Living Donor Decision-Making and the Complex Interplay of Finances and Other Motivators, Barriers, and Facilitators.

INTRODUCTION: The decision to become a living donor requires consideration of a complex, interactive array of factors that could be targeted for clinical, policy, and educational interventions. Our objective was to assess how financial barriers interact with motivators, other barriers, and facilitators during this process. METHODS: Data were obtained from a public survey assessing motivators, barriers, and facilitators of living donation. We used multivariable logistic regression and consensus k-means clustering to assess interactions between financial concerns and other considerations in the decision-making process. RESULTS: Among 1592 respondents, the average age was 43; 74% were female and 14% and 6% identified as Hispanic and Black, respectively. Among employed respondents (72%), 40% indicated that they would not be able to donate without lost wage reimbursement. Stronger agreement with worries about expenses and dependent care challenges was associated with not being able to donate without lost wage reimbursement (OR = 1.2, 95% CI = 1.0-1.3; OR = 1.2, 95% CI = 1.1-1.3, respectively). Four respondent clusters were identified. Cluster 1 had strong motivators and facilitators with minimal barriers. Cluster 2 had barriers related to health concerns, nervousness, and dependent care. Clusters 3 and 4 had financial barriers. Cluster 3 also had anxiety related to surgery and dependent care. CONCLUSIONS: Financial barriers interact primarily with health and dependent care concerns when considering living organ donation. Targeted interventions to reduce financial barriers and improve provider communication regarding donation-related risks are needed.

Use of Federal Reimbursement for Living Donor Costs by Racial and Ethnic Minorities: Implications for Disparities in Access to Living Donor Transplantation.

BACKGROUND: Minority race, ethnicity, and financial barriers are associated with lower rates of living donor (LD) kidney transplantation (LDKT). Financial reimbursement for LD costs may impact social determinants of health and, therefore, impact disparities in access to LDKT. METHODS: Among US LDKTs, we studied associations between racial and ethnic minority status and utilization of the National Living Donor Assistance Center (NLDAC), a means-tested reimbursement program for nonmedical LD costs. We analyzed demographic, clinical, income, and survey data from NLDAC and the Scientific Registry of Transplant Recipients (January 1, 2011, to December 31, 2022) to identify predictors of NLDAC utilization. RESULTS: Among 70 069 US LDKTs, 6093 NLDAC applicants were identified (9% of US LDKTs). Racial and ethnic minorities were over-represented in NLDAC-supported LDKTs compared with non-NLDAC US LDKTs (Black donors 12% versus 9%; Black recipients 15% versus 12%; Hispanic donors 21% versus 14%; Hispanic recipients 23% versus 15%; all P < 0.001). Among preemptive transplants, use of NLDAC by donors to Hispanic recipients (11%) was nearly twice as high as that of non-Hispanic recipients (6%) (P < 0.001). At time of NLDAC application, 72% stated NLDAC "will make it possible" to donate; higher proportions of minority applicants agreed (Black 80%, White 70%, P < 0.001; Hispanic 79%, non-Hispanic 70%, P < 0.001). Racial and ethnic minority-concordant transplants were significantly more likely to use NLDAC (donor/recipient: Black/Black risk-adjusted odds ratio [OR], 1.85, other/other OR 2.59, Hispanic/Hispanic OR 1.53; all P < 0.05). CONCLUSIONS: Reduction of LD financial barriers may increase access to LDKT, particularly in racial and ethnic minority communities.

Report From a Multidisciplinary Symposium on the Future of Living Kidney Donor Transplantation.

Virtually all clinicians agree that living donor renal transplantation is the optimal treatment for permanent loss of kidney function. Yet, living donor kidney transplantation has not grown in the United States for more than 2 decades. A virtual symposium gathered experts to examine this shortcoming and to stimulate and clarify issues salient to improving living donation. The ethical principles of rewarding kidney donors and the limits of altruism as the exclusive compelling stimulus for donation were emphasized. Concepts that donor incentives could save up to 40 000 lives annually and considerable taxpayer dollars were examined, and survey data confirmed voter support for donor compensation. Objections to rewarding donors were also presented. Living donor kidney exchanges and limited numbers of deceased donor kidneys were reviewed. Discussants found consensus that attempts to increase living donation should include removing artificial barriers in donor evaluation, expansion of living donor chains, affirming the safety of live kidney donation, and assurance that donors incur no expense. If the current legal and practice standards persist, living kidney donation will fail to achieve its true potential to save lives.

