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The American Journal of Pathology Mar 1987Renal tissues from two groups of patients with acquired immune deficiency syndrome (AIDS) were examined: Group A had severe proteinuria and varying degrees of renal... (Comparative Study)
Comparative Study
Renal tissues from two groups of patients with acquired immune deficiency syndrome (AIDS) were examined: Group A had severe proteinuria and varying degrees of renal insufficiency, designated AIDS-associated nephropathy (AAN), and Group B had no renal involvement. Control Group C consisted of patients with heroin-associated nephropathy (HAN) with proteinuria comparable to patients in Group A but without AIDS or its related complex (ARC). The most frequent finding, common to both AAN and HAN, was focal glomerular sclerosis. In contrast to HAN, AAN tissue showed mesangial hypocellularity, sparse interstitial infiltrates, severe tubular degenerative changes, tubular microcystic ectasia, Bowman's space dilatation, and presence of multiple complex inclusions both in the nuclei and cytoplasm in a variety of cells. Abundant tubuloreticular inclusions were found in the endothelial and occasionally in the interstitial cell cytoplasm. Nuclear bodies (NBs) were seen in greater frequency, complexity, size, and heterogeneity, and of budding configuration in Group A as compared with Groups B and C; NBs in Group C were mostly of simple types (I and II). In addition, a peculiar granulofibrillary transformation in many tubular and interstitial cell nuclei was observed in Group A. This transformation was rarely present in Group B and was never seen in Group C. Because complex NBs (Types III to V) and various intracytoplasmic and intranuclear inclusions present in Group A are often associated with viral invasion, their presence in kidneys of AIDS patients with proteinuria suggests a viral etiology for AAN.
Topics: Acquired Immunodeficiency Syndrome; Adult; Female; Fluorescent Antibody Technique; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Heroin Dependence; Humans; Kidney; Male; Microscopy, Electron; Proteinuria
PubMed: 3548410
DOI: No ID Found -
Nephrology, Dialysis, Transplantation :... Nov 2012HIV-1 associated nephropathy (HIVAN) is a clinical and renal histological disease characterized by the presence of heavy proteinuria associated with focal segmental...
HIV-1 associated nephropathy (HIVAN) is a clinical and renal histological disease characterized by the presence of heavy proteinuria associated with focal segmental glomerulosclerosis and microcystic tubular dilatation. These renal lesions lead to renal enlargement and rapid progression to kidney failure. People from African ancestry show a unique susceptibility to develop HIVAN. The study by Wearne and colleagues, which includes the largest group of patients of African ancestry with HIVAN studied so far, describes a novel renal histological variant of HIVAN, and suggests that antiretroviral therapies improve the clinical outcome of all HIV-associated renal diseases. These findings, when interpreted in the context of recent advances in our understanding of the molecular pathogenesis and genetics of HIVAN, will facilitate the recognition of all clinical variants of HIVAN as well the planning of better screening, prevention, and treatment programs for all HIV nephropathies.
Topics: AIDS-Associated Nephropathy; Female; Humans; Kidney; Male
PubMed: 22584790
DOI: 10.1093/ndt/gfs114 -
Frontiers in Medicine 2021Variants in the () gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an...
Variants in the () gene (G1-rs60910145, rs73885319, G2-rs71785313) are common in Africans and in individuals of recent African ancestry and are associated with an increased risk of non-diabetic chronic kidney disease (CKD) and in particular of HIV associated nephropathy (HIVAN). In light of the significantly increased risk of HIVAN in carriers of two risk alleles, a role in HIV infectivity has been postulated in the mechanism of associated kidney disease. Herein, we aim to explore the association between HIV viremia and genotype. In addition, we investigated interaction between BK and JC viruria, CKD and HIV viremia. A total of 199 persons living with HIV/AIDS (comprising 82 CKD cases and 117 controls) from among the participants in the ongoing Human Heredity and Health in Africa (H3Africa) Kidney Disease Research Network case control study have been recruited. The two renal risk alleles (RRA) genotypes were associated with a higher risk of CKD (OR 12.6, 95% CI 3.89-40.8, < 0.0001). Even a single APOL1 RRA was associated with CKD risk (OR 4.42, 95% CI 1.49-13.15, = 0.007). The 2 APOL1 RRA genotypes were associated with an increased probability of having HIV viremia (OR 2.37 95% CI 1.0-5.63, = 0.05). HIV viremia was associated with increased CKD risk (OR 7.45, 95% CI 1.66-33.35, = 0.009) and with a significant reduction of JC virus urine shedding (OR 0.35, 95% CI 0.12-0.98, = 0.046). In contrast to prior studies, JC viruria was not associated with CKD but was restricted in patients with HIV viremia, regardless of CKD status. These findings suggest a role of variants in HIV infectivity and emphasize that JC viruria can serve as biomarker for innate immune system activation.
