Faculty Bibliography

BACKGROUND:Living kidney donors have an increased risk of end-stage renal disease, with hypertension and diabetes as the predominant causes. In this study, we sought to better understand the timeline when these diseases occur, focusing on the early postdonation period. METHODS:We studied 41 260 living kidney donors in the United States between 2008 and 2014 from the Scientific Registry of Transplant Recipients and modeled incidence rates and risk factors for hypertension and diabetes. RESULTS:At 6 months, 1 year, and 2 years postdonation, there were 74, 162, and 310 cases, respectively, of hypertension per 10 000 donors. Donors who were older (per 10 y, adjusted incidence rate ratio [aIRR], 1.40; 95% confidence interval [CI], 1.29-1.51), male (aIRR, 1.31; 95% CI, 1.14-1.50), had higher body mass index (per 5 units, aIRR, 1.29; 95% CI, 1.17-1.43), and were related to their recipient (first-degree relative: aIRR, 1.28; 95% CI, 1.08-1.52; spouse: aIRR, 1.34; 95% CI, 1.08-1.66) were more likely to develop hypertension, whereas donors who were Hispanic/Latino were less likely (aIRR, 0.71; 95% CI, 0.55-0.93). At 6 months, 1 year, and 2 years, there were 2, 6, and 15 cases of diabetes per 10 000 donors. Donors who were older (per 10 y: aIRR, 1.42; 95% CI, 1.11-1.82), had higher body mass index (per 5 units: aIRR, 1.52; 95% CI, 1.04-2.21), and were Hispanic/Latino (aIRR, 2.45; 95% CI, 1.14-5.26) were more likely to develop diabetes. CONCLUSIONS:In this national study, new-onset diabetes was rare, but 3% of donors developed hypertension within 2 years of nephrectomy. These findings reaffirm that disease pathways for kidney failure differ by donor phenotype and estimate the population most at-risk for later kidney failure.

A recent study reported that kidney transplant recipients of offspring living donors had higher graft loss and mortality. This seemed counterintuitive, given the excellent HLA matching and younger age of offspring donors; we were concerned about residual confounding and other study design issues. We used Scientific Registry of Transplant Recipients data 2001-2016 to evaluate death-censored graft failure (DCGF) and mortality for recipients of offspring versus nonoffspring living donor kidneys, using Cox regression models with interaction terms. Recipients of offspring kidneys had lower DCGF than recipients of nonoffspring kidneys (15-year cumulative incidence 21.2% vs 26.1%, P < .001). This association remained after adjustment for recipient and transplant factors (adjusted hazard ratio [aHR] = _0.73 0.77_0.82 , P < .001), and was attenuated among African American donors (aHR _0.77 0.85_0.95 ; interaction: P = .01) and female recipients (aHR _0.77 0.84_0.91 , P < .001). Although offspring kidney recipients had higher mortality (15-year mortality 56.4% vs 37.2%, P < .001), this largely disappeared with adjustment for recipient age alone (aHR = _1.02 1.06_1.10 , P = .002) and was nonsignificant after further adjustment for other recipient characteristics (aHR = _0.93 0.97_1.01 , P = .1). Kidneys from offspring donors provided lower graft failure and comparable mortality. An otherwise eligible donor should not be dismissed because they are the offspring of the recipient, and we encourage continued individualized counseling for potential donors.

Historically, exception points for hepatocellular carcinoma (HCC) led to higher transplant rates and lower waitlist mortality for HCC candidates compared to non-HCC candidates. As of October 2015, HCC candidates must wait 6 months after initial application to obtain exception points; the impact of this policy remains unstudied. Using 2013-2017 SRTR data, we identified 39  350 adult, first-time, active waitlist candidates and compared deceased donor liver transplant (DDLT) rates and waitlist mortality/dropout for HCC versus non-HCC candidates before (October 8, 2013-October 7, 2015, prepolicy) and after (October 8, 2015-October 7, 2017, postpolicy) the policy change using Cox and competing risks regression, respectively. Compared to non-HCC candidates with the same calculated MELD, HCC candidates had a 3.6-fold higher rate of DDLT prepolicy (aHR = _3.49 3.69 _3.89 ) and a 2.2-fold higher rate of DDLT postpolicy (aHR = _2.09 2.21 _2.34 ). Compared to non-HCC candidates with the same allocation priority, HCC candidates had a 37% lower risk of waitlist mortality/dropout prepolicy (asHR = _0.54 0.63 _0.73 ) and a comparable risk of mortality/dropout postpolicy (asHR = _0.81 0.95 _1.11 ). Following the policy change, the DDLT advantage for HCC candidates remained, albeit dramatically attenuated, without any substantial increase in waitlist mortality/dropout. In the context of sickest-first liver allocation, the revised policy seems to have established allocation equity for HCC and non-HCC candidates.

