Right Ventricular Dysfunction and Adverse Outcomes after Renal Transplantation

INTRODUCTION: Pulmonary hypertension is common among patients with end-stage renal disease, although data regarding the impact of right ventricular (RV) failure on postoperative outcomes remain limited. We hypothesized that echocardiographic findings of RV dilation and dysfunction are associated with adverse clinical outcomes after renal transplant. METHODS: A retrospective review of adult renal transplant recipients at a single institution from January 2008 to June 2010 was conducted. Patients with transthoracic echocardiograms (TTEs) within 1 year leading up to transplant were included. The primary end point was a composite of delayed graft function, graft failure, and all-cause mortality. RESULTS: Eighty patients were included. Mean follow-up time was 9.4 ± 0.8 years. Eight patients (100%) with qualitative RV dysfunction met the primary end point, while 39/65 patients (60.0%) without RV dysfunction met the end point (p = 0.026). Qualitative RV dilation was associated with a significantly shorter time to all-cause graft failure (p = 0.03) and death (p = 0.048). RV systolic pressure was not measurable in 45/80 patients (56%) and was not associated with outcomes in the remaining patients. CONCLUSION: RV dilation and dysfunction are associated with adverse outcomes after renal transplant. TTE assessment of RV size and function should be a standard part of the pre-kidney transplant cardiovascular risk assessment

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

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

Stroke and kidney transplantation

PURPOSE OF REVIEW: This review will focus on the epidemiological data, risk factors, and management of stroke before and after kidney transplant. Stroke is highly prevalent in waitlisted patients as well as kidney transplant recipients and is associated with impaired transplant outcomes. Multiple traditional, nontraditional, and transplanted risk factors increase the risk of stroke. RECENT FINDINGS: Although the risk of stroke is reduced after kidney transplantation compared with remaining on dialysis, the morbidity and mortality from stroke after transplantation remain significant. SUMMARY: Early screening for risk factors before and after a kidney transplant and following the Kidney Disease Improving Global Outcomes (KDIGO) management guidelines could minimize the incidence of stroke and transplant outcomes

Cardiopulmonary Exercise Measures of Men and Women with HFrEF Differ in Their Relationship to Prognosis: The Henry Ford Hospital Cardiopulmonary Exercise Testing (FIT-CPX) Project

BACKGROUND: This study evaluated if different prognostic characteristics exist for peak oxygen consumption (VO2), percent predicted peak VO2 (ppVO2), and the slope of the change in minute ventilation to volume of carbon dioxide produced (VE-VCO2) slope between men and women with heart failure and reduced ejection fraction (HFrEF). METHODS: Analysis of the Henry Ford Hospital Cardiopulmonary Exercise Testing database (n = 1085; 33% women, 55% black) of individuals with HFrEF who completed a physician-referred cardiopulmonary exercise testing (CPX) between 1997 and 2010. Primary outcome was a composite of all-cause death, left ventricular assist device placement, and orthotopic heart transplant . Logistic and Cox regressions were performed and Kaplan-Meier survival curves were developed to describe relationships of the CPX variables and the composite outcome within and between men and women. RESULTS: All patients were followed-up for a minimum of 5 years, during which there were 643 combined events (62%; 499 deaths, 64 left ventricular assist device implants, 80 orthotopic heart transplant). Each CPX variable was significantly related to event-free survival among both men and women. Log-rank assessment of Kaplan-Meier curves noted survival differences for peak VO2 and VE-VCO2 slope (p ≤ .002), but not ppVO2 (P = .32), between men and women. CONCLUSIONS: Prognostic values for peak VO2 and the VE-VCO2 slope might be considered separately for men and women, whereas the ppVO2 value corresponding to 1- and 3-year survival rates may not be different between the sexes

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)

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

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