Faculty Bibliography

This report describes the results of 2 international randomized trials (total of 508 kidney transplant recipients). The primary objective was to assess the noninferiority of rabbit anti-thymocyte globulin (rATG, Thymoglobulin^® ) versus interleukin-2 receptor antagonists (IL2RAs) for the quadruple endpoint (treatment failure defined as biopsy-proven acute rejection, graft loss, death, or loss to follow-up) to serve as the pivotal data for United States (US) regulatory approval of rATG. The pooled analysis provided an incidence of treatment failure of 25.1% in the rATG and 36.0% in the IL2RA treatment groups, an absolute difference of -10.9% (95% confidence interval [CI] -18.8% to -2.9%) supporting noninferiority (noninferiority margin was 10%) and superiority of rATG to IL2RA. In a meta-analysis of 7 trials comparing rATG with an IL2RA, the difference in the proportion of patients with BPAR at 12 months was -4.8% (95% CI -8.6% to -0.9%) in favor of rATG. In conclusion, a rigorous reanalysis of patient-level data from 2 prior randomized, controlled trials comparing rATG versus IL-2R monoclonal antibodies provided support for regulatory approval for rATG for induction therapy in renal transplant, making it the first T cell-depleting therapy approved for the prophylaxis of acute rejection in patients receiving a kidney transplant in the United States.

Several single-center reports of using HCV-viremic organs for HCV-uninfected (HCV-) recipients were recently published. We sought to characterize national utilization of HCV-exposed donors for HCV- recipients (HCV D+/R-) in kidney transplantation (KT) and liver transplantation (LT). Using SRTR data (April 1, 2015-December 2, 2018) and Gini coefficients, we studied center-level clustering of 1193 HCV D+/R- KTs and LTs. HCV-viremic (NAT+) D+/R- KTs increased from 1/month in 2015 to 22/month in 2018 (LTs: 0/month to 12/month). HCV-aviremic (Ab+/NAT-) D+/R- KTs increased from < 1/month in 2015 to 26/month in 2018 (LTs: <1/month to 8/month). HCV- recipients of viremic and aviremic kidneys spent a median (interquartile range [IQR]) of 0.7 (0.2-1.6) and 1.6 (0.4-3.5) years on the waitlist versus 1.8 (0.5-4.0) among HCV D-/R-. HCV- recipients of viremic and aviremic livers had median (IQR) MELD scores of 24 (21-30) and 25 (21-32) at transplantation versus 29 (23-36) among HCV D-/R-. 12 KT and 14 LT centers performed 81% and 76% of all viremic HCV D+/R- transplants; 11 KT and 13 LT centers performed 76% and 69% of all aviremic HCV D+/R- transplants. There have been marked increases in HCV D+/R- transplantation, although few centers are driving this practice; centers should continue to weigh the risks and benefits of HCV D+/R- transplantation.

OBJECTIVES:Older adults who undergo kidney transplantation (KT) are living longer with a functioning graft and are at risk for age-related adverse events including fractures. Understanding recipient, transplant, and donor factors and the outcomes associated with fractures may help identify older KT recipients at increased risk. We determined incidence of hip, vertebral, and extremity fractures; assessed factors associated with incident fractures; and estimated associations between fractures and subsequent death-censored graft loss (DCGL) and mortality. DESIGN:This was a prospective cohort study of patients who underwent their first KT between January 1, 1999, and December 31, 2014. SETTING:We linked data from the Scientific Registry of Transplant Recipients to Medicare claims through the US Renal Data System. PARTICIPANTS:The analytic population included 47 815 KT recipients aged 55 years or older. MEASUREMENTS:We assessed the cumulative incidence of and factors associated with post-KT fractures (hip, vertebral, or extremity) using competing risks models. We estimated risk of DCGL and mortality after fracture using adjusted Cox proportional hazards models. RESULTS:The 5-year incidence of post-KT hip, vertebral, and extremity fracture for those aged 65 to 69 years was 2.2%, 1.0%, and 1.7%, respectively. Increasing age was associated with higher hip (adjusted hazard ratio [aHR] = 1.37 per 5-y increase; 95% confidence interval [CI] = 1.30-1.45) and vertebral (aHR = 1.31; 95% CI = 1.20-1.42) but not extremity (aHR = .97; 95% CI = .91-1.04) fracture risk. DCGL risk was higher after hip (aHR = 1.34; 95% CI = 1.12-1.60) and extremity (aHR = 1.30; 95% CI = 1.08-1.57) fracture. Mortality risk was higher after hip (aHR = 2.31; 95% CI = 2.11-2.52), vertebral (aHR = 2.80; 95% CI = 2.44-3.21), and extremity (aHR = 1.85; 95% CI = 1.64-2.10) fracture. CONCLUSION:Our findings suggest that older KT recipients are at higher risk for hip and vertebral fracture but not extremity fracture; and those with hip, vertebral, or extremity fracture are more likely to experience subsequent graft loss or mortality. These findings underscore that different fracture types may have different underlying etiologies and risks, and they should be approached accordingly. J Am Geriatr Soc 67:1680-1688, 2019.

