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American Journal of Physiology. Renal... Aug 2020Human immunodeficiency virus (HIV) infection of kidney cells can lead to HIV-associated nephropathy (HIVAN) and aggravate the progression of other chronic kidney...
Human immunodeficiency virus (HIV) infection of kidney cells can lead to HIV-associated nephropathy (HIVAN) and aggravate the progression of other chronic kidney diseases. Thus, a better understanding of the mechanisms of HIV-induced kidney cell injury is needed for effective therapy against HIV-induced kidney disease progression. We have previously shown that the acetylation and activation of key inflammatory regulators, NF-κB p65 and STAT3, were increased in HIVAN kidneys. Here, we demonstrate the key role of sirtuin 1 (SIRT1) deacetylase in the regulation of NF-κB and STAT3 activity in HIVAN. We found that SIRT1 expression was reduced in the glomeruli of human and mouse HIVAN kidneys and that HIV-1 gene expression was associated with reduced SIRT1 expression and increased acetylation of NF-κB p65 and STAT3 in cultured podocytes. Interestingly, SIRT1 overexpression, in turn, reduced the expression of negative regulatory factor in podocytes stably expressing HIV-1 proviral genes, which was associated with inactivation of NF-κB p65 and a reduction in HIV-1 long terminal repeat promoter activity. In vivo, the administration of the small-molecule SIRT1 agonist BF175 or inducible overexpression of SIRT1 specifically in podocytes markedly attenuated albuminuria, kidney lesions, and expression of inflammatory markers in Tg26 mice. Finally, we showed that the reduction in SIRT1 expression by HIV-1 is in part mediated through miR-34a expression. Together, our data provide a new mechanism of SIRT1 regulation and its downstream effects in HIV-1-infected kidney cells and indicate that SIRT1/miR-34a are potential drug targets to treat HIV-related kidney disease.
Topics: AIDS-Associated Nephropathy; Animals; Humans; Kidney; Kidney Glomerulus; Mice; Podocytes; Renal Insufficiency, Chronic; Sirtuin 1; Transcription Factor RelA
PubMed: 32657157
DOI: 10.1152/ajprenal.00140.2020 -
HIV Medicine Mar 2022HIV-associated kidney disease is common but data on the pathology spectrum of kidney biopsy in China is lacking. This study aimed to illustrate the clinical...
OBJECTIVES
HIV-associated kidney disease is common but data on the pathology spectrum of kidney biopsy in China is lacking. This study aimed to illustrate the clinical presentation, laboratory findings and pathological spectrum of different subtypes of HIV-associated kidney disease in China.
METHODS
Eighteen HIV patients with renal biopsy indications at the Peking Union Medical College Hospital from January 2002 to October 2021 were retrospectively enrolled. All had CD4 counts and HIV viral load measurements. Renal biopsies were examined with light microscopy, immunofluorescence, and electron microscopy. Shapiro-Wilk test was used to test whether the data was normally distributed. The data is presented as medians (interquartile range), number (%), or means (±SD) according to their distribution.
RESULTS
Seventeen patients had glomerular disease, and one patient had interstitial nephritis. Membranous nephropathy was present in eight patients (47.1%), and IgA nephropathy in four patients (23.5%). The difference in urine protein and serum albumin before and after treatment was statistically significant and no deaths or dialysis were observed to the end of follow-up.
CONCLUSION
This study found that classic HIV-associated nephropathy (HIVAN) was uncommon in Chinese HIV patients. HIV immune complex kidney (HIVICK) disease, such as membranous or IgA nephropathy, was more common, and associated with better prognosis. Antiretroviral therapy, ACE inhibitors, and angiotensin II receptor blockers were effective in decreasing proteinuria and preserving renal function. The use of corticosteroids and immunosuppressive agents seems safe. However, the nephrotoxic effect of antiretroviral agents and other medications should be carefully monitored.