PubMed: 34513880
DOI: 10.3389/fmed.2021.718300 -
Current Opinion in Nephrology and... Jan 2010This paper reviews recent efforts to identify genetic variants conferring risk for chronic kidney disease. A brief overview of methods for identifying gene variants is... (Review)
Review
PURPOSE OF REVIEW
This paper reviews recent efforts to identify genetic variants conferring risk for chronic kidney disease. A brief overview of methods for identifying gene variants is provided, along with genetic associations and new avenues under exploration.
RECENT FINDINGS
The role of renal failure susceptibility genes, including MYH9, ELMO1, UMOD and ACTN4, has become clearer over the past 18 months. The spectrum of MYH9-associated kidney disease, including focal segmental glomerulosclerosis, global glomerulosclerosis and collapsing glomerulopathy, related entities contributing to approximately 43% of end-stage renal disease in African-Americans, has come to light.
SUMMARY
MYH9 will re-categorize focal segmental glomerulosclerosis and related disorders, and has clarified the relationship between hypertension and kidney disease. MYH9 polymorphisms account for much of the excess risk of HIV-associated nephropathy and nondiabetic kidney disease in African-Americans. Kidney disease associations with ELMO1 and UMOD have been replicated and applications of genome-wide association studies based on expression data are providing novel insights on renal protein expression. These breakthroughs will alter our approach to kidney disease surveillance and lead to new therapeutic options.
Topics: AIDS-Associated Nephropathy; Actinin; Adaptor Proteins, Signal Transducing; Black or African American; Chromosome Mapping; Diabetic Nephropathies; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Humans; Kidney; Kidney Diseases; Linkage Disequilibrium; Molecular Motor Proteins; Mucoproteins; Myosin Heavy Chains; Phenotype; Uromodulin
PubMed: 19838113
DOI: 10.1097/MNH.0b013e3283331e50 -
Kidney International Aug 2014Despite improved outcomes among persons living with HIV who are treated with antiretroviral therapy, they remain at increased risk for acute and chronic kidney diseases.... (Review)
Review
Despite improved outcomes among persons living with HIV who are treated with antiretroviral therapy, they remain at increased risk for acute and chronic kidney diseases. Moreover, since HIV can infect renal epithelial cells, the kidney might serve as a viral reservoir that would need to be eradicated when attempting to achieve full virologic cure. In recent years, much progress has been made in elucidating the mechanism by which HIV infects renal epithelial cells and the viral and host factors that promote development of kidney disease. Polymorphisms in APOL1 confer markedly increased risk of HIV-associated nephropathy; however, the mechanism by which ApoL1 variants may promote kidney disease remains unclear. HIV-positive persons are at increased risk of acute kidney injury, which may be a result of a high burden of subclinical kidney disease and/or viral factors and frequent exposure to nephrotoxins. Despite the beneficial effect of antiretroviral therapy in preventing and treating HIVAN, and possibly other forms of kidney disease in persons living with HIV, some of these medications, including tenofovir, indinavir, and atazanavir can induce acute and/or chronic kidney injury via mitochondrial toxicity or intratubular crystallization. Further research is needed to better understand factors that contribute to acute and chronic kidney injury in HIV-positive patients and to develop more effective strategies to prevent and treat kidney disease in this vulnerable population.
