors for early hospital readmission (EHR) following kidney transplantation (KT). We now sought to quantify the independent associations between EHR and post-KT outcomes, including late hospital readmission (LHR: 1 year after EHR window), death-censored graft loss and mortality, among Medicare-primary KT recipients (2000-2005). Of 32961 KT recipients, 7.7% had at least one readmission within 3 days of discharge, 14.8% within 7 days, 22.4% within 14 days and 30.5% within 30 days of discharge after the initial KT hospitalization. KT recipients who experienced EHR within 30 days of discharge after the initial KT hospitalization were more likely to have experienced LHR (29.6% vs. 9.0%, p<0.001) and were at 3.02 times higher (95% CI: 2.82-3.23, p<0.001) risk of LHR. Additionally, EHR was associated with death-censored graft loss (deceased donor recipients hazard ratio [HR]: 1.43, 95% CI: 1.36-1.51, p<0.001 and live donor recipients HR: 1.54, 95% CI: 1.40-1.70, p<0.001) and mortality (deceased donor recipients HR: 1.50, 95% CI: 1.43-1.58, p<0.001 and live donor recipients HR: 1.45, 95% CI: 1.32-1.60, p<0.001). Thirty days posttransplant represents a high-risk window for KT recipients and the readmissions during this window are strong predictors of adverse sequelae, particularly LHRs. Efforts should be made to implement and improve systems to reduce LHR and subsequent graft loss and mortality among recipients with EHR., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: We sought to describe the epidemiology and risk factors for Clostridium difficile infection (CDI) among kidney transplant recipients (KTR) between 1 January 2008 and 31 December 2010., Methods: A single-institution retrospective study was conducted among all adult KTR with CDI, defined as a positive test for C. difficile by a cell cytotoxic assay for C. difficile toxin A or B or polymerase chain reaction test for toxigenic C. difficile., Results: Among 603 kidney transplants performed between 1 January 2008 and 31 December 2010, 37 (6.1%) patients developed CDI: 12 (of 128; 9.4%) high-risk (blood group incompatible and/or anti-human leukocyte antigen donor-specific antibodies) vs. 25 (of 475; 5.3%, P = 0.08) standard-risk patients. The overall rate of CDI increased from 3.7% in 2008 to 9.4% in 2010 (P = 0.05). The median time to CDI diagnosis was 9 days, with 27 (73.0%) patients developing CDI within the first 30 days after their transplant, and 14 (51.8%) developing CDI within 7 days. A case-control analysis of 37 CDI cases and 74 matched controls demonstrated the following predictors for CDI among KTR: vancomycin-resistant Enterococcus colonization before transplant (odds ratio [OR]: 3.6, P = 0.03), receipt of an organ from Centers for Disease Control high-risk donor (OR: 5.9, P = 0.006), and administration of high-risk antibiotics within 30 days post transplant (OR: 6.6, P = 0.001)., Conclusions: CDI remains a common early complication in KTR, with rates steadily increasing during the study period. Host and transplant-related factors and exposure to antibiotics appeared to significantly impact the risk for CDI among KTR., (© 2012 John Wiley & Sons A/S.)

Giant cell tubulointerstitial nephritis in the kidney allograft caused by infection is rare, and donor-transmitted infection in transplanted kidneys is also rare. In this case report, we describe an unusual histological manifestation of Candida albicans in the graft biopsy of a 53-year-old male kidney transplant recipient with decreased renal function 12 days post transplant. Several giant cells were present in the tubulointerstitial inflammation, as well as yeasts, with no evidence of rejection, and the histological diagnosis was confirmed by urine culture. Donor urine culture was positive for C. albicans, suggestive of a possible donor-transmitted infection. Prompt antifungal treatment eradicated the infection, and averted systemic spread. To our knowledge, there are no previous reports of Candida infection with giant cell tubulointerstitial nephritis in human renal allograft., (© 2011 John Wiley & Sons A/S.)

UNet(SM) , the UNOS data collection and electronic organ allocation system, allows centers to specify organ offer acceptance criteria for patients on their kidney waiting list. We hypothesized that the system might not be fully utilized and that the criteria specified by most transplant centers would be much broader than the characteristics of organs actually transplanted by those centers. We analyzed the distribution of criteria values among waitlist patients (N = 304 385) between January 2000 and February 2009, mean criteria values among listed candidates on February 19, 2009 and differences between a center's specified criteria and the organs it accepted for transplant between July 2005 and April 2009. We found wide variation in use of criteria variables, with some variables mostly or entirely unused. Most centers specified very broad criteria, with little within-center variation by patient. An offer of a kidney with parameters more extreme than the maximum actually transplanted at that center was designated a 'surplus offer' and indicated a potentially avoidable delay in distribution. We found 7373 surplus offers (7.1% of all offers), concentrated among a small number of centers. The organ acceptance criteria system is currently underutilized, leading to possibly avoidable inefficiencies in organ distribution., (©2010 The Authors Journal compilation©2010 The American Society of Transplantation and the American Society of Transplant Surgeons.)

