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The FEBS Journal Oct 2021HIV-associated nephropathy (HIVAN) remains a concern among untreated HIV patients, notably of African descent, as patients can reach end-stage renal disease within... (Review)
Review
HIV-associated nephropathy (HIVAN) remains a concern among untreated HIV patients, notably of African descent, as patients can reach end-stage renal disease within 3 years. Two variants (G1 and G2) of the APOL1 gene, common in African populations to protect against African sleeping sickness, have been associated with an increased risk of several glomerular disorders including HIVAN, hypertension-attributed chronic kidney disease, and idiopathic focal segmental glomerulosclerosis and are accordingly named renal risk variants (RRVs). This review examines the mechanisms by which APOL1 RRVs drive glomerular injury in the setting of HIV infection and their potential application to patient management. Innate antiviral mechanisms activated by chronic HIV infection, especially those involving type 1 interferons, are of particular interest as they have been shown to upregulate APOL1 expression. Additionally, the downregulation of miRNA 193a (a repressor of APOL1) is also associated with the upregulation of APOL1. Interestingly, glomerular damage affected by APOL1 RRVs is caused by both loss- and gain-of-function changes in the protein, explicitly characterizing these effects. Their intracellular localization offers a further understanding of the nuances of APOL1 variant effects in promoting renal disease. Finally, although APOL1 variants have been recognized as a critical genetic player in mediating kidney disease, there are significant gaps in their application to patient management for screening, diagnosis, and treatment.
Topics: AIDS-Associated Nephropathy; Apolipoprotein L1; Genetic Variation; Glomerulosclerosis, Focal Segmental; HIV Infections; Humans; Kidney; MicroRNAs; Risk Factors
PubMed: 33340240
DOI: 10.1111/febs.15677 -
European Review For Medical and... Oct 2013The introduction of highly active antiretroviral therapy (HAART) has reduced mortality and improved life expectancy of HIV-positive patients. However, increased survival... (Review)
Review
The introduction of highly active antiretroviral therapy (HAART) has reduced mortality and improved life expectancy of HIV-positive patients. However, increased survival is associated with increased prevalence of comorbidities, such as cardiovascular disease, hepatic and renal disease. Kidney disease, including HIV-associated nephropathy, acute renal failure and chronic kidney disease, represents one of the main causes of morbidity and mortality, especially if associated to other risk factors, i.e. hypertension, diabetes, older age, black race and hepatitis C coinfection. Careful evaluation of renal function may help identifying kidney disease in its early stages. In addition, proper management of hypertension and diabetes is recommended. Even if HAART has changed the natural course of HIV-associated nephropathy, reducing the risk of End-stage Renal Disease (ERDS), some antiretroviral regimens have been related with the development of acute or chronic kidney disease. Further studies are needed to optimize the management of renal disease among HIV-infected patients.
Topics: AIDS-Associated Nephropathy; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Glomerular Filtration Rate; HIV Infections; Humans
PubMed: 24142615
DOI: No ID Found -
Current Opinion in HIV and AIDS Jul 2011Highly active antiretroviral therapy (HAART) has resulted in a marked decrease in AIDS-related conditions and death. With improved survival, cardiovascular disease,... (Review)
Review
PURPOSE OF REVIEW
Highly active antiretroviral therapy (HAART) has resulted in a marked decrease in AIDS-related conditions and death. With improved survival, cardiovascular disease, hepatic, renal disease, and non-AIDS-related cancers represent an increasing burden for HIV-infected individuals.
RECENT FINDINGS
HIV-associated nephropathy (HIVAN), acute renal injury, HAART, and comorbid conditions such as hepatitis C, hypertension, and diabetes are among the multiple causes of renal disease. In HIVAN there is incomplete understanding of the interaction of the virus with renal cells and the host genetics leading to susceptibility to this form of renal dysfunction. There is agreement that a baseline estimated glomerular filtration should be obtained and that renal function should be monitored during antiretroviral therapy. There is, however, no agreement as to the most accurate method of estimating GFR. Renal transplantation has emerged as a feasible and successful modality of management of end-stage renal disease (ESRD) in HIV-infected individuals.
