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Prince Mohan, Manish Kadian, Titte R Srinivas Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA Abstract: Perhaps as a consequence of increased obesity in the general population, the likelihood of obese patients receiving kidney transplants has more than doubled. Obesity confers increased risk for graft loss and death among renal transplant recipients. However, the relationship of changes in body weight and composition to outcome on the transplant waitlist and posttransplantation are not straightforward. Strategies to manage weight in the waitlisted and post-kidney transplantation patient must be performed in the context of a multidisciplinary approach and individualized to risk factors in particular patients. While retrospective studies offer considerable insight into the relationship between obesity and kidney transplant outcome, causal inferences must be made with great caution. Keywords: kidney transplant, obesity, delayed graft function, new onset diabetes after transplant, transplant outcomes

Maria Aurora Posadas Salas, Titte R Srinivas Division of Nephrology and Hypertension, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA Abstract: Adherence to immunosuppression and minimizing variability in drug exposure are important considerations in preventing rejection and maximizing overall transplant outcomes. The availability of once-daily tacrolimus may confer potential benefit by simplifying immunosuppressive regimens, thereby improving medication adherence among transplant recipients. Pharmacokinetic studies in healthy normal volunteers and stable transplant recipients suggest that once-daily tacrolimus is bioequivalent to twice-daily tacrolimus. Efficacy studies suggest that once-daily tacrolimus is noninferior to twice-daily tacrolimus with a concentration-dependent rejection risk. The incidence of biopsy-proven acute rejection, graft survival, and patient survival are more or less comparable between the two tacrolimus formulations. Once-daily tacrolimus has also been reported to have favorable effects on blood pressure, lipid profile, and glucose tolerance. Once-daily tacrolimus may be a viable option to consider for de novo immunosuppression or for conversion from conventional tacrolimus. Keywords: pharmacokinetics, toxicity, immunosuppression, adherence

Julio Pascual,1 Titte R Srinivas,2 Steven Chadban,3 Franco Citterio,4 Federico Oppenheimer,5 Helio Tedesco,6 Mitchell L Henry,7 Christophe Legendre,8 Yoshihiko Watarai,9 Claudia Sommerer,10 Po-Chang Lee,11 J Mark Hexham,12 Gaohong Dong,12 Peter Bernhardt,13 Flavio Vincenti14 1Nephrology Department, Hospital del Mar, Barcelona, Spain; 2Division of Nephrology, Medical University of South Carolina, Mt Pleasant, SC, USA; 3Department of Transplantation, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; 4Centro Trapianti d'Organo Istituto di Clinica Chirurgica, Università Cattolica del Sacro Cuore, Policlinico Universitario A Gemelli, Rome, Italy; 5Renal Transplant Unit, Hospital Clínic de Barcelona, Barcelona, Spain; 6Nephrology Division, Hospital do Rim, UNIFESP, São Paulo, Brazil; 7The Comprehensive Transplant Center, The Ohio State University, Wexner Medical Center, Columbus, OH, USA; 8Service de Transplantation Adultes, Université Paris Descartes and Hôpital Necker, Paris, France; 9Department of Transplant Surgery, Nagoya Daini Red Cross Hospital, Nagoya City, Aich, Japan; 10Medizinische Klinik, Sektion Nephrologie, Universitätsklinikum Heidelberg, Heidelberg, Germany; 11Medical College, National Cheng Kung University, Tainan City, Taiwan; 12Biometrics and Statistical Science, Novartis Pharmaceuticals, East Hanover, NJ, USA; 13Research and Development, Novartis Pharma AG, Basel, Switzerland; 14Kidney Transplant Service, University of California San Francisco, San Francisco, CA, USA Abstract: Two well defined, modifiable risk factors for kidney allograft failure are acute rejection and poor graft function at one year post-transplant. Regulatory bodies and expert panels in the USA and Europe have recognized that both acute rejection and one-year graft function should be assessed when evaluating immunosuppressive regimens. TRANSFORM (Clinicaltrials.gov NCT01950819) is one of the first trials to adopt this approach and the first that applies a novel combined clinically meaningful endpoint to take the first step towards changing the paradigm for immunosuppression in kidney transplant patients. Everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy is a strategy designed to reduce the risk of chronic nephrotoxicity and other dose-dependent complications associated with CNI therapy. In TRANSFORM, de novo kidney transplant patients are randomized to everolimus with reduced-exposure CNI, or mycophenolic acid with standard-exposure CNI, both with induction therapy and maintenance steroids. The primary endpoint is a composite of treated biopsy-proven acute rejection or estimated glomerular filtration rate ,50 mL/min/1.73 m2 at month 12 post-transplant, which is expected to be sensitive both to the effects of acute and chronic allograft rejection and nephrotoxic side effects of immunosuppressive therapies. The construct of this endpoint allows the integration of a continuous outcome (graft function) with a logistic outcome (rejection). The trial uses a randomized, multicenter, open-label, two-arm design. After completion of a 2-year core study, patients enter a further 3-year prospective observational study. By capturing follow-up to 5 years, TRANSFORM will provide substantial data on the incidence of graft loss, graft dysfunction, cancer, cardiovascular events, and other patient-relevant outcomes. TRANSFORM will determine whether de novo CNI reduction with an everolimus-based regimen achieves short-term outcomes compared with standard CNI. As the largest clinical trial undertaken to date in kidney transplantation, recruiting more than 2,000 patients, and with extended follow-up to 5 years, TRANSFORM will provide critical data required to help maximize long-term outcomes. Keywords: mTOR inhibitor, calcineurin inhibitor, reduced exposure

The past year was marked by several excellent studies that represent important therapeutic advances in kidney transplantation or that further our understanding of the genetic basis of chronic allograft dysfunction, clinical tolerance and outcomes of kidney transplantation. [ABSTRACT FROM AUTHOR]

This article describes the articulation, development, and deployment of a machine learning (ML) model-driven value solution for chronic kidney disease (CKD) in a health system. The ML model activated an electronic medical record (EMR) trigger that alerted CKD patients to seek primary care. Simultaneously, primary care physicians (PCPs) received an alert that a CKD patient needed an appointment. Using structured checklists, PCPs addressed and controlled comorbid conditions, reconciled drug dosing and choice to CKD stage, and ordered prespecified laboratory and imaging tests pertinent to CKD. After completion of checklist prescribed tasks, PCPs referred patients to nephrology. CKD patients had multiple comorbidities and ML recognition of CKD provided a facile insight into comorbid burden. Operational results of this program have exceeded expectations and the program is being expanded to the entire health system. This paradigm of ML-driven, checklist-enabled care can be used agnostic of EMR platform to deliver value in CKD through structured engagement of complexity in health systems.

