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APOL1 associated nephropathy

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https://www.readbyqxmd.com/read/28699644/roles-of-apol1%C3%A2-g1-and-g2-variants-in-sickle-cell-disease-patients-kidney-is-the-main-target
#1
Raphaël Kormann, Anne-Sophie Jannot, Céline Narjoz, Jean-Antoine Ribeil, Sandra Manceau, Marianne Delville, Valentin Joste, Dominique Prié, Jacques Pouchot, Eric Thervet, Marie Courbebaisse, Jean-Benoît Arlet
In African-American patients with sickle cell disease (SCD), APOL1 G1 and G2 variants are associated with increased risk of sickle cell nephropathy (SCN). To determine the role of APOL1 variants in SCD patients living in Europe, we genotyped 152 SCD patients [aged 30·4 (24·3-36·4) years], mainly of Sub-Saharan African ancestry, for APOL1 G1 and G2 and for variants of four genes with kidney tropism (GSTM1, GSTT1, GSTP1, and HMOX1). Homozygous or double-heterozygous APOL G1 and G2 genotypes were strongly associated with end stage renal disease (P = 0·003) and worse Kidney Disease: Improving Global Outcomes stages (P = 0·001)...
July 12, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28578979/hiv-associated-kidney-diseases-clarifying-concordance-between-renal-failure-in-hiv-infection-and-histopathologic-manifestations-at-kidney-biopsy
#2
REVIEW
Carla L Ellis
Patients with HIV infection have a wide spectrum of renal diseases. Some are known to be the direct effect of the viral infection while others are renal diseases that also occur in uninfected populations. HIV associated nephropathy (HIVAN) is considered to be a subtype of primary focal and segmental glomerulosclerosis that is distinct in HIV infected patients. It is more frequent in the African-American population and associated with mutations of the apolipoprotein L1 (APOL1) gene. HIV associated immune complex kidney disease (HIVICD) encompasses a spectrum of HIV associated renal diseases characterized by the presence of immune complex deposition within glomeruli...
July 2017: Seminars in Diagnostic Pathology
https://www.readbyqxmd.com/read/28391347/therapeutics-for-apol1-nephropathies-putting-out-the-fire-in-the-podocyte
#3
Jurgen Heymann, Cheryl A Winkler, Maarten Hoek, Katalin Susztak, Jeffrey B Kopp
APOL1 nephropathies comprise a range of clinical and pathologic syndromes, which can be summarized as focal segmental glomerulosclerosis, in various guises, and arterionephrosclerosis, otherwise known as hypertensive kidney diseases. Current therapies for these conditions may achieve therapeutic targets, reduction in proteinuria and control of blood pressure, respectively, but often fail to halt the progressive decline in kidney function. It appears that current therapies fail to address certain underlying critical pathologic processes that are driven, particularly in podocytes and microvascular cells, by the APOL1 renal risk genetic variants...
January 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339911/a-null-variant-in-the-apolipoprotein-l3-gene-is-associated-with-non-diabetic-nephropathy
#4
Karl L Skorecki, Jessica H Lee, Carl D Langefeld, Saharon Rosset, Shay Tzur, Walter G Wasser, Revital Shemer, Gregory A Hawkins, Jasmin Divers, Rulan S Parekh, Man Li, Matthew G Sampson, Matthias Kretzler, Martin R Pollak, Shrijal Shah, Daniel Blackler, Brendan Nichols, Michael Wilmot, Seth L Alper, Barry I Freedman, David J Friedman
Background: Inheritance of apolipoprotein L1 gene ( APOL1 ) renal-risk variants in a recessive pattern strongly associates with non-diabetic end-stage kidney disease (ESKD). Further evidence supports risk modifiers in APOL1 -associated nephropathy; some studies demonstrate that heterozygotes possess excess risk for ESKD or show earlier age at ESKD, relative to those with zero risk alleles. Nearby loci are also associated with ESKD in non-African Americans. Methods: We assessed the role of the APOL3 null allele rs11089781 on risk of non-diabetic ESKD...
February 20, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28298955/the-apolipoprotein-l1-gene-and-cardiovascular-disease
#5
REVIEW
Todd W Robinson, Barry I Freedman
Relative to those with European ancestry, African Americans have an excess incidence of nondiabetic chronic kidney disease predominantly due to two coding renal-risk variants in the apolipoprotein L1 gene (APOL1). This APOL1-kidney disease association is independent of systemic hypertension or blood pressure. Recent reports describe extra-renal effects of the APOL1 G1 and G2 renal-risk variants on cardiovascular disease (CVD), subclinical atherosclerosis, lipoprotein particle concentrations, and survival. However, results have been less consistent than those seen in kidney disease, and the observed APOL1 associations with CVD vary from risk to protective...