BACKGROUND:Body mass index of living kidney donors has increased substantially. Determining candidacy for live kidney donation among obese individuals is challenging because many donation-related risks among this subgroup remain unquantified, including even basic postdonation mortality. METHODS:We used data from the Scientific Registry of Transplant Recipients linked to data from the Centers for Medicare and Medicaid Services to study long-term mortality risk associated with being obese at the time of kidney donation among 119,769 live kidney donors (1987-2013). Donors were followed for a maximum of 20 years (interquartile range 6.0-16.0). Cox proportional hazards estimated the risk of postdonation mortality by obesity status at donation. Multiple imputation accounted for missing obesity data. RESULTS:Obese (body mass index ≥ 30) living kidney donors were more likely male, African American, and had higher blood pressure. The estimated risk of mortality 20 years after donation was 304.3/10,000 for obese and 208.9/10,000 for nonobese living kidney donors. Adjusting for age, sex, race/ethnicity, blood pressure, baseline estimated glomerular filtration rate, relationship to recipient, smoking, and year of donation, obese living kidney donors had a 30% increased risk of long-term mortality compared with their nonobese counterparts (adjusted hazard ratio: 1.32, 95% CI: 1.09-1.60, P = .006). The impact of obesity on mortality risk did not differ significantly by sex, race or ethnicity, biologic relationship, baseline estimated glomerular filtration rate, or among donors who did and did not develop postdonation kidney failure. CONCLUSION:These findings may help to inform selection criteria and discussions with obese persons considering living kidney donation.

PURPOSE OF REVIEW:We report the current state of HIV+ to HIV+ kidney transplantation in the United States and remaining challenges in implementing this practice nationally. RECENT FINDINGS:The HIV Organ Policy Equity (HOPE) Act, which was the first step in unlocking the potential of HIV+ organ donors, mandates clinical research on HIV+ to HIV+ transplantation. As of March 2019, there have been 57 HOPE donors, including both true and false positive HOPE donors resulting in more than 120 transplants. SUMMARY:The HOPE Act, signed in 2013, reversed the federal ban on the transplantation of organs from HIV+ donors into HIV+ recipients. Ongoing national studies are exploring the safety, feasibility, and efficacy of both kidney and liver transplantation in this population. If successfully and fully implemented, HIV+ to HIV+ transplantation could attenuate the organ shortage for everyone waiting, resulting in a far-reaching public health impact.

BACKGROUND:United States transplant centers are required to report follow-up data for living kidney donors for 2 years post-donation. However, living kidney donor (LKD) follow-up is often incomplete. Mobile health (mHealth) technologies could ease data collection burden but have not yet been explored in this context. METHODS:We conducted semi-structured in-depth interviews with a convenience sample of 21 transplant providers and thought leaders about challenges in LKD follow-up, and the potential role of mHealth in overcoming these challenges. RESULTS:Participants reported challenges conveying the importance of follow-up to LKDs, limited data from international/out-of-town LKDs, and inadequate staffing. They believed the 2-year requirement was insufficient, but expressed difficulty engaging LKDs for even this short time and inadequate resources for longer-term follow-up. Participants believed an mHealth system for post-donation follow-up could benefit LKDs (by simplifying communication/tasks and improving donor engagement) and transplant centers (by streamlining communication and decreasing workforce burden). Concerns included cost, learning curves, security/privacy, patient language/socioeconomic barriers, and older donor comfort with mHealth technology. CONCLUSIONS:Transplant providers felt that mHealth technology could improve LKD follow-up and help centers meet reporting thresholds. However, designing a secure, easy to use, and cost-effective system remains challenging.

