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Phuong-Thu T Pham,1 Kari L Edling,2 Harini A Chakkera,3 Phuong-Chi T Pham,4 Phuong-Mai T Pham51Department of Medicine, Nephrology Division, Kidney Transplant Program, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 3Department of Medicine, Nephrology Division Kidney Transplant Program, Mayo Clinic Hospital, Phoenix, AZ, USA; 4Department of Medicine, Nephrology Division, UCLA-Olive View Medical Center, Sylmar, CA, USA; 5Department of Medicine, Greater Los Angeles, Veterans Administration Health Care System, CA, USAAbstract: New-onset diabetes mellitus after transplantation (NODAT) is a serious and common complication following solid organ transplantation. NODAT has been reported in 2% to 53% of all solid organ transplants. Kidney transplant recipients who develop NODAT have variably been reported to be at increased risk of fatal and nonfatal cardiovascular events and other adverse outcomes including infection, reduced patient survival, graft rejection, and accelerated graft loss compared with those who do not develop diabetes. Limited clinical studies in liver, heart, and lung transplants similarly suggested that NODAT has an adverse impact on patient and graft outcomes. Early detection and management of NODAT must, therefore, be integrated into the treatment of transplant recipients. Studies investigating the best screening or predictive tool for identifying patients at risk for developing NODAT early after transplantation, however, are lacking. We review the clinical predictive values of fasting plasma glucose, oral glucose tolerance test, and A1C in assessing the risk for NODAT development and as a screening tool. Simple diabetes prediction models that incorporate clinical and/or metabolic risk factors (such as age, body mass index, hypertriglyceridemia, or metabolic syndrome) are also presented.Keywords: new-onset diabetes after transplantation, impaired fasting glucose, impaired glucose tolerance, oral glucose tolerance test, NODAT screening, diabetes prediction models

This single-center retrospective study investigated subclinical rejection prevalence and significance in simultaneous pancreas and kidney transplant (SPKT) recipients. We analyzed 352 SPKT recipients from July 2003 to April 2022. Our protocol included pancreas allograft surveillance biopsies at 1, 4, and 12months post-transplant. After excluding 153 patients unable to undergo pancreas biopsy, our study cohort comprised 199 recipients. Among the 199 patients with protocol pancreas biopsies, 107 had multiple protocol pancreas biopsies in the first year, totaling 323. Subclinical rejection was identified in 132 episodes (41%). Of these, 72% were Grade 1, 20% were indeterminate, and 8% were Banff Grade 2 or higher. All episodes of subclinical rejection were treated. Rates of pancreas graft loss (10% vs. 7%) and clinical rejection (21% vs. 20%) at 3 years were similar between those with and without subclinical rejection. Subclinical rejection Banff Grade 2 or more was associated with poor pancreas graft survival HR of 5.5 (95% CI: 1.24-24.37, p = 0.025). Of 236 simultaneous protocol kidney and pancreas biopsies, 102 (43%) showed pancreas subclinical rejection, while only 17% had concurrent kidney subclinical rejection. Our findings suggest limited predictive value of pancreatic enzymes and euglycemia in detecting pancreas rejection. Furthermore, poor concordance existed between pancreas and kidney subclinical rejection., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Inpatient hyperglycemia is an established independent risk factor among several patient cohorts for hospital readmission. This has not been studied after kidney transplantation. Nearly one-third of patients who have undergone a kidney transplant reportedly experience 30-day readmission., Methods: Data on first-time solitary kidney transplantations were retrieved between September 2015 and December 2018. Information was linked to the electronic health records to determine diagnosis of diabetes mellitus and extract glucometric and insulin therapy data. Univariate logistic regression analysis and the XGBoost algorithm were used to predict 30-day readmission. We report the average performance of the models on the testing set on bootstrapped partitions of the data to ensure statistical significance., Results: The cohort included 1036 patients who received kidney transplantation; 224 (22%) experienced 30-day readmission. The machine learning algorithm was able to predict 30-day readmission with an average area under the receiver operator curve (AUC) of 78% with (76.1%, 79.9%) 95% confidence interval (CI). We observed statistically significant differences in the presence of pretransplant diabetes, inpatient-hyperglycemia, inpatient-hypoglycemia, minimum and maximum glucose values among those with higher 30-day readmission rates. The XGBoost model identified the index admission length of stay, presence of hyper- and hypoglycemia, the recipient and donor body mass index (BMI) values, presence of delayed graft function, and African American race as the most predictive risk factors of 30-day readmission. Additionally, significant variations in the therapeutic management of blood glucose by providers were observed., Conclusions: Suboptimal glucose metrics during hospitalization after kidney transplantation are associated with an increased risk for 30-day hospital readmission. Optimizing hospital blood glucose management, a modifiable factor, after kidney transplantation may reduce the risk of 30-day readmission., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The objective of this study was to compare the long-term outcomes of Hispanic versus white recipients who underwent simultaneous pancreas kidney transplantation (SPKT). This single-center study, conducted from 2003 to 2022, had a median follow-up of 7.5 years. The study included 91 Hispanic and 202 white SPKT recipients. The mean age (44 vs. 46 years), percentage of males (67% vs. 58%), and body mass index (BMI) (25.6 vs. 25.3 kg/m 2 ) were similar between the Hispanic and white groups. The Hispanic group had more recipients with type 2 diabetes (38%) compared to the white group (5%, p < .001). The duration of dialysis was longer in Hispanics (640 vs. 473 days, p = .02), and fewer patients received preemptive transplants (10% vs. 29%, p < .01) compared to whites. Hospital length of stay, rates of BK Viremia, and acute rejection episodes within 1 year were similar between the groups. The estimated 5-year kidney, pancreas, and patient survival rates were also similar between the groups, 94%, 81%, and 95% in Hispanics, compared to 90%, 79%, and 90% in whites. Increasing age and longer duration of dialysis were risk factors for death. Although Hispanic recipients had a longer duration on dialysis and fewer preemptive transplants, the survival rates were similar to those of white recipients. However, referring providers and many transplant centers continue to overlook pancreas transplants for appropriately selected patients with type 2 diabetes, particularly among minority populations. As a transplant community, it is crucial that we make efforts to comprehend and tackle these obstacles to transplantation., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The objective of this study was to compare the long-term outcomes of older (50-65 y) type 1 diabetics with body mass index <35 kg/m 2 and type 2 diabetics with body mass index <30 kg/m 2 who received simultaneous pancreas kidney transplantation (SPKT) versus living donor kidney transplants (LDKTs). All subjects had insulin-dependent diabetes., Methods: This is a retrospective single-center study from July 2003 to March 2021 with a median follow-up of 7.5 y., Results: There were 104 recipients in the SPKT and 80 in the LDKT group. The mean age was 56 y in SPKT and 58 y in LDKT. There were 55% male recipients in the SPKT group versus 75% in LDKT. The duration of diabetes was 32 y in SPKT versus 25 y in LDKT. The number of preemptive transplants and length of dialysis were similar. However, the wait time was shorter for LDKT (269 versus 460 d). Forty-nine percent of the LDKT recipients received the organ within 6 mo of being waitlisted compared with 28% of SPKT recipients ( P = 0.001). Donor age was lower in the SPKT group (27 versus 41 y). The estimated 5-y death censored kidney survival was 92% versus 98%, and 5-y patient survival was 86% versus 89% for SPKT versus LDKT. Death censored kidney and patient survival, acute kidney rejection by 1 y, and BK viremia were similar between the 2 groups. There were 17 pancreas graft losses within 1 y of transplant, the majority related to surgical complications, and it was not associated with increased mortality., Conclusions: SPKT in selected recipients aged 50 and above can have excellent outcomes similar to LDKT recipients., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