October 2016: Methodist DeBakey Cardiovascular Journal
https://www.readbyqxmd.com/read/28265848/apol1-and-the-immune-response-of-patients-with-systemic-lupus-erythematosus
#6
REVIEW
Ashira D Blazer, Robert M Clancy
PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) confers up to a 50-fold increased risk of cardiovascular disease (CVD), and African Americans with SLE experience accelerated damage accrual and doubled cardiovascular risk when compared to their European American counterparts. RECENT FINDINGS: Genome-wide association studies have identified a substantial signal at 22q13, now assigned to variation at apolipoprotein L1 (APOL1), which has associated with progressive nondiabetic nephropathy, cardiovascular disease, and many immune-associated renal diseases, including lupus nephritis...
March 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28100445/apol1-variants-may-induce-hiv-associated-nephropathy-during-hiv-primary-infection
#7
Marine De Laroche, Geoffroy Desbuissons, Philippe Rouvier, Francis Barin, Gilbert Deray, Eric Caumes, Christine Katlama, Roland Tubiana, Corinne Isnard Bagnis
No abstract text is available yet for this article.
May 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27932478/most-apol1-is-secreted-by-the-liver
#8
Khuloud Shukha, Jessica L Mueller, Raymond T Chung, Michael P Curry, David J Friedman, Martin R Pollak, Anders H Berg
Two coding sequence variants in the APOL1 gene (G1 and G2) explain much of the increased risk for FSGS, HIV-associated nephropathy, and hypertension-attributed ESRD among people of recent African ancestry. The ApoL1 protein is expressed in a wide variety of cell tissues. It has been assumed that the majority of circulating ApoL1 is produced by the liver, but this has not been shown. Using mass spectrometry, we genotyped and quantified the circulating ApoL1 in two liver transplant recipients whose native APOL1 genotype differed from the genotype of the deceased donors, allowing us to differentiate liver- from nonliver-produced ApoL1...
April 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27599995/impact-of-apol1-polymorphism-and-il-1%C3%AE-priming-in-the-entry-and-persistence-of-hiv-1-in-human-podocytes
#9
Joanna Mikulak, Ferdinando Oriolo, Federica Portale, Paolo Tentorio, Xiqian Lan, Moin A Saleem, Karl Skorecki, Pravin C Singhal, Domenico Mavilio
BACKGROUND: Patients of African ancestry with untreated HIV-1 infection and carrying the G1 or G2 kidney disease risk variants (Vs) at the APOL1 gene have a tenfold higher risk of developing HIV-associated nephropathy (HIVAN) compared to those with the non-risk wild type (WT) G0 variant. However, the mechanistic contribution of the APOL1 allelic state to kidney injury in HIV-1 infection remains to be elucidated. RESULTS: Non-risk WT APOL1 is associated with lower intracellular levels of HIV-1 in conditionally immortalized human podocytes, while the over expression of G1 or G2 risk Vs significantly increases viral accumulation...
September 6, 2016: Retrovirology
https://www.readbyqxmd.com/read/27509583/from-man-to-fish-what-can-zebrafish-tell-us-about-apol1-nephropathy
#10
Opeyemi Olabisi, Khaldoun Al-Romaih, Joel Henderson, Ritu Tomar, Iain Drummond, Calum MacRae, Martin Pollak
BACKGROUND: Risk variant Apolipoprotein L1 (G1/G2) are strongly associated with a spectrum of kidney disease in people of recent African descent. The mechanism of ApoL1 nephropathy is unknown. Podocytes and/or endothelial cells are the presumed target kidney cells. Given the close homology in structure and function of zebrafish (ZF) pronephros and human nephron, we studied the effect of podocyte-specific or endothelium-specific expression of ApoL1 (G0, G1, or G2) on the structure and function of ZF pronephros...
2016: Clinical Nephrology
https://www.readbyqxmd.com/read/27461219/association-of-kidney-structure-related-gene-variants-with-type-2-diabetes-attributed-end-stage-kidney-disease-in-african-americans
#11
Meijian Guan, Jun Ma, Jacob M Keaton, Latchezar Dimitrov, Poorva Mudgal, Mary Stromberg, Jason A Bonomo, Pamela J Hicks, Barry I Freedman, Donald W Bowden, Maggie C Y Ng
African Americans (AAs) are at higher risk for developing end-stage kidney disease (ESKD) compared to European Americans. Genome-wide association studies have identified variants associated with diabetic and non-diabetic kidney diseases. Nephropathy loci, including SLC7A9, UMOD, and SHROOM3, have been implicated in the maintenance of normal glomerular and renal tubular structure and function. Herein, 47 genes important in podocyte, glomerular basement membrane, mesangial cell, mesangial matrix, renal tubular cell, and renal interstitium structure were examined for association with type 2 diabetes (T2D)-attributed ESKD in AAs...
