APOL1 Risk Variants, Race, and Progression of Chronic Kidney Disease

New England Journal of Medicine, Journal Year: 2013, Volume and Issue: 369(23), P. 2183 - 2196

Published: Nov. 9, 2013

Among patients in the United States with chronic kidney disease, black are at increased risk for end-stage renal as compared white patients.In two studies, we examined effects of variants gene encoding apolipoprotein L1 (APOL1) on progression disease. In African American Study Kidney Disease and Hypertension (AASK), evaluated 693 disease attributed to hypertension. Chronic Renal Insufficiency Cohort (CRIC) study, 2955 (46% whom had diabetes) according whether they 2 copies high-risk APOL1 (APOL1 group) or 0 1 copy low-risk group). AASK primary outcome was a composite doubling serum creatinine level. CRIC outcomes were slope estimated glomerular filtration rate (eGFR) reduction 50% eGFR from baseline.In occurred 58.1% group 36.6% those (hazard ratio group, 1.88; P<0.001). There no interaction between status trial interventions presence baseline proteinuria. more rapid decline higher than did patients, among diabetes without (P<0.001 all comparisons).Renal associated rates that observed regardless status. (Funded by National Institute Diabetes Digestive Diseases others.).

Language: Английский

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Innate immunity pathways regulate the nephropathy gene Apolipoprotein L1

Kidney International, Journal Year: 2014, Volume and Issue: 87(2), P. 332 - 342

Published: Aug. 6, 2014

Language: Английский

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Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice

Nature Medicine, Journal Year: 2017, Volume and Issue: 23(4), P. 429 - 438

Published: Feb. 20, 2017

Language: Английский

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APOL1 Risk Variants Are Strongly Associated with HIV-Associated Nephropathy in Black South Africans

Journal of the American Society of Nephrology, Journal Year: 2015, Volume and Issue: 26(11), P. 2882 - 2890

Published: March 19, 2015

APOL1 variants are associated with HIV-associated nephropathy and FSGS in African Americans. The prevalence of these populations CKD HIV-1 infection has not been investigated. We determined the role 120 patients 108 controls from a South-African black population. Patients were selected on basis histology. Genotypes successfully for G1 G2 42 single nucleotide polymorphisms, including 18 ancestry informative markers, 116 (96.7%; 38 nephropathy, 39 HIV-positive CKD, HIV-negative CKD), (100%). Overall, 79% 2% population carried two risk alleles. In recessive model, individuals carrying any combination alleles had 89-fold higher odds (95% confidence interval, to 912; P<0.001) developing compared controls. Population allele frequencies 7.3% 11.1% G2. significantly other forms CKD. These results indicate HIV-positive, antiretroviral therapy-naïve blacks at very high nephropathy. Further studies required determine effect kidney diseases regions sub-Saharan Africa.

Language: Английский

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APOL1 Variants Associate with Increased Risk of CKD among African Americans

Journal of the American Society of Nephrology, Journal Year: 2013, Volume and Issue: 24(9), P. 1484 - 1491

Published: June 14, 2013

Although case-control studies suggest that African Americans with common coding variants in the APOL1 gene are 5–29 times more likely than those individuals without such to have focal segmental glomerulosclerosis, HIV-associated nephropathy, or ESRD, prospective not yet evaluated impact of these on CKD a community-based sample Americans. Here, we studied whether G1 and G2 risk alleles associate development progression ESRD by analyzing data from 3067 Atherosclerosis Risk Communities Study who did at baseline. Carrying two associated 1.49-fold increased (95% CI=1.02 2.17) 1.88-fold CI=1.20 2.93) compared zero one allele; associations persisted after adjusting for European ancestry. Among participants developed CKD, were progress their counterparts allele (HR=2.22, 95% CI=1.01 4.84). In conclusion, factors among general population.

Language: Английский

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APOL1 kidney disease risk variants cause cytotoxicity by depleting cellular potassium and inducing stress-activated protein kinases

Proceedings of the National Academy of Sciences, Journal Year: 2015, Volume and Issue: 113(4), P. 830 - 837

Published: Dec. 23, 2015

Significance People of recent African ancestry develop chronic kidney disease and end stage failure at rates five times that European-Americans. Two coding variants in the apolipoprotein-L1 (APOL1) gene account for nearly all this excess risk. The mechanisms by which APOL1 cause are not understood. Recent evidence suggests transports cations, including K + , across lipid bilayers. Here, we show tetracycline-induced expression risk T-REx-293 cells causes significant net efflux intracellular which, turn, activates stress-activated protein kinases (SAPKs) p38 MAPK JNK, ultimately resulting cytotoxicity. We propose nephropathy may be mediated variant-induced loss aberrant activation SAPK signaling.

Language: Английский

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The evolving story of apolipoprotein L1 nephropathy: the end of the beginning

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(5), P. 307 - 320

Published: Feb. 25, 2022

Language: Английский

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The APOL1 Genotype of African American Kidney Transplant Recipients Does Not Impact 5-Year Allograft Survival

American Journal of Transplantation, Journal Year: 2012, Volume and Issue: 12(7), P. 1924 - 1928

Published: April 4, 2012

Apolipoprotein L-1 (APOL1) gene variants are associated with end-stage renal disease in African Americans (AAs). Here we investigate the impact of recipient APOL1 distributions on kidney allograft outcomes. We conducted a retrospective analysis 119 AA transplant recipients, and found that 58 (48.7%) carried two risk variants. Contrary to association seen native disease, there is no difference survival at 5-year posttransplant for recipients high-risk genotypes. Thus, were able conclude genotypes do not increase loss after transplantations, carrying 2 alleles should be an impediment transplantation.

Language: Английский

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APOL1 risk variants enhance podocyte necrosis through compromising lysosomal membrane permeability

AJP Renal Physiology, Journal Year: 2014, Volume and Issue: 307(3), P. F326 - F336

Published: June 5, 2014

Development of higher rates nondiabetic glomerulosclerosis (GS) in African Americans has been attributed to two coding sequence variants (G1 and G2) the APOL1 gene. To date, cellular function role (Vs) GS are still unknown. In this study, we examined effects overexpressing wild-type (G0) kidney disease risk human podocytes using a lentivirus expression system. Interestingly, G0 inflicted podocyte injury only at concentration; however, G1 G2 promoted moderate lower concentrations. APOL1Vs expressing displayed diffuse distribution both Lucifer yellow dye cathepsin L as manifestations enhanced lysosomal membrane permeability (LMP). Chloroquine attenuated APOL1Vs-induced increase injury, consistent with targeting lysosomes. The chloride channel blocker DIDS prevented APOL1Vs- induced indicating for influx osmotic swelling Direct exposure noninfected conditioned media from G1- G2-expressing also suggesting contributory secreted component well. Adverse host factors (AHFs) such hydrogen peroxide, hypoxia, TNF-α, puromycin aminonucleoside augmented APOL1- while effect immunodeficiency virus (HIV) on was overwhelming under conditions APOLVs expression. We conclude that have potential induce manner which is further by AHFs, HIV infection being especially prominent.

Language: Английский

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Epidemiology of Hypertension in CKD

Advances in Chronic Kidney Disease, Journal Year: 2015, Volume and Issue: 22(2), P. 88 - 95

Published: Feb. 20, 2015

Language: Английский

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