The measurement of outcomes in kidney transplantation has been more accurately documented than almost any other surgical procedure result in recent decades. With significant improvements in short- and long-term outcomes related to optimized immunosuppression, outcomes have gradually shifted away from conventional clinical endpoints (ie, patient and graft survival) to surrogate and composite endpoints. This article reviews how outcomes measurements have evolved in the past 2 decades in the setting of increased data collection and summarizes recent advances in outcomes measurements pertaining to clinical, histopathological, and immune outcomes. Finally, we discuss the use of composite endpoints and Bayesian concepts, specifically focusing on the integrative box risk prediction score, in conjunction with machine learning to refine prognostication., Competing Interests: T.R.S. is employed by CareDx, which has licensed integrative box for use in the United States, and S.J.K. has been a consultant to Novartis, Sanofi, and Viela Bio. The other authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The longitudinal time-course of dd-cfDNA after kidney transplant (KTx) is not well-described. The cut off values of dd-cfDNA in KTx derive from biopsy-coupled single measurements. Meaningful interpretation necessitates understanding of: (1) time variance of dd-cfDNA levels post-KTx, (2) factors determining biologic variability, and (3) relationship to donor and recipient characteristics. We hypothesized that an understanding of the aforementioned factors would better inform clinical decision-making using dd-cfDNA., Methods: One hundred and twenty five KTx patients with dd-cfDNA obtained longitudinally were included. Univariate analyses were directed at inter-patient variability and intra-patient inter-occasion variability of dd-cfDNA. Multivariate linear regression was used in analyses accounting for repeat measures., Results: At 1-month post KTx median dd-cfDNA: (1) were higher in repeat KTx (.57%, P < .001), and dual KTx (1.10%, P = ns) versus a first KTx (.31%); (2) showed a significant difference in donor after cardiac death (DCD [.45%]) versus living related (LRD [.27%]) donors (P = .036). Longitudinal (1-3 months) dd-cfDNA measurements showed a significant downtrend for all donor types. Panel-reactive antibodies (PRA) were positively correlated with dd-cfDNA., Conclusions: Repeat Tx, dual Tx, DCD, and PRA are associated with a higher dd-cfDNA. Incorporation of donor/recipient variables and time down post transplant is material for rational interpretation of dd-cfDNA., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Type 1 Diabetes (T1D) poses an increasing threat to public health, as incidence rates continue to rise globally. However, the etiology of T1D is still poorly understood, especially from the perspective of geography. The objective of this research is to examine the incidence of T1D among youth and to identify high-risk clusters and their association with socio-demographic and geographic variables. The study area was the entire state of Utah and included youth with T1D from birth to 19 years of age from 1998 to 2015 (n = 4161). Spatial clustering was measured both globally and locally using the Moran's I statistic and spatial scan statistic. Ordinary least squares (OLS) regression was used to measure the association of high-risk clusters with certain risk factors at the Census Block Group (CBG) level. The mean age at diagnosis was 9.3 years old. The mean incidence rate was 25.67 per 100,000 person-years (95% CI, 24.57-26.75). The incidence rate increased by 14%, from 23.94 per100,000 person-years in 1998 to 27.98 per 100,000 person-years in 2015, with an annual increase of 0.80%. The results of the spatial scan statistic found 42 high-risk clusters throughout the state. OLS regression analysis found a significant association with median household income, population density, and latitude. This study provides evidence that incidence rates of T1D are increasing annually in the state of Utah and that significant geographic high-risk clusters are associated with socio-demographic and geographic factors., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background Limited literature exists that evaluated outcomes of kidney transplant-eligible patients who are having dialysis and who are undergoing valve replacement. Our main objective in this study was to compare mortality, reoperation, and bleeding episodes between bioprosthetic and mechanical valve procedures among kidney transplant-eligible patients who are having dialysis. Methods and Results We studied 887 and 1925 dialysis patients from the United States Renal Data System, who underwent mitral valve replacement and aortic valve replacement (AVR) after being waitlisted for a kidney transplant (2000-2015), respectively. Time to death, time to reoperation, and time to bleeding requiring hospitalizations were compared separately for AVR and mitral valve replacement. Kaplan-Meier survival curves, Cox proportional hazards model for time to death, accelerated time to event model for time to reoperation, and counting process model for time to recurrent bleeding were used. There were no differences in mortality (hazard ratio [HR], 0.92; 95% CI, 0.77-1.09) or risk of reoperation or risk of significant bleeding events between bioprosthetic and mechanical mitral valve replacement. However, mechanical AVR was associated with a modestly significant less hazard of death (HR, 0.83; 95% CI, 0.74-0.94) compared with bioprosthetic AVR. There were no differences in time to reoperation, or time to significant bleeding events between bioprosthetic and mechanical AVR. Conclusions For kidney transplant waitlisted patients who are on dialysis and who are undergoing surgical valve replacement, bioprosthetic and mechanical valves have comparable survival, reoperation rates, and bleeding episodes requiring hospitalizations at both mitral and aortic locations. These findings emphasize that an individualized informed decision is recommended when choosing the type of valve for this special group of patients having dialysis.

TRANSFORM (TRANSplant eFficacy and safety Outcomes with an eveRolimus-based regiMen) was a 24-month, prospective, open-label trial in 2037 de novo renal transplant recipients randomized (1:1) within 24 hours of transplantation to receive everolimus (EVR) with reduced-exposure calcineurin inhibitor (EVR + rCNI) or mycophenolate with standard-exposure CNI. Consistent with previously reported 12-month findings, noninferiority of the EVR + rCNI regimen for the primary endpoint of treated biopsy-proven acute rejection (tBPAR) or estimated glomerular filtration rate (eGFR) <50 mL/min per 1.73 m 2 was achieved at month 24 (47.9% vs 43.7%; difference = 4.2%; 95% confidence interval = -0.3, 8.7; P = .006). Mean eGFR was stable up to month 24 (52.6 vs 54.9 mL/min per 1.73 m 2 ) in both arms. The incidence of de novo donor-specific antibodies (dnDSA) was lower in the EVR + rCNI arm (12.3% vs 17.6%) among on-treatment patients. Although discontinuation rates due to adverse events were higher with EVR + rCNI (27.2% vs 15.0%), rates of cytomegalovirus (2.8% vs 13.5%) and BK virus (5.8% vs 10.3%) infections were lower. Cytomegalovirus infection rates were significantly lower with EVR + rCNI even in the D+/R- high-risk group (P < .0001). In conclusion, the EVR + rCNI regimen offers comparable efficacy and graft function with low tBPAR and dnDSA rates and significantly lower incidence of viral infections relative to standard-of-care up to 24 months. Clinicaltrials.gov number: NCT01950819., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The mammalian target of rapamycin (mTOR) inhibitor, everolimus, in combination with reduced-exposure calcineurin inhibitor (CNI), has been demonstrated in clinical trials to have comparable efficacy in low-to-moderate immunological risk kidney transplant recipients to the Standard of Care, mycophenolic acid (MPA) in combination with standard-exposure CNI. Current treatment guidelines consider mTOR inhibitors to be a second-line therapy in the majority of cases; however, given that everolimus-based regimens are associated with a reduced rate of viral infections after transplantation, their wider use could have great benefits for kidney transplant patients. In this evidence-based practice guideline, we consider the de novo use of everolimus in kidney transplant recipients. The main outcomes of our consideration of the available evidence are that: 1. Everolimus, in combination with reduced-exposure CNI and low dose steroids, is a suitable regimen for the prophylaxis of kidney transplant rejection in the majority of low-to-moderate immunological risk adult patients, with individualized management; 2. Induction with either basiliximab or rabbit anti-thymocyte globulin is an effective therapy for kidney transplant recipients when initiating an everolimus-based, reduced-exposure CNI regimen; and 3. An individualized approach should be adopted when managing kidney transplant recipients on everolimus-based therapy., (Copyright © 2019. Published by Elsevier Inc.)