November 2016: Human Genetics
https://www.readbyqxmd.com/read/27342958/apol1-renal-risk-variants-associate-with-reduced-cerebral-white-matter-lesion-volume-and-increased-gray-matter-volume
#12
Barry I Freedman, Crystal A Gadegbeku, R Nick Bryan, Nicholette D Palmer, Pamela J Hicks, Lijun Ma, Michael V Rocco, S Carrie Smith, Jianzhao Xu, Christopher T Whitlow, Benjamin C Wagner, Carl D Langefeld, Amret T Hawfield, Jeffrey T Bates, Alan J Lerner, Dominic S Raj, Mohammad S Sadaghiani, Robert D Toto, Jackson T Wright, Donald W Bowden, Jeff D Williamson, Kaycee M Sink, Joseph A Maldjian, Nicholas M Pajewski, Jasmin Divers
To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58...
August 2016: Kidney International
https://www.readbyqxmd.com/read/27157696/apol1-renal-risk-genotypes-associate-with-longer-hemodialysis-survival-in-prevalent-nondiabetic-african-american-patients-with-end-stage-renal-disease
#13
Lijun Ma, Carl D Langefeld, Mary E Comeau, Jason A Bonomo, Michael V Rocco, John M Burkart, Jasmin Divers, Nicholette D Palmer, Pamela J Hicks, Donald W Bowden, Janice P Lea, Jenna O Krisher, Margo J Clay, Barry I Freedman
Relative to European Americans, evidence supports that African Americans with end-stage renal disease (ESRD) survive longer on dialysis. Renal-risk variants in the apolipoprotein L1 gene (APOL1), associated with nondiabetic nephropathy and less subclinical atherosclerosis, may contribute to dialysis outcomes. Here, APOL1 renal-risk variants were assessed for association with dialytic survival in 450 diabetic and 275 nondiabetic African American hemodialysis patients from Wake Forest and Emory School of Medicine outpatient facilities...
August 2016: Kidney International
https://www.readbyqxmd.com/read/27054572/deceased-donor-apolipoprotein-l1-renal-risk-variants-have-minimal-effects-on-liver-transplant-outcomes
#14
MULTICENTER STUDY
Casey R Dorr, Barry I Freedman, Pamela J Hicks, W Mark Brown, Gregory B Russell, Bruce A Julian, Stephen O Pastan, Michael D Gautreaux, Amutha Muthusamy, Srinath Chinnakotla, Vera Hauptfeld, Robert A Bray, Allan D Kirk, Jasmin Divers, Ajay K Israni
BACKGROUND: Apolipoprotein L1 gene (APOL1) G1 and G2 renal-risk variants, common in populations with recent African ancestry, are strongly associated with non-diabetic nephropathy, end-stage kidney disease, and shorter allograft survival in deceased-donor kidneys (autosomal recessive inheritance). Circulating APOL1 protein is synthesized primarily in the liver and hydrodynamic gene delivery of APOL1 G1 and G2 risk variants has caused hepatic necrosis in a murine model. METHODS: To evaluate the impact of these variants in liver transplantation, this multicenter study investigated the association of APOL1 G1 and G2 alleles in deceased African American liver donors with allograft survival...
2016: PloS One
https://www.readbyqxmd.com/read/27035887/brief-report-apol1-renal-risk-variants-are-associated-with-chronic-kidney-disease-in-children-and-youth-with-perinatal-hiv-infection
#15
Murli U Purswani, Kunjal Patel, Cheryl A Winkler, Stephen A Spector, Rohan Hazra, George R Seage, Lynne Mofenson, Brad Karalius, Gwendolyn B Scott, Russell B Van Dyke, Jeffrey B Kopp
APOL1 renal risk alleles are associated with chronic kidney disease (CKD) in adults, with the strongest effect being for HIV-associated nephropathy. Their role in youth with perinatal HIV-1 infection (PHIV) has not been studied. In a nested case-control study of 451 PHIV participants in the Pediatric HIV/AIDS Cohort Study, we found a 3.5-fold increased odds of CKD in those carrying high-risk APOL1 genotypes using a recessive model [95% confidence interval (CI): 1.2 to 10.0]. We report an unadjusted incidence of 1...