Deceased donor kidney transplantation (DDKT) rates for highly sensitized (HS) candidates increased early after implementation of the Kidney Allocation System (KAS) in 2014. However, this may represent a bolus effect, and a granular investigation of the current state of DDKT for HS candidates remains lacking. We studied 270 722 DDKT candidates from the SRTR from 12/4/2011 to 12/3/2014 ("pre-KAS") and 12/4/2014 to 12/3/2017 ("post-KAS"), analyzing DDKT rates for HS candidates using adjusted negative binomial regression. Post-KAS, candidates with the highest levels of sensitization had an increased DDKT rate compared with pre-KAS (cPRA 98% adjusted incidence rate ratio [aIRR]:_1.27 1.77_2.46 P = .001, cPRA 99% aIRR:_3.18 4.36_5.98 P < .001, cPRA 99.5-99.9% aIRR:_16.91 24.29_34.89 P < .001, and cPRA 99.9%+ aIRR:_8.79 11.58_15.26 P < .001). To determine whether these changes produced more equitable access to DDKT, we compared DDKT rates of HS to non-HS candidates (cPRA 0-79%). Post-KAS, cPRA, 98% candidates had an equivalent DDKT rate (aIRR:_0.65 0.94_1.36 , P = .8) to non-HS candidates, whereas 99% candidates had a higher DDKT rate (aIRR:_1.19 1.68_2.38 , P = .02). Although cPRA 99.5-99.9% candidates had an increased DDKT rate (aIRR:_2.46 3.50_4.98 , P < .001) compared to non-HS candidates, cPRA 99.9%+ candidates had a significantly lower DDKT rate (aIRR:_0.29 0.40_0.56 , P < .001). KAS has improved access to DDKT for HS candidates, although substantial imbalance exists between cPRA 99.5-99.9% and 99.9%+ candidates.

Low T cell counts and acute rejection are associated with increased cardiovascular events (CVEs); T cell-depleting agents decrease both. Thus, we aimed to characterize the risk of CVEs by using an induction agent used in kidney transplant recipients. We conducted a secondary data analysis of patients who received a kidney transplant and used Medicare as their primary insurance from 1999 to 2010. Outcomes of interest were incident CVE, all-cause mortality, CVE-related mortality, and a composite outcome of mortality and CVE. Of 47 258 recipients, 29.3% received IL-2 receptor antagonist (IL-2RA), 33.3% received anti-thymocyte globulin (ATG), 7.3% received alemtuzumab, and 30.0% received no induction. Compared with IL-2RA, there was no difference in the risk of CVE in the ATG (adjusted hazard ratio [aHR] 0.98, 95% confidence interval [CI] 0.92-1.05) and alemtuzumab group (aHR 1.01, 95% CI 0.89-1.16), but slightly higher in the no induction group (aHR 1.06, 95% CI 1.00-1.14). Acute rejection did not modify this association in the latter group but did increase CVE by 46% in the alemtuzumab group. There was no difference in the hazard of all-cause or CVE-related mortality. Only in the ATG group, a 7% lower hazard of the composite outcome of mortality and CVE was noted. Induction agents are not associated with incident CVE, although prospective trials are needed to determine a personalized approach to prevention.