Rationale and Design of the Diet, CKD, and Apolipoprotein L1 Study in Low-Income and Middle-Income Countries.

Introduction: Diet, chronic kidney disease (CKD), and Apolipoprotein L1 (APOL1) (DCA) Study is examining the role of dietary factors in CKD progression and APOL1 nephropathy. We describe enrollment and retention efforts and highlight facilitators and barriers to enrollment and operational challenges, as well as accommodations made in the study protocol. Methods: The DCA study is enrolling participants in 7 centers in West Africa. Participants who consented were invited to complete dietary recalls and 24-hour urine collections in year 1. We conducted focus groups and semistructured interviews among study personnel to identify facilitators and barriers to enrollment as well as retention and operational challenges in the execution of the study protocol. We analyzed emerging themes using content analyses. Results: A total of 712 participants were enrolled in 18 months with 1256 24-hour urine and 1260 dietary recalls. Barriers to enrollment were the following: (i) a lack of understanding of research, (ii) the burden of research visits, and (iii) incorporating cultural and traditional nuances when designing research protocols. Factors facilitating enrollment were the following: (i) designing convenient research visits, (ii) building rapport and increased communication between the research team and participants, and (iii) cultural sensitivity - adapting research protocols for the populations involved. Offering home visits, providing free dietary counseling, reducing the volume of study blood collection, and reducing the frequency of visits were some changes made in the study protocol that increased participant satisfaction. Conclusion: Adopting a participant-centered approach with accommodations in the protocol for cultural adaptability and incorporating participant feedback is vital for carrying out research in low-income and middle-income regions.

Cardiovascular Risk Factor Burden and Association With CKD in Ghana and Nigeria.

Introduction: Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD); however, the burden of cardiovascular risk factors in patients with CKD in Africa is not well characterized. We determined the prevalence of selected cardiovascular risk factors, and association with CKD in the Human Heredity for Health in Africa Kidney Disease Research Network study. Methods: We recruited patients with and without CKD in Ghana and Nigeria. CKD was defined as estimated glomerular filtration rate of <60 ml/min per 1.73 m2 and/or albuminuria as albumin-to-creatinine ratio <3.0 mg/mmol (<30 mg/g) for ≥3 months. We assessed self-reported (physician-diagnosis and/or use of medication) hypertension, diabetes, and elevated cholesterol; and self-reported smoking as cardiovascular risk factors. Association between the risk factors and CKD was determined by multivariate logistic regression. Results: We enrolled 8396 participants (cases with CKD, 3956), with 56% females. The mean age (45.5 ± 15.1 years) did not differ between patients and control group. The prevalence of hypertension (59%), diabetes (20%), and elevated cholesterol (9.9%), was higher in CKD patients than in the control participants (P < 0.001). Prevalence of risk factors was higher in Ghana than in Nigeria. Hypertension (adjusted odds ratio [aOR] = 1.69 [1.43-2.01, P < 0.001]), elevated cholesterol (aOR = 2.0 [1.39-2.86, P < 0.001]), age >50 years, and body mass index (BMI) <18.5 kg/m2 were independently associated with CKD. The association of diabetes and smoking with CKD was modified by other risk factors. Conclusion: Cardiovascular risk factors are prevalent in middle-aged adult patients with CKD in Ghana and Nigeria, with higher proportions in Ghana than in Nigeria. Hypertension, elevated cholesterol, and underweight were independently associated with CKD.

Patient-Centered Outcomes With a Multidisciplinary CKD Care Team Approach: An Observational Study.

