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https://www.readbyqxmd.com/read/27916972/chronic-kidney-disease-mechanisms-of-apol1-associated-renal-disease
#1
Ellen F Carney
No abstract text is available yet for this article.
December 5, 2016: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/27900314/renal-and-cardiovascular-morbidities-associated-with-apol1-status-among-african-american-and-non-african-american-children-with-focal-segmental-glomerulosclerosis
#2
Robert P Woroniecki, Derek K Ng, Sophie Limou, Cheryl A Winkler, Kimberly J Reidy, Mark Mitsnefes, Matthew G Sampson, Craig S Wong, Bradley A Warady, Susan L Furth, Jeffrey B Kopp, Frederick J Kaskel
BACKGROUND AND OBJECTIVES: African-American (AA) children with focal segmental glomerulosclerosis (FSGS) have later onset disease that progresses more rapidly than in non-AA children. It is unclear how APOL1 genotypes contribute to kidney disease risk, progression, and cardiovascular morbidity in children. DESIGN SETTING PARTICIPANTS AND MEASUREMENTS: We examined the prevalence of APOL1 genotypes and associated cardiovascular phenotypes among children with FSGS in the Chronic Kidney Disease in Children (CKiD) study; an ongoing multicenter prospective cohort study of children aged 1-16 years with mild to moderate kidney disease...
2016: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/27864431/apol1-mediated-cell-injury-involves-disruption-of-conserved-trafficking-processes
#3
Etty Kruzel-Davila, Revital Shemer, Ayala Ofir, Ira Bavli-Kertselli, Ilona Darlyuk-Saadon, Pazit Oren-Giladi, Walter G Wasser, Daniella Magen, Eid Zaknoun, Maya Schuldiner, Adi Salzberg, Daniel Kornitzer, Zvonimir Marelja, Matias Simons, Karl Skorecki
APOL1 harbors C-terminal sequence variants (G1 and G2), which account for much of the increased risk for kidney disease in sub-Saharan African ancestry populations. Expression of the risk variants has also been shown to cause injury to podocytes and other cell types, but the underlying mechanisms are not understood. We used Drosophila melanogaster and Saccharomyces cerevisiae to help clarify these mechanisms. Ubiquitous expression of the human APOL1 G1 and G2 disease risk alleles caused near-complete lethality in D...
November 18, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27864430/apol1-g1-in-nephrocytes-induces-hypertrophy-and-accelerates-cell-death
#4
Yulong Fu, Jun-Yi Zhu, Adam Richman, Yi Zhang, Xuefang Xie, Jharna R Das, Jinliang Li, Patricio E Ray, Zhe Han
People of African ancestry carrying certain APOL1 mutant alleles are at elevated risk of developing renal diseases. However, the mechanisms underlying APOL1-associated renal diseases are unknown. Because the APOL1 gene is unique to humans and some primates, new animal models are needed to understand the function of APOL1 in vivo We generated transgenic Drosophila fly lines expressing the human APOL1 wild type allele (G0) or the predominant APOL1 risk allele (G1) in different tissues. Ubiquitous expression of APOL1 G0 or G1 in Drosophila induced lethal phenotypes, and G1 was more toxic than was G0...
November 18, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27862962/effect-of-replacing-race-with-apolipoprotein-l1-genotype-in-calculation-of-kidney-donor-risk-index
#5
B A Julian, R S Gaston, W M Brown, A M Reeves-Daniel, A K Israni, D P Schladt, S O Pastan, S Mohan, B I Freedman, J Divers
Renal allografts from deceased African Americans with two apolipoprotein L1 gene (APOL1) renal-risk variants fail sooner than kidneys from donors with fewer variants. Kidney Donor Risk Index (KDRI) was developed to evaluate organ offers by predicting allograft longevity and includes African American race as a risk factor. Substituting APOL1 genotype for race may refine the KDRI. For 622 deceased African American kidney donors, we applied 10-fold cross-validation approach to estimate contribution of APOL1 variants to a revised KDRI...
November 14, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27821631/apol1-renal-risk-variants-induce-mitochondrial-dysfunction
#6
Lijun Ma, Jeff W Chou, James A Snipes, Manish S Bharadwaj, Ann L Craddock, Dongmei Cheng, Allison Weckerle, Snezana Petrovic, Pamela J Hicks, Ashok K Hemal, Gregory A Hawkins, Lance D Miller, Anthony J A Molina, Carl D Langefeld, Mariana Murea, John S Parks, Barry I Freedman
APOL1 G1 and G2 variants facilitate kidney disease in blacks. To elucidate the pathways whereby these variants contribute to disease pathogenesis, we established HEK293 cell lines stably expressing doxycycline-inducible (Tet-on) reference APOL1 G0 or the G1 and G2 renal-risk variants, and used Illumina human HT-12 v4 arrays and Affymetrix HTA 2.0 arrays to generate global gene expression data with doxycycline induction. Significantly altered pathways identified through bioinformatics analyses involved mitochondrial function; results from immunoblotting, immunofluorescence, and functional assays validated these findings...