Aim: Identifying kidney transplant patients at highest risk for graft loss prior to loss may allow for effective interventions to improve 5 years survival., Methods: We performed a 10 years retrospective cohort study of adult kidney transplant recipients (n = 1747). We acquired data from electronic health records, United Network of Organ Sharing, social determinants of health, natural language processing data extraction, and real-time capture of dynamically evolving clinical data obtained within 1 year of transplant; from which we developed a 5 years graft survival model., Results: Total of 1439 met eligibility; 265 (18.4%) of them experienced graft loss by 5 years. Graft loss patients were characterized by: older age, being African-American, diabetic, unemployed, smokers, having marginal donor kidneys and cardiovascular comorbidities. Predictive dynamic variables included: low mean blood pressure, higher pulse pressures, higher heart rate, anaemia, lower estimated glomerular filtration rate peak, increased tacrolimus variability, rejection and readmissions. This Big Data analysis generated a 5 years graft loss model with an 82% predictive capacity, versus 66% using baseline United Network of Organ Sharing data alone., Conclusion: Our analysis yielded a 5 years graft loss model demonstrating superior predictive capacity compared with United Network of Organ Sharing data alone, allowing post-transplant individualized risk-assessed care prior to transitioning back to community care., (© 2018 Asian Pacific Society of Nephrology.)

Sustained and rapid loss of glomerular filtration rate (GFR) is the predominant clinical feature of diabetic kidney disease and a requisite for the development of end-stage renal disease. Although GFR trajectories have been studied in several cohorts with diabetes and without diabetes, whether rapid renal decline clusters in families with diabetes has not been examined. To determine this, we estimated GFR (eGFR) from serum creatinine measurements obtained from 15,612 patients with diabetes at the University of Utah Health Sciences Center and established their renal function trajectories. Patients with rapid renal decline (eGFR slope < -5 mL/min/1.73 m 2 /year) were then mapped to pedigrees using extensive genealogical records from the Utah Population Database to identify high-risk rapid renal decline pedigrees. We identified 2,127 (13.6%) rapid decliners with a median eGFR slope of -8.0 mL/min/1.73 m 2 /year and 51 high-risk pedigrees (ranging in size from 1,450 to 24,501 members) with excess clustering of rapid renal decline. Familial analysis showed that rapid renal decline aggregates in these families and is associated with its increased risk among first-degree relatives. Further study of these families is necessary to understand the magnitude of the influence of shared familial factors, including environmental and genetic factors, on rapid renal decline in diabetes., (© 2018 by the American Diabetes Association.)

Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation. Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m 2 at post-transplant month 12 using a 10% noninferiority margin. Results In the intent-to-treat population (everolimus n =1022, MPA n =1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, -1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, -1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events. Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function., (Copyright © 2018 by the American Society of Nephrology.)

Background: Low tacrolimus concentrations have been associated with higher risk of acute rejection, particularly within African American (AA) kidney transplant recipients; little is known about intrapatient tacrolimus variabilities impact on racial disparities., Methods: Ten year, single-center, longitudinal cohort study of kidney recipients. Intrapatient tacrolimus variability was assessed using the coefficient of variation (CV) measured between 1 month posttransplant and the clinical event, with a comparable period assessed in those without events. Pediatrics, nontacrolimus/mycophenolate regimens, and nonrenal transplants were excluded. Multivariable Cox regression models were used to analyze data., Results: One thousand four hundred eleven recipients were included (54.4% AA) with 39 521 concentrations used to assess intrapatient tacrolimus CV. Overall, intrapatient tacrolimus CV was higher in AAs versus non-AAs (39.9 ± 19.8 % vs 34.8 ± 15.8% P < 0.001). Tacrolimus variability was a significant risk factor for deleterious clinical outcomes. A 10% increase in tacrolimus CV augmented the risk of acute rejection by 20% (adjusted hazard ratio, 1.20, 1.13-1.28; P < 0.001) and the risk of graft loss by 30% (adjusted hazard ratio, 1.30, 1.23-1.37; P < 0.001), with significant effect modification by race for acute rejection, but not graft loss. High tacrolimus variability (CV >40%) was a significant explanatory variable for disparities in AAs; the crude relative risk of acute rejection in AAs was reduced by 46% when including tacrolimus variability in modeling and reduced by 40% for graft loss., Conclusions: These data demonstrate that intrapatient tacrolimus variability is strongly associated with acute rejection in AAs and graft loss in all patients. Tacrolimus variability is a significant explanatory variable for disparities in AA recipients.

We sought proof of concept of a Big Data Solution incorporating longitudinal structured and unstructured patient-level data from electronic health records (EHR) to predict graft loss (GL) and mortality. For a quality improvement initiative, GL and mortality prediction models were constructed using baseline and follow-up data (0-90 days posttransplant; structured and unstructured for 1-year models; data up to 1 year for 3-year models) on adult solitary kidney transplant recipients transplanted during 2007-2015 as follows: Model 1: United Network for Organ Sharing (UNOS) data; Model 2: UNOS & Transplant Database (Tx Database) data; Model 3: UNOS, Tx Database & EHR comorbidity data; and Model 4: UNOS, Tx Database, EHR data, Posttransplant trajectory data, and unstructured data. A 10% 3-year GL rate was observed among 891 patients (2007-2015). Layering of data sources improved model performance; Model 1: area under the curve (AUC), 0.66; (95% confidence interval [CI]: 0.60, 0.72); Model 2: AUC, 0.68; (95% CI: 0.61-0.74); Model 3: AUC, 0.72; (95% CI: 0.66-077); Model 4: AUC, 0.84, (95 % CI: 0.79-0.89). One-year GL (AUC, 0.87; Model 4) and 3-year mortality (AUC, 0.84; Model 4) models performed similarly. A Big Data approach significantly adds efficacy to GL and mortality prediction models and is EHR deployable to optimize outcomes., (© 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Non-adherence to medication is a well-studied and known cause of late allograft loss, but it is difficult to measure and prospectively monitor. The aim of this study was to assess if appointment non-adherence was correlated with medication non-adherence and a predictor of graft outcomes., Methods: This was a longitudinal cohort study that used the National United States Renal Data System and veterans affairs health records data with time-to-event analyses conducted to assess the impact on graft and patient survival., Results: The number of transplants that were included in the analysis was 4,646 (3,656 with complete records); 14.6% of patients had an appointment no show rate of ≥12% (non-adherence). Appointment and medication non-adherence were highly correlated and both were significant independent predictors of outcomes. Those with appointment non-adherence had 1.5 times the risk of acute rejection (22.0 vs. 14.7%, p < 0.0001) and a 65% higher risk of graft loss (adjusted hazards ratio (aHR) 1.65, 95% CI 1.38-1.97, p < 0.0001). There was a significant interaction between appointment and medication non-adherence; those with appointment and medication non-adherence were at very high risk of graft loss (aHR 4.18, 95% CI 3.39-5.15, p < 0.0001), compared to those with only appointment non-adherence (aHR 1.39, 95% CI 0.97-2.01, p = 0.0766) or only medication non-adherence (aHR 2.44, 95% CI 2.11-2.81, p < 0.0001)., Conclusion: These results demonstrate that non-adherence to health care appointments is a significant and independent risk factor for graft loss., Competing Interests: Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number K23DK099440., (© 2016 S. Karger AG, Basel.)

