Faculty Bibliography

Cooperative kidney paired donation (KPD) networks account for an increasing proportion of all living donor kidney transplants in the United States. There are sparse data on the rate of primary nonfunction (PNF) losses and their consequences within KPD networks. We studied National Kidney Registry (NKR) transplants (February 14, 2009 to December 31, 2017) and quantified PNF, graft loss within 30 days of transplantation, and graft losses in the first-year posttransplant and assessed potential risk factors. Of 2364 transplants, there were 38 grafts (1.6%) lost within the first year, 13 (0.5%) with PNF. When compared to functioning grafts, there were no clinically significant differences in blood type compatibility, degree of HLA mismatch, number of veins/arteries, cold ischemia, and travel times. Of 13 PNF cases, 2 were due to early venous thrombosis, 2 to arterial thrombosis, and 2 to failure of desensitization and development of antibody-mediated rejection (AMR). Given the low rate of PNF, the NKR created a policy to allocate chain-end kidneys to recipients with PNF following event review and attributable to surgical issues of donor nephrectomy. It is expected that demonstration of low incidence of poor early graft outcomes and the presence of a "safety net" would further encourage program participation in national KPD.

Importance:Living kidney donation is associated with increased long-term risk of end-stage renal disease (ESRD). An early postdonation marker of ESRD risk could improve postdonation risk assessment and counseling for kidney donors and allow early intervention for donors at increased risk. Objective:To determine the association between renal function in the first 6 months postdonation and subsequent risk of ESRD in kidney donors. Design, Setting, and Participants:This secondary analysis of a prospective national cohort uses a population-based registry of all living kidney donors in the United States between October 26, 1999, and January 1, 2018, with follow-up through December 31, 2018. All kidney donors who had donated in the date range and had serum creatinine measured at 6 months (±3 months) postdonation were included. Exposures:Renal function as measured by estimated glomerular filtration rate 6 months after donation (eGFR6). Main Outcomes and Measures:End-stage renal disease, ascertained via linkage to Centers for Medicare & Medicaid Services data. Results:A total of 71 468 living kidney donors were included (of 109 065 total donors over this period). Their median (interquartile range) eGFR6 was 63 (54-74) mL/min/1.73 m2. Cumulative incidence of ESRD at 15 years postdonation ranged from 11.7 donors per 10 000 donors with eGFR6 values greater than 70 mL/min/1.73 m2 to 33.1 donors per 10 000 donors with eGFR6 values of 50 mL/min/1.73 m2 or less. Adjusting for age, race, sex, body mass index, and biological relationship, every 10 mL/min/1.73 m2 reduction in eGFR6 was associated with a 28% increased risk of ESRD (adjusted hazard ratio, 1.28 [95% CI, 1.06-1.54]; P = .009). The association between predonation eGFR and ESRD was not significant and was fully mediated by eGFR6 (adjusted hazard ratio, 1.00 [95% CI, 0.86-1.17]; P = .97). The postdonation eGFR value was a better marker of ESRD than eGFR decline after donation or the ratio of eGFR6 to predonation eGFR, as determined by the Akaike information criterion (in which a lower value indicates a better model fit; eGFR6, 1495.61; predonation eGFR - eGFR6, 1503.58; eGFR6 / predonation eGFR, 1502.30). Conclusions and Relevance:In this study, there was an independent association of eGFR6 with subsequent ESRD risk in living kidney donors, even after adjusting for predonation characteristics. The findings support measurement of early postdonation serum creatinine monitoring in living kidney donors, and the use of these data to help identify donors who might need more careful surveillance and early intervention.

BACKGROUND:Optimizing antithymocyte globulin (ATG) dosage is critical, particularly for high-risk kidney transplant (KT) recipients without cytomegalovirus (CMV) prophylaxis. METHODS:We studied 630 KT recipients with expanded criteria donors or panel reactive antibody ≥50% at Hospital do Rim, Brazil (January 1, 2013 to May 21, 2015) to determine whether a single ATG dose was safe and effective in patients without CMV prophylaxis. Patients received ≥4 doses (1-1.5 mg/kg/per dose) until June 17, 2014, when the induction protocol changed to a single ATG dose (3 mg/kg). We used Cox regression to compare the risk of CMV infection and acute rejection (AR) among KT recipients by ATG dose. RESULTS:Adjusting for clinical and transplant factors, a single ATG dose was associated with a lower risk of CMV infection (adjusted hazard ratio [aHR]: 0.63; 95% confidence interval [CI], 0.42-0.93; P = 0.02) and a similar risk of AR (aHR: 1.16; 95% CI, 0.47-2.83; P = 0.8), compared to multiple doses. We found no differences in death-censored graft loss (5.0% versus 4.8%, aHR: 1.06; 95% CI, 0.51-2.23; P = 0.9) or mortality (4.7% versus 3.4%; aHR: 1.42; 95% CI, 0.62-3.24; P = 0.4) at 1-year post-KT by ATG dose. CONCLUSIONS:In our study of high-risk KT recipients without CMV prophylaxis, a single ATG dose decreased the risk of CMV infection without increasing the risk of AR or compromising graft or patient survival.