Topics: AIDS-Associated Nephropathy; Biopsy; Female; Glomerulonephritis, IGA; HIV Infections; Humans; Kidney; Male; Retrospective Studies
PubMed: 35293105
DOI: 10.1111/hiv.13246 -
Journal of the American Society of... Nov 2017In developed countries, remarkable advances in antiretroviral therapy have transformed HIV infection into a chronic condition. As a result, HIV-associated nephropathy,... (Review)
Review
In developed countries, remarkable advances in antiretroviral therapy have transformed HIV infection into a chronic condition. As a result, HIV-associated nephropathy, the classic HIV-driven kidney lesion among individuals of African descent, has largely disappeared in these regions. However, HIV-positive blacks continue to have much higher rates of ESRD than HIV-positive whites, which could be attributed to the renal risk variants. Additionally, HIV-positive individuals face adverse consequences beyond HIV itself, including traditional risk factors for CKD and nephrotoxic effects of antiretroviral therapy. Concerns for nephrotoxicity also extend to HIV-negative individuals using tenofovir disoproxil fumarate-based pre-exposure prophylaxis for the prevention of HIV infection. Therefore, CKD remains an important comorbid condition in the HIV-positive population and an emerging concern among HIV-negative persons receiving pre-exposure prophylaxis. With the improved longevity of HIV-positive individuals, a kidney transplant has become a viable option for many who have progressed to ESRD. Herein, we review the growing knowledge regarding the renal risk variants in the context of HIV infection, antiretroviral therapy-related nephrotoxicity, and developments in kidney transplantation among HIV-positive individuals.
Topics: AIDS-Associated Nephropathy; Anti-Retroviral Agents; Apolipoprotein L1; Apolipoproteins; HIV Infections; Humans; Kidney Transplantation; Lipoproteins, HDL; Renal Insufficiency, Chronic; Risk Factors; Tenofovir
PubMed: 28784698
DOI: 10.1681/ASN.2017040468 -
Cureus Mar 2023Human immunodeficiency virus (HIV) is a viral infection which progressively leads to acquired immunodeficiency syndrome (AIDS) in the absence of treatment. This happens... (Review)
Review
Human immunodeficiency virus (HIV) is a viral infection which progressively leads to acquired immunodeficiency syndrome (AIDS) in the absence of treatment. This happens through the destruction of crucial cells in the immune system, such as the helper T cells, dendritic cells, and macrophages. Since the first case was isolated in the 20th century, the disease has spread rapidly among humans, with significant renal, cardiovascular, respiratory, and neurological complications. It is predominantly sexually transmitted but non-sexual transmission. A relationship between HIV and renal diseases has been suggested for a long time, but only a few systematic studies have centered on this association. This systematic review aims to analyze the possible association between HIV and renal diseases as well as the range and pathogenesis of these renal diseases. HIV remains a critical infectious disease globally, inciting substantial morbidity and mortality. Studies have shown that people living with HIV (PLWH) are at increased risk of acute and chronic kidney disease. This review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Google Scholar, and Cochrane databases were searched exhaustively using the inclusion criteria of free full-text English papers that have exclusively studied humans in the last 20 years. Sixteen articles were selected including a systematic review, observational studies, and comprehensive narrative reviews on the role of HIV in the etiology of renal diseases, and were systemically reviewed and analyzed to elicit the wide range of possible renal complications resulting from HIV infection.
PubMed: 37123789
DOI: 10.7759/cureus.36755 -
Revista Da Associacao Medica Brasileira... Jan 2020The scenario of infection by the human immunodeficiency virus (HIV) has been undergoing changes in recent years, both in relation to the understanding of HIV infection... (Review)
Review
The scenario of infection by the human immunodeficiency virus (HIV) has been undergoing changes in recent years, both in relation to the understanding of HIV infection and regarding the treatments available. As a result, the disease, which before was associated with high morbidity and mortality, is now seen as a chronic disease that can be controlled, regarding both transmission and symptoms. However, even when the virus replication is well controlled, the infected patient remains at high risk of developing renal involvement, either by acute kidney injury not associated with HIV, nephrotoxicity due to antiretroviral drugs, chronic diseases associated with increased survival, or glomerular disease associated to HIV. This review will cover the main aspects of kidney failure associated with HIV.
