The Value of Protocol Biopsies to Identify Patients With De Novo Donorâ Specific Antibody at High Risk for Allograft Loss

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137430/1/ajt14161_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137430/2/ajt14161-sup-0001-TableS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137430/3/ajt14161.pd

Safety and efficacy of direct- acting oral anticoagulants versus warfarin in kidney transplant recipients: a retrospective single- center cohort study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155941/1/tri13599.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155941/2/tri13599_am.pd

Factors at de novo donorâ specific antibody initial detection associated with allograft loss: a multicenter study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149234/1/tri13395-sup-0001-FigS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149234/2/tri13395_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149234/3/tri13395.pd

Delayed kidney transplantation in combined liver-kidney transplantation: A validation analysis by the UNOS registry

Background: Delayed kidney transplantation (KT) for patients undergoing combined liver-kidney transplant (CLKT) have been suggested to improve outcomes compared to simultaneous KT in CLKT. This study aims to validate the efficacy of delayed KT in CLKT using the UNOS registry. Methods: We examined all adult CLKT from 01/01/2003 to 03/31/2017. Delayed KT in CLKT was defined as the difference between kidney and liver cold ischemia time ≥24hr and simultaneous KT as ≤6hr. Delayed and simultaneous KT in CLKT were matched by propensity scores adjusting for recipient and donor factors. Multivariable cox and logistic models were fitted to compare various outcomes. Results: We analyzed 4460 simultaneous KT and 915 delayed KT in CLKT. Delayed KT was associated with worse 1-year patient (HR = 1.42; P = 0.036), liver (HR = 1.44; P = 0.024), and kidney (HR = 1.45; P =0.021) survival compared to simultaneous KT in those with MELD ≥35. Delayed KT was a protective factor for delayed kidney graft function (DGF) in MELD ≤25 (HR = 0.65; P = 0.039) and ≥35 (HR = 0.67; P = 0.023). No differences in 3, 6, or 12-month eGFR were observed. Conclusions: Delayed KT in CLKT is associated with worse 1-year patient, liver, and kidney survival in MELD ≥35, protective against DGF in recipients with MELD ≤25 and ≥35, and have comparable post-transplant eGFR compared to simultaneous KT. Risk stratification based on MELD should be considered among patients receiving delayed KT in CLKT. (Figure Presented)

Increasing net immunosuppression after BK polyoma virus infection

BackgroundReducing immunosuppression can effectively treat BK viremia (BKV) and BK nephropathy, but has been associated with increased risks for acute rejection and development of donor- specific antibodies (DSA). To date there have been no systematic evaluations of re- escalating immunosuppression in transplant patients with resolving BKV. Importantly, the safety of this approach and impact on graft survival is unclear.MethodsWe performed a single- center retrospective review of kidney transplant recipients between July 2011 and June 2013 who had immunosuppression reduction after developing BKV (plasma PCR - ¥Â 1000 copies/ml). Changes in immunosuppression and patient outcomes were tracked until occurrence of a complication event: biopsy- proven acute rejection (BPAR), detection of de novo DSA, or recurrent BKV. Patients were grouped according to whether or not net immunosuppression was eventually increased.ResultsOut of 88 patients with BKV, 44 (50%) had net immunosuppression increased while the other 44 did not. Duration of viremia, peak viremia, induction, and sensitization status were similar between the two groups. In a Kaplan- Meier analysis, increasing immunosuppression was associated with less BPAR (P = .001) and a trend toward less de novo DSA development (P = .06). Death- censored graft survival (P = .27) was not different between the two groups. In the net immunosuppression increase group, recurrent BKV occurred in 22.7% without any BKV- related graft losses.ConclusionThese findings support potential benefits of increasing immunosuppression in patients with low- level or resolved BKV, but prospective trials are needed to better understand such an approach.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167446/1/tid13472_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167446/2/tid13472.pd