Topics: AIDS-Associated Nephropathy; Acute Kidney Injury; Anti-HIV Agents; Apolipoprotein L1; Apolipoproteins; Genes, Viral; Genetic Predisposition to Disease; HIV-1; Humans; Immune Complex Diseases; Kidney Tubules; Lipoproteins, HDL; Models, Biological; Podocytes; Polymorphism, Genetic; Risk Factors; Thrombotic Microangiopathies
PubMed: 24827777
DOI: 10.1038/ki.2014.167 -
American Journal of Nephrology 2020Impaired mobility is associated with functional dependence, frailty, and mortality in prevalent patients undergoing dialysis. We investigated risk factors for mobility... (Observational Study)
Observational Study
BACKGROUND
Impaired mobility is associated with functional dependence, frailty, and mortality in prevalent patients undergoing dialysis. We investigated risk factors for mobility impairment, (poor gait speed) in patients incident to dialysis, and changes in gait speed over time in a 2-year longitudinal study.
METHODS
One hundred eighty-three patients enrolled within 6 months of dialysis initiation were followed up 6, 12, and 24 months later. Grip strength, health-related quality of life, and comorbidities were assessed at baseline. Outcomes were (a) baseline gait speed and (b) change in gait speed over time. Gait speed was assessed by 4-meter walk. Multivariate linear regression was used to identify risk factors for low gait speed at baseline. For longitudinal analyses, linear mixed effects modeling with gait speed modeled over time was used as the outcome.
RESULTS
Participants were 54.7 ± 12.8 years old, 52.5% men, 73.9% black with mean dialysis vintage of 100.1 ± 46.9 days and median gait speed 0.78 (0.64-0.094) m/s. Lower health utility and grip strength, diabetic nephropathy, and walking aids were associated with lower baseline gait speed. Loss of 0.1 m/s gait speed occurred in 24% of subjects at 1 year. In multivariate mixed effects models, only age, walking aid use, lower health utility, and lower handgrip strength were significantly associated with gait speed loss.
CONCLUSIONS
In our cohort of incident dialysis patients, overall gait speed is very low and 54.2% of the subjects continue to lose gait speed over 2 years. Older age, lower handgrip strength, and quality of life are risk factors for slowness. Patients at highest risk of poor gait speed can be identified at dialysis initiation to allow targeted implementation of therapeutic options.
Topics: Adult; Age Factors; Aged; Disease Progression; Female; Follow-Up Studies; Frailty; Hand Strength; Humans; Longitudinal Studies; Male; Middle Aged; Quality of Life; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Walking Speed
PubMed: 32781443
DOI: 10.1159/000509225 -
Kidney International Aug 2010The burden of renal disease in human immunodeficiency virus (HIV) and AIDS patients living in Africa is adversely influenced by inadequate socio-economic and health care... (Review)
Review
The burden of renal disease in human immunodeficiency virus (HIV) and AIDS patients living in Africa is adversely influenced by inadequate socio-economic and health care infrastructures. Acute kidney injury in HIV-positive patients, mainly as a result of acute tubular necrosis, may arise from a combination of hemodynamic, immunological, and toxic insult. A variety of histopathological forms of chronic kidney disease is also seen in HIV patients; HIV-associated nephropathy (HIVAN) and immune complex disease may require different treatment strategies, which at present are unknown. The role of host and viral genetics is still to be defined, especially in relation to the different viral clades found in various parts of the world and within Africa. The arrival and availability of highly active antiretroviral therapy in Africa has given impetus to research into the outcome of the renal diseases that are found in those with HIV. It has also generated a new look into policies governing dialysis and transplantation in this group where previously there were none.