The OPTN/UNOS utilizes the calculated estimated posttransplant survival (EPTS) score as the measure of post-kidney transplant survival to guide allocation of deceased donor kidney transplantation. This score does not include any metric of functional capacity. Peak oxygen uptake (VO 2peak ), is an established predictor of survival among both the general and diseased populations. We assessed the association and discriminative capacity of VO 2peak and that of EPTS score and all-cause mortality post-kidney transplant. Additionally, we assessed the "mortality risk" lower VO 2peak conferred on those patients with low EPTS score. Among a cohort of 293 transplant recipients with at least 3-years post-transplant follow-up, the median VO 2peak was 15.0 ml/Kg/min. Lower pre-transplant VO 2peak and higher EPTS score conferred higher risk of post-transplant mortality. Among the cohort of "low-risk" patients (patients with EPTS score < 50) those with lower VO 2peak had significantly higher risk of mortality (log rank p = 0.045). In fact, the mortality risk among those with low-EPTS (< 50) and low VO 2peak  < 12 ml/Kg/min was equivalent to those with high EPTS (> 80) score. We concluded functional capacity as defined by VO 2peak is an important reflection of post-transplant survival. VO 2peak is able to identify those with low EPTS who have similar survival to that of high EPTS phenotype., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The study aims is to use the fragility index (FI) to examine the strength of evidence of randomized controlled trials (RCTs) published in the last decade on kidney transplantation., Methods: We searched MEDLINE for studies on kidney transplantation. We included the RCTs that compared 2 groups with 1:1 randomization and reported significant P values (<0.05) for a dichotomous outcome and were published in the top 10 transplant journals. We calculated the FI; a calculation used to determine the minimum number of subjects needed to change from a nonevent to an event to make the study results nonsignificant (P ≥ 0.05)., Results: Fifty-seven RCTs met our inclusion criteria. The median sample size was 100 participants in each arm, the median number of events was 16 (interquartile range, 8-30) in the intervention group. Among the included trials, 79% were industry-funded, 93% involved medications, and the majority were open label. The median FI was 3 (interquartile range, 1-11). In 43% of the trials, the number of patients reported lost to follow-up was higher than or equal to the FI. Only 4% of the RCTs imputed a value for the missing dichotomous outcome. Furthermore, the median number of subjects who discontinued the trial because of adverse effects was 21, which was greater than the FI in 60% of the RCTs., Conclusions: The arbitrary classification of results into "significant" and "nonsignificant" based on P value <0.05 should perhaps be interpreted with the help of other statistical parameters and FI is one of them., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Nephrolithiasis in living kidney donors is concerning due to the potential impact on long-term postdonation kidney function., Methods: We performed a cohort study of living kidney donors from 2 centers with a baseline computed tomography scan and implantation renal biopsy. Donors (>5 y since donation) completed a follow-up survey or underwent chart review to assess eGFR and incident hypertension. Stone formers were classified as symptomatic if they had a past symptomatic episode or asymptomatic if only incidental radiographic kidney stones were identified during donor evaluation. We compared baseline clinical, imaging, and biopsy characteristics by stone former status including review of metabolic evaluations in stone formers. Long-term risks of renal complications (low eGFR and hypertension) by stone former status were evaluated., Results: There were 12 symptomatic and 76 asymptomatic stone formers among 866 donors. Overall, baseline clinical characteristics and implantation biopsy findings were similar between stone formers and non-stone formers. After a median follow-up of 10 y, stone former status was not associated with eGFR <60 mL/min/1.73 m2, eGFR <45 mL/min/1.73 m 2 , or hypertension., Conclusions: Both asymptomatic and symptomatic SF have favorable histology findings at baseline. Long-term kidney outcomes were favorable in select stone formers with no evident increased long-term risk for decreased kidney function or hypertension after donation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Background: Participant withdrawal from clinical trials occurs for various reasons, predominantly adverse effects or intervention inefficacy. Because these missing participant data can have implications for the validity, reproducibility, and generalizability of study results, when conducting a systematic review, it is important to collect and appropriately analyze missing data information to assess its effects on the robustness of the study results., Methods: In this methodologic survey of missing participant data reporting and handling in systematic reviews, we included meta-analyses that provided pooled estimates of at least 1 dichotomous intervention outcome of a randomized controlled trial performed in adult kidney transplant subjects., Results: Eighty-three systematic reviews (17 Cochrane and 66 non-Cochrane reviews) met the inclusion criteria. The most common intervention was drugs (80%), with the majority involving immunosuppressant drugs 55% (n = 46), followed by surgery in 14% (n = 12). The median follow-up duration was 12 months (maximum, 240 mo). Intention-to-treat or modified intention-to-treat analysis was reported in 24% (n = 20) of the reviews (76% of Cochrane and 10% of non-Cochrane). Overall, the majority of systematic reviews did not quantify (90% [n = 60] non-Cochrane and 29% [n = 5] Cochrane) or include the reasons for missing participant data (88% [n = 58] non-Cochrane and 24% [n = 4] Cochrane). Eleven percent (n = 9) handled missing participant data, 5% (n = 4) justified the analytical method(s) used to handle it, and 2% (n = 2) performed a sensitivity analysis for it., Conclusions: Systematic reviews of kidney transplantation provide inadequate information on missing participant data and usually do not handle or discuss the associated risk of bias with it., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

BACKGROUND New-onset diabetes after transplantation (NODAT) is a complication of solid organ transplantation. We sought to determine the extent to which NODAT goes undiagnosed over the course of 1 year following transplantation, analyze missed or later-diagnosed cases of NODAT due to poor hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) collection, and to estimate the impact that improved NODAT screening metrics may have on long-term outcomes. MATERIAL AND METHODS This was a retrospective study utilizing 3 datasets from a single center on kidney, liver, and heart transplantation patients. Retrospective analysis was supplemented with an imputation procedure to account for missing data and project outcomes under perfect information. In addition, the data were used to inform a simulation model used to estimate life expectancy and cost-effectiveness of a hypothetical intervention. RESULTS Estimates of NODAT incidence increased from 27% to 31% in kidney transplantation patients, from 31% to 40% in liver transplantation patients, and from 45% to 67% in heart transplantation patients, when HbA1c and FBG were assumed to be collected perfectly at all points. Perfect screening for kidney transplantation patients was cost-saving, while perfect screening for liver and heart transplantation patients was cost-effective at a willingness-to-pay threshold of $100 000 per life-year. CONCLUSIONS Improved collection of HbA1c and FBG is a cost-effective method for detecting many additional cases of NODAT within the first year alone. Additional research into both improved glucometric monitoring as well as effective strategies for mitigating NODAT risk will become increasingly important to improve health in this population.