SUMMARY
Kidney disease represents an increasing concern in the care of HIV-infected persons, although there are questions remaining regarding the pathophysiology of HIVAN. Transplantation, however, can be carried out safely in infected persons with ESRD.
Topics: AIDS-Associated Nephropathy; Anti-HIV Agents; HIV Infections; Hepatitis C; Humans; Incidence
PubMed: 21519246
DOI: 10.1097/COH.0b013e3283476bc3 -
American Journal of Kidney Diseases :... Dec 2019African Americans have a 2- to 4-fold greater incidence of end-stage kidney disease (ESKD) than whites, which has long raised the possibility of a genetic cause for this... (Review)
Review
African Americans have a 2- to 4-fold greater incidence of end-stage kidney disease (ESKD) than whites, which has long raised the possibility of a genetic cause for this disparity. Recent advances in genetic studies have shown a causal association of polymorphisms at the apolipoprotein L1 gene (APOL1) with the markedly increased risk for the nondiabetic component of the overall disparity in ESKD in African Americans. Although APOL1-associated kidney disease is thought to account for a substantial proportion of ESKD in African Americans, not all the increased risk for ESKD is accounted for, and a complete cataloging of disparities in genetic causes of ESKD eludes our current understanding of genetic-associated kidney disease. Genetic testing aids the screening, diagnosis, prognosis, and treatment of diseases with a genetic basis. Widespread use of genetic testing in clinical practice is limited by the small number of actionable genetic variants, limited health literacy of providers and patients, and underlying complex ethical, legal, and social issues. This perspective reviews racial and ethnic differences associated with genetic diseases and the development of ESKD in African Americans and discusses potential uncertainties associated with our current understanding of penetrance of genetically linked kidney disease and population-attributable risk percent.
Topics: Black or African American; Apolipoprotein L1; Case-Control Studies; Female; Genetic Predisposition to Disease; Genetic Testing; Health Status Disparities; Healthcare Disparities; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Needs Assessment; Renal Dialysis; United States
PubMed: 31606237
DOI: 10.1053/j.ajkd.2019.06.006 -
Kidney International Reports Dec 2020Limited information is available describing the current prevalence of proteinuria and HIV-associated CKDs (HIV-CKDs) in children and adolescents living with HIV and...
INTRODUCTION
Limited information is available describing the current prevalence of proteinuria and HIV-associated CKDs (HIV-CKDs) in children and adolescents living with HIV and receiving antiretroviral therapy in the United States.
METHODS
To address this issue, we performed a retrospective study of children and adolescents living with HIV who received medical care at Children's National Hospital in Washington, DC, between January 2012 and July 2019. Demographic data, clinical parameters (mode of HIV transmission, viral loads, CD4 cell counts, serum creatinine, glomerular filtration rate [GFR], plasma lipid levels, proteinuria, blood pressure, renal biopsies), and medical treatments, all done as a standard of clinical care, were collected and analyzed.
RESULTS
The majority of the 192 patients enrolled were of African descent (88%) and acquired HIV through vertical transmission (97%). The prevalence of all HIV-CKDs was 6%. Of these patients, 39% had intermittent or persistent proteinuria, and 7% percent had proteinuria with a mild decline in GFR (60-80 ml/min per 1.73 m), and 6% had a mild decline in GFR without proteinuria. Documented hypertension was present in 6% of the patients, mainly in association with HIV-CKD. Patients with persistent proteinuria (3%) and biopsy-proven HIV-CKD had a slow but constant progression of their renal diseases.
CONCLUSIONS
The prevalence of persistent proteinuria and HIV-CKD was lower than that reported in previous studies conducted in the United States. However, intermittent proteinuria, mild reductions in GFR, and progression of established HIV-CKD were common findings in this group of patients with predominantly vertically acquired HIV who were receiving antiretroviral therapy.