Although outcome inequalities for non-Hispanic black (NHB) kidney transplant recipients are well documented, there is paucity in data assessing the impact of cardiovascular disease (CVD) risk factors on this disparity in kidney transplantation. This was a longitudinal study of a national cohort of veteran kidney recipients transplanted between January 2001 and December 2007. Data included baseline characteristics acquired through the United States Renal Data System linked to detailed clinical follow-up information acquired through the Veterans Affairs electronic health records. Analyses were conducted using sequential multivariable modeling (Cox regression), incorporating blocks of variables into iterative nested models; 3139 patients were included (2095 non-Hispanic whites [66.7%] and 1044 NHBs [33.3%]). NHBs had a higher prevalence of hypertension (100% versus 99%; P<0.01) and post-transplant diabetes mellitus (59% versus 53%; P<0.01) with reduced control of hypertension (blood pressure <140/90 60% versus 69%; P<0.01), diabetes mellitus (A1c <7%, 35% versus 47%; P<0.01), and low-density lipoprotein (<100 mg/dL, 55% versus 61%; P<0.01). Adherence to medications used to manage CVD risk was significantly lower in NHBs. In the fully adjusted models, the independent risk of graft loss in NHBs was substantially reduced (unadjusted hazard ratio, 2.00 versus adjusted hazard ratio, 1.49). CVD risk factors and control reduced the influence of NHB race by 9% to 18%. Similar trends were noted for mortality, and estimates were robust across in sensitivity analyses. These results demonstrate that NHB kidney transplant recipients have significantly higher rates of CVD risk factors and reduced CVD risk control. These issues are likely partly related to medication nonadherence and meaningfully contribute to racial disparities for graft outcomes., (© 2016 American Heart Association, Inc.)

Background: Socioeconomic status (SES) is a significant determinant of health outcomes and may be an important component of the causal chain surrounding racial disparities in kidney transplantation. The social adaptability index (SAI) is a validated and quantifiable measure of SES, with a lack of studies analyzing this measure longitudinally or between races., Methods: Longitudinal cohort study in adult kidney transplantation transplanted at a single-center between 2005 and 2012. The SAI score includes 5 domains (employment, education, marital status, substance abuse and income), each with a minimum of 0 and maximum of 3 for an aggregate of 0 to 15 (higher score → better SES)., Results: One thousand one hundred seventy-one patients were included; 624 (53%) were African American (AA) and 547 were non-AA. African Americans had significantly lower mean baseline SAI scores (AAs 6.5 vs non-AAs 7.8; P < 0.001). Cox regression analysis demonstrated that there was no association between baseline SAI and acute rejection in non-AAs (hazard ratio [HR], 0.92; 95% confidence interval [95% CI], 0.81-1.05), whereas it was a significant predictor of acute rejection in AAs (HR, 0.89; 95% CI, 0.80-0.99). Similarly, a 2-stage approach to joint modelling of time to graft loss and longitudinal SAI did not predict graft loss in non-AAs (HR, 1.01; 95% CI, 0.28-3.62), whereas it was a significant predictor of graft loss in AAs (HR, 0.23; 95% CI, 0.06-0.93)., Conclusions: After controlling for confounders, SAI scores were associated with a lower risk of acute rejection and graft loss in AA kidney transplant recipients, whereas neither baseline nor follow-up SAI predicted outcomes in non-AA kidney transplant recipients.

Background: There is a lack of conclusive evidence to suggest if calcineurin inhibitor (CNI) withdrawal or minimization with sirolimus is the best strategy for African Americans., Methods: This was a randomized, prospective, open-label, pilot study comparing the two mammalian target of rapamycin (mTOR) transition strategies in adult African Americans between six and 24 wk post-transplant. The primary outcome was a comparison of the eGFR at one yr after conversion., Results: Forty patients were randomized and analyzed in an intent-to-treat fashion. Median day of transition was day 96 (withdrawal) and 68 (minimization). Patients in the CNI-withdrawal group (n = 23) had significantly higher eGFR at one yr compared to the CNI-minimization group (n = 17, 73 vs. 56 mL/min, p = 0.03), as well as a significantly larger increase in eGFR from baseline (12 vs. 5 mL/min, p = 0.03). There were no differences in infections, acute rejection, death, or graft loss. Both regimens were constrained by disproportionately high discontinuation rates despite modest toxicity profiles., Conclusion: In spite of considerable withdrawal rate across both study arms, African American kidney transplant recipients who underwent early transition to a sirolimus-based CNI-withdrawal regimen had significantly better graft function at one yr compared to those transitioned to a sirolimus-based CNI-minimization regimen. Clinicaltrials.gov identifier: NCT01005706., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To determine if a pharmacist-executed comprehensive chart review could serve as sufficient substitution for direct participation during outpatient clinic visits in the postdischarge follow-up treatment of kidney transplant recipients., Design: Retrospective, longitudinal, cross-sectional study., Setting: Acute and chronic transplant clinics at the Medical University of South Carolina, Charleston, SC., Participants: 219 individual kidney transplant recipients., Main Outcome Measures: Effectiveness of chart review assessments (with written notes) as compared with in-clinic assessments (with verbal communication with transplant providers followed by documentation by pharmacists). An independent transplant provider graded pharmacist recommendations by severity. All recommendations were compared with the provider's plan to determine if the recommendations were incorporated., Results: During the 3-month study period, 170 pharmacist chart reviews were written and 175 clinic visits involved direct pharmacist participation. Providers accepted a greater percentage of recommendations that were delivered directly compared with recommendations presented via a note in the patient folder following chart review (92% vs. 28%, respectively; P <0.0001). Directly provided recommendations were also associated with higher severity scores., Conclusion: The results of this study suggest that comprehensive chart review by pharmacists prior to patient clinic visits may not be as effective as in-person consultation in communicating recommendations to providers. Further research is needed in similar clinic settings.

