Stephen O. Pastan

Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure

Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single‐center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two‐APOL1‐nephropathy‐variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed‐consent processes.

The Role of Race and Poverty on Steps to Kidney Transplantation in the Southeastern United States

Racial disparities in access to renal transplantation exist, but the effects of race and socioeconomic status (SES) on early steps of renal transplantation have not been well explored. Adult patients referred for renal transplant evaluation at a single transplant center in the Southeastern United States from 2005 to 2007, followed through May 2010, were examined. Demographic and clinical data were obtained from patients medical records and then linked with United States Renal Data System and American Community Survey Census data. Cox models examined the effect of race on referral, evaluation, waitlisting and organ receipt. Of 2291 patients, 64.9% were black, the mean age was 49.4 years and 33.6% lived in poor neighborhoods. Racial disparities were observed in access to referral, transplant evaluation, waitlisting and organ receipt. SES explained almost one‐third of the lower rate of transplant among black versus white patients, but even after adjustment for demographic, clinical and SES factors, blacks had a 59% lower rate of transplant than whites (hazard ratio = 0.41; 95% confidence interval: 0.28–0.58). Results suggest that improving access to healthcare may reduce some, but not all, of the racial disparities in access to kidney transplantation.

Dialysis Facility Characteristics and Variation in Employment Rates: A National Study

BACKGROUND Investigation of factors associated with variation in dialysis patient employment has focused primarily on patient-level factors. Little is known about facility-level factors that may be associated with patient employment. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS The ESRD Facility Survey (CMS-2744A) began in 2004 to collect counts of employed patients aged 18 to 54, in addition to dialysis unit census, types and timing of treatments offered, and staffing. Using the 2004 ESRD Facility Survey File, we investigated dialysis unit characteristics and facility employment rate of patients aged 18 to 54 in a logistic regression analysis that included hospital-based chronic renal care facilities, nonhospital renal disease treatment centers, independent special purpose renal dialysis facilities, and renal disease treatment centers. RESULTS Across all facilities, 18.9% of prevalent patients aged 18 to 54 were employed, but facility employment rates ranged from 0 to 100%. Facility employment rate was positively associated independently with availability of a 5 p.m. or later dialysis shift (odds ratio (OR) 1.54, 95% confidence interval (CI) 1.42 to 1.68), availability of peritoneal dialysis or home hemodialysis (HD) training (OR 1.19, 95% CI 1.11 to 1.28), and provision of frequent HD (OR 1.26, 95% CI 1.07 to 1.49), after adjusting for patient/social worker ratio, rurality of unit location, and unit size. In addition, patient receipt of Vocational Rehabilitation (VR) services was more often reported in facilities with higher employment rates. CONCLUSIONS Promoting gainful employment among ESRD patients continues to be a quality improvement need. A dataset that allows adjustment for patient-level variables would facilitate increased understanding of the contribution of dialysis facility variables to patient employment.

APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors.

Background Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impacting allograft survival from deceased AA kidney donors, APOL1 renal-risk variants were genotyped in additional AA kidney donors. Methods The APOL1 genotypes were linked to outcomes in 478 newly analyzed DDKTs in the Scientific Registry of Transplant Recipients. Multivariate analyses accounting for recipient age, sex, race, panel-reactive antibody level, HLA match, cold ischemia time, donor age, and expanded criteria donation were performed. These 478 transplantations and 675 DDKTs from a prior report were jointly analyzed. Results Fully adjusted analyses limited to the new 478 DDKTs replicated shorter renal allograft survival in recipients of APOL1 2-renal-risk-variant kidneys (hazard ratio [HR], 2.00; P = 0.03). Combined analysis of 1153 DDKTs from AA donors revealed donor APOL1 high-risk genotype (HR, 2.05; P = 3 × 10−4), older donor age (HR, 1.18; P = 0.05), and younger recipient age (HR, 0.70; P = 0.001) adversely impacted allograft survival. Although prolonged allograft survival was seen in many recipients of APOL1 2-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than that in recipients of 0/1 APOL1 renal-risk-variant kidneys. A competing risk analysis revealed that APOL1 impacted renal allograft survival, but not recipient survival. Interactions between donor age and APOL1 genotype on renal allograft survival were nonsignificant. Conclusions Shorter renal allograft survival is reproducibly observed after DDKT from APOL1 2-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.