PubMed: 33305123
DOI: 10.1016/j.ekir.2020.09.001 -
Frontiers in Medicine 2018HIV-associated nephropathy (HIVAN) is an important cause of secondary focal glomerulosclerosis that occurs primarily in persons of African ancestry with advanced HIV... (Review)
Review
HIV-associated nephropathy (HIVAN) is an important cause of secondary focal glomerulosclerosis that occurs primarily in persons of African ancestry with advanced HIV disease. Although HIVAN is characterized by severe proteinuria and rapid progression to end stage renal disease without treatment, the phenotype is markedly attenuated by treatment with antiretroviral medications. HIV infection of glomerular and tubular epithelial cells and subsequent viral gene expression is a key contributor to HIVAN pathogenesis and the kidney can serve as reservoir for HIV strains that differ those in blood. HIV gene expression in renal epithelial cells leads to dysregulation of cellular pathways including cell cycle, inflammation, cell death, and cytoskeletal homeostasis. Polymorphisms in the APOL1 gene explain the marked predilection of HIVAN to occur in persons of African descent and HIVAN. Since HIVAN has the strongest association with APOL1 genotype of any of the APOL1-associated nephropathies, studies to determine the mechanisms by which HIV and APOL1 risk variants together promote kidney injury hold great promise to improve our understanding of the pathogenesis of APOL1-mediated kidney diseases.
PubMed: 29930940
DOI: 10.3389/fmed.2018.00177 -
Clinical Journal of the American... Aug 2017Viruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or... (Review)
Review
Viruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or chronic. The variable responses of the adaptive immune system to each time period of viral infection results mechanistically in different histologic forms of glomerular injury. The unique presence of a chronic viremic carrier state with either hepatitis C (HCV) or HIV has led to the opportunity to study in detail various pathogenic mechanisms of viral-induced glomerular injury, including direct viral infection of renal tissue and the development of circulating immune complexes composed of viral antigens that deposit along the glomerular basement membrane. Epidemiologic data show that approximately 25%-30% of all HIV patients are coinfected with HCV and 5%-10% of all HCV patients are coinfected with HIV. This situation can often lead to a challenging differential diagnosis when glomerular disease occurs in this dual-infected population and requires the clinician to be familiar with the clinical presentation, laboratory workup, and pathophysiology behind the development of renal disease for both HCV and HIV. Both of these viruses can be categorized under the new classification of infection-associated GN as opposed to being listed as causes of postinfectious GN as has previously been applied to them. Neither of these viruses lead to renal injury after a latent period of controlled and inactive viremia. The geneses of HCV- and HIV-associated glomerular diseases share a total dependence on the presence of active viral replication to sustain renal injury so the renal disease cannot be listed under "postinfectious" GN. With the new availability of direct-acting antivirals for HCV and more effective combined antiretroviral therapy for HIV, successful remission and even regression of glomerular lesions can be achieved if initiated at an early stage.
Topics: AIDS-Associated Nephropathy; Adaptive Immunity; Anti-HIV Agents; Antiviral Agents; Coinfection; Glomerulonephritis; HIV; HIV Infections; Hepacivirus; Hepatitis C; Host-Pathogen Interactions; Humans; Kidney; Risk Factors; Treatment Outcome; Virus Replication
PubMed: 27797895
DOI: 10.2215/CJN.04320416 -
Seminars in Nephrology Nov 2008The classic kidney disease of human immunodeficiency virus (HIV) infection, HIV-associated nephropathy, is characterized by progressive acute renal failure, often... (Review)
Review
The classic kidney disease of human immunodeficiency virus (HIV) infection, HIV-associated nephropathy, is characterized by progressive acute renal failure, often accompanied by proteinuria and ultrasound findings of enlarged, echogenic kidneys. Definitive diagnosis requires kidney biopsy, which shows collapsing focal segmental glomerulosclerosis with associated microcystic tubular dilatation and interstitial inflammation. Podocyte proliferation is a hallmark of HIV-associated nephropathy, although this classic pathology is observed less frequently in antiretroviral-treated patients. The pathogenesis of HIV-associated nephropathy involves direct HIV infection of renal epithelial cells, and the widespread introduction of combination antiretroviral therapy has had a significant impact on the natural history and epidemiology of this unique disease. These observations have established antiretroviral therapy as the cornerstone of treatment for HIV-associated nephropathy in the absence of prospective clinical trials. Adjunctive therapy for HIV-associated nephropathy includes angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, as well as corticosteroids in selected patients with significant interstitial inflammation or rapid progression.