BACKGROUND AND OBJECTIVES:In the United States, kidney paired donation networks have facilitated an increasing proportion of kidney transplants annually, but transplant outcome differences beyond 5 years between paired donation and other living donor kidney transplant recipients have not been well described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:), and transplant factors (zero HLA mismatch). RESULTS:=0.2) between National Kidney Registry and control recipients. CONCLUSIONS:Even after transplanting patients with greater risk factors for worse post-transplant outcomes, nationalized paired donation results in equivalent outcomes when compared with control living donor kidney transplant recipients.

It has been hypothesized that transplanting simultaneous pancreas kidney (SPK) grafts from donors with a history of cardiac arrest and cardiopulmonary resuscitation (CACPR) leads to inferior posttransplant outcomes due to organ hypoperfusion during cardiac arrest and mechanical trauma during resuscitation. Using Scientific Registry of Transplant Recipients data, we identified 13 095 SPK transplants from 2000-2018, of which 810 (6.2%) were from donors with a history of CACPR. After inverse probability of treatment weighting on donor and recipient characteristics, we found that 1-, 5-, and 10-year patient (CACPR: 96.4%, 89.9%, and 78.9%; non-CACPR: 96.3%, 88.9%, and 76.0%; P = .3), death-censored pancreas graft survival (CACPR: 89.3%, 82.7%, 75.0%; non-CACPR: 89.9%, 82.7%, 76.3%; P = .7), and death-censored kidney graft survival (CACPR: 97.0%, 89.5%, 78.2%; non-CACPR: 96.9.9%, 88.7%, 80.0%; P = .4) were comparable between the two groups. There were no differences in the risk of pancreatitis (CACPR: 2.9%, non-CACPR: 2.4%; weighted OR = _0.74 1.22 _2.02 ; P = .4), anastomotic leak (CACPR: 1.6%, non-CACPR: 2.0%; weighted OR = _0.54 1.02 _1.93 ; P > .9), or median length of hospital stay (CACPR: 8 days, non-CACPR: 9 days; P = .6) for recipients of CACPR vs non-CACPR donors. Our findings suggest that CACPR donors could be used to expand the SPK donor pool without compromising short- or long-term outcomes.

Prioritization of highly sensitized (HS) candidates under the kidney allocation system (KAS) and growth of large, multicenter kidney-paired donation (KPD) clearinghouses have broadened the transplant modalities available to HS candidates. To quantify temporal trends in utilization of these modalities, we used SRTR data from 2009 to 2017 to study 39 907 adult HS (cPRA ≥ 80%) waitlisted candidates and 19 003 recipients. We used competing risks regression to quantify temporal trends in likelihood of DDKT, KPD, and non-KPD LDKT for HS candidates (Era 1: January 1, 2009-December 31, 2011; Era 2: January 1, 2012-December 3, 2014; Era 3: December 4, 2014-December 31, 2017). Although the likelihood of DDKT and KPD increased over time for all HS candidates (adjusted subhazard ratio [aSHR] Era 3 vs 1 for DDKT: _1.74 1.85_1.97 , P < .001 and for KPD: _1.70 2.20_2.84 , P < .001), the likelihood of non-KPD LDKT decreased (aSHR: _0.69 0.82_0.97 , P = .02). However, these changes affected HS recipients differently based on cPRA. Among recipients, more cPRA 98%-99.9% and 99.9%+ recipients underwent DDKT (96.2% in Era 3% vs 59.1% in Era 1 for cPRA 99.9%+), whereas fewer underwent non-KPD LDKT (1.9% vs 30.9%) or KPD (2.0% vs 10.0%). Although KAS increased DDKT likelihood for the most HS candidates, it also decreased the use of non-KPD LDKT to transplant cPRA 98%+ candidates.

