Faculty Bibliography

Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans (AAs). Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2571 AAs from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logistic regression models that adjusted for potentially important confounders tested for association between APOL1 risk variants and baseline clinical CVD (myocardial infarction, coronary, or carotid artery revascularization) and CKD (eGFR under 60 ml/min per 1.73 m(2) and/or UACR over 30 mg/g). AA SPRINT participants were 45.3% female with a mean (median) age of 64.3 (63) years, mean arterial pressure 100.7 (100) mm Hg, eGFR 76.3 (77.1) ml/min per 1.73 m(2), and UACR 49.9 (9.2) mg/g, and 8.2% had clinical CVD. APOL1 (recessive inheritance) was positively associated with CKD (odds ratio 1.37, 95% confidence interval 1.08-1.73) and log UACR estimated slope (β) 0.33) and negatively associated with eGFR (β -3.58), all significant. APOL1 risk variants were not significantly associated with prevalent CVD (1.02, 0.82-1.27). Thus, SPRINT data show that APOL1 risk variants are associated with mild CKD but not with prevalent CVD in AAs with a UACR under 1000 mg/g.

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.

CONTEXT/BACKGROUND:Vitamin D binding protein (DBP) is an important determinant of bioavailable vitamin D (BAVD) and may provide clues to racial variation in osteoporosis and atherosclerosis. OBJECTIVE:The objective was to assess relationships between DBP, BAVD, 25-hydroxyvitamin D (25OHD), and 1,25 di-hydroxyvitamin D (1,25OH2D) with kidney, bone, adipose, and atherosclerosis phenotypes in African Americans with type 2 diabetes. DESIGN/METHODS:Cross-sectional (N = 545) and longitudinal (N = 288; mean 5.1 ± 0.9-year follow-up) relationships between vitamin D concentrations with renal phenotypes, vertebral bone mineral density, aorto-iliac, coronary artery, and carotid artery calcified plaque (CP), and adipose tissue volumes were studied. SETTING/METHODS:African American-Diabetes Heart Study. PATIENTS/METHODS:Participants were 56.7% female with mean ± standard deviation (sd) age 55.6 ± 9.6 years, diabetes duration 10.3 ± 8.2 years, and eGFR 90.9 ± 22.1 ml/min/1.73 m(2). INTERVENTIONS/METHODS:None. MAIN OUTCOMES AND MEASURES/METHODS:Associations tested between vitamin D and the previously mentioned phenotypes adjusting for age, sex, African ancestry proportion, diabetes duration, statins, smoking, changes in estimated glomerular filtration rate, body mass index, hemoglobin A1c, and blood pressure. RESULTS:1,25OH2D was inversely associated with change in coronary artery CP (parameter estimate [β] -0.005, standard error [SE] 0.002; P = .037), with a trend for change in carotid artery CP (β -0.007, SE 0.004; P = .074). Further adjustment for renin-aldosterone-system blockade revealed inverse association between 1,25OH2D and change in albuminuria (β -0.004, SE 0.002; P = .037). DBP, BAVD, and 25OHD did not associate significantly with changes in albuminuria, CP, or bone mineral density. BAVD was inversely associated with visceral, subcutaneous, intermuscular, and pericardial adipose volumes. CONCLUSIONS:In contrast to BAVD and 25OHD, only 1,25OH2D levels were significantly and inversely associated with changes in subclinical atherosclerosis and albuminuria in African Americans, suggesting potential beneficial effects.

Variants in donor multidrug resistance protein 1 (ABCB1) and caveolin 1 (CAV1) genes are associated with renal allograft failure after transplantation in Europeans. Here we assessed transplantation outcomes of kidneys from 368 African American (AA) and 314 European American (EA) deceased donors based on 38 single-nucleotide polymorphisms (SNPs) spanning ABCB1 and 16 SNPs spanning CAV1, including previously associated index and haplotype-tagging SNPs. Tests for association with time to allograft failure were performed for the 1233 resultant kidney transplantations, adjusting for recipient age, sex, ethnicity, cold ischemia time, panel reactive antibody, human leukocyte antigen match, expanded-criteria donation, and APOL1-nephropathy variants in AA donors. Interaction analyses between APOL1 with ABCB1 and CAV1 were performed. In a meta-analysis of all transplantations, ABCB1 index SNP rs1045642 was associated with time to allograft failure and other ABCB1 SNPs were nominally associated, but not CAV1 SNPs. ABCB1 SNP rs1045642 showed consistent effects with the 558 transplantations from EA donors, but not with the 675 transplantations from AA donors. ABCB1 SNP rs956825 and CAV1 SNP rs6466583 interacted with APOL1 in transplants from AA donors. Thus, the T allele at ABCB1 rs1045642 is associated with shorter renal allograft survival for kidneys from American donors. Interactions between ABCB1 and CAV1 with APOL1 may influence allograft failure for transplanted kidneys from AA donors.