Objective: To determine whether microstructural features on a kidney biopsy specimen obtained during kidney transplant surgery predict long-term risk of chronic kidney disease in the donor., Patients and Methods: We studied kidney donors from May 1, 1999, through December 31, 2018, with a follow-up survey for the results of recent blood pressure and kidney function tests (estimated glomerular filtration rate [eGFR] and proteinuria). If not recently available, blood pressure and eGFRs were requested from a local clinic. Microstructural features on kidney biopsy at the time of donation were assessed as predictors of hypertension and kidney function after adjusting for years of follow-up, baseline age, sex, and clinical predictors., Results: There were 807 donors surveyed a mean 10.5 years after donation. An eGFR less than 45 mL/min/1.73 m 2 in 6.4% (43/673) of donors was predicted by larger glomerular volume per standard deviation (odds ratio [OR], 1.48; 95% CI, 1.08 to 2.04) and nephron number below the age-specific 5th percentile (OR, 3.38; 95% CI, 1.31 to 8.72). An eGFR less than 60 mL/min/1.73 m 2 in 42.5% (286/673) of donors was not predicted by any microstructural feature. Residual eGFR (postdonation/predonation eGFR) was predicted by nephron number below the age-specific 5th percentile (difference, -6.07%; 95% CI, -10.24% to -1.89%). Self-reported proteinuria in 5.1% (40/786) of donors was predicted by larger glomerular volume (OR, 1.42; 95% CI, 1.08 to 1.86). Incident hypertension in 18.8% (119/633) of donors was not predicted by any microstructural features., Conclusion: Low nephron number for age and larger glomeruli are important microstructural predictors for long-term risk of chronic kidney disease after living kidney donation., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: High glomerular filtration rate (GFR) is often used as a surrogate for single-nephron hyperfiltration. Our objective was to determine the definition for high GFR that best reflects clinical and structural characteristics of hyperfiltration., Methods: We studied living kidney donors at the Mayo Clinic and Cleveland Clinic. Potential donors underwent evaluations that included measured GFR (mGFR) by iothalamate clearance and estimated GFR (eGFR) by the serum creatinine-based Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI) equation. High GFR was defined by the 95th percentile for each method (mGFR or eGFR) using either overall or age-specific thresholds. High mGFR was defined as both corrected and uncorrected for body surface area. The association of high GFR by each definition with clinical characteristics and radiologic findings (kidney volume) was assessed. In the subset that donated, the association of high GFR with kidney biopsy findings (nephron number and glomerular volume) and single-nephron GFR was assessed., Results: We studied 3317 potential donors, including 2125 actual donors. The overall 95th percentile for corrected mGFR was 134 mL/min/1.73 m2 and for eGFR was 118 mL/min/1.73 m2. The age-based threshold for uncorrected mGFR was 198 mL/min - 0.943×Age, for corrected mGFR it was 164 mL/min/1.73 m2 - 0.730×Age and for eGFR it was 146 mL/min/1.73 m2 - 0.813×Age. High age-based uncorrected mGFR had the strongest associations with higher single-nephron GFR, larger glomerular volume, larger kidney volume, male gender, higher body mass index and higher 24-h urine albumin, but also had the strongest association with high nephron number. A high age-height-gender-based uncorrected mGFR definition performed almost as well but had a weaker association with nephron number and did not associate with male gender., Conclusions: High age-based uncorrected mGFR showed the most consistent associations reflective of hyperfiltration. However, high age-based uncorrected mGFR has limited clinical utility because it does not distinguish between hyperfiltration and high nephron number., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Nephrosclerosis, nephron size, and nephron number vary among kidneys transplanted from living donors. However, whether these structural features predict kidney transplant recipient outcomes is unclear., Methods: Our study used computed tomography (CT) and implantation biopsy to investigate donated kidney features as predictors of death-censored graft failure at three transplant centers participating in the Aging Kidney Anatomy study. We used global glomerulosclerosis, interstitial fibrosis/tubular atrophy, artery luminal stenosis, and arteriolar hyalinosis to measure nephrosclerosis; mean glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area to measure nephron size; and calculations from CT cortical volume and glomerular density on biopsy to assess nephron number. We also determined the death-censored risk of graft failure with each structural feature after adjusting for the predictive clinical characteristics of donor and recipient., Results: The analysis involved 2293 donor-recipient pairs. Mean recipient follow-up was 6.3 years, during which 287 death-censored graft failures and 424 deaths occurred. Factors that predicted death-censored graft failure independent of both donor and recipient clinical characteristics included interstitial fibrosis/tubular atrophy, larger cortical nephron size (but not nephron number), and smaller medullary volume. In a subset with 12 biopsy section slides, arteriolar hyalinosis also predicted death-censored graft failure., Conclusions: Subclinical nephrosclerosis, larger cortical nephron size, and smaller medullary volume in healthy donors modestly predict death-censored graft failure in the recipient, independent of donor or recipient clinical characteristics. These findings provide insights into a graft's "intrinsic quality" at the time of donation, and further support the use of intraoperative biopsies to identify kidney grafts that are at higher risk for failure., (Copyright © 2020 by the American Society of Nephrology.)

This retrospective study analyzed glycemic trends, incidence of post-transplant diabetes mellitus (PTDM) incidence and associated risk factors in a cohort of patients who underwent first-time heart transplantation (HT). Univariate analyses compared patient with and without pretransplant diabetes mellitus (DM). Multivariate regression analyses were conducted to determine association between PTDM and different risk factors. Finally, trends in glucometrics and other outcomes are described across follow-up time points. There were 152 patients who underwent HT between 2010 and 2015, 109 of whom had no pretransplant history of DM. PTDM incidence was 38% by the 1-year follow-up. Pretransplant body mass index (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.01 to 1.23, p = 0.03), insulin use during the final 24 hours of inpatient stay (OR 4.26, 95% CI 1.72 to 10.56, p <0.01), mean inpatient glucose (OR 2.21, 95% CI 1.33 to 3.69, p <0.01), and mean glucose in the final 24 hours before discharge (OR 1.29, 95% CI 1.03 to 1.60, p = 0.03) were associated with increased odds of PTDM at 1 year. In patients on insulin before discharge, blood glucose values were significantly higher compared with those who were not (136 mg/dl vs 114 mg/dl at 1 to 3 months, 112 vs 100 at 4 to 6 months, 109 vs 98 at 8 to 12 months, all p <0.01). This analysis improves understanding of PTDM incidence, glucometric trends, and risk differences by DM status in the HT population. Similar to liver and kidney patients, inpatient glucometrics may be informative of PTDM risk in HT patients. Guidelines for this population should be developed to account for risk heterogeneity and need for differential management., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Most prior studies characterizing post-transplantation diabetes mellitus (PTDM) have been limited to single-cohort, single-organ studies. This retrospective study determined PTDM across organs by comparing incidence and risk factors among 346 liver and 407 kidney transplant recipients from a single center., Methods: Univariate and multivariate regression-based analyses were conducted to determine association of various risk factors and PTDM in the two cohorts, as well as differences in glucometrics and insulin use across time points., Results: There was a higher incidence of PTDM among liver versus kidney transplant recipients (30% vs. 19%) at 1-year post-transplant. Liver transplant recipients demonstrated a 337% higher odds association to PTDM (OR 3.37, 95% CI (1.38-8.25), p<0.01). 1-month FBG was higher in kidney patients (135 mg/dL vs 104 mg/dL; p < .01), while 1-month insulin use was higher in liver patients (61% vs 27%, p < .01). Age, BMI, insulin use, and inpatient FBG were also significantly associated with differential PTDM risk., Conclusions: Kidney and liver transplant patients have different PTDM risk profiles, both in terms of absolute PTDM risk as well as time course of risk. Management of this population should better reflect risk heterogeneity to short-term need for insulin therapy and potentially long-term outcomes., Competing Interests: The authors have declared that no competing interests exist.