In the United States, kidney donation from international (noncitizen/nonresident) living kidney donors (LKDs) is permitted; however, given the heterogeneity of healthcare systems, concerns remain regarding the international LKD practice and recipient outcomes. We studied a US cohort of 102 315 LKD transplants from 2000-2016, including 2088 international LKDs, as reported to the Organ Procurement and Transplantation Network. International LKDs were more tightly clustered among a small number of centers than domestic LKDs (Gini coefficient 0.76 vs 0.58, P < .001). Compared with domestic LKDs, international LKDs were more often young, male, Hispanic or Asian, and biologically related to their recipient (P < .001). Policy-compliant donor follow-up was substantially lower for international LKDs at 6, 12, and 24 months postnephrectomy (2015 cohort: 45%, 33%, 36% vs 76%, 71%, 70% for domestic LKDs, P < .001). Among international LKDs, Hispanic (aOR = _0.23 0.36_0.56 , P < .001) and biologically related (aOR = _0.39 0.59_0.89 , P < .01) donors were more compliant in donor follow-up than white and unrelated donors. Recipients of international living donor kidney transplant (LDKT) had similar graft failure (aHR = _0.78 0.89_1.02 , P = .1) but lower mortality (aHR = _0.53 0.62_0.72 , P < .001) compared with the recipients of domestic LDKT after adjusting for recipient, transplant, and donor factors. International LKDs may provide an alternative opportunity for living donation. However, efforts to improve international LKD follow-up and engagement are warranted.

BACKGROUND:Every year, more than 5500 healthy people in the United States donate a kidney for the medical benefit of another person. The Organ Procurement and Transplantation Network (OPTN) requires transplant hospitals to monitor living kidney donors (LKDs) for 2 years postdonation. However, the majority (115/202, 57%) of transplant hospitals in the United States continue to fail to meet nationally mandated requirements for LKD follow-up. A novel method for collecting LKD follow-up is needed to ease both the transplant hospital-level and patient-level burden. We built mKidney-a mobile health (mHealth) system designed specifically to facilitate the collection and reporting of OPTN-required LKD follow-up data. The mKidney mobile app was developed on the basis of input elicited from LKDs, transplant providers, and thought leaders. OBJECTIVE:The primary objective of this study is to evaluate the impact of the mKidney smartphone app on LKD follow-up rates. METHODS:We will conduct a two-arm randomized controlled trial (RCT) with LKDs who undergo LKD transplantation at Methodist Specialty and Transplant Hospital in San Antonio, Texas. Eligible participants will be recruited in-person by a study team member at their 1-week postdonation clinical visit and randomly assigned to the intervention or control arm (1:1). Participants in the intervention arm will receive the mHealth intervention (mKidney), and participants in the control arm will receive the current standard of follow-up care. Our primary outcome will be policy-defined complete (all components addressed) and timely (60 days before or after the expected visit date) submission of LKD follow-up data at required 6-month, 1-year, and 2-year visits. Our secondary outcome will be hospital-level compliance with OPTN reporting requirements at each visit. Data analysis will follow the intention-to-treat principle. Additionally, we will collect quantitative and qualitative process data regarding the implementation of the mKidney system. RESULTS:We began recruitment for this RCT in May 2018. We plan to enroll 400 LKDs over 2 years and follow participants for the 2-year mandated follow-up period. CONCLUSIONS:This pilot RCT will evaluate the impact of the mKidney system on rates of LKD and hospital compliance with OPTN-mandated LKD follow-up at a large LKD transplant hospital. It will provide valuable information on strategies for implementing such a system in a clinical setting and inform effect sizes for future RCT sample size calculations. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)/UNASSIGNED:DERR1-10.2196/11000.

