Peter P. Reese

Cardiovascular disease in kidney donors: matched cohort study

Objective To determine whether people who donate a kidney have an increased risk of cardiovascular disease. Design Retrospective population based matched cohort study. Participants All people who were carefully selected to become a living kidney donor in the province of Ontario, Canada, between 1992 and 2009. The information in donor charts was manually reviewed and linked to provincial healthcare databases. Matched non-donors were selected from the healthiest segment of the general population. A total of 2028 donors and 20 280 matched non-donors were followed for a median of 6.5 years (maximum 17.7 years). Median age was 43 at the time of donation (interquartile range 34-50) and 50 at the time of follow-up (42-58). Main outcome measures The primary outcome was a composite of time to death or first major cardiovascular event. The secondary outcome was time to first major cardiovascular event censored for death. Results The risk of the primary outcome of death and major cardiovascular events was lower in donors than in non-donors (2.8 v 4.1 events per 1000 person years; hazard ratio 0.66, 95% confidence interval 0.48 to 0.90). The risk of major cardiovascular events censored for death was no different in donors than in non-donors (1.7 v 2.0 events per 1000 person years; 0.85, 0.57 to 1.27). Results were similar in all sensitivity analyses. Older age and lower income were associated with a higher risk of death and major cardiovascular events in both donors and non-donors when each group was analysed separately. Conclusions The risk of major cardiovascular events in donors is no higher in the first decade after kidney donation compared with a similarly healthy segment of the general population. While we will continue to follow people in this study, these interim results add to the evidence base supporting the safety of the practice among carefully selected donors.

Automated, electronic alerts for acute kidney injury: a single-blind, parallel-group, randomised controlled trial

BACKGROUND Acute kidney injury often goes unrecognised in its early stages when effective treatment options might be available. We aimed to determine whether an automated electronic alert for acute kidney injury would reduce the severity of such injury and improve clinical outcomes in patients in hospital. METHODS In this investigator-masked, parallel-group, randomised controlled trial, patients were recruited from the hospital of the University of Pennsylvania in Philadelphia, PA, USA. Eligible participants were adults aged 18 years or older who were in hospital with stage 1 or greater acute kidney injury as defined by Kidney Disease Improving Global Outcomes creatinine-based criteria. Exclusion criteria were initial hospital creatinine 4·0 mg/dL (to convert to μmol/L, multiply by 88·4) or greater, fewer than two creatinine values measured, inability to determine the covering provider, admission to hospice or the observation unit, previous randomisation, or end-stage renal disease. Patients were randomly assigned (1:1) via a computer-generated sequence to receive an acute kidney injury alert (a text-based alert sent to the covering provider and unit pharmacist indicating new acute kidney injury) or usual care, stratified by medical versus surgical admission and intensive care unit versus non-intensive care unit location in blocks of 4-8 participants. The primary outcome was a composite of relative maximum change in creatinine, dialysis, and death at 7 days after randomisation. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01862419. FINDINGS Between Sept 17, 2013, and April 14, 2014, 23,664 patients were screened. 1201 eligible participants were assigned to the acute kidney injury alert group and 1192 were assigned to the usual care group. Composite relative maximum change in creatinine, dialysis, and death at 7 days did not differ between the alert group and the usual care group (p=0·88), or within any of the four randomisation strata (all p>0·05). At 7 days after randomisation, median maximum relative change in creatinine concentrations was 0·0% (IQR 0·0-18·4) in the alert group and 0·6% (0·0-17·5) in the usual care group (p=0·81); 87 (7·2%) patients in the alert group and 70 (5·9%) patients in usual care group had received dialysis (odds ratio 1·25 [95% CI 0·90-1·74]; p=0·18); and 71 (5·9%) patients in the alert group and 61 (5·1%) patients in the usual care group had died (1·16 [0·81-1·68]; p=0·40). INTERPRETATION An electronic alert system for acute kidney injury did not improve clinical outcomes among patients in hospital. FUNDING Penn Center for Healthcare Improvement and Patient Safety.

Chronic Kidney Disease after Nonrenal Solid-Organ Transplantation

Chronic kidney disease (CKD) is a common complication after nonrenal solid-organ transplantation. The risk for CKD is influenced by many factors, some of which have a direct impact on how such patients are treated in the pre-, peri-, and posttransplantation settings. This review describes hazards for acute and chronic kidney injury, with particular emphasis on calcineurin inhibitor-mediated nephrotoxicity. Rather than a detailed description of management issues that are common to the general CKD population, highlighted are aspects that are more specific to nonrenal solid-organ transplant recipients with a focus on liver, heart, and lung recipients. Strategies to minimize nephrotoxic insults and retard progressive renal injury are discussed, as are issues that are pertinent to dialysis and transplantation. Finally, future approaches to prevent and treat CKD without compromising function of the transplanted organ are addressed.

Substantial variation in the acceptance of medically complex live kidney donors across US renal transplant centers.