It is unclear whether structural findings in the kidneys of living kidney donors predict postdonation kidney function. We studied living kidney donors who had a kidney biopsy during donation. Nephron size was measured by glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area. Age-specific thresholds were defined for low nephron number (calculated from CT and biopsy measures) and nephrosclerosis (global glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis). These structural measures were assessed as predictors of postdonation measured GFR, 24-hour urine albumin, and hypertension. Analyses were adjusted for baseline age, gender, body mass index, systolic and diastolic blood pressure, hypertension, measured GFR, urine albumin, living related donor status, and time since donation. Of 2673 donors, 1334 returned for a follow-up visit at a median 4.4 months after donation, with measured GFR <60 mL/min/1.73 m 2 in 34%, urine albumin >5 mg/24 h in 13%, and hypertension in 5.3%. Larger glomerular volume and interstitial fibrosis/tubular atrophy predicted follow-up measured GFR <60 mL/min/1.73 m 2 . Larger cortex volume per glomerulus and low nephron number predicted follow-up urine albumin >5 mg/24 h. Arteriosclerosis predicted hypertension. Microstructural findings predict GFR <60 mL/min/1.73 m 2 , modest increases in urine albumin, and hypertension shortly after kidney donation., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Interest in nephrology careers is declining, possibly due to perceptions of the field and/or training aspects. Understanding practices of medical schools successfully instilling nephrology interest could inform efforts to attract leading candidates to the specialty., Methods: The American Society of Nephrology Workforce Committee's Best Practices Project was one of several initiatives to increase nephrology career interest. Board-certified nephrologists graduating medical school between 2002 and 2009 were identified in the American Medical Association Masterfile and their medical schools ranked by production. Renal educators from the top 10 producing institutions participated in directed focus groups inquiring about key factors in creating nephrology career interest, including aspects of their renal courses, clinical rotations, research activities, and faculty interactions. Thematic content analysis of the transcripts (with inductive reasoning implementing grounded theory) was performed to identify factors contributing to their programs' success., Results: The 10 schools identified were geographically representative, with similar proportions of graduates choosing internal medicine (mean 26%) as the national graduating class (26% in the 2017 residency Match). Eighteen educators from 9 of these 10 institutions participated. Four major themes were identified contributing to these schools' success: (1) nephrology faculty interaction with medical students; (2) clinical exposure to nephrology and clinical relevance of renal pathophysiology materials; (3) use of novel educational modalities; and (4) exposure, in particular early exposure, to the breadth of nephrology practice., Conclusion: Early and consistent exposure to a range of clinical nephrology experiences and nephrology faculty contact with medical students are important to help generate interest in the specialty., (© 2019 S. Karger AG, Basel.)

Pancreas transplant has evolved significantly in recent years. It has now become a viable treatment option on type 1 diabetic patients with poorly controlled diabetes on conventional treatment, insulin intolerance, hypoglycaemia unawareness, brittle diabetes and/ or end-stage kidney disease. The purpose of this review is to provide an overview of pancreas transplant historical origins and current barriers to broader utilization of pancreata for transplant, with a focus on areas for future improvement to better pancreas transplant care. Donor pancreata remain underutilized; pancreatic allograft discard rates remain close to 30% in the United States. Donations after cardiac death (DCD) pancreata are seldom procured. Study groups from Europe and the United Kingdom showed that procurement professionalization and standardization of technique, as well as development of independent regional procurement teams might increase organ procurement efficiency, decrease discards and increase pancreatic allograft utilization. Pancreas transplant programs should consider exploring pancreas procurement opportunities on DCD and obese donors. Selected type 2 diabetics should be considered for pancreas transplant. Longer follow-up studies need to be performed in order to ascertain the long-term cardiovascular and quality of life benefits following pancreas transplant; the outcomes of which might eventually spearhead advocacy towards broader application of pancreas transplant among diabetics., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest.

Background: Significant heterogeneity exists in practice patterns and algorithms used for cardiac screening before kidney transplant. Cardiorespiratory fitness, as measured by peak oxygen uptake (VO 2peak ), is an established validated predictor of future cardiovascular morbidity and mortality in both healthy and diseased populations. The literature supports its use among asymptomatic patients in abrogating the need for further cardiac testing., Methods and Results: We outlined a pre-renal transplant screening algorithm to incorporate VO 2peak testing among a population of asymptomatic high-risk patients (with diabetes mellitus and/or >50 years of age). Only those with VO 2peak <17 mL/kg per minute (equivalent to <5 metabolic equivalents) underwent further noninvasive cardiac screening tests. We conducted a retrospective study of the a priori dichotomization of the VO 2peak <17 versus ≥17 mL/kg per minute to determine negative and positive predictive value of future cardiac events and all-cause mortality. We report a high (>90%) negative predictive value, indicating that VO 2peak ≥17 mL/kg per minute is effective to rule out future cardiac events and all-cause mortality. However, lower VO 2peak had low positive predictive value and should not be used as a reliable metric to predict future cardiac events and/or mortality. In addition, a simple mathematical calculation documented a cost savings of ≈$272 600 in the cardiac screening among our study cohort of 637 patients undergoing evaluation for kidney and/or pancreas transplant., Conclusions: We conclude that incorporating an objective measure of cardiorespiratory fitness with VO 2peak is safe and allows for a cost savings in the cardiovascular screening protocol among higher-risk phenotype (with diabetes mellitus and >50 years of age) being evaluated for kidney transplant., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Aim: New-onset diabetes after kidney transplant (NODAT) adversely impacts kidney allograft and patient survival. Epigenetic alterations in adipose tissue like DNA methylation may play a contributory role., Methods: Adipose tissue DNA of the patients with NODAT and their age, sex and BMI matched controls (nine each) were sequenced by reduced representation bisulfite sequencing. Differentially methylated CpGs (DMCs) and differentially methylated regions (DMRs) were studied., Results: Adipose tissue from the patients had reduced DNA methylation in intergenic and intronic regions. DMCs were found to be more hypomethylated in repeat regions and hypermethylated in CGIs and promoter region. About 900 DMRs were found and their associated genes were significantly enriched in 32 pathways, the top ones of which were associated with insulin resistance and inflammation. Some DMR or DMC genes have known T2DM associations., Conclusion: Changes in DNA methylation in adipose tissue may be suggestive of future NODAT.

Patients with end-stage renal disease undergoing kidney transplant often have diffuse atherosclerosis and high cardiovascular morbidity and mortality rates. We analyzed the correlation of peripheral arterial disease (PAD), here quantified by an abnormal ankle-brachial index (ABI) measured within the 5 years prior to kidney transplant, with graft failure and mortality rates (primary end points) after adjusting for known cardiovascular risk factors (age, sex, smoking history, hypertension, diabetes, stroke, known coronary artery disease or heart failure, years of dialysis). Of 1055 patients in our transplant population, 819 had arterial studies within the 5 years prior to transplant. Secondary end points included myocardial infarction; cerebrovascular accident; and limb ischemia, gangrene, or amputation. Low ABI was an independent and significant predictor of organ failure (OR, 2.77 (95% CI, 1.68-4.58), p<0.001), secondary end points (HR, 1.39 (95% CI, 0.97-1.99), p<0.076), and death (HR, 1.84 (95% CI, 1.26-2.68), p=0.002). PAD was common in this population: of 819 kidney transplant recipients, 46% had PAD. Low ABI was associated with a threefold greater risk of graft failure, a twofold greater risk of death after transplant, and a threefold greater risk of secondary end points. Screening for PAD is important in this patient population because of the potential impact on long-term outcomes.