Rationale & Objective: Multidisciplinary chronic kidney disease (CKD) care has been associated with improved clinical outcomes in comparison to general nephrology care. However, there is little research examining the impact of multidisciplinary care on patient-centered outcomes. We examined if a multidisciplinary approach to CKD care was associated with 4 patient-centered outcomes. Study Design: Cross-sectional study design using previously established surveys to assess patient-centered outcomes in participants with nondialysis CKD. Setting & Participants: Adults with CKD stages 1-5 who had not undergone transplant or were not on dialysis. Exposures: General nephrology care or multidisciplinary care. Patients receiving multidisciplinary care were seen by a pharmacist, social worker, dietitian, and nephrologist, whereas patients receiving general nephrology care only saw a nephrologist. Outcomes: Four patient-centered outcomes: CKD-specific knowledge, disease-related stress, perception of overall health, and perception of health status compared to 1 year ago. Analytical Approach: Differences were examined using a Welch 2-sample t test and linear regression model. Results: Mean age of participants was 60 years with standard deviation of 17 years. 182 (77%) patients were White, and 230 (96%) had formal education greater than or equal to high school. 121 (49%) were women, and 215 (88%) had CKD stage 3-5. 77 (31%) received multidisciplinary care. We did not identify any significant differences in patient knowledge, stress, or perception of health between multidisciplinary and general nephrology care. However, notably, patients in multidisciplinary care were older and had more advanced CKD than those in general nephrology care. Limitations: Cross-sectional study designs only identify associations. Study was conducted at clinics located within 30 miles of each other, limiting generalizability. Conclusions: Our results suggest that a team-based approach to care can better support sicker, more vulnerable patients so that they can achieve similar patient-centered outcomes compared to patients who are younger and with less advanced CKD.

Inaxaplin for Proteinuric Kidney Disease in Persons with Two APOL1 Variants.

BACKGROUND: Persons with toxic gain-of-function variants in the gene encoding apolipoprotein L1 (APOL1) are at greater risk for the development of rapidly progressive, proteinuric nephropathy. Despite the known genetic cause, therapies targeting proteinuric kidney disease in persons with two APOL1 variants (G1 or G2) are lacking. METHODS: We used tetracycline-inducible APOL1 human embryonic kidney (HEK293) cells to assess the ability of a small-molecule compound, inaxaplin, to inhibit APOL1 channel function. An APOL1 G2-homologous transgenic mouse model of proteinuric kidney disease was used to assess inaxaplin treatment for proteinuria. We then conducted a single-group, open-label, phase 2a clinical study in which inaxaplin was administered to participants who had two APOL1 variants, biopsy-proven focal segmental glomerulosclerosis, and proteinuria (urinary protein-to-creatinine ratio of ≥0.7 to <10 [with protein and creatinine both measured in grams] and an estimated glomerular filtration rate of ≥27 ml per minute per 1.73 m2 of body-surface area). Participants received inaxaplin daily for 13 weeks (15 mg for 2 weeks and 45 mg for 11 weeks) along with standard care. The primary outcome was the percent change from the baseline urinary protein-to-creatinine ratio at week 13 in participants who had at least 80% adherence to inaxaplin therapy. Safety was also assessed. RESULTS: In preclinical studies, inaxaplin selectively inhibited APOL1 channel function in vitro and reduced proteinuria in the mouse model. Sixteen participants were enrolled in the phase 2a study. Among the 13 participants who were treated with inaxaplin and met the adherence threshold, the mean change from the baseline urinary protein-to-creatinine ratio at week 13 was -47.6% (95% confidence interval, -60.0 to -31.3). In an analysis that included all the participants regardless of adherence to inaxaplin therapy, reductions similar to those in the primary analysis were observed in all but 1 participant. Adverse events were mild or moderate in severity; none led to study discontinuation. CONCLUSIONS: Targeted inhibition of APOL1 channel function with inaxaplin reduced proteinuria in participants with two APOL1 variants and focal segmental glomerulosclerosis. (Funded by Vertex Pharmaceuticals; VX19-147-101 ClinicalTrials.gov number, NCT04340362.).

HoLEPs: A Comparative Study of Men With Massive Prostate Volumes ≥150 mL and <150 mL.