Topics: AIDS-Associated Nephropathy; Acute Kidney Injury; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Atazanavir Sulfate; Chronic Disease; HIV Infections; Humans; Kidney; Risk Factors; Tenofovir
PubMed: 31939539
DOI: 10.1590/1806-9282.66.S1.75 -
Seminars in Nephrology Nov 2017Apolipoprotein L1 (APOL1) genetic variants are potent risk factors for glomerular disease, but one or more additional factors are required for expression of glomerular... (Review)
Review
Apolipoprotein L1 (APOL1) genetic variants are potent risk factors for glomerular disease, but one or more additional factors are required for expression of glomerular disease. Uncontrolled or poorly controlled human immunodeficiency virus (HIV) infection is the most potent susceptibility factor for APOL1 nephropathy that has been identified to date. APOL1 variants are associated with HIV-associated nephropathy (HIVAN), a podocyte disease, but not with HIV-immune complex disease, primarily a disease of the mesangium. The mechanism by which HIV brings out the latent glomerular disease risk remains to be defined. There are at least two classes of candidate mechanisms to explain the potent interaction between HIV-1 and APOL1. First, APOL1 variant proteins and HIV accessory proteins implicated in HIVAN may target the same or related intracellular pathways in podocytes. Recent data suggest roles for interleukin 1b and transcription factor EB. Second, features of uncontrolled HIV infection, including increased circulating factors such as interferon, may drive APOL1 gene transcription or act upon podocytes in other ways. Deeper probing of APOL1-HIV interactions may yield insights that will aid in understanding HIVAN, APOL1 nephropathy, and podocyte biology.
Topics: AIDS-Associated Nephropathy; Apolipoprotein L1; Glomerulosclerosis, Focal Segmental; Humans; Hypertension; Interferons; Mutation; Renal Insufficiency, Chronic; Risk Factors; Toll-Like Receptor 4
PubMed: 29110758
DOI: 10.1016/j.semnephrol.2017.07.004 -
Clinical Kidney Journal Jan 2024Diabetic nephropathy (DN) and non-diabetic renal diseases (NDRD) represent intricate challenges in diagnosis and treatment within the context of the global diabetes... (Review)
Review
Diabetic nephropathy (DN) and non-diabetic renal diseases (NDRD) represent intricate challenges in diagnosis and treatment within the context of the global diabetes epidemic. As the prevalence of diabetes continues to escalate, effective management of renal complications becomes paramount. Recent advancements in comprehending the multifaceted nature of renal damage, fueled by insights from histopathological investigations, offer unprecedented prospects for refining diagnostic strategies and customizing therapeutic interventions. Renal biopsies have emerged as indispensable tools for unraveling the diverse phenotypes of renal damage in diabetes. The pioneering study by Mazzucco identified three classes of renal damage in type 2 diabetes patients: classical diabetic glomerulosclerosis (DN), vascular and ischemic glomerular changes (NDRD), and other glomerulonephritides in the presence (DN + NDRD, mixed forms) or absence of DN (NDRD). The prevalence of these classes varies widely in published studies, influenced by factors such as ethnicity, geography and selection criteria for renal biopsy. Moreover, the international Renal Pathology Society consensus classification system has stratified the classical diabetic nephropathy into progressive categories of renal impairment, a breakthrough that aids in prognostication. Histopathological scrutiny, particularly the intricate correlation between glomerular and tubulointerstitial lesions, contributes profoundly to enhancing our grasp of the phenotype's heterogeneity. This amplified comprehension holds the potential to steer personalized treatment strategies. Cutting-edge interventions, encompassing sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists and anti-endothelin receptor agents, are broadening the arsenal against renal injury in diabetes. When combined with the profound insights garnered from histopathological, omics, imaging and clinical data, these therapeutic avenues promise a transformative shift towards precision-driven care paradigms. Collaborative efforts uniting researchers, clinicians and patients are indispensable for propelling our knowledge of diabetic renal damage and ameliorating patient outcomes. The fusion of histopathological, omics and imaging findings into clinical decision-making harbors the potential to customize interventions and optimize care for individuals grappling with diabetes-associated renal complications. Furthermore, groundbreaking initiatives like the iBeat Study within the BEAt-DKD (Biomarker Enterprise to Attack Diabetic Kidney Disease) project (https://www.beat-dkd.eu/), elucidating distinct phenotypes of renal damage within diabetes, underscore the imperative necessity of integrating histopathological data into the broader framework of diabetic renal management.