Background: Donor obesity, defined as donor body mass index (D-BMI) of 30 kg/m or greater, has been associated with increased risk of technical failure and poor pancreas allograft outcomes. Many transplant centers establish a threshold of D-BMI of 30 kg/m to decline donor offers for pancreas transplantation. However, no previous studies differentiate the impact of mild (D-BMI, 30-35 kg/m) versus severe obesity (D-BMI, ≥35 kg/m) on pancreas allograft outcomes., Methods: We examined Organ Procurement Transplant Network database records for 9916 simultaneous pancreas-kidney transplants (SPKT) performed between 2000 and 2013. We categorized donor body mass index (D-BMI) into 4 groups: 20 to 25 (n = 5724), 25 to 30 (n = 3303), 30 to 35 (n = 751), and 35 to 50 kg/m (n= 138). Associations of D-BMI with pancreas and kidney allograft failure were assessed by multivariate Cox regression adjusted for recipient, donor, and transplant factors., Results: Compared with D-BMI 20 to 25 kg/m, only D-BMI 35 to 50 kg/m was associated with significantly higher pancreas allograft [adjusted hazard ratio [aHR], 1.37; 95% confidence interval (CI], 1.04-1.79] and kidney allograft (aHR, 1.36; CI, 1.02-1.82) failure over the study period (13 years). Donor BMI 30 to 35 kg/m did not impact pancreas allograft (aHR, 0.99; CI, 0.86-1.37) or kidney allograft (aHR, 0.98; CI, 0.84-1.15) failure. Similar patterns were noted at 3 months, and 1, 5, and 10 years posttransplant., Conclusions: These data support that pancreata from mildly obese donors (BMI, 30-35 kg/m) can be safely used for transplantation, with comparable short-term and long-term outcomes as organs from lean donors. Consideration of pancreata from obese donors may decrease the pancreas discard rate.

Background: Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years., Methods: Using the United Network for Organ Sharing data, we identified first kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches and stratified by donor origin. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine impact of HLA compatibility on kidney allograft survival for all living donors and for living related and living unrelated subsets., Results: There were 66 596 first adult transplants from living donors with 348 960 years of follow-up. We found a linear relationship between HLA mismatch and allograft survival. In adjusted analyses, among all living donors, 1 mismatch conferred a 44% higher risk, whereas 6 mismatches conferred a twofold higher risk of allograft failure. When using 0-mismatched full siblings as a reference, living-donor kidneys reduce the hazard of failure by approximately 34% when compared with deceased donors. Twenty-five years of transplant experience, stratified by donor source, was summarized and presented as a guide for allocation., Conclusions: These data reinforce the importance of optimizing HLA matching to further improve survival in first adult kidney allografts in the future, especially in living unrelated donations, when possible., Competing Interests: The authors declare no conflict of interest.

Nephron number may be an important determinant of kidney health but has been difficult to study in living humans. We evaluated 1638 living kidney donors at Mayo Clinic (MN and AZ sites) and Cleveland Clinic. We obtained cortical volumes of both kidneys from predonation computed tomography scans. At the time of kidney transplant, we obtained and analyzed the sections of a biopsy specimen of the cortex to determine the density of both nonsclerotic and globally sclerotic glomeruli; the total number of glomeruli was estimated from cortical volume×glomerular density. Donors 18-29 years old had a mean 990,661 nonsclerotic glomeruli and 16,614 globally sclerotic glomeruli per kidney, which progressively decreased to 520,410 nonsclerotic glomeruli per kidney and increased to 141,714 globally sclerotic glomeruli per kidney in donors 70-75 years old. Between the youngest and oldest age groups, the number of nonsclerotic glomeruli decreased by 48%, whereas cortical volume decreased by only 16% and the proportion of globally sclerotic glomeruli on biopsy increased by only 15%. Clinical characteristics that independently associated with fewer nonsclerotic glomeruli were older age, shorter height, family history of ESRD, higher serum uric acid level, and lower measured GFR. The incomplete representation of nephron loss with aging by either increased glomerulosclerosis or by cortical volume decline is consistent with atrophy and reabsorption of globally sclerotic glomeruli and hypertrophy of remaining nephrons. In conclusion, lower nephron number in healthy adults associates with characteristics reflective of both lower nephron endowment at birth and subsequent loss of nephrons., (Copyright © 2016 by the American Society of Nephrology.)

Introduction: Decreased insulin sensitivity blunts the normal increase in gene expression from skeletal muscle after exercise. In addition, chronic inflammation decreases insulin sensitivity. Chronic kidney disease (CKD) is an inflammatory state. How CKD and, subsequently, kidney transplantation affects skeletal muscle gene expression after exercise are unknown., Methods: Study cohort: non-diabetic male/female 4/1, age 52±2 years, with end-stage CKD who underwent successful kidney transplantation. The following were measured both pre-transplant and post-transplant and compared to normals: Inflammatory markers, euglycemic insulin clamp studies determine insulin sensitivity, and skeletal muscle biopsies performed before and within 30 minutes after an acute exercise protocol. Microarray analyses were performed on the skeletal muscle using the 4x44K Whole Human Genome Microarrays. Since nuclear factor of activated T cells (NFAT) plays an important role in T cell activation and calcineurin inhibitors are mainstay immunosuppression, calcineurin/NFAT pathway gene expression was compared at rest and after exercise. Log transformation was performed to prevent skewing of data and regression analyses comparing measures pre- and post-transplant performed., Result: Markers of inflammation significantly improved post-transplantation. Insulin infusion raised glucose disposal slightly lower post-transplant compared to pre-transplant, but not significantly, thus concluding differences in insulin sensitivity were similar. The overall pattern of gene expression in response to exercise was reduced both pre-and post-transplant compared to healthy volunteers. Although significant changes were observed among NFAT/Calcineurin gene at rest and after exercise in normal cohort, there were no significant differences comparing NFAT/calcineurin pathway gene expression pre- and post-transplant., Conclusions: Despite an improvement in serum inflammatory markers, no significant differences in glucose disposal were observed post-transplant. The reduced skeletal muscle gene expression, including NFAT/calcineurin gene expression, in response to a single bout of exercise was not improved post-transplant. This study suggests that the improvements in inflammatory mediators post-transplant are unrelated to changes of NFAT/calcineurin gene expression.

Background: Liver transplant recipients are at increased risk of metabolic complications, including new-onset diabetes mellitus after transplantation (NODAT) and post-transplant metabolic syndrome (PTMS), both of which are associated with decreased patient survival. We prospectively monitored traditional and novel metabolic parameters in nondiabetic liver transplantation (LT) candidates to determine their role in detecting these conditions., Methods: Nondiabetic adults undergoing initial LT were prospectively identified. NODAT and PTMS were defined according to WHO and ATP III criteria. Metabolic measures were collected at pre-LT, 4, and 12 months post-LT., Results: Of 49 subjects enrolled, 24.5% were found to be diabetic pre-LT by 2-hr oral glucose tolerance test (OGTT) despite fasting glucose below the diabetic range. Two patients developed NODAT post-LT. A single patient was found to have MS at baseline, while PTMS developed in 26% and 31.3% of patients at 4 and 12 months. Novel metabolic markers did not detect these conditions., Conclusions: Screening OGTT detected pre-LT diabetes in patients with normal fasting glucose. Serial measurement of metabolic parameters allowed earlier detection of PTMS. Novel metabolic parameters did not correspond to post-LT outcomes, but provided a baseline for future study. More frequent and intensive metabolic monitoring appears reasonable, but larger studies are needed to clarify its efficacy.

