Evaluation of Effective Half-Life and Its Impact on Time to Steady State for Oral MeltDose Tacrolimus (LCPT) in De Novo Kidney Transplant Recipients.

Background: For extended-release drug formulations, effective half-life (t 1/2eff ) is a relevant pharmacokinetic parameter to inform dosing strategies and time to reach steady state. Tacrolimus, an immunosuppressant commonly used for the prophylaxis of organ rejection in transplant patients, is available as both immediate- and extended-release formulations. To the best of our knowledge, the t 1/2eff of tacrolimus from these different formulations has not yet been assessed.

Pretransplant Cognitive Function and Kidney Transplant Outcomes: A Prospective Cohort Study.

Background & Hypothesis: Cognitive impairment is common in patients being evaluated for a kidney transplant (KT). The association between pretransplant cognitive function and posttransplant outcomes is unclear.

Study Design: We performed a prospective cohort study to assess the association between pretransplant cognitive function and clinically relevant posttransplant outcomes.

Posoleucel in Kidney Transplant Recipients with BK Viremia: Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

Key Points: Posoleucel was generally safe, well tolerated, and associated with a greater reduction of BK viremia compared with placebo. BK viremia reduction occurred coincident with an increase in the circulating frequency of BK virus–specific T cells in posoleucel recipients. The presence and persistence of posoleucel was confirmed by T-cell receptor variable sequencing.

Should Transplant Nephrology Pursue Recognition from the Accreditation Council for Graduate Medical Education (ACGME)?

Kidney transplant is not only the best treatment for patients with advanced kidney disease but it also reduces health care expenditure. The management of transplant patients is complex as they require special care by transplant nephrologists who have expertise in assessing transplant candidates, understand immunology and organ rejection, have familiarity with perioperative complications, and have the ability to manage the long-term effects of chronic immunosuppression. This skill set at the intersection of multiple disciplines necessitates additional training in Transplant Nephrology.

Pre-transplant cognitive screening is a poor predictor of post-transplant cognitive status.

Introduction: Transplant centers hesitate to transplant patients with cognitive impairment. It is unclear if pre-kidney transplant (KT) cognitive screening can predict post-KT cognitive function.

Methods: We evaluated pre- to post-KT cognitive function with the Montreal Cognitive Assessment (MoCA) in a cohort of 108 patients.

Pretransplant Psoas Muscle Cross-Sectional Area and Postkidney Transplant Outcomes.

Background: Sarcopenia is associated with adverse outcomes in end-stage kidney disease. We evaluated if pretransplant sarcopenia affects posttransplant outcomes in kidney transplant (KT) recipients.

Methods: In this single-center retrospective study of adult patients with end-stage kidney disease, we analyzed the association between pre-KT psoas muscle cross-sectional area and critical posttransplant outcomes of decline in estimated glomerular filtration rate (eGFR), graft loss, rehospitalization, and mortality using Cox proportional hazard model adjusted for age, sex, and race.

Posttransplant proteinuria due to Apolipoprotein E2 deposition in a kidney allograft.

Lipoprotein deposition disorders limited to the kidney and causing proteinuria are rare. We present a case of nephrotic range proteinuria presenting within 4 months after deceased donor renal transplantation in a patient with end-stage kidney disease presumed secondary to hypertension. Two transplant kidney biopsies were performed sixteen weeks after transplantation, and one year after the first biopsy, both showing lipoprotein deposits in the glomeruli, progressive focal segmental glomerulosclerosis, and effacement of visceral foot processes.

Nonoperative management of gastrointestinal bleeding after a simultaneous pancreas and kidney transplant.

With a shift toward enteric drainage techniques, the complications associated with simultaneous pancreas and kidney (SPK) transplant have also changed. Gastrointestinal (GI) bleeding is one of the most common complications associated with SPK. This case report describes the treatment of a postoperative GI hemorrhage using the push endoscopy technique.

Podocyte stress and detachment measured in urine are related to mean arterial pressure in healthy humans.

Hypertension-associated progressive glomerulosclerosis is a significant driver of both de novo and all-cause chronic kidney disease leading to end-stage kidney failure. The progression of glomerular disease proceeds via continuing depletion of podocytes from the glomeruli into the ultrafiltrate. To non-invasively assess injury patterns associated with mean arterial pressure (MAP), we conducted an observational study of 87 healthy normotensive individuals who were cleared for living kidney donation.

Subclinical Cognitive Impairment and Listing for Kidney Transplantation.

Background And Objectives: Cognitive impairment is common in patients with kidney disease and can affect physicians' perception and/or patients' ability to complete the pretransplant evaluation. We examined whether cognitive impairment influences the likelihood for transplant listing and whether patients with cognitive impairment take longer to be listed.

Design, Setting, Participants, & Measurements: We conducted a single-center longitudinal cohort study.

Accelerated podocyte detachment early after kidney transplantation is related to long-term allograft loss of function.

Background: Kidney allograft half-life has not improved despite excellent short-term survival. Recent long-term surveillance biopsy studies identify accumulating glomerulosclerosis (GS) to be associated with late allograft loss. While podocyte depletion is well known to drive proteinuria and GS in animal models and human glomerular diseases, its role in renal allograft loss of function is generally not recognized.

A LASSO Method to Identify Protein Signature Predicting Post-transplant Renal Graft Survival.

Identifying novel biomarkers to predict renal graft survival is important in post-transplant clinical practice. Serum creatinine, currently the most popular surrogate biomarker, offers limited information of the underlying allograft profiles. It is known to perform unsatisfactorily to predict renal function.