OBJECTIVE: To assess outcomes following Holmium Laser Enucleation of Prostate (HoLEP) in men with prostate volumes ≥150cc and compare this to men with prostate volumes ≤150 cc. PATIENTS & METHODS: We analyzed our prospective database of consecutive patients undergoing HoLEP in a single tertiary public hospital between October 2016 and January 2019. We excluded patients with clinically significant prostate cancer or neurogenic bladders. Preoperative prostate volume was measured on MRI or ultrasonography. Perioperative variables and functional outcomes were recorded. RESULTS: Of 304 HoLEPs performed, we included 97 patients with prostate volume of ≥150 cc and 186 patients with prostate volume <150 cc. Comparing both cohorts (≥150 cc vs <150 cc): mean age was 71.5 vs 68.3 years, prostate volume 195 cc vs 93 cc, preoperative Qmax 9.6mL/s vs 10mL/s, American Urology Association Symptom Score (IPSS) 21 points vs 20.5 points; mean PSA 13.2µg/L vs 8.8µg/L; laser duration 86 vs 59 minutes; morcellation duration 29 vs 14 minutes; enucleated weight was 124 g vs 60 g. One patient (1%) from the ≥150 cc cohort required a surgical procedure for stress urinary incontinence, and none from the <150 cc cohort, but this did not achieve statistical significance (P = .12). There were no statistically significant differences in postoperative Qmax (32.3 vs 26.4 mL/s; P = .12), IPSS (5.9 points vs 7.3points; P = .23), mean PSA (3.9 µg/L vs 2.2 µg/L; P = .60), stricture incidence (1% vs 2.7%; P = .63), or significant stress urinary incontinence (4.1% vs 0.5%; P = .08). CONCLUSION: Our large series demonstrates that HoLEP is safe and effective in patients with massive prostates (≥150 cc), with similar outcomes compared to patients with prostates <150 cc.

HIV Viremia Is Associated With APOL1 Variants and Reduced JC-Viruria.

Variants in the Apolipoprotein L1 (APOL1) gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two APOL1 risk alleles, a role in HIV infectivity has been postulated in the mechanism of APOL1 associated kidney disease. Herein, we aim to explore the association between HIV viremia and APOL1 genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two APOL1 renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89-40.8, p < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49-13.15, p = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0-5.63, p = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66-33.35, P = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12-0.98, p = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of APOL1 variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.

Association of Life-Course Educational Attainment and Breast Cancer Grade in the MEND Study.

Background: Nigeria reports the highest age-standardized mortality rate for breast cancer (BC) among African countries and disproportionately high rates of high-grade cancer. Histological grade is a strong predictor of mortality, and evidence suggests that educational attainment influences cancer outcomes. Objective: We characterize the association between educational trends across the life-course and BC grade at diagnosis. Methods: Data on 224 BC patients enrolled in the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Nigerian Women (MEND) study was analyzed. Participant and parental (mother and father) education was categorized as low (primary school or less) or high (secondary school or greater). Accordingly, the educational trend across the life-course was determined for each participant relative to each parent: stable high, increasing, decreasing, or stable low. BC grade was classified as high (grade 3) or low (grades 1-2). Findings: About 34% of participants, 71% of fathers, and 85% of mothers had low education. Approximately one-third of participants were diagnosed with high-grade BC. Participants with low-grade BC were more likely to have highly educated fathers (p = 0.04). After adjusting for age, comorbidities, marital status and mammogram screening, participants with highly educated fathers were 60% less likely to have high-grade BC (aOR 0.41; 95% CI 0.20 to 0.84) compared to those with less-educated fathers. Stable high life-course education relative to father was also associated with a significantly lower likelihood of having high-grade BC (aOR 0.36; 95% CI 0.15 to 0.87) compared to stable low life-course education. No significant associations were observed for the participant's education, mother's education, or life-course education relative to mother. Conclusions: Early-life socioeconomic status (SES) may influence BC grade. This deserves further study to inform policies that may be useful in reducing high-grade BC in Nigeria.

Acceptance of COVID-19 Vaccination Among Health System Personnel.