Background. Sparse data limit the interpretation of Montreal Cognitive Assessment (MoCA) scores, particularly in minority populations. Additionally, there are no published data on how MoCA scores compare to the widely used Modified Mini Mental State Examination (3MSE). We provide performance data on the MoCA in a large cohort of African Americans and compare 3MSE and MoCA scores, providing a "crosswalk" for interpreting scores. Methods. Five hundred and thirty African Americans with type 2 diabetes were enrolled in African American-Diabetes Heart Study-MIND, a cross-sectional study of cognition and structural and functional brain imaging. After excluding participants with possible cognitive impairment (n = 115), mean (SD) MoCA and 3MSE scores are presented stratified by age and education. Results. Participant mean age was 58.2 years (range: 35-83); 61% were female; and 64.9% had >12 years of education. Mean (SD) 3MSE and MoCA scores were 86.9 (8.2) and 19.8 (3.8), respectively. 93.5% of the cohort had a "positive" screen on the MoCA, scoring <26 (education-adjusted), compared with 47.5% on the 3MSE (cut-point < 88). A 3MSE score of 88 corresponded to a MoCA score of 20 in this population. Conclusion. The present data suggest the need for caution when applying proposed MoCA cutoffs to African Americans.

BACKGROUND:Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in disorders of serum phosphorus concentration and vitamin D. The role of FGF23 in vascular calcification remains controversial. METHODS:Relationships between FGF23 and coronary artery calcified atherosclerotic plaque (CAC), aortoiliac calcified plaque (CP), carotid artery CP, volumetric bone mineral density (vBMD), albuminuria, and estimated glomerular filtration rate (eGFR) were determined in 545 African Americans with type 2 diabetes (T2D) and preserved kidney function in African American-Diabetes Heart Study participants. Generalized linear models were fitted to test associations between FGF23 and cardiovascular, bone, and renal phenotypes, and change in measurements over time, adjusting for age, gender, African ancestry proportion, body mass index, diabetes duration, hemoglobin A1c, blood pressure, renin-angiotensin-system inhibitors, statins, calcium supplements, serum calcium, and serum phosphate. RESULTS:The sample was 56.7% female with a mean (SD) age of 55.6 (9.6) years, diabetes duration of 10.3 (8.2) years, eGFR 90.9 (22.1) ml/min/1.73 m2, urine albumin:creatinine ratio (UACR) 151 (588) (median 13) mg/g, plasma FGF23 161 (157) RU/ml, and CAC 637 (1,179) mg. In fully adjusted models, FGF23 was negatively associated with eGFR (p < 0.0001) and positively associated with UACR (p < 0.0001) and CAC (p = 0.0006), but not with carotid CP or aortic CP. Baseline FGF23 concentration did not associate with changes in vBMD or CAC after a mean of 5.1 years follow-up. CONCLUSIONS:Plasma FGF23 concentrations were independently associated with subclinical coronary artery disease, albuminuria, and kidney function in the understudied African American population with T2D. Findings support relationships between FGF23 and vascular calcification, but not between FGF23 and bone mineral density, in African Americans lacking advanced nephropathy.

We determined the awareness and context of cyber-harassment among secondary school students (653 survey respondents and 18 in-depth interviewees) in Oyo state, Nigeria. Respondents' mean age was 14.2 ± 2.2 years and 53.9% were aware of cyber-harassment occurring in their school or among their friends. Cyber-harassment was often perpetrated via phone calls (62.5%), text messaging (36.9%), chat rooms (28.7%), through pictures or video clips sent via mobile phones (11.9%), emails (6.8%) or websites (5.9%). Cyber-harassment behaviours mentioned were the use of abusive words (25.4%), saying mean things or making fun of the victim (13.9%), solicitations for relationships (7.9%) or sex (6.8%) and spreading rumours about the victim (6.8%). In-depth interviewees recounted experiences of cyber-harassment suffered by their friends. Many were relationship-related, sexual solicitations and threats and corroborated quantitative findings. Respondents are aware of cyber-harassment occurring among students in the study area. Comprehensive interventions to address the problem need to be instituted.