We tested the hypothesis that xanthine oxidase inhibition among African Americans receiving the thiazide-type diuretic chlorthalidone may improve blood pressure control with fewer hyperuricemia-related side effects. We performed a randomized, double-blind, placebo-controlled study of African Americans with Stage 1 hypertension without clinically significant renal disease. One hundred fifty African American men or women between the ages of 18 and 65 years who met the exclusion/inclusion criteria with untreated or treated hypertension were started on chlorthalidone (25 mg/d) and potassium chloride. After a 5-week run-in on chlorthalidone, baseline testing was performed and they were randomized to allopurinol (300 mg/dL) or placebo with doses adjusted based on uric acid levels and followed for 8 weeks. One hundred ten subjects completed the study. Baseline systolic blood pressures after the 5-week chlorthalidone run-in were 119.9 ± 13.6 in the allopurinol group and 117 ± 11.2 in the placebo group indicating excellent blood pressure control with the single agent. After at least 4 week postrandomization, the difference in mean change in systolic blood pressure in allopurinol less placebo from visits 5 to 3 was 4.3 mm Hg (95% confidence interval, -0.2 to 8.7; P = .059). The difference in mean change in uric acid levels over the same period was 2.1 mg/dL (95% confidence interval, 1.7-2.6; P < .001). The use of chlorthalidone with or without allopurinol resulted in excellent blood pressure control. The addition of allopurinol tended to improve clinic blood pressure, but the difference from the group receiving chlorthalidone alone was not statistically significant., (Published by Elsevier Inc.)

Identifying a short-term endpoint for use in clinical trials that accurately reflects the influence of specific immunosuppressive regimens on long-term kidney graft survival is challenging. The number, timing, type (T-cell-mediated or antibody mediated), and severity of biopsy-proven acute rejection (BPAR) episodes in terms of histological changes and functional impact are highly influential for graft prognosis, and a crude measure of overall acute rejection incidence alone is unlikely to be a robust predictor of graft outcome. A series of studies has shown remarkably consistent results in terms of the cutoff point for one-yr renal function which predicts poor long-term graft survival, indicating that a threshold of 50 mL/min/1.73 m(2) is likely to be appropriate. Estimated glomerular filtration rate at one yr post-transplant discriminates effectively among immunosuppressive regimens with regard to graft survival, primarily calcineurin inhibitor reduction strategies. Several other factors that can affect graft survival, such as pathological changes in the graft, may be partly influenced by the immunosuppressive regimen, but the contribution of drug therapy is difficult to define. A combined approach in which both treated BPAR and renal function at one yr are used to assess novel immunosuppressive regimens appears to be promising as the emphasis shifts toward sustaining kidney allograft survival over the long term., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Study Objective: To determine the effect of tacrolimus trough concentrations on clinical outcomes in kidney transplantation, while assessing if African-American (AA) race modifies these associations., Design: Retrospective longitudinal cohort study of solitary adult kidney transplants., Setting: Large tertiary care transplant center., Patients: Adult solitary kidney transplant recipients (n=1078) who were AA (n=567) or non-AA (n=511)., Exposure: Mean and regressed slope of tacrolimus trough concentrations. Subtherapeutic concentrations were lower than 8 ng/ml., Measurements and Main Results: AA patients were 1.7 times less likely than non-AA patients to achieve therapeutic tacrolimus concentrations (8 ng/ml or higher) during the first year after kidney transplant (35% vs 21%, respectively, p<0.001). AAs not achieving therapeutic concentrations were 2.4 times more likely to have acute cellular rejection (ACR) as compared with AAs achieving therapeutic concentrations (20.8% vs 8.5%, respectively, p<0.01) and 2.5 times more likely to have antibody-mediated rejection (AMR; 8.9% vs 3.6%, respectively, p<0.01). Rates of ACR (8.3% vs 6.7%) and AMR (2.0% vs 0.9% p=0.131) were similar in non-AAs compared across tacrolimus concentration groups. Multivariate modeling confirmed these findings and demonstrated that AAs with low tacrolimus exposure experienced a mild protective effect for the development of interstitial fibrosis/tubular atrophy (IF/TA; hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.47-1.32) with the opposite demonstrated in non-AAs (HR 2.2, 95% CI 0.90-5.1)., Conclusion: In contradistinction to non-AAs, AAs who achieve therapeutic tacrolimus concentrations have substantially lower acute rejection rates but are at risk of developing IF/TA. These findings may reflect modifiable time-dependent racial differences in the concentration-effect relationship of tacrolimus. Achievement of therapeutic tacrolimus trough concentrations, potentially through genotyping and more aggressive dosing and monitoring, is essential to minimize the risk of acute rejection in AA kidney transplant recipients., (© 2015 Pharmacotherapy Publications, Inc.)

Background: Chronic kidney disease (CKD) is associated with accelerated atherosclerosis and adverse cardiovascular outcomes, but mechanisms are unclear. We hypothesized that mild CKD independently predicts adverse outcomes in women with symptoms and signs of ischemia., Methods: We categorized 876 women from the Women's Ischemia Syndrome Evaluation cohort according to estimated glomerular filtration rate (eGFR) (eGFR ≥90 mL/min per 1.73 m(2) [normal], 60-89 mL/min per 1.73 m(2) [mild CKD], ≤59 mL/min per 1.73 m(2) [severe CKD]). Time to death from all-cause and cardiovascular causes and major adverse outcomes were assessed by multivariate regression adjusted for baseline covariates., Results: Obstructive coronary artery disease (CAD) was present only in few patients (39%). Even after adjusting for CAD severity, renal function remained a strong independent predictor of all-cause and cardiac mortality (P < .001). Every 10-unit decrease in eGFR was associated with a 14% increased risk of all-cause mortality (adjusted hazard ratio [AHR] 1.14 [1.08-1.20], P < .0001), 16% increased risk of cardiovascular mortality (AHR 1.16 [1.09-1.23], P < .0001), and 9% increased risk of adverse cardiovascular events (AHR 1.09 [1.03-1.15], P = .002)., Conclusions: Even mild CKD is a strong independent predictor of all-cause and cardiac mortality in women with symptoms/signs of ischemia, regardless of underlying obstructive CAD severity, underscoring the need to better understand the interactions between ischemic heart disease and CKD., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Thirty-day readmissions (30DRA) are a highly scrutinized measure of healthcare quality and relatively frequent among kidney transplants (KTX). Development of predictive risk models is critical to reducing 30DRA and improving outcomes. Current approaches rely on fixed variables derived from administrative data. These models may not capture clinical evolution that is critical to predicting outcomes., Methods: We directed a retrospective analysis toward: (1) developing parsimonious risk models for 30DRA and (2) comparing efficiency of models based on the use of immutable versus dynamic data. Baseline and in-hospital clinical and outcomes data were collected from adult KTX recipients between 2005 and 2012. Risk models were developed using backward logistic regression and compared for predictive efficacy using receiver operating characteristic curves., Results: Of 1147 KTX patients, 123 had 30DRA. Risk factors for 30DRA included recipient comorbidities, transplant factors, and index hospitalization patient level clinical data. The initial fixed variable model included 9 risk factors and was modestly predictive (area under the curve, 0.64; 95% confidence interval [95% CI], 0.58-0.69). The model was parsimoniously reduced to 6 risks, which remained modestly predictive (area under the curve, 0.63; 95% CI, 0.58-0.69). The initial predictive model using 13 fixed and dynamic variables was significantly predictive (AUC, 0.73; 95% CI, 0.67-0.80), with parsimonious reduction to 9 variables maintaining predictive efficacy (AUC, 0.73; 95% CI, 0.67-0.79). The final model using dynamically evolving clinical data outperformed the model using static variables (P=0.009). Internal validation demonstrated that the final model was stable with minimal bias., Conclusions: We demonstrate that modeling dynamic clinical data outperformed models using immutable data in predicting 30DRA.