Impact of a Patient Education Program on Disparities in Kidney Transplant Evaluation

BACKGROUND AND OBJECTIVES In 2007, the Emory Transplant Center (ETC) kidney transplant program implemented a required educational session for ESRD patients referred for renal transplant evaluation to increase patient awareness and decrease loss to follow-up. The purpose of this study was to evaluate the association of the ETC education program on completion of the transplant evaluation process. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Incident, adult ESRD patients referred from 2005 to 2008 were included. Patient data were abstracted from medical records and linked with data from the United States Renal Data System. Evaluation completion was compared by pre- and posteducational intervention groups in binomial regression models accounting for temporal confounding. RESULTS A total of 1126 adult ESRD patients were examined in two transplant evaluation eras (75% pre- and 25% postintervention). One-year evaluation completion was higher in the post- versus preintervention group (80.4% versus 44.7%, P<0.0001). In adjusted analyses controlling for time trends, the adjusted probability of evaluation completion at 1 year was higher among the intervention versus nonintervention group (risk ratio=1.38, 95% confidence interval=1.12-1.71). The effect of the intervention was stronger among black patients and those patients living in poor neighborhoods (likelihood ratio test for interaction, P<0.05). CONCLUSIONS Standardizing transplant education may help reduce some of the racial and socioeconomic disparities observed in kidney transplantation.

A Randomized Evaluation of Two Health Care Quality Improvement Program (HCQIP) Interventions to Improve the Adequacy of Hemodialysis Care of ESRD Patients: Feedback Alone versus Intensive Intervention

End-stage renal disease (ESRD) Networks are quality improvement organizations that collect, analyze, and report information to clinicians and allied health providers about discrepancies between observed patterns of care of ESRD patients and what has been recommended by clinical practice guidelines. The Networks facilitate response to this information by assisting ESRD treatment centers to develop quality improvement programs to redress inadequate care. The authors evaluated this process of quality improvement by selecting 42 treatment centers in a single ESRD Network with the lowest facility-specific mean urea reduction ratio (URR). The treatment centers were randomly assigned to two intervention strategies: (1) feedback alone; (2) an intensive intervention that included feedback, workshops, distribution of educational materials and clinical practice guidelines, technical assistance with the development of quality improvement plans, and continued monitoring. The intensive intervention had greater improvement in the increased proportions of patients dialyzed with prescribed blood flow (P = 0.02) and documented review of prescription (P = 0.01). Furthermore, the mean center URR increased nearly 3% among intensive intervention centers (from 68.1 to 70.9) but only 0.09% among the feedback centers (68.2 to 69.1) (P = 0.002). Similarly, time on dialysis increased 7.5 min on average among patients in intervention centers but decreased 2 min for patients in comparison centers (P = 0.03). These results demonstrate that Network feedback, coupled with the intensive intervention, resulted in improvement in care that would otherwise not have occurred.

Dialysis Facility and Network Factors Associated With Low Kidney Transplantation Rates Among United States Dialysis Facilities

Variability in transplant rates between different dialysis units has been noted, yet little is known about facility‐level factors associated with low standardized transplant ratios (STRs) across the United States End‐stage Renal Disease (ESRD) Network regions. We analyzed Centers for Medicare & Medicaid Services Dialysis Facility Report data from 2007 to 2010 to examine facility‐level factors associated with low STRs using multivariable mixed models. Among 4098 dialysis facilities treating 305 698 patients, there was wide variability in facility‐level STRs across the 18 ESRD Networks. Four‐year average STRs ranged from 0.69 (95% confidence interval [CI]: 0.64–0.73) in Network 6 (Southeastern Kidney Council) to 1.61 (95% CI: 1.47–1.76) in Network 1 (New England). Factors significantly associated with a lower STR (p < 0.0001) included for‐profit status, facilities with higher percentage black patients, patients with no health insurance and patients with diabetes. A greater number of facility staff, more transplant centers per 10 000 ESRD patients and a higher percentage of patients who were employed or utilized peritoneal dialysis were associated with higher STRs. The lowest performing dialysis facilities were in the Southeastern United States. Understanding the modifiable facility‐level factors associated with low transplant rates may inform interventions to improve access to transplantation.