PubMed: 38186902
DOI: 10.1093/ckj/sfad266 -
The Journal of Infectious Diseases Jan 2018Despite achieving human immunodeficiency virus type 1 (HIV-1) RNA suppression below levels of detection and, for most, improved CD4+ T-cell counts, those aging with HIV... (Review)
Review
Despite achieving human immunodeficiency virus type 1 (HIV-1) RNA suppression below levels of detection and, for most, improved CD4+ T-cell counts, those aging with HIV experience excess low-level inflammation, hypercoagulability, and immune dysfunction (chronic inflammation), compared with demographically and behaviorally similar uninfected individuals. A host of biomarkers that are linked to chronic inflammation are also associated with HIV-associated non-AIDS-defining events, including cardiovascular disease, many forms of cancer, liver disease, renal disease, neurocognitive decline, and osteoporosis. Furthermore, chronic HIV infection may interact with long-term treatment toxicity and weight gain after ART initiation. These observations suggest that future biomarker-guided discovery and treatment may require attention to multiple biomarkers and, possibly, weighted indices. We are clinical trialists, epidemiologists, pragmatic trialists, and translational scientists. Together, we offer an operational definition of a biomarker and consider how biomarkers might facilitate progress along the translational pathway from therapeutic discovery to intervention trials and clinical management among people aging with or without HIV infection.
Topics: AIDS Dementia Complex; AIDS-Associated Nephropathy; Anti-Retroviral Agents; Biomarkers; Biomedical Research; Cardiovascular Diseases; Drug Discovery; HIV Infections; HIV-Associated Lipodystrophy Syndrome; Humans; Sustained Virologic Response
PubMed: 29165684
DOI: 10.1093/infdis/jix586 -
AIDS Research and Therapy Mar 2020Chronic kidney disease (CKD) is a comorbidity of major clinical significance amongst people living with HIV (PLWHIV) and is associated with significant morbidity and... (Review)
Review
Chronic kidney disease (CKD) is a comorbidity of major clinical significance amongst people living with HIV (PLWHIV) and is associated with significant morbidity and mortality. The prevalence of CKD is rising, despite the widespread use of antiretroviral therapy (ART) and is increasingly related to prevalent non-infectious comorbidities (NICMs) and antiretroviral toxicity. There are great disparities evident, with the highest prevalence of CKD among PLWHIV seen in the African continent. The aetiology of kidney disease amongst PLWHIV includes HIV-related diseases, such as classic HIV-associated nephropathy or immune complex disease, CKD related to NICMs and CKD from antiretroviral toxicity. CKD, once established, is often relentlessly progressive and can lead to end-stage renal disease (ESRD). Identifying patients with risk factors for CKD, and appropriate screening for the early detection of CKD are vital to improve patient outcomes. Adherence to screening guidelines is variable, and often poor. The progression of CKD may be slowed with certain clinical interventions; however, data derived from studies involving PLWHIV with CKD are sparse and this represent an important area for future research. The control of blood pressure using angiotensin converting enzyme inhibitors and angiotensin receptor blockers, in particular, in the setting of proteinuria, likely slows the progression of CKD among PLWHIV. The cohort of PLWHIV is facing new challenges in regards to polypharmacy, drug-drug interactions and adverse drug reactions. The potential nephrotoxicity of ART is important, particularly as cumulative ART exposure increases as the cohort of PLWHIV ages. The number of PLWHIV with ESRD is increasing. PLWHIV should not be denied access to renal replacement therapy, either dialysis or kidney transplantation, based on their HIV status. Kidney transplantation amongst PLWHIV is successful and associated with an improved prognosis compared to remaining on dialysis. As the cohort of PLWHIV ages, comorbidity increases and CKD becomes more prevalent; models of care need to evolve to meet the new and changing chronic healthcare needs of these patients.
Topics: Anti-HIV Agents; Clinical Trials as Topic; Comorbidity; Disease Progression; HIV Infections; Humans; Prevalence; Renal Insufficiency; Renal Insufficiency, Chronic; Risk Factors
PubMed: 32178687
DOI: 10.1186/s12981-020-00266-3 -
Frontiers in Microbiology 2015In 1970s, Heroin-associated Nephropathy (HAN), one form of focal and segmental glomerulosclerosis (FSGS), was a predominant cause of End-stage Kidney Disease (ESKD) in... (Review)
Review
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.
PubMed: 26106375
DOI: 10.3389/fmicb.2015.00571