INTRODUCTION: One-third of the general public will not accept Coronavirus disease 2019 (COVID-19) vaccination but factors influencing vaccine acceptance among health care personnel (HCP) are not known. We investigated barriers and facilitators to vaccine acceptance within 3 months of regulatory approval (primary outcome) among adult employees and students at a tertiary-care, academic medical center. METHODS: We used a cross-sectional survey design with multivariable logistic regression. Covariates included age, gender, educational attainment, self-reported health status, concern about COVID-19, direct patient interaction, and prior influenza immunization. RESULTS: Of 18,250 eligible persons, 3,347 participated. Two in 5 (40.5%) HCP intend to delay (n = 1020; 30.6%) or forgo (n = 331; 9.9%) vaccination. Male sex (adjusted OR [aOR], 2.43; 95% confidence interval [CI], 2.00-2.95; P < .001), prior influenza vaccination (aOR, 2.35; 95% CI, 1.75-3.18; P < .001), increased concern about COVID-19 (aOR, 2.40; 95% CI, 2.07-2.79; P < .001), and postgraduate education (aOR, 1.41; 95% CI, 1.21-1.65; P < .001) - but not age, direct patient interaction, or self-reported overall health - were associated with vaccine acceptance in multivariable analysis. Barriers to vaccination included concerns about long-term side effects (n = 1197, 57.1%), safety (n = 1152, 55.0%), efficacy (n = 777, 37.1%), risk-to-benefit ratio (n = 650, 31.0%), and cost (n = 255, 12.2%).Subgroup analysis of Black respondents indicates greater hesitancy to accept vaccination (only 24.8% within 3 months; aOR 0.13; 95% CI, 0.08-0.21; P < .001). CONCLUSIONS: Many HCP intend to delay or refuse COVID-19 vaccination. Policymakers should impartially address concerns about safety, efficacy, side effects, risk-to-benefit ratio, and cost. Further research with minority subgroups is urgently needed.

Novel Risk Factors for Progression of Diabetic and Nondiabetic CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Identification of novel risk factors for chronic kidney disease (CKD) progression may inform mechanistic investigations and improve identification of high-risk subgroups. The current study aimed to characterize CKD progression across levels of numerous risk factors and identify independent risk factors for CKD progression among those with and without diabetes. STUDY DESIGN: The Chronic Renal Insufficiency Cohort (CRIC) Study is a prospective cohort study of adults with CKD conducted at 7 US clinical centers. SETTING & PARTICIPANTS: Participants (N=3,379) had up to 12.3 years of follow-up; 47% had diabetes. PREDICTORS: 30 risk factors for CKD progression across sociodemographic, behavioral, clinical, and biochemical domains at baseline. OUTCOMES: Study outcomes were estimated glomerular filtration rate (eGFR) slope and the composite of halving of eGFR or initiation of kidney replacement therapy. ANALYTICAL APPROACH: Stepwise selection of independent risk factors was performed stratified by diabetes status using linear mixed-effects and Cox proportional hazards models. RESULTS: Among those without and with diabetes, respectively, mean eGFR slope was-1.4±3.3 and-2.7±4.7mL/min/1.73m2 per year. Among participants with diabetes, multivariable-adjusted hazard of the composite outcome was approximately 2-fold or greater with higher levels of the inflammatory chemokine CXCL12, the cardiac marker N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the kidney injury marker urinary neutrophil gelatinase-associated lipocalin (NGAL). Among those without diabetes, low serum bicarbonate and higher high-sensitivity troponin T, NT-proBNP, and urinary NGAL levels were all significantly associated with a 1.5-fold or greater rate of the composite outcome. LIMITATIONS: The observational study design precludes causal inference. CONCLUSIONS: Strong associations for cardiac markers, plasma CXCL12, and urinary NGAL are comparable to that of systolic blood pressure≥140mm Hg, a well-established risk factor for CKD progression. This warrants further investigation into the potential mechanisms that these markers indicate and opportunities to use them to improve risk stratification.

H3Africa partnerships to empower clinical research sites to generate high-quality biological samples.

BACKGROUND: The Institute of Human Virology Nigeria (IHVN) - Human Heredity and Health in Africa (H3Africa) Biorepository (I-HAB) seeks to provide high-quality biospecimens for research. This depends on the ability of clinical research sites (CRS) - who provide biospecimens - to operate according to well-established industry standards. Yet, standards are often neglected at CRSs located in Africa. Here, I-HAB reports on its four-pronged approach to empower CRSs to prepare high-quality biospecimens for research. OBJECTIVES: I-HAB sought (1) to assess a four-pronged approach to improve biobanking practices and sample quality among CRSs, and (2) to build human capacity. METHODS: I-HAB partnered with two H3Africa principal investigators located in Nigeria and Ghana from August 2013 through to May 2017 to debut its four-pronged approach (needs assessment, training and mentorship, pilot, and continuous quality improvement) to empower CRSs to attain high-quality biospecimens. RESULTS: Close collaborations were instrumental in establishing mutually beneficial and lasting relationships. Improvements during the 12 months of engagement with CRSs involved personnel, procedural, and supply upgrades. In total, 51 staff were trained in over 20 topics. During the pilot, CRSs extracted 50 DNA biospecimens from whole blood and performed quality control. The CRSs shipped extracted DNA to I-HAB and I-HAB that comparatively analysed the DNA. Remediation was achieved via recommendations, training, and mentorship. Preanalytical, analytical and post-analytical processes, standard operating procedures, and workflows were systematically developed. CONCLUSION: Partnerships between I-HAB and H3Africa CRSs enabled research sites to produce high-quality biospecimens through needs assessment, training and mentorship, pilot, and continuous monitoring and improvement.