Temporal trends, center-level variation, and the impact of prevalent state obesity rates on acceptance of obese living kidney donors.

The impact of pre-donation obesity on long-term outcomes of living kidney donors remains controversial. Published guidelines offer varying recommendations regarding BMI (kg/m ) thresholds for donor acceptance. We examined temporal and center-level variation in BMI of accepted donors across US transplant centers.

Quantitative podocyte parameters predict human native kidney and allograft half-lives.

Background: Kidney function decreases with age. A potential mechanistic explanation for kidney and allograft half-life has evolved through the realization that linear reduction in glomerular podocyte density could drive progressive glomerulosclerosis to impact both native kidney and allograft half-lives.

Methods: Predictions from podometrics (quantitation of podocyte parameters) were tested using independent pathologic, functional, and outcome data for native kidneys and allografts derived from published reports and large registries.

Underutilization of Timely Kidney Transplants in Those With Living Donors.

Preemptive kidney transplant (PKTx) and kidney transplant (KTx) within 1 year of dialysis initiation have been associated with superior outcomes. Wait times should be minimal for transplants with living donors; however, there is lack of literature studying utilization of timely KTx in this population. We designed this retrospective study using data from United Network for Organ Sharing Standard Transplant Analysis and Research files from 2000 to 2012 to assess the trends in utilization of PKTx and Early KTx (combination of PKTx or transplant within 1 year of dialysis initiation) in recipients of living donor KTx.

The Impact of Obesity on Allograft Failure After Kidney Transplantation: A Competing Risks Analysis.

Background: The impact of pretransplant body mass index (BMI) on long-term allograft outcomes after kidney transplantation remains controversial. The conventional approach of using Kaplan-Meier method to calculate the cumulative risk of death-censored allograft failure may overestimate the risk of failure especially when competing failure risks are present.

Method: A retrospective cohort of adult first-time kidney transplant recipients was drawn from the Organ Procurement and Transplantation Network database (2001 to 2009).

Identification of a protein signature in renal allograft rejection.

Purpose: Serum creatinine functions as a poor surrogate marker of renal allograft dysfunction and long-term graft survival. By measuring multiple proteins simultaneously in the serum of transplant patients, we can identify unique protein signatures of graft dysfunction.

Experimental Design: We utilized training and validation cohorts composed of healthy and volunteer subjects, stable renal transplant patients, and renal transplant patients experiencing acute allograft rejection.

Mycophenolic acid pharmacokinetics in lung transplant recipients with cystic fibrosis.

Background: Lung transplantation is an established treatment for cystic fibrosis (CF) patients with end-stage lung disease. Current immunosuppression includes the prodrug mycophenolate mofetil (MMF), which has led to improved transplant outcomes. Given the pancreatic insufficiency and malabsorption in CF patients, some transplant centers give higher doses of MMF to these patients based on lower predose levels (C(0)), even though C(0) values correlate poorly with mycophenolic acid (MPA) exposure.

A history of chronic opioid usage prior to kidney transplantation may be associated with increased mortality risk.

Chronic opioid usage (COU) for analgesia is common among patients with end-stage renal disease. In order to test whether a prior history of COU negatively affects post-kidney transplant outcomes, we retrospectively examined clinical outcomes in adult kidney transplant patients. Among 1064 adult kidney transplant patients, 452 (42.

Randomized trial of everolimus-facilitated calcineurin inhibitor minimization over 24 months in renal transplantation.

Background: Strategies allowing calcineurin inhibitor minimization while maintaining efficacy may improve renal transplant outcomes.

Methods: A2309 was a 24-month, phase IIIb, open-label trial of 833 de novo renal transplant recipients randomized to everolimus, targeting trough concentrations of 3-8 or 6-12 ng/mL plus reduced-exposure cyclosporine A (CsA) or to mycophenolic acid (MPA) 1.44 g per day plus standard-exposure CsA.

Association of clinical events with everolimus exposure in kidney transplant patients receiving reduced cyclosporine.

Background: The association between clinical events and everolimus exposure in patients receiving reduced-exposure calcineurin inhibitor therapy is poorly explored.

Methods: In a pre-planned, descriptive analysis of data from a randomized controlled trial, events were correlated with everolimus trough concentrations in 556 newly transplanted kidney transplant patients receiving everolimus with reduced-exposure cyclosporine (CsA) and steroids. Influence of everolimus exposure on clinical events was stratified according to predefined time-normalized concentrations.

Randomized phase 2b trial of tofacitinib (CP-690,550) in de novo kidney transplant patients: efficacy, renal function and safety at 1 year.

In this Phase 2b study, 331 low-to-moderate risk de novo kidney transplant patients (approximately 60% deceased donors) were randomized to a more intensive (MI) or less intensive (LI) regimen of tofacitinib (CP-690, 550), an oral Janus kinase inhibitor or cyclosporine (CsA). All patients received basiliximab induction, mycophenolic acid and corticosteroids. Primary endpoints were: incidence of biopsy-proven acute rejection (BPAR) with a serum creatinine increase of ≥0.

The time interval between kidney and pancreas transplantation and the clinical outcomes of pancreas after kidney transplantation.

Pancreas after kidney (PAK) transplantation is one of the accepted pancreas transplant modalities. We studied the impact of time interval between kidney and pancreas transplantation on the outcomes of PAK transplantation. Using OPTN/SRTR data, we included 1853 PAK transplants performed between 1996 and 2005 with follow-up until November 1, 2008.