September 1, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/26945671/structural-characterization-of-the-c-terminal-coiled-coil-domains-of-wild-type-and-kidney-disease-associated-mutants-of-apolipoprotein-l1
#16
Alok K Sharma, David J Friedman, Martin R Pollak, Seth L Alper
Trypanosomes that cause sleeping sickness endocytose apolipoprotein L1 (APOL1)-containing trypanolytic factors from human serum, leading to trypanolytic death through generation of APOL1-associated lytic pores in trypanosomal membranes. The trypanosome Trypanosoma brucei rhodesiense counteracts trypanolysis by expressing the surface protein serum response-associated (SRA), which can bind APOL1 common variant G0 to block its trypanolytic activity. However, two missense variants in the C terminal predicted coiled-coil (CC) domains of human APOL1 G1 (S342G/I384M) and G2 (ΔN388Y389) decrease or abrogate APOL1 binding to T...
May 2016: FEBS Journal
https://www.readbyqxmd.com/read/26668025/association-of-apol1-genotype-with-renal-histology-among-black-hiv-positive-patients-undergoing-kidney-biopsy
#17
Mohamed G Atta, Michelle M Estrella, Karl L Skorecki, Jeffrey B Kopp, Cheryl A Winkler, Walter G Wasser, Revital Shemer, Lorraine C Racusen, Michael Kuperman, Matthew C Foy, Gregory M Lucas, Derek M Fine
BACKGROUND AND OBJECTIVES: Prior studies have shown that the APOL1 risk alleles are associated with a greater risk of HIV-associated nephropathy and FSGS among blacks who are HIV positive. We sought to determine whether the APOL1 high-risk genotype incrementally improved the prediction of these underlying lesions beyond conventional clinical factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a cross-sectional study, we analyzed data from 203 blacks who are HIV positive, underwent kidney biopsies between 1996 and 2011, and were genotyped for the APOL1 G1 and G2 alleles...
February 5, 2016: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/26586272/characterization-of-circulating-apol1-protein-complexes-in-african-americans
#18
Allison Weckerle, James A Snipes, Dongmei Cheng, Abraham K Gebre, Julie A Reisz, Mariana Murea, Gregory S Shelness, Gregory A Hawkins, Cristina M Furdui, Barry I Freedman, John S Parks, Lijun Ma
APOL1 gene renal-risk variants are associated with nephropathy and CVD in African Americans; however, little is known about the circulating APOL1 variant proteins which reportedly bind to HDL. We examined whether APOL1 G1 and G2 renal-risk variant serum concentrations or lipoprotein distributions differed from nonrisk G0 APOL1 in African Americans without nephropathy. Serum APOL1 protein concentrations were similar regardless of APOL1 genotype. In addition, serum APOL1 protein was bound to protein complexes in two nonoverlapping peaks, herein referred to as APOL1 complex A (12...
January 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/26553514/hypertension-attributed-nephropathy-what-s-in-a-name
#19
REVIEW
Barry I Freedman, Arthur H Cohen
Unrelated disease processes commonly occur in non-diabetic individuals with mild-to-moderate hypertension and low level or absent proteinuria who present with chronic kidney disease: primary glomerulosclerosis in those with recent African ancestry, and arteriolar nephrosclerosis with resultant glomerular ischaemia potentially related to hypertension and vascular disease risk factors in other cases. Unfortunately, nephrologists often indiscriminately apply a diagnosis of 'hypertensive nephrosclerosis' to patients in either scenario, which implies that the hypertension is causative of their renal disease...
January 2016: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/26343748/re-sequencing-of-the-apol1-apol4-and-myh9-gene-regions-in-african-americans-does-not-identify-additional-risks-for-ckd-progression
#20
Gregory A Hawkins, David J Friedman, Lingyi Lu, David R McWilliams, Jeff W Chou, Satria Sajuthi, Jasmin Divers, Rulan S Parekh, Man Li, Giulio Genovese, Martin R Pollack, Pamela J Hicks, Donald W Bowden, Lijun Ma, Barry I Freedman, Carl D Langefeld
BACKGROUND: In African Americans (AAs), APOL1 G1 and G2 nephropathy risk variants are associated with non-diabetic end-stage kidney disease (ESKD) in an autosomal recessive pattern. Additional risk and protective genetic variants may be present near the APOL1 loci, since earlier age ESKD is observed in some AAs with one APOL1 renal-risk variant, and because the adjacent gene MYH9 is associated with nephropathy in populations lacking G1 and G2 variants. METHODS: Re-sequencing was performed across a ∼275 kb region encompassing the APOL1-APOL4 and MYH9 genes in 154 AA cases with non-diabetic ESKD and 38 controls without nephropathy who were heterozygous for a single APOL1 G1 or G2 risk variant...
2015: American Journal of Nephrology
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