Regional Patterns and Association Between Obesity and Hypertension in Africa: Evidence From the H3Africa CHAIR Study.

Hypertension and obesity are the most important modifiable risk factors for cardiovascular diseases, but their association is not well characterized in Africa. We investigated regional patterns and association of obesity with hypertension among 30 044 continental Africans. We harmonized data on hypertension (defined as previous diagnosis/use of antihypertensive drugs or blood pressure [BP]≥140/90 mmHg/BP≥130/80 mmHg) and obesity from 30 044 individuals in the Cardiovascular H3Africa Innovation Resource across 13 African countries. We analyzed data from population-based controls and the Entire Harmonized Dataset. Age-adjusted and crude proportions of hypertension were compared regionally, across sex, and between hypertension definitions. Logit generalized estimating equation was used to determine the independent association of obesity with hypertension (P value <5%). Participants were 56% women; with mean age 48.5±12.0 years. Crude proportions of hypertension (at BP≥140/90 mmHg) were 47.9% (95% CI, 47.4-48.5) for Entire Harmonized Dataset and 42.0% (41.1-42.7) for population-based controls and were significantly higher for the 130/80 mm Hg threshold at 59.3% (58.7-59.9) in population-based controls. The age-adjusted proportion of hypertension at BP≥140/90 mmHg was the highest among men (33.8% [32.1-35.6]), in western Africa (34.7% [33.3-36.2]), and in obese individuals (43.6%; 40.3-47.2). Obesity was independently associated with hypertension in population-based controls (adjusted odds ratio, 2.5 [2.3-2.7]) and odds of hypertension in obesity increased with increasing age from 2.0 (1.7-2.3) in younger age to 8.8 (7.4-10.3) in older age. Hypertension is common across multiple countries in Africa with 11.9% to 51.7% having BP≥140/90 mmHg and 39.5% to 69.4% with BP≥130/80 mmHg. Obese Africans were more than twice as likely to be hypertensive and the odds increased with increasing age.

Satisfaction with life and depressive symptoms in living organ donors and non-donors: New insights from the National Living Donor Assistance Center.

BACKGROUND: Previous studies indicate there may be psychological consequences of being unable to serve as a living donor, but these have not been explored in a large national cohort of low-income individuals who initiated living donor evaluation in US transplant centers. METHODS: Using data from 6574 National Living Donor Assistance Center (NLDAC) participants (November 1, 2007-December 31, 2018), we utilized a cross-sectional study design to evaluate short-term depressive symptoms and satisfaction with life in living donors and non-donors (those who were declined or withdrew from evaluation) using the Satisfaction with Life Scale (SWLS) and the PHQ-8, with and without risk adjustment using linear regression. RESULTS: National Living Donor Assistance Center participants originated from 207 US transplant centers. 52% of NLDAC participants responded to the survey (n = 3423; donors = 2848 (58.6% of all donors), non-donors = 575 (33.5% of all non-donors); ncenters  = 201)). Respondents were significantly older, more likely to be female, white, non-Hispanic, married, more educated, more full-time employed, and more likely to be unrelated to the recipient vs non-respondents (all, P < .001). Among survey respondents, donors were significantly younger, more likely to be non-Hispanic, employed, and related to the recipient compared to non-donors (all, P < .05). Higher PHQ-8 scores were correlated with lower SWL scores (r = -.32, P < .001). Both groups displayed high SWLS (donors vs non-donors: 27.1 vs 26.3, P = .002). Both groups had low levels of depressive symptoms overall, but donors had more symptoms than non-donors (3.5 vs 2.4, P < .001). After risk adjustment, non-donors had significantly less depressive symptoms by PHQ-8 (28% lower, P < .001), but had lower life satisfaction (1.2 points lower, P < .001). CONCLUSIONS: Donors and non-donors have high global levels of overall life satisfaction and low levels of depressive symptoms at 8 weeks after donation or denial. While small effect sizes were observed between groups in these outcomes, being a non-donor was an independent risk factor for lower life satisfaction, which warrants further evaluation.