Topics: AIDS-Associated Nephropathy; Acute Disease; Acute Kidney Injury; Africa; Antiretroviral Therapy, Highly Active; Chronic Disease; HIV Infections; Humans; Immune Complex Diseases; Kidney; Kidney Failure, Chronic
PubMed: 20531456
DOI: 10.1038/ki.2010.155 -
Advances in Chronic Kidney Disease Jan 2010With improved survival afforded by highly active antiretroviral therapy (HAART), CKD has emerged as one of the primary comorbid conditions affecting HIV-infected... (Review)
Review
With improved survival afforded by highly active antiretroviral therapy (HAART), CKD has emerged as one of the primary comorbid conditions affecting HIV-infected individuals. Although CKD in HIV-infected individuals is classically thought of as a consequence of advanced HIV infection such as in the case of HIV-associated nephropathy, several factors likely contribute to the development CKD in HIV infection. These factors include genetic predisposition, age-related decline in kidney function, HAART-related metabolic changes, exposure to multiple nephrotoxic medications, and concurrent conditions such as hepatitis C or illicit drug use. Similar to the general population, proteinuria and impaired kidney function are associated with faster progression to acquired immune deficiency syndrome and death. Given the prevalence and impact of kidney disease on the course of HIV infection and its management, current guidelines recommend screening all HIV-infected individuals for kidney disease. This review focuses on the current guidelines for kidney disease screening and discusses traditional as well as promising strategies for detecting CKD in this vulnerable population.
Topics: AIDS-Associated Nephropathy; Humans; Mass Screening; Practice Guidelines as Topic; Prevalence; Proteinuria; Renal Insufficiency, Chronic
PubMed: 20005486
DOI: 10.1053/j.ackd.2009.07.014 -
Current HIV Research 2018The implementation of combination antiretroviral therapy (cART) as the primary means of treatment for HIV infection has achieved a dramatic decline in deaths attributed... (Review)
Review
The implementation of combination antiretroviral therapy (cART) as the primary means of treatment for HIV infection has achieved a dramatic decline in deaths attributed to AIDS and the reduced incidence of severe forms of HIV-associated neurocognitive disorders (HAND) in infected individuals. Despite these advances, milder forms of HAND persist and prevalence of these forms of neurocognitive impairment are rising with the aging population of HIV infected individuals. HIV enters the CNS early in the pathophysiology establishing persistent infection in resident macrophages and glial cells. These infected cells, in turn, secrete neurotoxic viral proteins, inflammatory cytokines, and small metabolites thought to contribute to neurodegenerative processes. The viral envelope protein gp120 has been identified as a potent neurotoxin affecting neurodegeneration via indirect and direct mechanisms involving interactions with chemokine co-receptors CCR5 and CXCR4. This short review focuses on gp120 neurotropism and associated mechanisms of neurotoxicity linked to chemokine receptors CCR5 and CXCR4 with a new perspective on plasma membrane lipid rafts as an active participant in gp120-mediated neurodegeneration underlying HIV induced CNS pathology.
Topics: AIDS-Associated Nephropathy; HIV Envelope Protein gp120; Humans; Membrane Microdomains; Neurons; Receptors, CCR5; Receptors, CXCR4
PubMed: 30280668
DOI: 10.2174/1570162X16666181003144740 -
American Family Physician Feb 2011Patients with human immunodeficiency virus (HIV) infection often develop multiple complications and comorbidities. Opportunistic infections should always be considered... (Review)
Review
Patients with human immunodeficiency virus (HIV) infection often develop multiple complications and comorbidities. Opportunistic infections should always be considered in the evaluation of symptomatic patients with advanced HIV/AIDS, although the overall incidence of these infections has decreased. Primary care of HIV infection includes the early detection of some complications through screening at-risk and symptomatic patients with routine laboratory monitoring (e.g., comprehensive metabolic and lipid panels) and validated tools (e.g., the HIV Dementia Scale). Treatment of many chronic complications is similar for patients with HIV infection and those without infection; however, combination antiretroviral therapy has shown benefit for some conditions, such as HIV-associated nephropathy. For other complications, such as cardiovascular disease and lipoatrophy, management may include switching antiretroviral regimens to reduce exposure to HIV medications known to cause toxicity.
Topics: AIDS-Associated Nephropathy; AIDS-Related Opportunistic Infections; Anti-Retroviral Agents; HIV Infections; Humans; Incidence; United States
PubMed: 21322514
DOI: No ID Found