Prospective clinical trials are constructed with high levels of internal validity. Sample size and power considerations usually address primary endpoints. Primary endpoints have traditionally included events that are becoming increasingly less common and thus have led to growing use of composite endpoints and noninferiority trial designs in transplantation. This approach may mask real clinical benefit in one or the other domain with regard to either clinically relevant secondary endpoints or other unexpected findings. In addition, endpoints solely chosen based on power considerations are prone to misjudgment of actual treatment effect size as well as consistency of that effect. In the instances where treatment effects may have been underestimated, valuable information may be lost if buried within a composite endpoint. In all these cases, analyses and post hoc analyses of data become relevant in informing practitioners about clinical benefits or safety signals that may not be captured by the primary endpoint. On the other hand, there are many pitfalls in using post hoc determined endpoints. This short review is meant to allow readers to appreciate post hoc analysis not as an entity with a single approach, but rather as an analysis with unique limitations and strengths that often raise new questions to be addressed in further inquiries.

Viral infections continue to cause significant morbidity in immunosuppressed kidney transplant patients. Although cytomegalovirus, Epstein-Barr virus and polyoma "BK" virus are more frequently encountered, the Adenovirus can cause multi-organ system infections, and may be difficult to diagnose because it is not often considered in the initial work up in kidney transplant recipients. We present an unusual case of a kidney recipient 1 year post-transplant with disseminated adenoviral infection, who had an initial presentation of lower urinary tract voiding dysfunction with hematuria and sterile pyuria. This progressed to a severe tubulointerstitial nephritis and acute kidney injury that improved with reduction of immunosuppression. Serial blood viral loads are useful for monitoring the course of infection. Urinary adenoviral infection should be considered in the differential diagnosis whenever a kidney transplant recipient presents with unexplained lower tract voiding dysfunction, hematuria, and sterile pyuria. The allograft kidney and bladder can be targets of viral proliferation. Early diagnosis with reduction of immunosuppressive therapy is essential to clear the virus and maintain allograft function.

End-stage renal disease (ESRD) and poverty are highly prevalent conditions in the Southeastern United States. The American Southeast also has some of the lowest attainments of health status among its constituents. Transplantation rates are particularly low in the Southeast compared with other regions of the United States. These low kidney transplantation rates in the Southeast likely reflect poor access to medical care. This disproportionate lack of access to medical care among ESRD patients in the Southeast reflects the convergence and interaction of socioeconomic and biologic forces at the patient level interacting with the financial and organizational structure of the health-care system. Improving kidney transplant access in the Southeast will take disruptive political, financial and health system changes whose scope transcends transplant centers and dialysis units., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

As of November 2013, 14.5% of the waitlist for a donor kidney comprised patients awaiting a retransplant. We performed a retrospective cohort study of 11,698 adult solitary kidney recipients using national Scientific Registry of Transplant Recipients data transplanted between 2002 and 2011. The aim was to investigate whether outcomes from patients' initial transplants are significant risk factors for patients' repeat transplants or for likelihood of relisting after a failed primary transplant. Retransplant recipients were more likely to be treated for acute rejection [adjusted odds ratio (AOR), 95% confidence interval (CI) = 1.26 (1.07-1.48), p = 0.0053] or hospitalized (AOR = 1.19, 95% CI 1.08-1.31, p = 0.0005) within a year of retransplantation if these outcomes were experienced within a year of primary transplant. Delayed graft function following primary transplants was associated with 35% increased likelihood of recurrence (AOR = 1.35, 95% CI = 1.18-1.54, p < 0.0001). An increase in 1-year GFR after primary transplant was associated with GFR 1 year postretransplant (β = 6.82, p < 0.0001), and retransplant graft failure was inversely associated with 1-year primary transplant GFR (adjusted hazard ratio = 0.74, 95% CI = 0.71-0.76 per 10 mL/min/1.73 m(2) ). A decreased likelihood for relisting was associated with hospitalization and higher GFR following primary transplantation. The increasing numbers of individuals requiring retransplants highlights the importance of incorporating prior transplant outcomes data to better inform relisting decisions and prognosticating retransplant outcomes., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: The aim of this study was to determine the safety and efficacy of induction with rabbit antithymocyte globulin (RATG) compared with interleukin-2 receptor antagonists in a racially diverse kidney transplant patient population under modern immunosuppression., Background: The optimal induction therapy in patients at risk for rejection, particularly black recipients, in the modern era of immunosuppression with flow cytometry-based cross-matching is unclear., Methods: This was a prospective, risk-stratified, randomized, single-center, open-label study of 200 consecutively enrolled patients in a large academic teaching center. Patients were randomized to receive either daclizumab or basiliximab versus RATG for induction in combination with tacrolimus, mycophenolate mofetil, and corticosteroids. Patients were stratified between groups to ensure equal numbers of black, retransplants, high panel reactive antibodies (PRAs) (>20%), and prolonged cold ischemic times (>24 hours) in each group. Primary outcome measure is treatment efficacy defined as the incidence of biopsy-proven acute rejection and estimated creatinine clearance. Patients were followed up for 12 months. Renal transplant recipients were included if they were adult (≥18 years old) and received an allograft from a deceased, living unrelated, or nonhuman leukocyte antigen identical living-related donor., Results: A total of 200 patients (n = 98 in the interleukin-2 receptor antagonists, and n = 102 in the RATG) were enrolled from February 2009 through July 2011. One-year acute rejection rates were low and similar between groups (10% in the interleukin-2 receptor antagonist group vs 6% in the RATG group; P = 0.30). Creatinine clearance was also similar between groups (interleukin-2 receptor antagonist group 56 ± 20 mL/min per 1.73 m2 vs RATG group 55 ± 22 mL/min per 1.73 m2; P = 0.73). Subanalysis of recipient race revealed that in blacks only RATG was protective against 6- and 12-month acute rejection, without an increased risk of infection. Induction did not affect rejection rates according to recipient calculated PRAs; however, RATG was associated with an increased risk of BK virus in low-PRA patients., Conclusions and Relevance: RATG induction provides improved protection against early acute rejection in black renal transplant recipients, whereas sensitized patients do not seem to demonstrate a similar benefit from this therapy. This study is registered at Clinicaltrials.gov (NCT00859131).