Topics: AIDS-Associated Nephropathy; Anti-Retroviral Agents; Glomerulosclerosis, Focal Segmental; Humans; Kidney; Morbidity; United States
PubMed: 19013322
DOI: 10.1016/j.semnephrol.2008.08.005 -
Advances in Chronic Kidney Disease May 2019Viral infections in an immunocompetent host can cause both acute and chronic kidney diseases, either by direct damage to the infected kidney cells or as a consequence of... (Review)
Review
Viral infections in an immunocompetent host can cause both acute and chronic kidney diseases, either by direct damage to the infected kidney cells or as a consequence of systemic immune responses that impact the kidneys' function. Viruses have evolved mechanisms to hijack signaling pathways of the infected cell, including the mammalian target of rapamycin pathway to support viral replication, and to evade antiviral immune responses such as those mediated by miR-155 via microRNA mimetics expressed by the virus. At both the cellular and systemic levels, the host has also evolved mechanisms to counter the viral subversion strategies in the evolutionary battle for mutual survival. In the era of genomic medicine, understanding individual genetic variations that lead to differences in susceptibilities to infection and variabilities in immune responses may open new avenues for treatment, such as the recently described functions of apolipoprotein L1 risk alleles in HIV-associated nephropathy. In addition, state-of-the-art high-throughput sequencing methods have discovered new viruses as the cause for chronic diseases not previously attributed to an infection. The potential application of these methods to idiopathic kidney diseases may reveal similar occult infections by unknown viruses. Precision medicine objectives to optimize host-directed and pathogen-directed therapies for kidney diseases associated with infectious causes will only be achieved through detailed understanding of genetic susceptibility associated with immune responses and viral tropism.
Topics: AIDS-Associated Nephropathy; Acute Kidney Injury; Adaptive Immunity; Apolipoprotein L1; Autophagic Cell Death; Cytokines; Gene-Environment Interaction; Genetic Predisposition to Disease; High-Throughput Nucleotide Sequencing; Host Microbial Interactions; Humans; Immune Complex Diseases; Immune Evasion; Immunity, Innate; Metagenome; Nephritis, Interstitial; Pyroptosis; Renal Insufficiency, Chronic; Sequence Analysis, DNA; Sequence Analysis, RNA; Viral Tropism; Virus Diseases
PubMed: 31202388
DOI: 10.1053/j.ackd.2018.12.002 -
Central European Journal of Urology 2020The polyomaviruses are omnipresent in nature. The major sites of BK virus appearance are the kidney tubular epithelial cells and urinary bladder surface transitional... (Review)
Review
INTRODUCTION
The polyomaviruses are omnipresent in nature. The major sites of BK virus appearance are the kidney tubular epithelial cells and urinary bladder surface transitional cells.
MATERIAL AND METHODS
A literature search according to PRISMA guidelines within the Medline database was conducted in July 2019 for articles presenting data about BK virus in urologic aspect without setting time limits, using the terms 'BK virus' in conjunction with transplantation, nephropathy, stenosis, cancer, bladder, prostate, kidney.
RESULTS
The BK virus usually stays latent, however, its replication may become active in various clinical situations of impaired immunocompetence such as solid organ transplantation, bone marrow transplantation, AIDS, pregnancy, multiple sclerosis, administration of chemotherapy or biologic therapy. BK virus is associated with two main complications after transplantation: polyomavirus-associated nephropathy in kidney transplant patients and polyomavirus-associated hemorrhagic cystitis in allogeneic hematopoietic stem cell transplant patients.
CONCLUSIONS
The aim of this article was to present available data on urologic aspects of BK virus infection, its detection methods and available treatment.
PubMed: 32395331
DOI: 10.5173/ceju.2020.0034