November 7, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27753822/pl-01-3-should-hypertension-treatment-targets-differ-according-to-region-and-ethnicity
#7
Lawrence Appel
With the exception of a few isolated populations, elevated blood pressure is a worldwide pandemic with staggering consequences for individuals, care givers, health care delivery systems, and insurers, including governments. It is well-recognized that the burden of hypertension and its adverse consequences is greater in low- and middle-income countries than economically developed countries. BP-related outcomes also differ by region, with a predominance of stroke in southeast Asian countries and a predominance of ischemic heart disease in the US and Western Europe...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27711207/genetic-modifiers-of-white-blood-cell-count-albuminuria-and-glomerular-filtration-rate-in-children-with-sickle-cell-anemia
#8
Beverly A Schaefer, Jonathan M Flanagan, Ofelia A Alvarez, Stephen C Nelson, Banu Aygun, Kerri A Nottage, Alex George, Carla W Roberts, Connie M Piccone, Thad A Howard, Barry R Davis, Russell E Ware
Discovery and validation of genetic variants that influence disease severity in children with sickle cell anemia (SCA) could lead to early identification of high-risk patients, better screening strategies, and intervention with targeted and preventive therapy. We hypothesized that newly identified genetic risk factors for the general African American population could also impact laboratory biomarkers known to contribute to the clinical disease expression of SCA, including variants influencing the white blood cell count and the development of albuminuria and abnormal glomerular filtration rate...
2016: PloS One
https://www.readbyqxmd.com/read/27658436/apol1-alpha-thalassemia-and-bcl11a-variants-as-a-genetic-risk-profile-for-progression-of-chronic-kidney-disease-in-sickle-cell-anemia
#9
Santosh L Saraf, Binal N Shah, Xu Zhang, Jin Han, Bamidele O Tayo, Taimur Abbasi, Adam Ostrower, Elizabeth Guzman, Robert E Molokie, Michel Gowhari, Johara Hassan, Shivi Jain, Richard S Cooper, Roberto F Machado, James P Lash, Victor R Gordeuk
No abstract text is available yet for this article.
September 22, 2016: Haematologica
https://www.readbyqxmd.com/read/27650483/african-ancestry-specific-alleles-and-kidney-disease-risk-in-hispanics-latinos
#10
Holly J Kramer, Adrienne M Stilp, Cathy C Laurie, Alex P Reiner, James Lash, Martha L Daviglus, Sylvia E Rosas, Ana C Ricardo, Bamidele O Tayo, Michael F Flessner, Kathleen F Kerr, Carmen Peralta, Ramon Durazo-Arvizu, Matt Conomos, Timothy Thornton, Jerome Rotter, Kent D Taylor, Jainwen Cai, John Eckfeldt, Han Chen, George Papanicolau, Nora Franceschini
African ancestry alleles may contribute to CKD among Hispanics/Latinos, but whether associations differ by Hispanic/Latino background remains unknown. We examined the association of CKD measures with African ancestry-specific APOL1 alleles that were directly genotyped and sickle cell trait (hemoglobin subunit β gene [HBB] variant) on the basis of imputation in 12,226 adult Hispanics/Latinos grouped according to Caribbean or Mainland background. We also performed an unbiased genome-wide association scan of urine albumin-to-creatinine ratios...
September 20, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27644073/the-african-diaspora-history-adaptation-and-health
#11
Charles N Rotimi, Fasil Tekola-Ayele, Jennifer L Baker, Daniel Shriner
The trans-Atlantic slave trade brought millions of Africans to the New World. Advances in genomics are providing novel insights into the history and health of Africans and the diasporan populations. Recent examples reviewed here include the unraveling of substantial hunter-gatherer and 'Eurasian' admixtures across sub-Saharan Africa, expanding our understanding of ancestral African genetics; the global ubiquity of mixed ancestry; the revealing of African ancestry in Latin Americans that likely derived from the slave trade; and understanding of the ancestral backgrounds of APOL1 and LPL found to influence kidney disease and lipid levels, respectively, providing specific insights into disease etiology and health disparities...
September 16, 2016: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/27642875/pl-01-3-should-hypertension-treatment-targets-differ-according-to-region-and-ethnicity
#12
Lawrence Appel
With the exception of a few isolated populations, elevated blood pressure is a worldwide pandemic with staggering consequences for individuals, care givers, health care delivery systems, and insurers, including governments. It is well-recognized that the burden of hypertension and its adverse consequences is greater in low- and middle-income countries than economically developed countries. BP-related outcomes also differ by region, with a predominance of stroke in southeast Asian countries and a predominance of ischemic heart disease in the US and Western Europe...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27638911/an-investigation-of-apol1-risk-genotypes-and-preterm-birth-in-african-american-population-cohorts
#13
Catherine C Robertson, Christopher E Gillies, Rosemary K B Putler, Derek Ng, Kimberly J Reidy, Brendan Crawford, Matthew G Sampson
BACKGROUND: Two genetic variants in apolipoprotein L1 (APOL1) are associated with increased risk of focal segmental glomerulosclerosis as well as other glomerular phenotypes. These risk variants are common in individuals of African ancestry but absent in other racial groups. Yet, the majority of individuals with two APOL1 risk alleles [high-risk (HR) genotype] do not have renal disease. It is critical to identify environmental and secondary genetic influences that, when combined with these alleles, lead to kidney disease...
