Dataset Information

APOL1 Risk Genotypes Are Associated With Early Kidney Damage in Children in Sub-Saharan Africa.

ABSTRACT: Introduction:Apolipoprotein-L1 (APOL1) risk variants G1 and G2 increase the risk of chronic kidney disease (CKD), including HIV-related CKD, among African Americans. However, such data from populations living in Africa, especially children, remain limited. Our research aimed to determine the prevalence of APOL1 risk variants and to assess the association between these variants and early-stage CKD in the general pediatric population and HIV-infected children. Methods:In a cross-sectional study, we enrolled 412 children from the general population and 401 HIV-infected children in Kinshasa, Democratic Republic of Congo (DRC). APOL1 high-risk genotype (HRG) was defined by the presence of 2 risk variants (G1/G1, G2/G2, or G1/G2), and low-risk genotype (LRG) by the presence of 0 or 1 risk variants. The main outcome was elevated albuminuria, defined as a urinary albumin/creatinine ratio ?30 mg/g. Results:APOL1 sequence analysis revealed that in the general population, 29 of 412 participants (7.0%) carried HRG, 84 of 412 (20.4%) carried the G1/G0 genotype, and 61 of 412 (14.8%) carried the G2/G0 genotype. In HIV-infected children, 23 of 401 (5.7%) carried HRG, and the same trend as in the general population was observed in regard to the prevalence of LRG. Univariate analysis showed that in the general population, 5 of 29 participants (17.2%) carrying HRG had elevated albuminuria, compared with 35 of 383 (9.0%) with LRG (odds ratio [OR] 2.1, 95% confidence interval [CI] 0.6-6.0; P = 0.13). In HIV-infected children, participants who carried APOL1 HRG had almost 22-fold increased odds of albuminuria compared to those with LRG. Conclusion:The APOL1 risk variants are prevalent in children living in DRC. HRG carriers have increased odds of early kidney disease, and infection with HIV dramatically increases this probability.

SUBMITTER: Ekulu PM

PROVIDER: S-EPMC6612006 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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<i>APOL1</i> Risk Genotypes Are Associated With Early Kidney Damage in Children in Sub-Saharan Africa.

Ekulu Pepe M PM Nkoy Agathe B AB Betukumesu Dieumerci K DK Aloni Michel N MN Makulo Jean Robert R JRR Sumaili Ernest K EK Mafuta Eric M EM Elmonem Mohamed A MA Arcolino Fanny O FO Kitetele Faustin N FN Lepira François B FB van den Heuvel Lambertus P LP Levtchenko Elena N EN

Kidney international reports 20190411 7

<h4>Introduction</h4>Apolipoprotein-L1 (<i>APOL1</i>) risk variants G1 and G2 increase the risk of chronic kidney disease (CKD), including HIV-related CKD, among African Americans. However, such data from populations living in Africa, especially children, remain limited. Our research aimed to determine the prevalence of <i>APOL1</i> risk variants and to assess the association between these variants and early-stage CKD in the general pediatric population and HIV-infected children.<h4>Methods</h4> ...[more]

PMID: 31317115

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Project description:Sub-Saharan Africa represents 69% of the total number of individuals living with HIV infection worldwide and 72% of AIDS deaths globally. Pulmonary infection is a common and frequently fatal complication, though little is known regarding the lower airway microbiome composition of this population. Our objectives were to characterize the lower airway microbiome of Ugandan HIV-infected patients with pneumonia, to determine relationships with demographic, clinical, immunological, and microbiological variables and to compare the composition and predicted metagenome of these communities to a comparable cohort of patients in the US (San Francisco). Bronchoalveolar lavage samples from a cohort of 60 Ugandan HIV-infected patients with acute pneumonia were collected. Amplified 16S ribosomal RNA was profiled and aforementioned relationships examined. Ugandan airway microbiome composition and predicted metagenomic function were compared to US HIV-infected pneumonia patients. Among the most common bacterial pulmonary pathogens, Pseudomonas aeruginosa was most prevalent in the Ugandan cohort. Patients with a richer and more diverse airway microbiome exhibited lower bacterial burden, enrichment of members of the Lachnospiraceae and sulfur-reducing bacteria and reduced expression of TNF-alpha and matrix metalloproteinase-9. Compared to San Franciscan patients, Ugandan airway microbiome were significantly richer, and compositionally distinct with predicted metagenomes that encoded a multitude of distinct pathogenic pathways e.g secretion systems. Ugandan pneumonia-associated airway microbiome is compositionally and functionally distinct from those detected in comparable patients in developed countries, a feature which may contribute to adverse outcomes in this population. Please note that the data from the comparable cohort of patients in the USUS data was published as supplemental material of PMID: 22760045 but not submitted to GEO The 'patient_info.txt' contains 12 clinical, 7 immunological and 3 microbiological variables for each patient.