OBJECTIVE:This study examined the association between young age and poor road safety practices of commercial motorcyclists in Oyo state, Nigeria. METHODS:A cross-sectional study of 371 commercial motorcyclists selected via a multistage sampling technique was conducted. Information on sociodemographic characteristics and road safety practices (possession of a valid license, helmet use, number of passengers carried per trip, and compliance with 10 selected traffic signs) was obtained with the aid of an interviewer-administered questionnaire. Individual road safety practice items were scored and a total score was obtained giving minimum and maximum obtainable scores of 0 and 35. Respondents with scores ≤ 17.5 (i.e., less than or equal to half of the maximum obtainable score of 35) were categorized as having poor road safety practices. Descriptive statistics, chi-square, and multiple logistic regression tests were conducted. Selected sociodemographic and occupation-related factors were controlled for in the logistic regression analysis. RESULTS:All respondents were male, 80.1% had been riding for commercial purposes for less than 5 years, and 73.0% had other jobs in addition to commercial riding. Road safety practices were generally poor; that is, 84.4% of commercial riders were categorized as having poor road safety practices. Almost all (98.6%) respondents aged < 25 years compared to 84.3% of those aged 25 to <35 years and 76.8% of those ≥35 years had poor road safety practices. This difference was statistically significant. Following logistic regression, younger age (<25 years) remained predictive of poor road safety practices. Motorcyclists aged < 25 years had about 16 times higher odds of having poor road safety practices compared to those aged 35 years and more (odds ratio = 15.72, 95% confidence interval, 1.82-135.91). CONCLUSION/CONCLUSIONS:Most studies conduct only bivariate analysis to test the association between age and road practices of commercial motorcyclists; however, we investigated the influence of potential confounding variables using multivariate analysis. Our findings confirmed young age as a predictor of poor road safety practices among our sample of commercial motorcyclists and emphasizes the need for road safety programs to target this category of riders. The current minimum age for obtaining a rider's license in Nigeria is 18 years; our findings suggest that it might be beneficial to increase the age at which riders in our study area can obtain a commercial rider's license to above 25 years.

BACKGROUND:Prompt prehospital care is essential for improving outcomes of road crash victims; however, this service is sub-optimal in developing countries because Emergency Medical Services (EMS) are not readily available. Training of lay responders in first aid has been suggested as a means of filling this gap in settings with inadequate EMS. This study was conducted to determine the effect of first aid training on the first aid knowledge and skills of commercial drivers. METHODS:A before-and-after study was conducted among 128 commercial drivers (62 intervention and 66 controls) selected by multi-stage sampling. Drivers' first aid knowledge and skills were assessed at baseline, immediate, and three months post-intervention. The intervention involved a 2-day training session in first aid. Repeated measures ANOVA was used to test for differences in respondents' pre- and post-intervention scores over the three assessment points. RESULTS:Mean first aid knowledge scores for intervention drivers were 48.9% (SD=12.0), 57.8% (SD=11.2), and 59.2% (SD=9.0) at baseline, immediate, and three months post-intervention. Corresponding scores for the controls were 48.3% (SD=12.8), 39.2% (SD=15.3), and 46.8% (SD=15.3). Mean first aid skill scores for intervention drivers were 17.5% (SD=3.8), 80.7% (SD=8.3), and 72.3% (SD=16.8). Scores for control drivers were 16.5% (SD=4.5), 16.3% (SD=4.7), and 20.4% (SD=9.1), respectively. Repeated measures ANOVA showed significant differences in first aid knowledge and skills scores over the three phases. Independent t-test revealed significant differences in scores between the intervention and control groups post-intervention. CONCLUSION/CONCLUSIONS:The training led to significant improvement in first aid knowledge and skills of intervention drivers. This confirms that lay responders can be trained in provision of first aid. The slight drop in skills scores, which occurred three months post-intervention, highlights the need for periodic refresher trainings to be conducted for the drivers in order to maintain the knowledge and skills acquired.