Variation in Dialysis Facility Referral for Kidney Transplantation Among Patients With End-Stage Renal Disease in Georgia

IMPORTANCE Dialysis facilities in the United States are required to educate patients with end-stage renal disease about all treatment options, including kidney transplantation. Patients receiving dialysis typically require a referral for kidney transplant evaluation at a transplant center from a dialysis facility to start the transplantation process, but the proportion of patients referred for transplantation is unknown. OBJECTIVE To describe variation in dialysis facility-level referral for kidney transplant evaluation and factors associated with referral among patients initiating dialysis in Georgia, the US state with the lowest kidney transplantation rates. DESIGN, SETTING, AND PARTICIPANTS Examination of United States Renal Data System data from a cohort of 15,279 incident, adult (18-69 years) patients with end-stage renal disease from 308 Georgia dialysis facilities from January 2005 to September 2011, followed up through September 2012, linked to kidney transplant referral data collected from adult transplant centers in Georgia in the same period. MAIN OUTCOMES AND MEASURES Referral for kidney transplant evaluation within 1 year of starting dialysis at any of the 3 Georgia transplant centers was the primary outcome; placement on the deceased donor waiting list was also examined. RESULTS The median within-facility percentage of patients referred within 1 year of starting dialysis was 24.4% (interquartile range, 16.7%-33.3%) and varied from 0% to 75.0%. Facilities in the lowest tertile of referral (<19.2%) were more likely to treat patients living in high-poverty neighborhoods (absolute difference, 21.8% [95% CI, 14.1%-29.4%]), had a higher patient to social worker ratio (difference, 22.5 [95% CI, 9.7-35.2]), and were more likely nonprofit (difference, 17.6% [95% CI, 7.7%-27.4%]) compared with facilities in the highest tertile of referral (>31.3%). In multivariable, multilevel analyses, factors associated with lower referral for transplantation, such as older age, white race, and nonprofit facility status, were not always consistent with the factors associated with lower waitlisting. CONCLUSIONS AND RELEVANCE In Georgia overall, a limited proportion of patients treated with dialysis were referred for kidney transplant evaluation between 2005 and 2011, but there was substantial variability in referral among facilities. Variables associated with referral were not always associated with waitlisting, suggesting that different factors may account for disparities in referral.

Kidney Transplant Access in the Southeast: View From the Bottom

The Southeastern region of the United States has the highest burden of end‐stage renal disease (ESRD) but the lowest rates of kidney transplantation in the nation. There are many patient‐, dialysis facility–, ESRD Network– and health system–level barriers that contribute to this regional disparity. Compared to the rest of the nation, the Southeast has a larger population of African‐Americans and higher poverty, as well as more prevalent ESRD risk factors including hypertension, obesity and diabetes. Dialysis facilities—where ESRD patients receive the majority of their healthcare—play an important role in transplant access. Identifying characteristics of individual dialysis units with low rates of kidney transplantation, such as understaffing or for‐profit status, can help identify targets for quality improvement initiatives. Geographic differences across the country can identify opportunities to increase funding for healthcare resources in proportion to patient and disease burden. Focusing interventions among dialysis facilities with the lowest transplant rates within the Southeast, such as provider and patient education, has the potential to increase referrals for kidney transplantation, leading to higher rates of kidney transplants in this region. Referral for transplantation should be measured on a national level to monitor disparities in early access to transplantation. Transplant centers have an obligation to assist underserved populations in ensuring equity in access to services. Policies that improve access to care for patients, such as the Affordable Care Act and Medicaid expansion, are particularly important for Southern states and may alleviate geographic disparities.

A Randomized Trial to Reduce Disparities in Referral for Transplant Evaluation

Georgia has the lowest kidney transplant rates in the United States and substantial racial disparities in transplantation. We determined the effectiveness of a multicomponent intervention to increase referral of patients on dialysis for transplant evaluation in the Reducing Disparities in Access to kidNey Transplantation Community Study (RaDIANT), a randomized, dialysis facility-based, controlled trial involving >9000 patients receiving dialysis from 134 dialysis facilities in Georgia. In December of 2013, we selected dialysis facilities with either low transplant referral or racial disparity in referral. The intervention consisted of transplant education and engagement activities targeting dialysis facility leadership, staff, and patients conducted from January to December of 2014. We examined the proportion of patients with prevalent ESRD in each facility referred for transplant within 1 year as the primary outcome, and disparity in the referral of black and white patients as a secondary outcome. Compared with control facilities, intervention facilities referred a higher proportion of patients for transplant at 12 months (adjusted mean difference [aMD], 7.3%; 95% confidence interval [95% CI], 5.5% to 9.2%; odds ratio, 1.75; 95% CI, 1.36 to 2.26). The difference between intervention and control facilities in the proportion of patients referred for transplant was higher among black patients (aMD, 6.4%; 95% CI, 4.3% to 8.6%) than white patients (aMD, 3.7%; 95% CI, 1.6% to 5.9%; P<0.05). In conclusion, this intervention increased referral and improved equity in kidney transplant referral for patients on dialysis in Georgia; long-term follow-up is needed to determine whether these effects led to more transplants.