Project description:BACKGROUND:Rapid epidemiological health transitions occurring in vulnerable populations in Africa that have an existing burden of infectious and non-communicable diseases predict an increased risk and consequent prevalence of kidney disease. However, few studies have characterised the true burden of kidney damage and associated risk factors in Africans. We investigated the prevalence of markers for kidney damage and known risk factors in rural and urban settings in sub-Saharan Africa. METHODS:In this cross-sectional population study (Africa Wits-International Network for the Demographic Evaluation of Populations and their Health Partnership for Genomic Studies [AWI-Gen]), we recruited unrelated adult participants aged 40-60 years from four rural community research sites (Nanoro, Burkina Faso; Navrongo, Ghana; Agincourt and Dikgale, South Africa), and two urban community research sites (Nairobi, Kenya; and Soweto, South Africa). Participants were identified and selected using random sampling frames already in use at each site. Participants completed a lifestyle and medical history questionnaire, had anthropometric and blood pressure measurements taken, and blood and urine samples were collected. Markers of kidney damage were defined as low estimated glomerular filtration rate (eGFR; <60 mL/min per 1·73 m2), presence of albuminuria (urine albumin creatinine ratio >3 mg/mmol); or chronic kidney disease (low eGFR or albuminuria, or both). We calculated age-adjusted prevalence of chronic kidney disease, low eGFR, and albuminuria by site and sex and used logistic regression models to assess risk factors of kidney damage. FINDINGS:Between August, 2013, and August, 2016, we recruited 10?702 participants, of whom 8110 were analysable. 4120 (50·8%) of analysable participants were male, with a mean age of 49·9 years (SD 5·8). Age-standardised population prevalence was 2·4% (95% CI 2·1-2·8) for low eGFR, 9·2% (8·4-10·0) for albuminuria, and 10·7% (9·9-11·7) for chronic kidney disease, with higher prevalences in South African sites than in west African sites (14·0% [11·9-16·4] in Agincourt vs 6·6% [5·5-7·9] in Nanoro). Women had a higher prevalence of chronic kidney disease (12·0% [10·8-13·2] vs 9·5% [8·3-10·8]) and low eGFR (3·0% [2·6-3·6] vs 1·7% [1·3-2·3]) than did men, with no sex-specific differences for albuminuria (9·9% [8·8-11·0] vs 8·4% [7·3-9·7]). Risk factors for kidney damage were older age (relative risk 1·04, 95% CI 1·03-1·05; p<0·0001), hypertension (1·97, 1·68-2·30; p<0·0001), diabetes (2·22, 1·76-2·78; p<0·0001), and HIV (1·65, 1·36-1·99; p<0·0001); whereas male sex was protective (0·85, 0·73-0·98; p=0·02). INTERPRETATION:Regional differences in prevalence and risks of chronic kidney disease in sub-Saharan Africa relate in part to varying stages of sociodemographic and epidemiological health transitions across the area. Public health policy should focus on integrated strategies for screening, prevention, and risk factor management in the broader non-communicable disease and infectious diseases framework. FUNDING:National Human Genome Research Institute, Office of the Director, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, the Office of AIDS Research, and National Institute of Diabetes and Digestive and Kidney Diseases, all of the National Institutes of Health, and the South African Department of Science and Technology.

Dataset Information

APOL1 Risk Genotypes Are Associated With Early Kidney Damage in Children in Sub-Saharan Africa.

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<i>APOL1</i> Risk Genotypes Are Associated With Early Kidney Damage in Children in Sub-Saharan Africa.

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