Approach to High Volume Enrollment in Clinical Research: Experiences from an All of Us Research Program Site.

Clinical trials and cohort studies are required to meet target recruitment of study participants within stipulated timelines, especially when the priority is to include populations traditionally unrepresented in biomedical research. By the third quarter of 2019, the University of Arizona-Banner Health Provider Organization (UA-Banner HPO) has enrolled > 30,000 core participants into the All of Us Research Program (AoURP), the research cohort of the Precision Medicine Initiative. The majority of enrolled participants meet the criteria for individuals under-represented in biomedical research. The enrollment goals were calculated based on a target of 20,000 as set by the National Institutes of Health and our health provider organization achieved enrollment numbers between 17% and 86% above the targeted daily enrollment. We evaluated enrollment methods and challenges to enrollments encountered by the UA-Banner Health Provider Organization into the AoURP. Challenges to enrollment centered around the need for high-touch engagement methods, time investment necessary for stakeholder inclusion, and the use of purely digital enrollment methods especially in populations under-represented in biomedical research. These challenges occurred at the level of the individual, provider, institutions, and community, and cumulatively impacted participant enrollment. Successful strategies for engagement and enrollment leveraged provider partners as advocates for the program. For high-volume enrollment in clinical research, it is important to engage leaders in the healthcare setting, patient providers, and tailor engagement and enrollment to potential participant needs. We emphasize the need for precision engagement and enrollment methods tailored to individual needs.

The Association Between Selected Molecular Biomarkers and Ambulatory Blood Pressure Patterns in African Chronic Kidney Disease and Hypertensive Patients Compared With Normotensive Controls: Protocol for a Longitudinal Study.

BACKGROUND: Chronic kidney disease (CKD) is a burgeoning epidemic in sub-Saharan Africa. Abnormal blood pressure variations are prevalent in CKD and potentiate the risk of cardiovascular morbidity and mortality. Certain genetic variants (angiotensin II receptor type 1 1166 A>C and angiotensin-converting enzyme insertion and deletion polymorphisms) and biomarkers such as interleukin-6, tumor necrosis factor, soluble (s) E-selectin, homocysteine, and highly sensitive C-reactive protein have been shown to affect blood pressure variability among non-African CKD, hypertensive. and nonhypertensive CKD population. However, the contributions of the pattern, genetic, and environmental determinants of ambulatory blood pressure in African CKD have not been characterized. Understanding these interactions may help to develop interventions to prevent major cardiovascular events among people with CKD. OBJECTIVE: The overarching objective of this study is to identify, document, and develop approaches to address related phenomic, genetic, and environmental determinants of ambulatory blood pressure patterns in African CKD and non-CKD hypertensive patients compared with normotensive controls. METHODS: This is a longitudinal short-term follow-up study of 200 adult subjects with CKD and 200 each of age-matched hypertensives without CKD and apparently healthy controls. Demographic information, detailed clinical profile, electrocardiography, echocardiography, and 24-hr ambulatory blood pressure measurements will be obtained. Blood samples will be collected to determine albumin-creatinine ratio, fasting plasma glucose, lipid profile, electrolytes, urea and creatinine, C-reactive protein, serum homocysteine, fibroblast growth factor-23, and complete blood count, while 2 mL blood aliquot will be collected in EDTA (ethylenediaminetetraacetic acid) tubes and mixed using an electronic rolling system to prevent blood clots and subsequently used for DNA extraction and genetic analysis. RESULTS: A total of 239 participants have been recruited so far, and it is expected that the recruitment phase will be complete in June 2020. The follow-up phase will continue with data analysis and publications of results. CONCLUSIONS: This study will help stratify Nigerian CKD patients phenotypically and genotypically in terms of their blood pressure variations with implications for targeted interventions and timing of medications to improve prognosis. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14820.