RATIONALE & OBJECTIVE:Intact cognition is generally a prerequisite for navigating through and completing evaluation for kidney transplantation. Despite kidney transplantation being contraindicated for those with severe dementia, screening for more mild forms of cognitive impairment before referral is rare. Candidates may have unrecognized cognitive impairment, which may prolong evaluation, elevate mortality risk, and hinder access to kidney transplantation. We estimated the burden of cognitive impairment and its association with access to kidney transplantation and waitlist mortality. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:3,630 participants (January 2009 to June 2018) with cognitive function measured (by the Modified Mini-Mental State Examination [3MS]) at kidney transplantation evaluation at 1 of 2 transplantation centers. PREDICTORS:Cognitive impairment (3MS score<80). OUTCOMES:Listing, waitlist mortality, and kidney transplantation. ANALYTICAL APPROACH:We estimated the adjusted chance of listing (Cox regression), risk for waitlist mortality (competing-risks regression), and kidney transplantation rate (Poisson regression) by cognitive impairment. Given potential differences in cause of cognitive impairment among those with and without diabetes, we tested whether these associations differed by diabetes status using a Wald test. RESULTS:=0.02). Among candidates without diabetes, those with cognitive impairment were at 2.47 (95% CI, 1.31-4.66) times greater risk for waitlist mortality; cognitive impairment was not associated with this outcome among candidates with diabetes. LIMITATIONS:Single measure of cognitive impairment. CONCLUSIONS:Cognitive impairment is associated with a lower chance of being placed on the waitlist, and among patients without diabetes, with increased mortality on the waitlist. Future studies should investigate whether implementation of screening for cognitive impairment improves these outcomes.

Understanding the economic implications of induction and maintenance immunosuppression (ISx) is important in developing personalized kidney transplant (KTx) care. Using data from a novel integrated data set including financial records from the University Health System Consortium, Medicare, and pharmacy claims (2007-2014), we estimated the differences in the impact of induction and maintenance ISx regimens on transplant hospitalization costs and Medicare payments from KTx to 3 years. Use of thymoglobulin (TMG) significantly increased transplant hospitalization costs ($12 006; P = .02), compared with alemtuzumab and basiliximab. TMG resulted in lower Medicare payments in posttransplant years 1 (-$2058; P = .05) and 2 (-$1784; P = .048). Patients on steroid-sparing ISx incurred relatively lower total Medicare spending (-$10 880; P = .01) compared with patients on triple therapy (tacrolimus, antimetabolite, and steroids). MPA/AZA-sparing, mammalian target of rapamycin inhibitors-based, and cyclosporine-based maintenance ISx regimens were associated with significantly higher payments. Alternative ISx regimens were associated with different KTx hospitalization costs and longer-term payments. Future studies of clinical efficacy should also consider cost impacts to define the economic effectiveness of alternative ISx regimens.

BACKGROUND:We sought to identify factors that are associated with LOS following pediatric (<18 years) liver transplantation in order to provide personalized counseling and discharge planning for recipients and their families. METHODS:We identified 2726 infants (≤24 months) and 3210 children (>24 months) who underwent pediatric liver-only transplantation from 2002-2017 using the Scientific Registry of Transplant Recipients. We used multilevel multivariable negative binomial regression to analyze associations between LOS and recipient and donor characteristics and calculated the MLOSR to quantify heterogeneity in LOS across centers. RESULTS:) were associated with a longer LOS. The MLOSR was 1.25 in infants and 1.26 in children, meaning if an infant received a transplant at another center with a longer LOS, we would expect a 1.25-fold difference in LOS driven by center practices alone. CONCLUSIONS:While center-level practices account for substantial variation in LOS, consideration of donor and recipient factors can help clinicians provide more personalized counseling for families of pediatric liver transplant candidates.

Stakeholders have expressed concerns regarding decreased deceased donor kidney transplant (DDKT) rates for pediatric candidates under the Kidney Allocation System (KAS). To better understand what might be driving this, we studied Scientific Registry of Transplant Recipients kidney offer data for 3642 pediatric (age <18 years) kidney-only transplant candidates between December 31, 2012 to December 3, 2014 (pre-KAS) and December 4, 2014 to January 6, 2017 (post-KAS). We used negative binomial regression and multilevel logistic regression to compare offer and acceptance rates pre- and post-KAS. We stratified by donor age (<18, 18-34, and 35+ years) and KDPI (<35% and ≥35%) to reflect differing allocation prioritization pre-KAS and post-KAS. As might be expected from prioritization changes, post-KAS candidates were less likely to receive offers for donors 18-34 years old with KDPI ≥ 35% (adjusted incidence rate ratio [aIRR]: _0.18 0.21_0.25 , P < .001), and more likely to receive offers for donors 18-34 years old and KDPI < 35% (aIRR: _1.12 1.20_1.29 , P < .001). However, offer acceptance practices also changed post-KAS: kidneys from donors 18-34 years old and KDPI < 35% were 23% less likely to be accepted post-KAS (adjusted odds ratio: _0.61 0.77_0.98 , P = .03). Using kidneys from donors 18-34 years old with KDPI < 35% post-KAS to the same extent they were used pre-KAS might be an effective strategy to mitigate any decrease in DDKT rates for pediatric candidates.