We recently showed that DonorNet 2007 has reduced the efficiency of kidney distribution in the United States, particularly for those with prolonged cold ischemia time (CIT), by requiring systematic allocation of all kidneys regardless of quality. Reliable early identification of those most likely to be discarded or significantly delayed would enable assigning them to alternate, more efficient distribution strategies. Based on 39 035 adult kidneys recovered for possible transplantation between 2005 and 2008, we created a regression model that reliably (AUC 0.83) quantified the probability that a given kidney was either discarded or delayed beyond 36 h of CIT (Probability of Discard/Delay, PODD). We then analyzed two PODD cutoffs: a permissive cutoff that successfully flagged over half of those kidneys that were discarded/delayed, while only flagging 7% of kidneys that were not eventually discarded/delayed, and a more stringent cutoff that erroneously flagged only 3% but also correctly identified only 34%. Kidney transplants with high PODD were clustered in a minority of centers. Modifications of the kidney distribution system to more efficiently direct organs with high PODD to the centers that actually use them may result in reduced CIT and fewer discards.

Certain patient groups are predicted to derive significant survival benefit from transplantation with expanded criteria donor (ECD) kidneys. An algorithm published in 2005 by Merion and colleagues characterizes this group: older adults, diabetics and registrants at centers with long waiting times. Our goal was to evaluate ECD listing practice patterns in the United States in terms of these characteristics. We reviewed 142 907 first-time deceased donor kidney registrants reported to United Network for Organ Sharing (UNOS) between 2003 and 2008. Of registrants predicted to benefit from ECD transplantation according to the Merion algorithm ('ECD-benefit'), 49.8% were listed for ECD offers ('ECD-willing'), with proportions ranging from 0% to 100% by transplant center. In contrast, 67.6% of adults over the age of 65 years were ECD-willing, also ranging from 0% to 100% by center. In multivariate models, neither diabetes nor center waiting time was significantly associated with ECD-willingness in any subgroup. From the time of initial registration, irrespective of eventual transplantation, ECD-willingness was associated with a significant adjusted survival advantage in the ECD-benefit group (HR for death 0.88, p < 0.001) and in older adults (HR 0.89, p < 0.001), but an increased mortality in non-ECD-benefit registrants (HR 1.11, p < 0.001). In conclusion, ECD listing practices are widely varied and not consistent with published recommendations, a pattern that may disenfranchise certain transplant registrants.

A program was established within our regional procurement organization to permit evaluation of altruistic living donors (LD) interested in nondirected kidney or liver segment donation prior to transplant center referral. During the initial 30 months of program operations, 731 donor inquiries were received of which 131 individuals called back after review of mailed information materials. Forty-seven candidates initiated and 19 completed the evaluation process. Seven underwent donation to include six kidneys and one liver segment, five are actively pending donation, five were excluded from donation following transplant center evaluation and two took no further action after their intended liver recipients received deceased donor (DD) transplants. Psychological evaluation of these 19 candidates found them to be free of psychopathology, highly cooperative and self-directed. They did not exhibit attention-seeking or religious motivations for their actions. All seven donors and recipients continue to do well postoperatively. This evaluation program has made possible large-scale screening and education of prospective altruistic LD within the general population and also provides a unique opportunity to further our understanding of those individuals interested in living-nondirected donation.

Background: Targeting 2-hr postdose cyclosporine (C2) levels to 1,000 to 1,700 mg/dL during the first 6 months after renal transplantation is recommended for triple immunosuppressive regimens. This trial determines whether lower C2 levels could be targeted safely in de novo kidney transplant recipients under a quadruple regimen compared with a similar cohort monitored with trough (C0) levels., Methods: This single-center, sequential, cohort-designed trial included patients who received Thymoglobulin, corticosteroids, an antimetabolite, and cyclosporine monitored by C2 (n=50) or C0 (n=50). Cyclosporine was tapered to maintain the C2 between 1,000 and 1,200 ng/mL months 0 to 3 and between 600 and 1,000 ng/mL thereafter and C0 between 250 and 350 ng/mL months 0 to 3 and between 100 and 250 ng/mL thereafter., Results: Baseline patient and donor characteristics were similar. There were no differences in graft survival (100% C2 vs. 100% C0), acute rejection (4% C2 vs. 6% C0), allograft function, or adverse events at 6 months. C2 levels were lower than the suggested guidelines throughout the study (33% lower at 1 month and 48% lower at 6 months). Lower cyclosporine doses were achieved in the C2 arm compared with the C0 arm by 1 month and were sustained throughout the trial, which translated into an average cyclosporine cost savings of USD $773 in the C2 arm during the 6-month period (P<0.001)., Conclusion: With a quadruple immunosuppressive regimen and lower C2 targets than recommended for triple therapy, safe and effective cyclosporine minimization was achieved. Lower cyclosporine doses were achieved in C2-monitored patients compared with C0-monitored patients, translating into lower immunosuppressive costs.