Search

Background. High-risk cytomegalovirus (CMV) and Epstein-Barr virus (EBV) mismatches (ie, seropositive donors to seronegative recipients) among kidney transplant recipients lead to increased healthcare utilization, inferior allograft outcomes, and high mortality. We assessed the interest among prospective kidney donor and recipient candidates to participate in kidney paired donation (KPD) for averting CMV/EBV high-risk mismatches. Methods. We surveyed 51 potential living donors and 102 kidney recipient candidates presenting for their evaluation visit at the University of Pittsburgh Medical Center between October 2022 and May 2023. We evaluated their general inclination toward KPD and their interest in KPD under various risk-benefit scenarios, particularly emphasizing the mitigation of high-risk mismatches associated with EBV and CMV. This was done using a 5-point Likert scale (1-low interest; 5-high interest) customized survey. Results. There was high interest in KPD among both donor and recipient candidates (median score 4 versus 4; P = 0.09). However, donor candidates had a lower interest in KPD if they were compatible with their intended recipient (median score 2 versus 4; P

Background. Early acute kidney rejection remains an important clinical issue. Methods. The current study included 552 recipients who had 1–2 surveillance or indication biopsy within the 1 y posttransplant. We evaluated the impact of type of allograft inflammation on allograft outcome. They were divided into 5 groups: no inflammation (NI: 95), subclinical inflammation (SCI: 244), subclinical T cell–mediated rejection (TCMR) (SC-TCMR: 110), clinical TCMR (C-TCMR: 83), and antibody-mediated rejection (AMR: 20). Estimated glomerular filtration rate (eGFR) over time using linear mixed model, cumulative chronic allograft scores/interstitial fibrosis and tubular atrophy (IFTA) ≥2 at 12 mo, and survival estimates were compared between groups. Results. The common types of rejections were C-TCMR (15%), SC-TCMR (19.9%), and AMR (3.6%) of patients. Eighteen of 20 patients with AMR had mixed rejection with TCMR. Key findings were as follows: (i) posttransplant renal function: eGFR was lower for patients with C-TCMR and AMR (P

Background. Renal transplantation is the treatment of choice for patients with end-stage renal disease. Because kidneys are the primary excretory organs for various drugs/drug metabolites, changes in renal graft function would significantly alter the clearance and exposure of renally secreted drugs. Renal allografts from living and deceased donors normally undergo numerous insults, including injuries associated with prolonged cold ischemic time, reperfusion, and nephrotoxicity due to calcineurin inhibitors. These physiologic and pharmacologic stresses can alter the expression and functional capacity of renal organic anionic transporters (OATs). Methods. The objectives of this study were to assess the longitudinal changes in renal anionic secretion in kidney transplant patients, to study the effect of prolonged cold ischemic time on OAT secretion in kidney transplant patients (living- versus deceased-donor recipients), and to compare OAT secretory capacity of renal transplant recipients with healthy volunteers. Cefoxitin was used as a probe drug to assess OAT secretion. Cefoxitin pharmacokinetics was studied in 15 de novo renal transplant recipients following intravenous administration of 200 mg cefoxitin within 14 d and beyond 90 d posttransplantation. Results. No longitudinal changes in real OAT secretion in early posttransplant period were observed, and there were no differences in renal OAT secretion between living- and deceased-donor renal transplant recipients. Overall, cefoxitin exposure was 2.6-fold higher and half-life increased by 2.2-fold in renal transplant recipients when compared with historical healthy controls. Conclusions. These results suggest that OAT system is functioning well, but renal transplant recipients would need significantly lower dosage of drugs that are primarily secreted via the OAT system compared with normal subjects.

Background. High calcineurin inhibitor (CNI) intrapatient variability (IPV) has been associated with poor kidney allograft outcomes. However, the relationship between early allograft histological changes, their progression, and CNI-IPV is less well studied. Hence, we evaluated effect of CNI-IPV defined by the degree of fluctuation of CNI levels in all kidney transplant patients over 2 to 12 months posttransplant on early allograft inflammation, subsequent chronicity, and later clinical outcomes. Methods. Two hundred eighty-six patients transplanted from January 2013 to November 2014 were enrolled with protocol and indication biopsies. The mean CNI-IPV was 28.5% and a quarter of our cohort had IPV of 35% or greater (high CNI IPV). Baseline demographic differences were similar between high and low CNI IPV groups. Results. High CNI-IPV was associated with a higher incidence of acute rejection (AR) within 1 year (52% vs 31% P < 0.001), more persistent/recurrent AR by 1 year (18.2% vs 6.2%, P = 0.002), higher-grade AR (≥Banff 1B, 27.5% vs 7.3%, P < 0.001), and worse interstitial fibrosis/tubular atrophy (P = 0.005). High CNI-IPV was associated with increased graft loss (GL) and impending graft loss (iGL, defined as eGFR30% decline in eGFR from baseline), regardless of donor-specific antibody, delayed graft function, rejection, or race. In a multivariate Cox Proportional Hazards Model, high CNI-IPV was independently associated with GL + iGL (hazard ratio, 3.1; 95% confidence interval, 1.6–5.9, P < 0.001). Conclusions. High CNI-IPV within 1 year posttransplant is associated with higher incidence of AR, severe AR, allograft chronicity, GL, and iGL. This represents a subset of patients who are at risk for poor kidney transplant outcomes and potentially a modifiable risk factor for late allograft loss.