Margaux N. Mustian

Landscape of ABO-Incompatible Live Donor Kidney Transplantation in the US

BACKGROUND Widespread implementation of ABO-incompatible (ABOi) living donor kidney transplantation (LDKT) has been proposed as a means to partially ameliorate the national shortage of deceased donor kidneys. Acceptance of this practice has been encouraged by reports from experienced centers demonstrating acute rejection (AR) rates similar to those obtained with ABO-compatible (ABOc) LDKT. Acute rejection rate and graft survival after ABOi LDKT on a national level have yet to be fully determined. STUDY DESIGN We studied adult (>18 years) LDKT recipients, from 2000 to 2015, reported to the Scientific Registry of Transplant Recipients. Acute rejection rates in the first post-transplant year (modified Poisson regression) and graft survival (Cox proportional hazards) were assessed by ABO compatibility status (ABOi: 930; ABOc: 89,713). RESULTS Patients undergoing ABOi LDKT had an AR rate of 19.4% compared with 10.5% for ABOc recipients (p < 0.0001). After adjusting for recipient- and donor-related risk factors, patients undergoing ABOi LDKT were found to have a 1.76-fold greater risk for AR within 1 year of transplantation compared with ABOc LDKT recipients (adjusted relative risk [aRR] 1.76; 95% CI 1.54 to 2.01). Moreover, there was a 2.34-fold greater risk of death-censored graft loss at 1-year post-transplant among ABOi vs ABOc LDKT recipients (adjusted hazard ratio [aHR] 2.34; 95% CI 1.85 to 2.96). CONCLUSIONS Based on these findings, the low rates of AR and excellent short-term graft survival presented in single center series may not be sustainable on a national level. These findings highlight the potential utility for identification of centers of excellence and regionalization of ABOi LDKT.

Center Variation in Six-Month Post-Donation Follow-up of Obese Living Kidney Donors

Introduction While post-donation follow-up in the United States has improved since implementation of minimum center compliance standards, it is still suboptimal and brief (only 2 years total required). Despite being at greater risk for developing post-donation kidney failure, living kidney donors with obesity at the time of donation are more likely to have incomplete post-donation follow-up. We sought to examine whether center-level variation exists in follow-up at 6 months post-donation among a cohort of obese living donors. Materials and Methods Using data from the Scientific Registry for Transplant Recipients and the Organ Procurement and Transplantation Network from January 2005-July 2015, we included all adult kidney donors with obesity (body mass index ≥ 30 kg/m2) at time of donation (n=13,831). We used a multilevel logistic regression model with a random intercept for recovery center and empirical Bayes estimates, to explore the presence of center variation in recording of 6-month post-donation serum creatinine. FIGURE 1. Adjusted percentage with 6-moth creatinine by transplant center, adjusting center, adjusting for donor age, sex, education, marital status, history of hypertension, smoking, insurance status, relationship to recipient, working for income, era of donation (pre or post introduction of compliance regulations in February 2013), and total center volume of living donors. Results After adjusting for various donor and center-level characteristics, 24% of the variation in recording of 6-month serum creatinine was accounted for by center (intraclass correlation coefficient: 0.237, p < 0.001). When examining the predicted probability of 6-month creatinine by center, the adjusted probability ranged from 10% to 91.5%, with an average of 49.5% (Figure) and 91 of 192 centers had less than 50% predicted probability of complete 6-month creatinine. Conclusion Tremendous variation in recording of 6-month post-donation serum creatinine exists among obese living donors across US transplant centers. Given the increased risk for post-donation kidney failure among obese living donors, center-level efforts targeted specifically at increasing post-donation follow-up should be developed and implemented.