BACKGROUND:Frail kidney transplant (KT) recipients have higher risk of adverse post-KT outcomes. Yet, there is interest in measuring frailty at KT evaluation and then using this information for post-KT risk stratification. Given long wait times for KT, frailty may improve or worsen between evaluation and KT. Patterns, predictors, and post-KT adverse outcomes associated with these changes are unclear. METHODS:Five hundred sixty-nine adult KT candidates were enrolled in a cohort study of frailty (November 2009-September 2017) at evaluation and followed up at KT. Patterns of frailty transitions were categorized as follows: (1) binary state change (frail/nonfrail), (2) 3-category state change (frail/intermediate/nonfrail), and (3) raw score change (-5 to 5). Adjusted Cox proportional hazard and logistic regression models were used to test whether patterns of frailty transitions were associated with adverse post-KT outcomes. RESULTS:Between evaluation and KT, 22.0% became more frail, while 24.4% became less frail. Black race (relative risk ratio, 1.98; 95% confidence interval [CI], 1.07-3.67) was associated with frail-to-nonfrail transition, and diabetes (relative risk ratio, 2.56; 95% CI, 1.22-5.39) was associated with remaining stably frail. Candidates who became more frail between 3-category states (hazard ratio, 2.27; 95% CI, 1.11-4.65) and frailty scores (hazard ratio, 2.36; 95% CI, 1.12-4.99) had increased risk of post-KT mortality and had higher odds of length of stay ≥2 weeks (3-category states: odds ratio, 2.02; 95% CI, 1.20-3.40; frailty scores: odds ratio, 1.92; 95% CI, 1.13-3.25). CONCLUSIONS:Almost half of KT candidates experienced change in frailty between evaluation and KT, and those transitions were associated with mortality and longer length of stay. Monitoring changes in frailty from evaluation to admission may improve post-KT risk stratification.

Background/UNASSIGNED:Limited data are available regarding clinical implications of lower renal function after living kidney donation. We examined a novel integrated database to study associations between postdonation estimated glomerular filtration rate (eGFR) and use of antihypertensive medication (AHM) treatment after living kidney donation. Methods/UNASSIGNED:) between AHM use and postdonation eGFR levels (random effect) with fixed effects for baseline donor factors. Results/UNASSIGNED:). Conclusions/UNASSIGNED:This novel linkage illustrates the ability to identify postdonation kidney function and associate it with clinically meaningful outcomes; lower eGFR after living kidney donation is a correlate of AHM treatment requirements. Further work should define relationships of postdonation renal function, hypertension, and other morbidity measures.

BACKGROUND AND OBJECTIVES:Hypertension in older kidney donor candidates is viewed as safe. However, hypertension guidelines have evolved and long-term outcomes have not been explored. We sought to quantify the 15-year risk of ESKD and mortality in older donors (≥50 years old) with versus those without hypertension. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:A United States cohort of 24,533 older donors from 1999 to 2016, including 2265 with predonation hypertension, were linked to Centers for Medicare and Medicaid Services data and the Social Security Death Master File to ascertain ESKD development and mortality. The exposure of interest was predonation hypertension. From 2004 to 2016, hypertension was defined as documented predonation use of antihypertensive therapy, regardless of systolic BP or diastolic BP; from 1999 to 2003, when there was no documentation of antihypertensive therapy, hypertension was defined as predonation systolic BP ≥140 or diastolic BP ≥90 mm Hg. RESULTS:=0.34). CONCLUSIONS:Compared with older donors without hypertension, older donors with hypertension had higher risk of ESKD, but not mortality, for 15 years postdonation. However, the absolute risk of ESKD was small.