Background: Even among ostensibly healthy adults, there is often mild pathology in the kidney. The detection of kidney microstructural variation and pathology by imaging and the clinical pattern associated with these structural findings is unclear., Study Design: Cross-sectional (clinical-pathologic correlation)., Setting & Participants: Living kidney donors at Mayo Clinic (Minnesota and Arizona sites) and Cleveland Clinic 2000 to 2011., Predictors: Predonation kidney function, risk factors, and contrast computed tomographic scan of the kidneys. These scans were segmented for cortical volume and medullary volume, reviewed for parenchymal cysts, and scored for kidney surface roughness., Outcomes: Nephrosclerosis (glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis) and nephron size (glomerular volume, mean profile tubular area, and cortical volume per glomerulus) determined from an implantation biopsy of the kidney cortex at donation., Results: Among 1,520 living kidney donors, nephrosclerosis associated with increased kidney surface roughness, cysts, and smaller cortical to medullary volume ratio. Larger nephron size (nephron hypertrophy) associated with larger cortical volume. Nephron hypertrophy and larger cortical volume associated with higher systolic blood pressure, glomerular filtration rate, and urine albumin excretion; larger body mass index; higher serum uric acid level; and family history of end-stage renal disease. Both nephron hypertrophy and nephrosclerosis associated with older age and mild hypertension. The net effect of both nephron hypertrophy and nephrosclerosis associating with cortical volume was that nephron hypertrophy diminished volume loss with age-related nephrosclerosis and fully negated volume loss with mild hypertension-related nephrosclerosis., Limitations: Kidney donors are selected on health, restricting the spectrum of pathologic findings. Kidney biopsies in living donors are a small tissue sample leading to imprecise estimates of structural findings., Conclusions: Among apparently healthy adults, the microstructural findings of nephron hypertrophy and nephrosclerosis differ in their associations with kidney function, macrostructure, and risk factors., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Carfilzomib is a selective proteosome inhibitor approved for treatment of relapsed and refractory multiple myeloma. Recent reports have linked exposure to carfilzomib with development of thrombotic microangiopathy (TMA). We describe two cases of biopsy proven thrombotic microangiopathy that occurred after the initiation of carfilzomib (dosed at 32 mg/m(2) and 23 mg/m(2), respectively) for relapsed multiple myeloma. Both patients were managed with discontinuation of the drug, therapeutic plasma exchange (TPE) and supportive care. Hemoglobin, platelets and renal function did not improve with TPE. TMA resolved with creatinine returning to baseline several weeks after discontinuation of the drug. The outcomes suggest that TPE is not beneficial for treating carfilzomib-induced TMA., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Since the beginning of the technology, there has been active debate about the role of human leucocyte antigen (HLA) matching in kidney allograft survival. Recent studies have reported diminishing importance of HLA matching, which have, in turn, been challenged by reports that suggest the continuing importance of these loci. Given the controversies, we examined the effect of HLA compatibility on kidney allograft survival by studying all first adult kidney transplants in the United States from a deceased donor., Methods: Using the United Network for Organ Sharing data, we identified first deceased donor kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine the impact of HLA compatibility on kidney allograft survival., Results: Study cohort included 189 141 first adult kidney alone transplants, with a total of 994 558 years of kidney allograft follow-up time. Analyses adjusted for recipient and donor characteristics demonstrated a 13% higher risk (hazard ratio, 1.13; 95% confidence interval, 1.06-1.21) with 1 mismatch and a 64% higher risk (hazard ratio, 1.64, 95% confidence interval, 1.56-1.73) with 6 mismatches. Dividing the mismatch categories into 27 ordered permutations, and testing their 57 within mismatch category differences, demonstrated that all but 1 were equal, independent of locus., Conclusions: A significant linear relationship of hazard ratios was associated with HLA mismatch and affects allograft survival even during the recent periods of increasing success in renal transplantation.

The aim of this study was to determine the clinical and histologic outcomes related to transplanting kidneys from deceased donors with glomerular fibrin thrombi (GFT). We included all cases transplanted between October 2003 and October 2014 that had either a preimplantation biopsy or an immediate postreperfusion biopsy showing GFT. The study cohort included 61 recipients (9.9%) with GFT and 557 in the control group without GFT. Delayed graft function occurred in 49% of the GFT group and 39% in the control group (p = 0.14). Serum creatinine at 1, 4, and 12 months and estimated GFR at 12 months were similar in the two groups. Estimated 1-year graft survival was 93.2% in the GFT group and 95.1% in the control group (p = 0.22 by log-rank). Fifty-two of the 61 patients in the GFT group (85%) had a 1-month protocol biopsy, and only two biopsies (4%) showed residual focal glomerular thrombi. At the 1-year protocol biopsy, the prevalence of moderate to severe interstitial fibrosis and tubular atrophy was 24% in the GFT group and 30% in the control group (p = 0.42). We concluded that GFT resolves rapidly after transplantation and that transplanting selected kidneys from deceased donors with GFT is a safe practice., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Aim: High blood glucose levels in the hospital are common among transplant recipients., Methods: Retrospective analysis, stratified by diagnosis of pretransplant diabetes mellitus (DM)., Results: Of 346 patients, 96 had pretransplant DM (insulin, n = 60; no insulin, n = 36) and 250 did not. Patients with pretransplant DM had higher inpatient mean glucose levels and more hyperglycemia and hypoglycemia (all p < 0.01). For patients without pretransplant DM, the need for insulin at discharge increased 23% for every 5-year age increase (odds ratio: 1.23; 95% CI: 1.06-1.44; p = 0.007) and 51% for every five units of glucose measurements >180 mg/dl (OR: 1.51; 95% CI: 1.23-1.95; p < 0.01)., Conclusion: Inpatient hyperglycemia was common in liver transplant recipients. Hospital practitioners must anticipate the need to teach self-management skills to liver transplant recipients., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Background: While simultaneous pancreas kidney transplant (SPKTx) is a therapeutic option for patients with type 1 diabetes (T1DM) and renal failure, few centers offer SPKTx to "select" non-T1DM patients. To address concerns that existing insulin resistance may limit the benefits of the pancreas allograft among non-T1DM, we compared several indices of glucose homeostasis, in "select" non-T1DM and T1DM patients who received SPKTx., Methods: Criteria for "select" non-T1DM included the following: positive C-peptide, BMI <30 kg/m(2) , treatment with oral agents before insulin initiation, and insulin at <1 unit/kg/d. We compared several indices of glucose homeostasis within 1 yr post-SPKTx among seven "select" patients with non-T1DM and nine patients with T1DM with similar age, BMI, and immunosuppression. Measurements of insulin resistance included the following: homeostatic model, insulin sensitivity index, and insulin-glucose ratio; insulin secretion measures included the following: corrected insulin response., Results: Non-T1DM had similar pre-transplant metabolic (fasting glucose, HbA1c, blood pressure, and lipid) parameters to the T1DM cohort. There were no significant differences in the various measures of insulin resistance and secretion between T1DM and "select" non-T1DM patients., Conclusion: Our results suggest SPKTx should be considered in the therapeutic armamentarium among carefully select non-T1DM with features of minimal insulin resistance; however, a larger cohort with longer follow-up is needed to confirm our results., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Global glomerulosclerosis is characteristic of chronic kidney disease and also occurs with normal aging. Our goal was to determine the upper limit of normal for number of globally sclerotic glomeruli., Methods: Core-needle biopsies of the renal cortex were obtained at the time of living kidney transplantation at three centers between 1998 and 2011. The number of globally sclerotic glomeruli was averaged across two biopsy sections. Quantile regression was used to estimate the 95th percentile for globally sclerotic glomeruli as the upper reference limit. There were 2052 donors (mean age 43 years, 41% male, 10% hypertensive), with a mean (SD) of 16.0 (9.7) glomeruli and 0.47 (0.99) globally sclerotic glomeruli on biopsy; only 2.6% had >5% fibrosis., Results: In a multivariable model excluding hypertensive donors, independent predictors of the number of globally sclerotic glomeruli were age, total number of glomeruli and cortex area. A simplified model was used to estimate the 95th percentile for number of globally sclerotic glomeruli by total number of glomeruli and age. For a biopsy section with 17-32 total glomeruli, the 95th percentile ranged from 1 for a 20-year old to 5.5 for a 70-year old donor. Hypertensive donors were more likely to have an abnormal number of globally sclerotic glomeruli (OR = 1.79, P = 0.035)., Conclusions: We have derived the 95% reference limit for number of globally sclerotic glomeruli in ostensibly healthy individuals accounting for age and the biopsy characteristics. Numbers of globally sclerotic glomeruli in a kidney biopsy that exceed these thresholds suggest chronic pathological injury in excess of that expected with normal aging., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Hyperglycemia following solid organ transplant is common among patients without pre-existing diabetes mellitus (DM). Post-transplant hyperglycemia can occur once or multiple times, which if continued, causes new-onset diabetes after transplantation (NODAT)., Objective: To study if the first and recurrent incidence of hyperglycemia are affected differently by immunosuppressive regimens, demographic and medical-related risk factors, and inpatient hyperglycemic conditions (i.e., an emphasis on the time course of post-transplant complications)., Methods: We conducted a retrospective analysis of 407 patients who underwent kidney transplantation at Mayo Clinic Arizona. Among these, there were 292 patients with no signs of DM prior to transplant. For this category of patients, we evaluated the impact of (1) immunosuppressive drugs (e.g., tacrolimus, sirolimus, and steroid), (2) demographic and medical-related risk factors, and (3) inpatient hyperglycemic conditions on the first and recurrent incidence of hyperglycemia in one year post-transplant. We employed two versions of Cox regression analyses: (1) a time-dependent model to analyze the recurrent cases of hyperglycemia and (2) a time-independent model to analyze the first incidence of hyperglycemia., Results: Age (P = 0.018), HDL cholesterol (P = 0.010), and the average trough level of tacrolimus (P<0.0001) are significant risk factors associated with the first incidence of hyperglycemia, while age (P<0.0001), non-White race (P = 0.002), BMI (P = 0.002), HDL cholesterol (P = 0.003), uric acid (P = 0.012), and using steroid (P = 0.007) are the significant risk factors for the recurrent cases of hyperglycemia., Discussion: This study draws attention to the importance of analyzing the risk factors associated with a disease (specially a chronic one) with respect to both its first and recurrent incidence, as well as carefully differentiating these two perspectives: a fact that is currently overlooked in the literature.