Importance:In light of the growing population of older adults in the United States, older donors (aged ≥70 years) represent an expansion of the donor pool; however, their organs are underused. Liver grafts from older donors were historically associated with poor outcomes and higher discard rates, but clinical protocols, organ allocation, and the donor pool have changed in the past 15 years. Objective:To evaluate trends in demographics, discard rates, and outcomes among older liver donors and transplant recipients of livers from older donors in a large national cohort. Design, Setting, and Participants:Prospective cohort study of 4127 liver grafts from older donors and 3350 liver-only recipients of older donor grafts and 78 990 liver grafts from younger donors (aged 18-69 years) and 64 907 liver-only recipients of younger donor grafts between January 1, 2003, and December 31, 2016, in the United States. The Scientific Registry of Transplant Recipients, which includes data on all transplant recipients in the United States that are submitted by members of the Organ Procurement and Transplantation Network, was used. Exposures:Year of liver transplant and age of liver donor. Main Outcomes and Measures:Odds of graft discard and posttransplant outcomes of all-cause graft loss and mortality. Results:In this study, 4127 liver grafts from older donors were recovered for liver transplant across the study period (2003-2016); 747 liver grafts from older donors were discarded, and 3350 liver grafts from older donors were used for liver-only recipients. After adjusting for donor characteristics other than age and accounting for Organ Procurement Organization-level variation, liver grafts from older donors were more likely to be discarded compared with liver grafts from younger donors in 2003-2006 (adjusted odds ratio [aOR], 1.97; 95% CI, 1.68-2.31), 2007-2009 (aOR, 2.55; 95% CI, 2.17-3.01), 2010-2013 (aOR, 2.04; 95% CI, 1.68-2.46), and 2013-2016 (aOR, 2.37; 95% CI, 1.96-2.86) (P < .001 for all). Transplants of liver grafts from older donors represented a progressively lower proportion of all adult liver transplants, from 6.0% (n = 258 recipients) in 2003 to 3.2% (n = 211 recipients) in 2016 (P = .001). However, outcomes in recipients of grafts from older donors improved over time, with 40% lower graft loss risk (adjusted hazard ratio, 0.60; 95% CI, 0.53-0.68; P < .001) and 41% lower mortality risk (adjusted hazard ratio, 0.59; 95% CI, 0.52-0.68; P < .001) in 2010 through 2016 vs 2003 through 2009; these results were beyond the general temporal improvements in graft loss (interaction P = .03) and mortality risk (interaction P = .04) among recipients of liver grafts from younger donors. Conclusions and Relevance:These findings show that from 2003 to 2016, liver graft loss and mortality among recipients of liver grafts from older donors improved; however, liver graft discard from older donors remained increased and the number of transplants performed with liver grafts from older donors decreased. Expansion of the donor pool through broader use of liver grafts from older donors might be reasonable.

BACKGROUND:Kidneys from infectious risk donors (IRD) confer substantial survival benefit in adults, yet the benefit of IRD kidneys to pediatric candidates remains unclear in the context of high waitlist prioritization. METHODS:Using 2010-2016 Scientific Registry of Transplant Recipients data, we studied 2417 pediatric candidates (age <18 y) who were offered an IRD kidney that was eventually used for transplantation. We followed candidates from the date of first IRD kidney offer until the date of death or censorship and used Cox regression to estimate mortality risk associated with IRD kidney acceptance versus decline, adjusting for age, sex, race, diagnosis, and dialysis time. RESULTS:Over the study period, 2250 (93.1%) pediatric candidates declined and 286 (11.8%) accepted an IRD kidney offer; 119 (41.6%) of the 286 had previously declined a different IRD kidney. Cumulative survival among those who accepted versus declined the IRD kidney was 99.6% versus 99.4% and 96.3% versus 97.8% 1 and 6 years post decision, respectively (P = 0.1). Unlike the substantial survival benefit seen in adults (hazard ratio = 0.52), among pediatric candidates, we did not detect a survival benefit associated with accepting an IRD kidney (adjusted hazard ratio: 0.791.723.73, P = 0.2). However, those who declined IRD kidneys waited a median 9.6 months for a non-IRD kidney transplant (11.2 mo among those <6 y, 8.8 mo among those on dialysis). Kidney donor profile index (KDPI) of the eventually accepted non-IRD kidneys (median = 13, interquartile range = 6-23) was similar to KDPI of the declined IRD kidneys (median = 16, interquartile range = 9-28). CONCLUSIONS:Unlike in adults, IRD kidneys conferred no survival benefit to pediatric candidates, although they did reduce waiting times. The decision to accept IRD kidneys should balance the advantage of faster transplantation against the risk of infectious transmission.