Concern exists about accepting live kidney donation from ‘medically complex donors’—those with risk factors for future kidney disease. This studys aim was to examine variation in complex kidney donor use across US transplant centers. We conducted a retrospective cohort study of live kidney donors using organ procurement and transplantation network data. Donors with hypertension, obesity or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 were considered medically complex. Among 9319 donors, 2254 (24.2%) were complex: 1194 (12.8%) were obese, 956 (10.3%) hypertensive and 392 (4.2%) had low eGFR. The mean proportion of medically complex donors at a center was 24% (range 0–65%). In multivariate analysis, donor characteristics associated with medical complexity included spousal relationship to the recipient (OR 1.29, CI 1.06–1.56, p < 0.01), low education (OR 1.19, CI 1.04–1.37, p = 0.01), older age (OR 1.01 per year, CI 1.01–1.02, p < 0.01) and non‐US citizenship (OR 0.70, CI 0.51–0.97, p = 0.03). Renal transplant centers with the highest transplant volume (OR 1.26, CI 1.02–1.57, p = 0.03), and with a higher proportion of (living donation)/(all kidney transplants) (OR 1.97, CI 1.23–3.16, p < 0.01) were more likely to use medically complex donors. Though controversial, the use of medically complex donors is widespread and varies widely across centers.

Solid-organ transplantation in older adults: Current status and future research

An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short‐term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long‐term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events. Approaches to transplantation in older adults vary across programs, but despite recent gains in access and the increased use of marginal organs, older patients remain less likely than other groups to receive a transplant, and those who do are highly selected. Moreover, few studies have addressed geriatric issues in transplant patient selection or management, or the implications on health span and disability when patients age to late life with a transplanted organ. This paper summarizes a recent trans‐disciplinary workshop held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK and AGS, to address issues related to kidney, liver, lung, or heart transplantation in older adults and to propose a research agenda in these areas.

Living kidney donation: outcomes, ethics, and uncertainty

Since the first living-donor kidney transplantation in 1954, more than half a million living kidney donations have occurred and research has advanced knowledge about long-term donor outcomes. Donors in developed countries have a similar life expectancy and quality of life as healthy non-donors. Living kidney donation is associated with an increased risk of end-stage renal disease, although this outcome is uncommon (<0·5% increase in incidence at 15 years). Kidney donation seems to elevate the risks of gestational hypertension and pre-eclampsia. Many donors incur financial expenses due to factors such as lost wages, need for sick days, and travel expenses. Yet, most donors have no regrets about donation. Living kidney donation is practised ethically when informed consent incorporates information about risks, uncertainty about outcomes is acknowledged when it exists, and a donors risks are proportional to benefits for the donor and recipient. Future research should determine whether outcomes are similar for donors from developing countries and donors with pre-existing conditions such as obesity.

Trial of Transplantation of HCV-Infected Kidneys into Uninfected Recipients

An open-label pilot trial involving 10 patients shows that hepatitis C virus genotype 1–infected kidneys transplanted into HCV-negative recipients, followed by direct-acting antiviral therapy, can result in excellent allograft function with cure of HCV infection.

Transplanting Hepatitis C–Positive Kidneys

New antiviral therapies for hepatitis C virus infection, with cure rates exceeding 95%, should prompt transplant-community leaders to view HCV-positive organs as a valuable opportunity for transplant candidates with or without preexisting HCV infection.

Recipient risk factors associated with delayed graft function: a paired kidney analysis.

Background. Delayed graft function (DGF) is a common complication of deceased donor kidney transplantation that occurs because of a complex interplay between donor organ quality and the biologic milieu of the recipient. The purpose of the study is to better understand the recipient risk factors leading to DGF. Methods. We performed a retrospective cohort study using United Network for Organ sharing data and identified pairs of primary, adult kidney-only transplants that were procured from the same adult donor with discordant occurrence of DGF (i.e., one kidney of the pair had DGF). Results. A total of 5382 recipient pairs were analyzed. Recipients with DGF were more likely to be male (67% vs. 59%, P<0.01), African American (36% vs. 27%, P<0.01), obese (30% vs. 19%, P<0.01), diabetic (28% vs. 22%, P<0.01), on maintenance dialysis (92% vs. 83%, P<0.01), and to have longer wait-time (571 vs. 471 days, P<0.01), longer cold ischemia time (22 vs. 20 hr, P<0.01), and donor and recipient size mismatch (32% vs. 24%, P<0.01). Multivariable analyses confirmed these associations and identified panel reactive antibody more than 10% and low center volume as additional risk factors for DGF (odds ratio for panel reactive antibody >10%: 1.17, confidence interval 1.05–1.29, P<0.01; and odds ratio for <83 transplants/year: 1.29, confidence interval 1.17–1.44, P<0.01). Conclusions. After fully matching for donor factors, many recipient characteristics were noted to be associated with DGF. Better management of modifiable recipient and transplant risk factors such as obesity, wait time, and cold time may help to reduce the occurrence of DGF.

The American Society of Transplantation Consensus Conference on the Use of Hepatitis C Viremic Donors in Solid Organ Transplantation

The availability of direct‐acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These changes have affected the practice of solid organ transplantation by altering the framework by which patients with end‐stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV‐viremic patients into non–HCV‐viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C–infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.