September 16, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/27610422/apol1-risk-alleles-are-associated-with-more-severe-arteriosclerosis-in-renal-resistance-vessels-with-aging-and-hypertension
#14
Michael D Hughson, Wendy E Hoy, Susan A Mott, Victor G Puelles, John F Bertram, Cheryl L Winkler, Jeffrey B Kopp
The increased risk of end-stage kidney disease (ESKD) among hypertensive African Americans is partly related to APOL1 allele variants. Hypertension-associated arterionephrosclerosis consists of arteriosclerosis, glomerulosclerosis, and cortical fibrosis. The initial glomerulosclerosis, attributed to preglomerular arteriosclerosis and ischemia, consists of focal global glomerulosclerosis (FGGS), but in biopsy studies, focal segmental glomerulosclerosis (FSGS) is found with progression to ESKD, particularly in African Americans...
May 2016: KI Reports
https://www.readbyqxmd.com/read/27600725/collapsing-glomerulopathy-in-a-young-woman-with-apol1-risk-alleles-following-acute-parvovirus-b19-infection-a-case-report-investigation
#15
Whitney Besse, Sherry Mansour, Karan Jatwani, Cynthia C Nast, Ursula C Brewster
BACKGROUND: Collapsing Glomerulopathy (CG), also known as the collapsing variant of Focal Segmental Glomerulosclerosis (FSGS), is distinct in both its clinical severity and its pathophysiologic characteristics from other forms of FSGS. This lesion occurs disproportionally in patients carrying two APOL1 risk alleles, and is the classic histologic lesion resulting from Human Immunodeficiency Virus (HIV) infection of podocytes. Other viral infections, including parvovirus B19, and drugs such as interferon that perturb the immune system, have also been associated with CG...
September 6, 2016: BMC Nephrology
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
#16
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...
2016: Retrovirology
https://www.readbyqxmd.com/read/27588375/apol1-associated-end-stage-renal-disease-in-a-living-kidney-transplant-donor
#17
N A Zwang, A Shetty, N Sustento-Reodica, E J Gordon, J Leventhal, L Gallon, J J Friedewald
Homozygosity for apolipoprotein-L1 (APOL1) risk variants has emerged as an important predictor of renal disease in individuals of African descent over the past several years. Additionally, these risk variants may be important predictors of renal allograft failure when present in a living or deceased donor. Currently, there is no universal recommendation for screening of potential donors. We present a case of end-stage renal disease with focal segmental glomerulosclerosis in a living donor 7 years following donor nephrectomy...
October 6, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27576016/a-genome-wide-association-study-to-identify-single-nucleotide-polymorphisms-for-acute-kidney-injury
#18
Bixiao Zhao, Qiongshi Lu, Yuwei Cheng, Justin M Belcher, Edward D Siew, David E Leaf, Simon C Body, Amanda A Fox, Sushrut W Waikar, Charles D Collard, Heather Thiessen-Philbrook, T Alp Ikizler, Lorraine B Ware, Charles L Edelstein, Amit X Garg, Murim Choi, Jennifer A Schaub, Hongyu Zhao, Richard P Lifton, Chirag R Parikh
RATIONALE: Acute kidney injury is a common and severe complication of critical illness and cardiac surgery. Despite significant attempts at developing treatments, therapeutic advances to attenuate acute kidney injury and expedite recovery have largely failed. OBJECTIVES: Identifying genetic loci associated with increased risk of acute kidney injury may reveal novel pathways for therapeutic development. METHODS: We conducted an exploratory genome-wide association study to identify single-nucleotide polymorphisms associated with genetic susceptibility to in-hospital acute kidney injury...
August 30, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27559702/apolipoprotein-l-expression-correlates-with-neutrophil-cell-death-in-critically-ill-patients
#19
Israa Akl, Christophe Lelubre, Pierrick Uzureau, Michael Piagnerelli, Patrick Biston, Alexandre Rousseau, Bassam Badran, Hussein Fayyad-Kazan, Mohammad Ezedine, Jean Louis Vincent, Karim Zouaoui Boudjeltia, Luc Vanhamme
Delayed neutrophil apoptosis has been demonstrated in sepsis and may contribute to organ damage. It has recently been proposed that apolipoprotein L (ApoL) may be involved in programmed cell death, but the expression and functions of ApoLs in leukocytes (especially neutrophils) during sepsis and other inflammatory conditions are currently unknown. In this prospective observational study in a 36-bed university hospital medico-surgical intensive care unit (ICU), we included 78 adult ICU patients with (n = 41) or without (n = 37) sepsis and 47 healthy volunteers...
August 24, 2016: Shock
https://www.readbyqxmd.com/read/27509583/from-man-to-fish-what-can-zebrafish-tell-us-about-apol1-nephropathy
#20
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
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