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      Apolipoprotein L1 (APOL1) Variants (Vs) a possible link between Heroin-associated Nephropathy (HAN) and HIV-associated Nephropathy (HIVAN)

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          In 1970s, Heroin-associated Nephropathy (HAN), one form of focal and segmental glomerulosclerosis (FSGS), was a predominant cause of End-stage Kidney Disease (ESKD) in African-Americans (AAs). In 1980s, with the surge of Acquired Immune Deficiency Syndrome (AIDS) in AAs, HAN more or less disappeared, and the incidence of Human Immunodeficiency Virus associated Nephropathy (HIVAN) markedly increased. Recent studies in AAs have identified APOL1 variants (Vs) as a major risk factor for the development and progression of non-diabetic kidney diseases including idiopathic FSGS and hypertension-attributed nephrosclerosis. These observations have also offered partial insights into the mechanisms of development, and higher rate of occurrence of both HAN and HIVAN in AAs. AAs with APOL1Vs develop idiopathic FSGS at four-fold higher rate compared to European Americans (EAs). Similarly, HIV infected AAs with APOL1Vs (if not on antiviral therapy), risk a 50% (10-fold greater) chance of developing HIVAN. It has been suggested that APOL1Vs expression may render podocytes more vulnerable to various types of injury: bacterial, viral, and others. However, in addition to genetic variants, additional factors such as persistence of a second hit may determine the nature and severity of glomerular disease. In patients with HAN, heroin or contaminants may have been the offending second insult(s) which caused renal disease in susceptible AA patients. In the 80's, since heroin-induced second hit was neither consistent nor sustained (depending on drug availability in the street), the disease was masked or replaced HIV infected patients (especially in untreated subjects), by an overwhelming second hit by the virus which was both intense as well as persistent. It appears that APOL1Vs may be one of the links between the disappearance of HAN and emergence of HIVAN in AA patients.

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          The DNA sequence of human chromosome 22.

          Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.
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            Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome.

            Of the 92 patients with the acquired immunodeficiency syndrome (AIDS) who were seen at our institution over a two-year period, 9 acquired the nephrotic syndrome (urinary protein greater than 3.5 g per 24 hours) and 2 had azotemia with lesser amounts of urinary protein. Five of these 11 patients had a history of intravenous-heroin addiction, but in the remaining six, there were no known predisposing factors for nephropathy. In nine patients (including the six non-addicts) the course of renal disease was marked by rapid progression to severe uremia. Renal tissue examined by biopsy in seven patients and at autopsy in three revealed focal and segmental glomerulosclerosis with intraglomerular deposition of IgM and C3. In the 11th patient, renal biopsy revealed an increase in mesangial matrix and cells, with deposition of IgG and C3 consistent with a mild immune-complex glomerulonephritis, and severe interstitial nephritis. We conclude that focal and segmental glomerulosclerosis may be associated with AIDS and suggest that rapid deterioration to uremia may characterize this renal disease.
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              Twenty-one-year trend in ESRD due to focal segmental glomerulosclerosis in the United States.

              Focal segmental glomerulosclerosis (FSGS) is a clinicopathologic syndrome with a substantial risk for progression to end-stage renal disease (ESRD). Recent studies of renal biopsy archives in the United States suggest that the incidence of FSGS has increased. FSGS has become the leading cause of idiopathic nephrotic syndrome in the United States, with the greatest incidence rates in the black population. In the absence of a population-based estimate of FSGS incidence, we wished to obtain a population-based estimate of incident ESRD cases caused by FSGS (FSGS ESRD) and characterize temporal changes in this group. We examined the incidence of FSGS ESRD during a 21-year period (1980 to 2000) using data from the United States Renal Data System. We excluded patients who were classified as having acquired immunodeficiency syndrome nephropathy. The annual incidence of FSGS ESRD has increased considerably, whether expressed as an absolute number or a fraction of the total incident ESRD population. Thus, the proportion of ESRD attributed to FSGS has increased 11-fold, from 0.2% in 1980 to 2.3% in 2000. The recent increase in incident FSGS ESRD cases likely is multifactorial in origin, with contributions from changes in renal biopsy practices, changes in disease classification, and a real increase in the incidence of FSGS disease. Black individuals have a 4-fold greater risk of FSGS ESRD than white or Asian individuals. The peak decade for FSGS ESRD incidence is 40 to 49 years among black subjects and 70 to 79 years among white and Asian individuals. Males have 1.5- to 2-fold greater risk than females. The incidence of FSGS ESRD has increased considerably in the United States, with black individuals at greatest risk. Idiopathic FSGS now is the most common cause of ESRD caused by primary glomerular disease in the United States in both the black and white populations.

                Author and article information

                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                09 June 2015
                : 6
                1Hofstra North Shore-LIJ School of Medicine Long Island, NY, USA
                2Department of Medicine, State University of New York Downstate Medical Center Brooklyn, NY, USA
                3Department of Pathology, New York Medical College Valhalla, NY, USA
                4Technion Institute of Technology and Rambam Medical Center Haifa, Israel
                Author notes

                Edited by: Venkata Subba Rao Atluri, Florida International University, USA

                Reviewed by: Vecihi Batuman, Tulane University, USA; Richard Joseph Noel, Ponce Health Sciences University, USA

                *Correspondence: Pravin C. Singhal, Hofstra North Shore-LIJ School of Medicine, 225 West, Community Drive, Great Neck, Long Island, NY 11021, USA psinghal@

                This article was submitted to Virology, a section of the journal Frontiers in Microbiology

                Copyright © 2015 Lan, Rao, Chander, Skorecki and Singhal.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 79, Pages: 6, Words: 5209
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                Microbiology & Virology

                podocytes, opiates, hiv-associated nephropathy, apol1, heroin nephropathy


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