Increasing Obesity Prevalence in the United States Pediatric End-Stage Renal Disease Population

Introduction Obesity prevalence among children in the United States (US) is high, but the rate of increase has slowed over time. Among pediatric end-stage renal disease (ESRD) patients, poor appetite and delayed growth are common, and it is unknown if the pediatric ESRD population mirrors the obesity epidemic observed in the general US pediatric population. Materials and Methods Incident pediatric ESRD patients with complete body mass index (BMI, kg/m2) data were identified from the United States Renal Data System from 01/01/1999-12/31/2012 (n=9,046). Data from the National Health and Nutrition Examination Survey represented the pediatric US population when weighted. All BMI values were age and sex standardized to BMI z scores using the CDC standards for United States children. BMI z scores were used to define obesity. Trends in BMI and obesity were examined by year of dialysis initiation. Trends in BMI slope were compared between the ESRD and US pediatric populations using linear regression. Results and Discussion The mean BMI of pediatric ESRD patients from 1999-2000 was 21.2 as compared to 21.9 in 2011-2012, a 3.3% increase. Similarly, the US population’s mean BMI increased from 19.3 in 1999-2000 to 19.8, a 2.6% increase. A similar but more pronounced increase was noted with respect to the prevalence of obesity (Table). A statistically significant increase in mean BMI over time (&bgr;: 0.07, 95% CI: 0.01, 0.12, p=0.03) and among ESRD patients independently was observed (&bgr;: 1.66, 95% CI: 1.34, 1.99, p<0.001); however, there was no significant interaction between year and patient population, suggesting rate of BMI increase for ESRD patients does not differ significantly from the total US population (&bgr;: 0.05, 95% CI: -0.03, 0.12, p=0.22). Conclusion BMI of pediatric ESRD patients and the prevalence of obesity among pediatric ESRD patients are increasing consistently with the US population. Given the increased dialysis-survival and decreased likelihood of transplantation associated with obesity in the adult population, future research should be directed at examining mortality on dialysis, transplantation rates, and medical expenditures among obese pediatric ESRD patients. Figure. No caption available.

Risk Factors for Failure to Complete Post-Donation Follow-up Among Obese Living Kidney Donors

Introduction Living kidney donors in the United States who were obese at the time of donation are at greater risk of end-stage renal disease than their non-obese counterparts, and may benefit from more intensive post-donation follow-up. Compared to their non-obese counterparts, obese living donors are less likely to have complete follow-up data. It is unknown what factors may be driving greater risk for incomplete follow-up among obese living donors. Materials and Methods Adult living kidney donors with obesity (body mass index ≥ 30 kg/m2) at donation and reported to the Scientific Registry of Transplant Recipients from January 2005-July 2015 were included (n=13,831). Donor characteristics were compared based on having a recorded serum creatinine at 6-months post-donation, and multilevel logistic regression models were used to estimate odds of 6-month creatinine measurement, with a random intercept for recovery center. Results Obese donors who were older, female, Caucasian, married, had a history of hypertension, and were insured at donation were more likely to have a 6-month serum creatinine recorded on unadjusted analyses; obese donors with less than a college education or those biologically related to their recipient were less likely to have a 6-month serum creatinine (Table 1). After adjustment, older age, female sex, and donation following the implementation of new center follow-up requirements were associated with higher odds of 6-month creatinine, while lower odds of 6-month creatinine were seen for biologically-related donors and donors at centers with higher total living donor volume (Table 2). Conclusion Obese donors biologically related to their recipient or who donated at a high volume living donor center were less likely to have 6-month follow-up. These findings suggest the need for targeted education and intervention both at the patient and center level to increase follow-up among obese living donors. Table. No title available.

Impact of the New Kidney Allocation System A2/A2B--> B Policy on Access to Transplantation among Minority Candidates

