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OBJECTIVE - The aim of this study was to develop a novel chronic kidney disease (CKD) risk prediction tool for young potential living kidney donors.
SUMMARY OF BACKGROUND DATA - Living kidney donor selection practices have evolved from examining individual risk factors to a risk calculator incorporating multiple characteristics. Owing to limited long-term data and lack of genetic information, current risk tools lack precision among young potential living kidney donors, particularly African Americans (AAs).
METHODS - We identified a cohort of young adults (18-30 years) with no absolute contraindication to kidney donation from the longitudinal cohort study Coronary Artery Risk Development in Young Adults. Risk associations for CKD (estimated glomerular filtration rate <60 mL/min/1.73 m) were identified and assigned weighted points to calculate risk scores.
RESULTS - A total of 3438 healthy adults were identified [mean age 24.8 years; 48.3% AA; median follow-up 24.9 years (interquartile range: 24.5-25.2)]. For 18-year olds, 25-year projected CKD risk varied by ethnicity and sex even without baseline clinical and genetic abnormalities; risk was 0.30% for European American (EA) women, 0.52% for EA men, 0.52% for AA women, 0.90% for AA men. Among 18-year-old AAs with apolipoprotein L1 gene (APOL1) renal-risk variants without baseline abnormalities, 25-year risk significantly increased: 1.46% for women and 2.53% for men; among those with 2 APOL1 renal-risk variants and baseline abnormalities, 25-year risk was higher: 2.53% to 6.23% for women and 4.35% to 10.58% for men.
CONCLUSIONS - Young AAs were at highest risk for CKD, and APOL1 renal-risk variants drove some of this risk. Understanding the genetic profile of young AA potential living kidney donors in the context of baseline health characteristics may help to inform candidate selection and counseling.
Morphometric assessments, such as muscle density and body fat distribution, have emerged as strong predictors of cardiovascular risk and postoperative morbidity and mortality. To date, no study has examined morphometric mortality risk prediction among kidney transplant (KT) candidates. KT candidates, waitlisted 2008-2009, were identified (n=96) and followed to the earliest of transplant, death, or administrative end of study. Morphometric measures, including abdominal adipose tissue, paraspinous and psoas muscle composition, and aortic calcification, were measured from CTs. Risk of waitlist mortality was examined using Cox proportional hazard regression. On adjusted analyses, radiologic measures remained independently and significantly associated with lower waitlist mortality; the addition of radiologic measures significantly improved model predictive ability over models containing traditional risk factors alone (net reclassification index: 0.56, 95% CI: 0.31-0.75). Higher psoas muscle attenuation (indicative of leaner muscle) was associated with decreased risk of death (aHR: 0.93, 95% CI: 0.91-0.96, P<.001), and for each unit increase in lean paraspinous volume, there was an associated 2% decreased risk for death (aHR: 0.98, 95% CI: 0.96-0.99, P=.03). Radiologic measures of lean muscle mass, such as psoas muscle attenuation and paraspinous lean volume, may improve waitlist mortality risk prediction and candidate selection.
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
BACKGROUND - Sarcoidosis is a presumptive autoimmune disorder characterized by the presence of noncaseating granulomas and is usually treated successfully with immunosuppression.
METHODS AND RESULTS - Here, we describe the case of a 63-year-old male renal transplant recipient with a remote history of pulmonary sarcoidosis on chronic immunosuppression who developed recurrent aseptic meningitis and underwent brain biopsy revealing a diagnosis of neurosarcoidosis.
CONCLUSIONS - This case highlights the possibility of recurrence of sarcoidosis in the setting of maintenance immunosuppression, the need for heightened awareness of alternative sites of recurrence of autoimmune disease, and future studies to determine the underlying mechanism of recurrence in organ transplant recipients.
BACKGROUND - The leading cause of death in end stage renal disease is cardiovascular disease (CVD). Kidney transplantation is associated with improved survival over dialysis. We hypothesized that arterial stiffness, a marker of CVD, would improve in patients post kidney transplant, potentially explaining one mechanism of survival benefit from transplant.
METHODS - After obtaining Institutional Review Board approval and informed consent, we performed a longitudinal prospective cohort study of 66 newly transplanted adult kidney transplant recipients, using aortic pulse wave velocity (PWV) to assess arterial stiffness over a 12 month period. All patients were assessed within one month of transplant (baseline) and 12 months post transplant. The primary outcome was change in PWV score at 12 months which we assessed using Wilcoxon Signed Rank test. Secondary analyses included correlation of predictors with PWV score at both time points.