Living donor kidney transplantation (LDKT) offers better quality of life and clinical outcomes, including patient survival, compared with remaining on dialysis or receiving a deceased donor kidney transplant. Although LDKT education within transplant centers for both potential recipients and living donors is very important, outreach and education to kidney patients in settings other than transplant centers and to the general public is also critical to increase access to this highly beneficial treatment. In June 2014, the American Society of Transplantation's Live Donor Community of Practice, with the support of 10 additional sponsors, convened a consensus conference to determine best practices in LDKT, including a workgroup focused on developing a set of recommendations for optimizing outreach and LDKT education outside of transplant centers. Members of this workgroup performed a structured literature review, conducted teleconference meetings, and met in person at the 2-day conference. Their efforts resulted in consensus around the following recommendations. First, preemptive transplantation should be promoted through increased LDKT education by primary care physicians and community nephrologists. Second, dialysis providers should be trained to educate their own patients about LDKT and deceased donor kidney transplantation. Third, partnerships between community organizations, organ procurement organizations, religious organizations, and transplant centers should be fostered to support transplantation. Fourth, use of technology should be improved or expanded to better educate kidney patients and their support networks. Fifth, LDKT education and outreach should be improved for kidney patients in rural areas. Finally, a consensus-driven, evidence-based public message about LDKT should be developed. Discussion of the effect and potential for implementation around each recommendation is featured, particularly regarding reducing racial and socioeconomic disparities in access to LDKT. To accomplish these recommendations, the entire community of professionals and organizations serving kidney patients must work collaboratively toward ensuring accurate, comprehensive, and up-to-date LDKT education for all patients, thereby reducing barriers to LDKT access and increasing LDKT rates., (Copyright © 2015 by the American Society of Nephrology.)

A 37-year-old African-American woman with end-stage renal disease presumed to be secondary to diabetes mellitus type 2, on daily peritoneal dialysis, was admitted for a painful left lower extremity lesion. Examination revealed a large, dusky, tender region over the left lateral thigh. She was on warfarin for mechanical heart valves. Despite discontinuation of warfarin and placement on heparin, the lesion progressed to extend to the medial left thigh and medial and lateral right thigh. CT scan demonstrated arteriolar medial calcification and vascular calcification of the small subcutaneous vessels, without evidence of abscess or haematoma. The patient declined punch biopsy. Given the known risk factors of high calcium-phosphate and radiological findings, a diagnosis of calcific uraemic arteriolopathy was made. Phosphate-binder therapy was optimised. She was transitioned to daily haemodialysis, and sodium thiosulfate was initiated. Skin lesions demonstrated improvement at her 5 weeks posthospitalisation follow-up., (2015 BMJ Publishing Group Ltd.)

Our aim was to determine outcomes with transplanting kidneys from deceased donors with acute kidney injury, defined as a donor with terminal serum creatinine ≥2.0 mg/dL, or a donor requiring acute renal replacement therapy. We included all patients who received deceased donor kidney transplant from June 2004 to October 2013. There were 162 AKI donor transplant recipients (21% of deceased donor transplants): 139 in the standard criteria donor (SCD) and 23 in the expanded criteria donor (ECD) cohort. 71% of the AKI donors had stage 3 (severe AKI), based on acute kidney injury network (AKIN) staging. Protocol biopsies were done at 1, 4, and 12 months posttransplant. One and four month formalin-fixed paraffin embedded (FFPE) biopsies from 48 patients (24 AKI donors, 24 non-AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). DGF was more common in the AKI group but eGFR, graft survival at 1 year and proportion with IF/TA>2 at 1 year were similar for the two groups. At 1 month, there were 898 differentially expressed genes in the AKI group (p-value <0.005; FDR <10%), but by 4 months there were no differences. Transplanting selected kidneys from deceased donors with AKI is safe and has excellent outcomes., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Body mass index (BMI) is a convenient measure used to assess obesity and is used to select candidates for kidney donation. Glomerulomegaly is an early indicator of obesity-related kidney disease. Whether obesity assessment by BMI best reflects underlying glomerulomegaly and is predictive of adverse changes in renal function postdonation is unclear., Methods: We performed a retrospective study on a cohort of 1065 living donors at the Mayo Clinic in Rochester; obesity measures by BMI and by computed tomography were compared between 20 donors with largest to 20 donors with the smallest glomerular volumes (on implantation biopsy). In addition, the change in kidney function postdonation (mean 7 months) was compared across BMI groups (<25, 25-29, 30-34, ≥35 kg/m 2 ) in about 500 donors., Results: We observed that larger glomerular volume was more strongly associated with BMI per standard deviation (SD) (odds ratio [OR] =5.0, P = 0.002) than waist circumference/height 2 per SD (OR = 3.9, P = 0.02), visceral fat/height 2 per SD (OR = 2.4, P = 0.02), subcutaneous fat/height 2 per SD (OR = 2.0, P = 0.06), renal hilar fat/height 2 per SD (OR = 1.6, P = 0.19), or peri/pararenal fat/height 2 per SD (OR = 1.5, P = 0.23). Postdonation changes in glomerular filtration rate, blood pressure, and albuminuria were similar across BMI categories., Conclusions: The BMI outperforms various computed tomography measures of abdominal fat in detecting obesity-related glomerulomegaly. Despite this strong association with glomerulomegaly, short-term renal function outcomes are similar across BMI categories. Long-term follow-up is required to definitively define the impact of obesity on kidney function after donation.