Introduction Blood group B kidney transplant candidates, many of whom represent ethnic minorities, have historically had diminished access to deceased donor kidney transplantation (DDKT). However, due to the decreased antigenicity of the blood group subtype A2, A2 incompatible (A2i) transplantation can be achieved successfully without the need for additional immunomodulation. Therefore, in an effort to address the ethnic and blood group disparity in access to DDKT, the new national kidney allocation system (KAS) implemented in December 2014, preferentially allocates deceased donor kidneys from blood group A2 and A2B donors to blood group B recipients. To date, no study has examined the impact of KAS on A2i DDKT rates overall for blood group B recipients or among ethnic minorities. Materials and Methods A case-control study of adult blood group B DDKT recipients was performed from 2013 through 2017, as reported to the Scientific Registry of Transplant Recipients. The likelihood of A2i DDKT was compared from the pre-KAS period (1/1/2013-12/3/2014) to the post-KAS period (12/4/2014-2/28/2017) using multivariate logistic regression. Results Following the implementation of KAS, there was a 4.9-fold increase in the likelihood of A2i DDKT for blood group B recipients, compared to the pre-KAS period (OR 4.92, 95% CI: 3.67-6.60). Likewise, the number of transplant centers that had performed one or more A2/A2B to B DDKT increased from 6.9% in the pre-KAS period, to 26.4% post-KAS. However, compared to White blood group B recipients, there was no change in the likelihood of A2i DDKT in the post-KAS era among the following minority groups: African Americans (aOR 0.90, 95% CI: 0.43-1.86 pre-KAS, aOR 0.91, 95%CI: 0.69-1.21 post-KAS); Asians (aOR 1.23, 95% CI 0.49-3.04 pre-KAS, aOR 1.02 95%CI 0.68-1.53 post-KAS); and Hispanics (aOR 1.32, 95% CI 0.51-3.42 pre-KAS, aOR 1.38, 95% CI 0.94-2.03 post-KAS)(Table). Conclusion Although the implementation of KAS has resulted in an increase in A2i DDKT for blood group B recipients, the likelihood of A2i DDKT among minorities, relative to Whites, was not improved. Further discussion regarding A2/A2B --> B policy revisions aimed to increase access to DDKT for ethnic minorities is warranted. Figure. No caption available. American Society of Transplant Surgeons (ASTS) Diversity Affairs Committee. National Institutes of Health- National Research Service Award, through Grant Award Number T32 DK007545. Health Resources and Services Administration contract 234-2005-37011C.

Population level outcomes and cost-effectiveness of hepatitis C treatment pre- vs postkidney transplantation

Direct‐acting antivirals approved for use in patients with end‐stage renal disease (ESRD) now exist. HCV‐positive (HCV+) ESRD patients have the opportunity to decrease the waiting times for transplantation by accepting HCV‐infected kidneys. The optimal timing for HCV treatment (pre‐ vs posttransplant) among kidney transplant candidates is unknown. Monte Carlo microsimulation of 100 000 candidates was used to examine the cost‐effectiveness of HCV treatment pretransplant vs posttransplant by liver fibrosis stage and waiting time over a lifetime time horizon using 2 regimens approved for ESRD patients. Treatment pretransplant yielded higher quality‐adjusted life years (QALYs) compared with posttransplant treatment in all subgroups except those with Meta‐analysis of Histological Data in Viral Hepatitis stage F0 (pretransplant: 5.7 QALYs vs posttransplant: 5.8 QALYs). However, treatment posttransplant was cost‐saving due to decreased dialysis duration with the use of HCV‐infected kidneys (pretransplant:

Impact of the new kidney allocation system A2/A2B → B policy on access to transplantation among minority candidates

735 700 vs posttransplant:

The psychosocial impact of inpatient management of monoamniotic twin gestations

682 400). Using a willingness‐to‐pay threshold of

Increasing Obesity and Diabetes Prevalence in the United States End-Stage Renal Disease Population

100 000, treatment pretransplant was not cost‐effective except for those with Meta‐analysis of Histological Data in Viral Hepatitis stage F3 whose fibrosis progression was halted. If HCV+ candidates had access to HCV‐infected donors and were transplanted ≥9 months sooner than HCV‐negative candidates, treatment pretransplant was no longer cost‐effective (incremental cost‐effectiveness ratio [ICER]:

Ethnic and Age Disparities in Outcomes among Liver Transplant Waitlist Candidates

107 100). In conclusion, optimal timing of treatment depends on fibrosis stage and access to HCV+ kidneys but generally favors posttransplant HCV eradication.