RESULTS - The median age of the cohort was 49.7 years at transplant, with 27 % Black and 27 % female. At baseline, 43 % had tobacco use, 30 % had a history of CVD, and 42 % had diabetes. Median baseline calcium was 9.1 mg/dL and median phosphorus was 5.1 mg/dL. Median PWV score was 9.25 and 8.97 m/s at baseline versus month 12, respectively, showing no significant change (median change of -0.07, p = 0.7). In multivariable regression, subjects with increased age at transplant (p = 0.008), diabetes (p = 0.002), and a higher baseline PWV score (p < 0.001) were at increased risk of having a high PWV score 12 months post transplant.
CONCLUSION - Aortic arterial stiffness does not progress in the first year post kidney transplant. Increasing age, diabetes, and higher baseline PWV score identify patients at risk for increased arterial stiffness. Further research that assesses patients for greater than one year and includes a control dialysis group would be helpful in further understanding the change in arterial stiffness post transplantation.
BACKGROUND - Some patients referred for kidney transplant evaluation fail to attend the visit. Our goal was to compare demographic, socioeconomic, and psychologic factors between evaluation visit attendees and absentees.
METHODS - A convenience sample of patients referred and scheduled for kidney transplant evaluation at a single center from November 2012 to December 2013 participated in a phone survey reporting socioeconomic, demographic, and clinical characteristics; health literacy; and perceived knowledge and concerns about transplantation. Absentees were matched by race with attendees. Analyses of differences between groups were performed with chi-square test, Fisher exact test, and t tests. Multivariable logistic regression was adjusted for relevant demographic characteristics.
RESULTS - One hundred four adults participated (61% men, 46% white, 52 ± 12 years). Financial concerns were the most prevalent (67.3% affording medication, 64.1% affording operation). Previous evaluation at a different transplant center (P = 0.029) and being on dialysis (P = 0.008) were significantly associated with absence. Attendance was associated with concerns about finding a living donor (P = 0.038) and higher perceived general knowledge about transplantation (P ≤ 0.001). No differences were appreciated in demographic, socioeconomic, or health literacy factors between groups.
CONCLUSION - Both attendee and absentee patients were most concerned with the financial burden of kidney transplantation. Although concerns and perceived knowledge are important correlates of behavior, other considerations such as psychologic factors and prior medical experiences may influence patients' ability to complete the kidney transplant evaluation process. Although this pilot study was conducted in a small sample and has limited generalizability, our findings can guide future research.
Delayed graft function in kidney transplant recipients is a known complication associated with increased risk of acute rejection and reduced transplant survival after 1 year. There are multiple risk factors, including prolonged cold ischemia time, donor age, and cause of donor's death. Major causes of delayed graft function are acute kidney injury in the donor, often from prolonged terminal ischemia, reflected by acute tubular injury in the recipient. However, the differential diagnosis of delayed graft function includes acute rejection, recurrence of the primary glomerular diseases, and other less commonly encountered conditions. A transplant kidney biopsy usually is required to elucidate the correct cause and initiate the right treatment, which is crucial for transplant survival. We report a case of a transplant recipient who developed delayed graft function due to an uncommon cause. After correct diagnosis, the patient's transplant function improved.
Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
PURPOSE OF REVIEW - Pharmacogenomics is the study of differences in drug response on the basis of individual genetic background. With rapidly advancing genomic technologies and decreased costs of genotyping, the field of pharmacogenomics continues to develop. Application to patients with kidney disease provides growing opportunities for improving drug therapy.
RECENT FINDINGS - Pharmacogenomics studies are lacking in patients with chronic kidney disease and dialysis, but are abundant in the kidney transplant field. A potentially clinically actionable genetic variant exists in the CYP3A5 gene, with the initial tacrolimus dose selection being optimized based on CYP3A5 genotype. Although many pharmacogenomics studies have focused on transplant immunosuppression pharmacokinetics, an expanding literature on pharmacodynamic outcomes, such as calcineurin inhibitor toxicity and new onset diabetes, is providing new information on patients at risk.
SUMMARY - Appropriately powered pharmacogenomics studies with well-defined phenotypes are needed to validate existing studies and unearth new findings in patients with kidney disease, especially the chronic kidney disease and dialysis population.