Background and Objectives: The objective was to study the long-term impact of transient versus persistent BK viremia on kidney transplant outcomes., Design, Setting, Participants, & Measurements: In total, 609 recipients who underwent kidney transplant from 2007 to 2011 were screened at months 1-12 for the occurrence of polyomavirus BK viremia; 130 patients (21.7%) developed BK viremia during the first year post-transplant. BK viremia patients were classified according to duration of infection (more or less than 3 months), and BK viral loads (more or less than 10,000 copies/ml) were classified as transient low viremia (n=42), transient high viremia (n=18), persistent low viremia (n=23), and persistent high viremia (n=47). All patients were followed a median of 36 (3-66) months. The rates of BK polyomavirus-associated nephropathy, acute rejection, and 1-year graft function were compared with the polyomavirus BK-negative control group., Results: Patient and graft survival were not significantly different among the groups. Graft function (creatinine; milligrams per deciliter) at 1 year was significantly worse in the persistent high viremia (1.75±0.6) and transient high viremia (1.85±0.7) groups compared with aviremic controls (1.47±0.4; P=0.01 and P=0.01, respectively). The incidence of BK polyomavirus-associated nephropathy was limited to the persistent high viremia group (1.3%, P<0.001). The transient high viremia (50%) and persistent high viremia (34%) groups showed significantly (P=0.01) increased incidence of acute rejection versus aviremic controls (21.5%), transient low viremia (19%), or persistent low viremia (17.3%) groups., Conclusion: Low viral load BK viremia, either transient or persistent, was not associated with long-term transplant outcomes. Persistent high viremia was associated with a greater risk for BK polyomavirus-associated nephropathy and subsequent graft dysfunction. Although transient high viremia was not associated with BK polyomavirus-associated nephropathy, it was associated with worse graft function. These data support the role of surveillance for BK viremia after transplant.

Background: Cytomegalovirus (CMV) and BK virus (BKV) infections can cause significant morbidity after kidney and kidney-pancreas transplant. There are limited data on the epidemiology and interactions between these two viral pathogens., Methods: We prospectively screened 609 kidney or kidney-pancreas transplant recipients from January 2007 to June 2011 for BKV and/or CMV viremia. This included 7453 quantitative BKV polymerase chain reaction and 15,496 quantitative CMV polymerase chain reaction tests. We evaluated risk factors and timing of these infections and the impact of treatment of one infection on the other., Results: Among 609 recipients, 108 (17.7%) developed CMV viremia, of which 95 (88%) were asymptomatic, 5 (5%) had CMV syndrome, and 8 (7%) developed CMV tissue invasive disease at a median of 5.6 months after transplantation. Risk factors for CMV infection using multivariable analysis were D+R- serogroup (P≤0.0001), donor age >50 years (P=0.013), and higher mean tacrolimus (P=0.0009) and mycophenolate mofetil (P=0.01) blood levels. The incidence of BKV infection in the total population was 163 of 609 (26.7%), of which 150 (92%) occurred in patents without antecedent CMV viremia. Such patients demonstrated a higher rate of subsequent BKV viremia than patients with antecedent CMV viremia (P=0.003; hazard ratio, 2.05; 95% confidence interval, 1.2-3.4). Moreover, we found that only symptomatic CMV viremia had a significant negative impact on graft survival when compared with asymptomatic CMV viremia and those without CMV viremia (relative risk, 3.5; 95% confidence interval, 1.06-8.9; P=0.04)., Conclusion: CMV viremia may indirectly protect against subsequent BK viremia possibly due to a reduction of intensity of immunosuppression after diagnosis of CMV viremia.

Post-transplant hypertension is associated with decreased graft and patient survival and cardiovascular morbidity. Unfortunately, post-transplant hypertension is often poorly controlled. Important risk factors include immunosuppressive medications, complications of the transplant surgery, delayed graft function, rejection, and donor and recipient risk factors. The effects of immunosuppressive medications are multifactorial including increased vascular and sympathetic tone and salt and fluid retention. The immunosuppressive agents most commonly associated with hypertension are glucocorticoids and calcineurin inhibitors. Drug therapy for hypertension should be based on the comorbidities and pathophysiology. Evidence-based approaches to defining and treating hypertension in renal transplant recipients are predominantly extrapolated from large-scale studies performed in the general population. Thus, there continues to be a need for larger studies examining the pathophysiology, diagnosis and treatment of hypertension in renal transplant recipients.

Numerous factors impact patients' health beyond traditional clinical characteristics. We evaluated the association of risk factors in kidney transplant patients' communities with outcomes prior to transplantation. The primary exposure variable was a community risk score (range 0-40) derived from multiple databases and defined by factors including prevalence of comorbidities, access and quality of healthcare, self-reported physical and mental health and socioeconomic status for each U.S. county. We merged data with the Scientific Registry of Transplant Recipients (SRTR) and utilized risk-adjusted models to evaluate effects of community risk for adult candidates listed 2004-2010 (n = 209 198). Patients in highest risk communities were associated with increased mortality (adjusted hazard ratio [AHR] = 1.22, 1.16-1.28), decreased likelihood of living donor transplantation (adjusted odds ratio [AOR] = 0.90, 0.85-0.94), increased waitlist removal for health deterioration (AHR = 1.36, 1.22-1.51), decreased likelihood of preemptive listing (AOR = 0.85, 0.81-0.88), increased likelihood of inactive listing (AOR = 1.49, 1.43-1.55) and increased likelihood of listing for expanded criteria donor kidneys (AHR = 1.19, 1.15-1.24). Associations persisted with adjustment for rural-urban location; furthermore the independent effects of rural-urban location were largely eliminated with adjustment for community risk. Average community risk varied widely by region and transplant center (median = 21, range 5-37). Community risks are powerful factors associated with processes of care and outcomes for transplant candidates and may be important considerations for developing effective interventions and measuring quality of care of transplant centers., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