Urinary Podocin mRNA as Predictor of Renal Allograft Function Decline

Purpose: Traditional biomarkers (such as proteinuria, lyear eGFR) as well as validated risk prediction tools such as the Birmingham Risk Score predict risk of ESRD. However the ideal biomarker is one that is associated with smaller changes in allograft function such that early intervention is likely to be beneficial in retarding progression. In addition, biomarkers that are nephron segment specific will allow to delineate mechanistic processes driving allograft dysfunction. Methods: 125 consenting kidney transplant recipients had urines collected over the first year (2012-2015). Patients were followed till June 2017, graft failure or death whichever was earlier. Demographic and clinical data including EGFR was collected. Urines were analyzed for proteinuria as well as absolute mRNA quantification for podocin, nephrm (podocyte specific markers), Aquaporm2 (distal collecting tubule) and TGFbetal (measure of profibrotic activity). Absolute mRNA data was normalized to urine creatinine. Data on glomerulosclerosis (GS) and Interstitial Fibrosis Tubular Atrophy (TFTA) was obtained from year surveillance biopsies or last biopsy in the first year. Linear regressions were used to determine slope of EGFR decline for individual patient from time of first urine collection to end of follow-up. Progres-sors were defined as those in whom EGFR declined by \u3e3 ml/mm/year. K-fold cross validation techniques were used to split data into derivation and validation cohorts. Results: Overall 10, 327 follow up EGFR observations and 547 urine samples were available for analysis. Twenty grafts were lost in follow up with 10 due to death. Table below highlights comparison of selected urine mRNA markers with traditionally used predictors clinical and histological predictors. Urine mRNA markers outper-formed proteinuria, renal function and histological parameters in predicting risk of progression. Among urine mRNA markers only podocm and TGFbetal predicted risk of progression (LCL of 95%CI was \u3e0. 5). [Figure Presented] Other predators that were tested and not significant: Rejection, CMV and BKV infections. Nephrin was excluded due to collinearity with podocin. Conclusions: The average first year urine podocin mRNA is a good biomarker for predicting allograft function decline (of \u3e3 ml/mm/year over a median 4. 5years) compared to traditionally used biomarkers. Further internal and external validation studies as well as comparison with other mRNA markers are needed to establish clinical utility

Factors at de novo donor-specific antibody initial detection associated with allograft loss: a multicenter study

We aimed to evaluate patient factors including nonadherence and viral infection and de novo donor-specific antibody (dnDSA) characteristics [total immunoglobulin G (IgG), C1q, IgG3, and IgG4] as predictors of renal allograft failure in a multicenter cohort with dnDSA. We performed a retrospective observational study of 113 kidney transplant recipients with dnDSA and stored sera for analysis. Predictors of death-censored allograft loss were assessed by Cox proportional modeling. Death-censored allograft survival was 77.0% (87/113) during a median follow-up of 2.2 (IQR 1.2-3.7) years after dnDSA detection. Predictors of allograft failure included medication nonadherence [HR 6.5 (95% CI 2.6-15.9)], prior viral infection requiring immunosuppression reduction [HR 5.3 (95% CI 2.1-13.5)], IgG3 positivity [HR 3.8 (95% CI 1.5, 9.3)], and time post-transplant (years) until donor-specific antibody (DSA) detection [HR 1.2 (95% CI 1.0, 1.3)]. In the 67 patients who were biopsied at dnDSA detection, chronic antibody-mediated rejection [HR 11.4 (95% CI 2.3, 56.0)] and mixed rejection [HR 7.4 (95% CI 2.2, 24.8)] were associated with allograft failure. We conclude that patient factors, including a history of viral infection requiring immunosuppression reduction or medication nonadherence, combined with DSA and histologic parameters must be considered to understand the risk of allograft failure in patients with dnDSA

Survey of Salary and Job Satisfaction of Transplant Nephrologists in the United States

BACKGROUND AND OBJECTIVES: There are no standardized benchmarks to measure productivity and compensation of transplant nephrologists in the United States, and consequently, criteria set for general nephrologists are often used. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A web-based survey was sent to 809 nephrologists who were members of the American Society of Transplantation to gather data on measures of productivity, compensation, and job satisfaction. Factors associated with higher total compensation and job satisfaction were examined. RESULTS: Of 365 respondents, 260 were actively practicing in the United States and provided data on compensation. Clinical productivity was assessed variably, and although 194 (76%) had their work relative value units (wRVUs) reported to them, only 107 (44%) had an established RVU target; 234 (90%) had fixed base compensation, and 172 (66%) received a bonus on the basis of clinical workload (68%), academic productivity (31%), service (32%), and/or teaching responsibility (31%). Only 127 respondents (49%) filled out time studies, and 92 (35%) received some compensation for nonbillable transplant activity. Mean total compensation (base salary and bonus) was $274,460±$91,509. The unadjusted mean total compensation was higher with older age and was higher for men; Hispanic and White respondents; adult care transplant nephrologists; residents of the western United States; US medical school graduates; nonuniversity hospital employees; and those with an administrative title, higher academic rank, and a higher number of years in practice. Two hundred and nine respondents (80%) thought their compensation was unfair, and 180 (70%) lacked a clear understanding of how they were compensated. One hundred forty-five respondents (55%) reported being satisfied or highly satisfied with their job. Job satisfaction was greater among those with higher amounts of compensation and US medical school graduates. CONCLUSIONS: We report significant heterogeneity in the assessment of productivity and compensation for transplant nephrologists and the association of compensation with job satisfaction