Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P,0.001 (receiver operating characteristic area under the curve [AUC], 0.74; 95% confidence interval [95% CI], 0.61 to 0.86). Positive and negative predictive values for active rejection at a cutoff of 1.0% dd-cfDNA were 61% and 84%, respectively. The AUC for discriminating ABMR from samples without ABMR was 0.87 (95% CI, 0.75 to 0.97). Positive and negative predictive values for ABMR at a cutoff of 1.0% dd-cfDNA were 44% and 96%, respectively. Median dd-cfDNA was 2.9% (ABMR), 1.2% (T cell-mediated types $IB), 0.2% (T cellmediated type IA), and 0.3% in controls (P=0.05 for T cell-mediated rejection types $IB versus controls). Thus, ddcfDNA may be used to assess allograft rejection and injury; dd-cfDNA levels ,1% reflect the absence of active rejection (T cell-mediated type $IB or ABMR) and levels .1% indicate a probability of active rejection.

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Determining candidacy for live kidney donation among obese individuals remains challenging. Among healthy non-donors, body mass index (BMI) above 30 is associated with a 16% increase in risk of end-stage renal disease (ESRD). However, the impact on the ESRD risk attributable to donation and living with only one kidney remains unknown. Here we studied the risk of ESRD associated with obesity at the time of donation among 119 769 live kidney donors in the United States. Maximum follow-up was 20 years. Obese (BMI above 30) live kidney donors were more likely male, African American, and had higher blood pressure. Estimated risk of ESRD 20 years after donation was 93.9 per 10 000 for obese; significantly greater than the 39.7 per 10 000 for non-obese live kidney donors. Adjusted for age, sex, ethnicity, blood pressure, baseline estimated glomerular filtration rate , and relationship to recipient, obese live kidney donors had a significant 86% increased risk of ESRD compared to their non-obese counterparts (adjusted hazard ratio 1.86; 95% confidence interval 1.05–3.30). For each unit increase in BMI above 27kg/m2 there was an associated significant 7% increase in ESRD risk (1.07, 1.02–1.12). The impact of obesity on ESRD risk was similar for male and female donors, African American and Caucasian donors, and across the baseline estimated glomerular filtration rate spectrum. These findings may help to inform selection criteria and discussions with persons considering living kidney donation.

These findings support a role for ATG induction, and caution against the use of sirolimus-based maintenance therapy, in HIV-positive individuals undergoing KT.

Background Previous studies have demonstrated that donor-derived cell-free DNA (dd-cfDNA) found in circulating blood of transplant recipients may serve as a noninvasive biomarker of allograft rejection. To better interpret the clinical meaning of dd-cfDNA, it is essential to understand the biological variation of this biomarker in stable healthy recipients. This report establishes the biological variation and clinical reference intervals of dd-cfDNA in renal transplant recipients by using an analytically validated assay that has a CV of 6.8%. Methods We sampled venous blood at patient surveillance visits (typically at posttransplant months 1–4, 6, 9, and 12) in a 14-center observational study. Patients with stable renal allograft function spanning ≥3 serial visits were selected. We used AlloSure®, a targeted next-generation sequencing-based approach, to measure dd-cfDNA in the plasma and computed the intraindividual CV (CVI) and interindividual CV (CVG), the index of individuality (II), and reference change value (RCV). Results Of 93 patients, 61% were men, 56% were Caucasian, mean age was 49 years, and 63% were deceased donor kidney recipients. Of 380 blood samples, the dd-cfDNA median value was 0.21% (interquartile range 0.12%–0.39%) and the 97.5th percentile was 1.20%. In 18 patients with an average of 4.1 tests, the CVI was 21%, CVG was 37%, II was 0.57, and RCV was 61%. Conclusions In a renal transplant recipient, a dd-cfDNA level above 1.2% is out of range and potentially abnormal. A serial increase of up to 61% in level of dd-cfDNA in a patient may be attributable to biological variation. Clinicaltrials.gov Identifier: NCT02424227

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Our findings highlight the need for additional study to better understand disparities in access to kidney transplantation, particularly living donor kidney transplantation, among HIV+ kidney waitlist candidates.

Background: Coronary artery disease (CAD) is the predominant cause of sudden cardiac death in the general population, and sudden cardiac death is the leading cause of mortality in end-stage renal disease (ESRD). Hypothesis: QT-interval prolongation is an independent prognosticator in ESRD. Methods: We reviewed clinical, electrocardiographic, stress test, and coronary angiography data on ESRD patients evaluated for transplantation at our institution between 2000 and 2004 who underwent coronary angiography. The QT interval was corrected for heart rate and QRS duration (QTc). All-cause mortality data were prospectively collected and verified against the Social Security Death Index database. Results: During 40 ± 28 months of follow-up, 132 of the 280 (47%) patients died prior to renal transplantation. Patients with a prolonged QTc (39%) had 1-, 3-, and 5-year death-rates of 12%, 36%, and 47%, respectively, vs 8%, 24%, and 36% for those with normal QTc (log-rank P = 0.03). In a multivariate Cox regression model that adjusted for age, gender, diabetes mellitus, myocardial infarction, presence and severity of CAD on angiography, left ventricular (LV) hypertrophy, LV ejection fraction (EF), and multiple other variables, QTc remained to be an independent predictor of survival (hazard ratio [HR]: 1.008, 95% confidence interval [CI]: 1.001-1.014, P = 0.016). Female gender, decreasing LVEF, and decreasing severity of CAD on angiography were independent predictors of prolonged QTc. Conclusions: QTc prolongation is an independent predictor of mortality in ESRD patients being evaluated for renal transplantation. The prognostic information gained from the QTc is additive to that provided by the LVEF and the severity of CAD.