Background: Apolipoprotein L1 gene () variants are risk factors for chronic kidney disease (CKD) among Black Americans. Data are sparse on the genetic epidemiology of CKD and the clinical association of variants with CKD in West Africans, a major group in the Black population.
Methods: We conducted a case-control study involving participants from Ghana and Nigeria who had CKD stages 2 through 5, biopsy-proven glomerular disease, or no kidney disease.
Background: Apolipoprotein L1 (APOL1) high-risk variants are major determinants of chronic kidney disease (CKD) in people of African ancestry. Previous studies have identified epigenetic changes in relation to kidney function and CKD, but not in individuals with APOL1 high-risk genotypes. We conducted an epigenome-wide analysis of CKD and estimated glomerular filtration rate (eGFR) in in people of African ancestry and APOL1 high-risk genotypes with HIV.
View Article and Find Full Text PDFHIV disease remains prevalent in the USA and chronic kidney disease remains a major cause of morbidity in HIV-1-positive patients. Host double-stranded RNA (dsRNA)-activated protein kinase (PKR) is a sensor for viral dsRNA, including HIV-1. We show that PKR inhibition by compound C16 ameliorates the HIV-associated nephropathy (HIVAN) kidney phenotype in the Tg26 transgenic mouse model, with reversal of mitochondrial dysfunction.
View Article and Find Full Text PDFAlthough hyponatremia and salt wasting are common in patients with HIV/AIDS, the understanding of their contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the distal tubules and on the expression level of the Slc12a3 gene, encoding the sodium-chloride cotransporter (which is responsible for sodium reabsorption in distal nephron segments), single-nucleus RNA sequencing was performed on kidney cortices from three wild-type (WT) and three Vpr transgenic (Vpr Tg) mice.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
September 2024
Apolipoprotein L1 (APOL1) coding variants, termed G1 and G2, are established genetic risk factors for a growing spectrum of diseases, including kidney disease, in individuals of African ancestry. Evidence suggests that the risk variants, which show a recessive mode of inheritance, lead to toxic gain-of-function changes of the APOL1 protein. Disease occurrence and presentation vary, likely due to modifiers or second hits.
View Article and Find Full Text PDFKey Points: Apolipoprotein L1 (APOL1)-G1 induced kidney disease in the two APOL1 transgenic mouse models, HIV-associated nephropathy and IFN- administration. Glomerular single-nuclear RNA-sequencing identified genes differentially expressed among mice with APOL1-G1 and G0 variants at single-cell resolution.
Background: Apolipoprotein L1 () high-risk variants contribute to kidney disease among individuals with African ancestry.
The global research and pharmaceutical community rapidly mobilized to develop treatments for coronavirus disease 2019 (COVID-19). Existing treatments have been repurposed and new drugs have emerged. Here we summarize mechanisms and clinical trials of COVID-19 therapeutics approved or in development.
View Article and Find Full Text PDFAfrican Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.
View Article and Find Full Text PDFBackground: Pregnancy complications are risk factors for cardiovascular disease (CVD). Little is known about the role of renal biomarkers measured shortly after delivery, individually or in combination with pregnancy complications, in predicting subsequent severe maternal CVD.
Methods And Results: This study included 566 mothers of diverse races and ethnicities from the Boston Birth cohort, enrolled at delivery and followed prospectively.
Introduction: People with African ancestry have greater stroke risk and greater heritability of stroke risk than people of other ancestries. Given the importance of nitric oxide (NO) in stroke, and recent evidence that alpha globin restricts nitric oxide release from vascular endothelial cells, we hypothesized that alpha globin gene ( deletion would be associated with reduced risk of incident ischemic stroke.
Methods: We evaluated 8,947 participants self-reporting African ancestry in the national, prospective Reasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.
Background: Living kidney donation is possible for people living with HIV (PLWH) in the United States within research studies under the HIV Organ Policy Equity (HOPE) Act. There are concerns that donor nephrectomy may have an increased risk of end-stage renal disease (ESRD) in PLWH due to HIV-associated kidney disease and antiretroviral therapy (ART) nephrotoxicity. Here we report the first 3 cases of living kidney donors with HIV under the HOPE Act in the United States.
View Article and Find Full Text PDFBlack Americans have a significantly higher risk of developing chronic kidney disease (CKD), especially focal segmental glomerulosclerosis (FSGS), than European Americans. Two coding variants (G1 and G2) in the gene play a major role in this disparity. While 13% of Black Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.
View Article and Find Full Text PDFHIV-1 remains a global health crisis, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa, we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.
View Article and Find Full Text PDFBackground: Kidney transplant survival in African American recipients is lower compared with non-African American transplant recipients. APOL1 risk alleles (RA) have been postulated as likely contributors. We examined the graft outcomes in kidney transplant recipients (KTRs) stratified by APOL1 RA status in a multicenter observational prospective study.
View Article and Find Full Text PDFRationale & Objective: Dietary factors may impact inflammation and interferon production, which could influence phenotypic expression of Apolipoprotein1 () genotypes. We investigated whether associations of dietary patterns with kidney outcomes differed by genotypes.
Study Design: Prospective cohort.
high-risk variants partially explain the high kidney disease prevalence among African ancestry individuals. Many mechanisms have been reported in cell culture models, but few have been demonstrated in mouse models. Here we characterize two models: (1) HIV-associated nephropathy (HIVAN) Tg26 mice crossed with bacterial artificial chromosome (BAC)/APOL1 transgenic mice and (2) interferon-γ administered to BAC/APOL1 mice.
View Article and Find Full Text PDFIntroduction: People with African ancestry have greater stroke risk and greater heritability of stroke risk than people of other ancestries. Given the importance of nitric oxide (NO) in stroke, and recent evidence that alpha globin restricts nitric oxide release from vascular endothelial cells, we hypothesized that alpha globin gene ( deletion would be associated with reduced risk of incident ischemic stroke.
Methods: We evaluated 8,947 participants self-reporting African ancestry in the national, prospective Reasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.
Rationale & Objective: Pregnancy complications are risk factors for cardiovascular diseases (CVD). Little is known about the role of renal biomarkers measured shortly after delivery, individually or in combination with pregnancy complications, in predicting subsequent severe maternal CVD.
Methods: This study included 576 mothers of diverse ethnicities from the Boston Birth cohort, enrolled at delivery and followed prospectively.
Hyponatremia and salt wasting is a common occurance in patients with HIV/AIDS, however, the understanding of its contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the expression level of the gene, encoding the Na-Cl cotransporter, which is responsible for sodium reabsorption in distal nephron segments, we performed single-nucleus RNA sequencing of kidney cortices from three wild-type (WT) and three Vpr-transgenic (Vpr Tg) mice.
View Article and Find Full Text PDFRenal hypouricemia (RHUC) is a pathological condition characterized by extremely low serum urate and overexcretion of urate in the kidney; this inheritable disorder is classified into type 1 and type 2 based on causative genes encoding physiologically-important urate transporters, and , respectively; however, research on RHUC type 2 is still behind type 1. We herein describe a typical familial case of RHUC type 2 found in a Slovak family with severe hypouricemia and hyperuricosuria. clinico-genetic analyses including whole exome sequencing and functional assays, we identified an intronic variant, c.
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