We prospectively screened 609 consecutive kidney (538) and kidney-pancreas (71) transplant recipients for BK viremia over a 4-year interval using polymerase chain reaction viral load detection and protocol kidney biopsies. We found that BK viremia is common at our center: total cases 26.7%, cases during first year 21.3% (mean 4 months), and recipients with ≥ 10 000 copies/ml 12.3%. We found few predictive clinical or demographic risk factors for any BK viremia or viral loads ≥ 10,000 copies/ml, other than prior treatment of biopsy confirmed acute rejection and/or higher immunosuppressive blood levels of tacrolimus (P = 0.001) or mycophenolate mofetil (P = 0.007). Viral loads at diagnosis (<10 000 copies/ml) demonstrated little impact on graft function or survival. However, rising copy numbers demand early reductions in immunosuppressive drug doses of at least 30-50%. Viral loads >185 000 copies/ml at diagnosis were predictive of BK virus-associated nephropathy (BKVAN; OR: 113.25, 95% CI: 17.22-744.6, P < 0.001). Surveillance for BK viremia and rapid reduction of immunosuppression limited the incidence of BKVAN to 1.3%. The addition of leflunomide or ciprofloxacin to immunosuppressive dose reduction did not result in greater rates of viral clearance. These data support the role of early surveillance for BK viremia to limit the impact on transplant outcome, although the most effective schedule for screening awaits further investigation., (© 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background: Secondary hyperparathyroidism often accompanies chronic kidney disease, which can result in severe bone abnormalities and nephrolithiasis. Renal transplantation can correct the mineral abnormalities associated with chronic kidney disease, but one year after transplantation many recipients continue to exhibit persistent hyperparathyroidism., Case Report: Cinacalcet, a second-generation calcimimetic, has been shown to be effective in decreasing serum calcium levels in post kidney transplant patients with hyperparathyroidism. However a question remains whether patients with hyperparathyroidism who take Cinacalcet may be at increased risk of renal calcium deposits due to hypercalciuria and subsequent renal transplant dysfunction. We report the first well-documented case in which Cinacalcet contributed to the development of new renal calculi in a post-transplant patient with hyperparathyroidism (PTH 346 pg/mL), hypercalcemia (11.3 mg/dL), and good renal function (1.45 mg/dL). Interval imaging tracks the new onset of renal allograft stone formation after initiating Cinacalcet up to 60mg daily, which was accompanied by persistent hypercalciuria (478.2 mg/24 hours). The nephrolithiases resolved after discontinuing Cinacalcet and a subtotal parathyroidectomy., Conclusions: This case supports the interval monitoring of urinary calcium excretion and imaging of the transplanted kidney for those recipients treated with Cinacalcet for hyperparathyroidism after renal transplantation.

Report cards evaluating transplant center performance have received significant attention in recent years corresponding with the Centers for Medicare and Medicaid Services issue of the 2007 Conditions of Participation. Our primary aim was to evaluate the association of report card evaluations with transplant center volume. We utilized data from the Scientific Registry of Transplant Recipients (SRTR) along with six consecutive program-specific reports from January 2007 to July 2009 for adult kidney transplant centers. Among 203 centers, 46 (23%) were low performing (LP) with statistically significantly lower than expected 1-year graft or patient survival at least once during the study period. Among LP centers, there was a mean decline in transplant volume of 22.4 cases compared to a mean increase of 7.8 transplants among other centers (p = 0.001). Changes in volume between LP and other centers were significant for living, standard and expanded criteria deceased donor (ECD) transplants. LPs had a reduction in use of donors with extended cold ischemia time (p = 0.04) and private pay recipients (p = 0.03). Centers without low performance evaluations were more likely to increase the proportion of overall transplants that were ECDs relative to other centers (p = 0.04). Findings indicate a significant association between reduced kidney transplant volume and low performance report card evaluations., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Obesity confers increased risk for graft loss and death among renal transplant recipients. However the relationship of changes in body weight and composition to outcome on the transplant waitlist and post-transplantation is not straightforward. Strategies to manage weight in the waitlisted patient and after kidney transplantation must be performed in the context of a multidisciplinary approach and individualized based on risk factors in particular patients. Although retrospective studies offer considerable insights into the relationship between obesity and kidney transplant outcome, causal inferences must be made with great caution., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Living kidney donor transplantation is an increasingly used treatment for end-stage renal disease because it both confers excellent outcomes to transplant recipients, and is considered a safe procedure for prospective donors. The short- and long-term safety of prospective donors is paramount to the continued success of living donation. Although the initial experience with living kidney donors mostly included the healthiest donors, increasing need for organs and secular trends in the general population have subtly reshaped prevailing suitability criteria for donation. As the practice of living donation evolved over time, our understanding of kidney disease has also changed as we embraced the framework of the K-DOQI guidelines. It is not uncommon for donors to fit into some of the K-DOQI guidelines paradigms of risk and disease; however, whether there is a true biological consequence or whether it is a merely semantic conundrum remains unclear. Regardless, this is an important issue, and therefore future efforts should aim at addressing this matter., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the association of community health indicators with outcomes for kidney transplant recipients., Design: Retrospective observational cohort study using multivariable Cox proportional hazards models., Setting: Transplant recipients in the United States from the Scientific Registry of Transplant Recipients merged with health indicators compiled from several national databases and the Centers for Disease Control and Prevention, including the National Center for Health Statistics, the Behavioral Risk Factor Surveillance System, and the National Center for Chronic Disease Prevention and Health Promotion., Patients: A total of 100 164 living and deceased donor adult (aged 18 years) kidney transplant recipients who underwent a transplant between January 1, 2004, and December 31, 2010., Main Outcome Measures: Risk-adjusted time to posttransplant mortality and graft loss., Results: Multiple health indicators from recipients' residence were independently associated with outcomes, including low birth weight, preventable hospitalizations, inactivity rate, and smoking and obesity prevalence. Recipients in the highest-risk counties were more likely to be African American (adjusted odds ratio, 1.59, 95% CI, 1.51-1.68), to be younger (aged 18-39 years; 1.46; 1.32-1.60), to have lower educational attainment (

Increased cold ischemia time (CIT) predisposes to delayed graft function (DGF). DGF is considered a risk factor for graft failure after kidney transplantation, but DGF has multiple etiologies. To analyze the risk of CIT-induced DGF on graft survival, we evaluated paired deceased-donor kidneys (derived from the same donor transplanted to different recipients) in which one donor resulted in DGF and the other did not, using national Scientific Registry of Transplant Recipients data between 2000 and 2009. Of 54 565 kidney donors, 15 833 were excluded for mate kidney non-transplantation, 27 340 because both or neither kidney developed DGF and 2310 for same/unknown CIT. The remaining 9082 donors (18 164 recipients) were analyzed. The adjusted odds (aOR) of DGF were significantly higher when CIT was longer by ≥ 1 h (aOR 1.81, 95% CI 1.7-2.0), ≥ 5 h (aOR 2.5, 95% CI 2.3-2.9), ≥ 10 h (aOR 3.3, 95% CI 2.7-2.9) and ≥ 15 h (aOR 4.4, 95% CI 3.4-5.8) compared to shorter CIT transplants. In the multivariable models adjusted for recipient characteristics, graft survival between paired donor transplants, with and without DGF, were similar. These results suggest that DGF, specifically induced by prolonged CIT, has limited bearing on long-term outcomes, which may have important implications for kidney utilization., (©Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)