Background: Our aim was to determine the incidence of de novo donor-specific human leukocyte antigen (HLA) antibody (dnDSA) during the first year after kidney transplantation and the impact of early dnDSA on acute rejection and protocol biopsy findings., Methods: We selected all patients who received a kidney transplant at our center between July 2010 and March 2012. Single antigen bead assay was performed at 1, 4 and 12 months after transplantation. Only DSAs with a mean fluorescence intensity (MFI) of greater 999 were included., Results: We included 245 kidney transplant recipients who did not have a DSA before transplantation. At 12 months, 8.2% of the patients developed dnDSA; 2.4% of them were to HLA class I and 6.5% to HLA class II. Of the 32 patients with a dnDSA at 1 or 4 months, only 8 (25%) persisted at 12 months. The risk of antibody-mediated rejection (AMR) was higher in the dnDSA group. For the dnDSA group with MFI of 3,000 or greater (compared with the group with MFI<3,000), the hazard ratio for AMR was 10.6 (95% confidence interval, 2.27-49.5). The cumulative incidence of AMR or mixed rejection at 1 year was 30% in the group with dnDSA MFI level of 3,000 or greater but only 4% for the group with dnDSA with MFI less than 3,000. On 1-year protocol biopsies, the dnDSA group showed more interstitial inflammation, tubulitis, and glomerulitis., Conclusion: We conclude that dnDSA occurring during the first posttransplantation year may be transient, and the risk of AMR is higher in patients with a dnDSA MFI level that is greater than 3,000.

The kidney atrophies in patients with advanced chronic kidney disease (CKD) but factors influencing kidney size in normal adults are less clear. To help define this, we measured kidney volumes on contrast-enhanced computed tomographic images from 1344 potential kidney donors (aged 18-75 years). Cortical volume per body surface area progressively declined in both genders with increased age. Statistically, this was primarily dependent on the age-related decline in glomerular filtration rate (GFR). Independent predictors of increased cortical volume per body surface area were male gender, increased GFR, increased 24-h urine albumin, current smoker, and decreased high-density lipid cholesterol. Medullary volume per body surface area increased with age in men, while it increased with age in women until the age of 50 years followed by a subsequent decline. Independent predictors of increased medullary volume per body surface area were older age, male gender, increased GFR, increased 24-h urine albumin, increased serum glucose, and decreased serum uric acid. Thus, while cortical volume declines with age along the same biological pathway as the age-related decline in GFR, albuminuria and some risk factors are actually associated with increased cortical or medullary volume among relatively healthy adults. Underlying hypertrophy or atrophy of different nephron regions may explain these findings.

Since 1999, we have performed 2,302 kidney transplants at the Mayo Clinic in Arizona. Transplant volume has increased by 45% since 2010. Our center performed 269 kidney transplants in 2013. Our growth is related to multiple factors, including an experienced, committed team and strong support from our institution and referring nephrologists. Areas of program innovation at our center include: transplanting deceased donors with acute kidney injury, outcomes in older kidney transplant recipients, alemtuzumab induction with steroid avoidance, living donor paired kidney exchange-3 site experience, and other non-traditional deceased donor kidney transplants. Of the 162 acute kidney injury (AKI) donor transplants done at our program, 71% had severe AKI. The AKI donor kidneys had more delayed graft function; but graft survival, estimated glomerular filtration rate, and biopsy findings at 1 year were not different form the control group. We have transplanted 188 patients ≥ 70 years old at the time of transplantation. Graft survival at 1, 3, and 5 years was similar to that of patients < 70. Since 2008, 778 (37%) patients received alemtuzumab induction, therapy with excellent patient and graft survival. We have used steroid avoidance immunosuppression with excellent outcomes since 2003. Since starting kidney paired donation in 2009, it has resulted in 54 kidney transplants, including 4 compatible pairs. More than half of the deceased donor transplants done at our center are from non-traditional donors such as Public Health Service increased risk, donation after cardiac death, extended criteria donors/high kidney donor profile index, and pediatric en-bloc donors. One- and 3-year graft survival of the non-traditional deceased donor kidney transplants are not different than the traditional deceased donor kidney transplants.

Background: To quantify changes of left ventricular (LV) torsion in patients' pre and post kidney transplantation., Methods: A prospective study was conducted on 48 patients who received kidney transplantation for end stage renal disease and without myocardial infarction. The rotation, twist and torsion of LV were studied pre and post kidney transplantation (6 months post transplantation) using velocity vector imaging by echocardiography. The data is expressed as mean ± standard deviation and compared by paired t-test at the p < 0.05 significance level., Results: Six months post kidney transplantation, left ventricular ejection fraction (from 40.33 ± 11.42 to 61.00 ± 13.68%), ratio of mitral early and late diastolic filling velocity (from 1.04 ± 0.57 to 1.21 ± 0.52), rotation of basal LV (from 4.48 ± 2.66 to 5.65 ± 2.64 degree), rotation of apical LV (from 4.27 ± 3.08 to 5.50 ± 4.25 degree), LV twist (8.75 ± 4.45 to 11.14 ± 5.25 degree) and torsion (from 1.06 ± 0.54 to 1.33 ± 0.61 degree/cm) were increased significantly (p < 0.05). Interventricular septum thickness (from 11.67 ± 2.39 to 9.67 ± 0.48 mm), left ventricular mass index (from 104.00 ± 16.47 to 95.50 ± 21.44 g/m(2)), systolic blood pressure (from 143.50 ± 34.99 to 121.50 ± 7.09 mmHg), serum blood urea nitrogen (from 42.40 ± 7.98 to 30.43 ± 13.85 mg/dL) and creatinine (from 4.53 ± 1.96 to 2.73 ± 2.57 mg/dL) were decreased significantly (p < 0.05)., Conclusion: Kidney transplantation in end stage renal disease without myocardial infarction results in improvement in left ventricular structure, function and myocardial mechanics as detected by echocardiography and velocity vector imaging. Velocity vector imaging provided valuable information for detection and follow-up of cardiac abnormalities in patients with end stage renal disease.

Objective: Identification of patients at high risk for new-onset diabetes after kidney transplantation (NODAT) will facilitate clinical trials for its prevention., Research Design and Methods: We previously described a pretransplant predictive risk model for NODAT using seven pretransplant variables (age, planned use of maintenance corticosteroids, prescription for gout medicine, BMI, fasting glucose, fasting triglycerides, and family history of diabetes). We have now applied the initial model to a cohort of 474 transplant recipients from another center for validation. We performed two analyses in the validation cohort. The first was a standard model with variables derived from the original study. The second was a summary score model, in which the sum of dichotomized variables (all the variables dichotomized at clinically relevant cut points) was used to categorize, individuals into low (0-1), intermediate (2, 3), or high (4-7) risk groups. We also conducted a combined database analyses, merging the initial and validation cohorts (n=792) to obtain better estimates for a prediction equation., Results: Although the frequency of several risk factors differed significantly between the two cohorts, the models performed similarly in each cohort. Using the summary score model, incidences of NODAT in low-risk, medium-risk, and high-risk groups in the initial cohort were 12, 29, and 56%, and in the validation cohort incidences were 11, 29, and 51%., Conclusions: A pretransplant model for NODAT, including many type 2 diabetes risk factors, predicted NODAT in the validation cohort.