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Contributions To Nephrology 2021Clinical Background and Epidemiology: Worldwide, an estimated 38 million people are living with HIV infection. The classic kidney disease of HIV infection, commonly... (Review)
Review
Clinical Background and Epidemiology: Worldwide, an estimated 38 million people are living with HIV infection. The classic kidney disease of HIV infection, commonly known as HIV-associated nephropathy, is a collapsing form of focal segmental glomerulosclerosis that almost exclusively affects individuals of African descent with advanced HIV disease. People living with HIV are also at risk for immune-complex kidney diseases, antiretroviral nephrotoxicity, and kidney disease due to co-infections and comorbidities. Challenges: The burden of HIV-related kidney disease is greatest in traditionally disadvantaged populations in resource-limited settings in sub-Saharan Africa and the Caribbean and among minority populations in the United States and Europe. Factors contributing to these disparities include a higher prevalence of HIV infection, limited access to optimal antiretroviral therapy, and genetic susceptibility to kidney disease. Treatment and Prevention: Current treatment guidelines recommend the initiation of life-long antiretroviral therapy in all people living with HIV to prevent AIDS and non-AIDS complications, including kidney disease. People living with HIV who progress to end-stage kidney disease despite treatment are candidates for dialysis and kidney transplant, including the possibility of accepting organs from HIV-positive donors in some settings. Although HIV prevention is currently the only definitive solution, expanding access to antiretroviral therapy, dialysis, and kidney transplantation in people living with HIV are important intermediate steps to address the global burden of HIV-related kidney disease.
Topics: AIDS-Associated Nephropathy; HIV Infections; Humans; Kidney; Renal Dialysis; Renal Insufficiency; United States
PubMed: 34344001
DOI: 10.1159/000517702 -
Disease Models & Mechanisms Jul 2021People of African ancestry living with the human immunodeficiency virus-1 (HIV-1) are at risk of developing HIV-associated nephropathy (HIVAN). Children with HIVAN...
People of African ancestry living with the human immunodeficiency virus-1 (HIV-1) are at risk of developing HIV-associated nephropathy (HIVAN). Children with HIVAN frequently show high plasma fibroblast growth factor-2 (FGF-2) levels; however, the role of circulating FGF-2 in the pathogenesis of childhood HIVAN is unclear. Here, we explored how circulating FGF-2 affected the outcome of HIVAN in young HIV-Tg26 mice. Briefly, we demonstrated that FGF-2 was preferentially recruited in the kidneys of mice without pre-existing kidney disease, precipitating HIVAN by activating phosphorylated extracellular signal-regulated kinase (pERK) in renal epithelial cells, without inducing the expression of HIV-1 genes. Wild-type mice injected with recombinant adenoviral FGF-2 (rAd-FGF-2) vectors carrying a secreted form of human FGF-2 developed transient and reversible HIVAN-like lesions, including proteinuria and glomerular enlargement. HIV-Tg26 mice injected with rAd-FGF-2 vectors developed more-significant proliferative and pro-fibrotic inflammatory lesions, similar to those seen in childhood HIVAN. These lesions were partially reversed by treating mice with the FGF/VEGF receptor tyrosine kinase inhibitor PD173074. These findings suggest that high plasma FGF-2 levels may be an independent risk factor for precipitating HIVAN in young children.
Topics: AIDS-Associated Nephropathy; Animals; Child, Preschool; Disease Models, Animal; Fibroblast Growth Factor 2; HIV-1; Humans; Mice; Mice, Transgenic
PubMed: 34308967
DOI: 10.1242/dmm.048980 -
West African Journal of Medicine Apr 2021Human Immunodeficiency Virus (HIV) infects multiple tissues of the body, including the renal parenchyma, with HIV-associated Nephropathy (HIVAN) being the most common...
INTRODUCTION
Human Immunodeficiency Virus (HIV) infects multiple tissues of the body, including the renal parenchyma, with HIV-associated Nephropathy (HIVAN) being the most common form of the HIV-related renal disease and an important cause of End Stage Renal Disease (ESRD) in HIV infected patients. There is paucity of studies on HIVAN among children with renal diseases, most studies on HIVAN focused on prevalence among HIV patients with vertical transmission being the commonest route. We undertook this study to determine the prevalence and impact of HIVAN among our renal patients and to highlight the new route of HIV transmission observed in these group of patients in Port Harcourt, Southern Nigeria.
MATERIALS AND METHODS
The study was conducted among renal patients managed in the Paediatric department of the University of Port Harcourt Teaching Hospital from December 2016 to March 2019. The information on the HIVAN patients were stored and retrieved from the renal register where all cases of renal diseases were enrolled. The diagnosis of HIVAN was made based on presence of significant proteinuria (≥ 1+), with one or more of the following: abnormal microscopic examination of urinary sediments, rising serum creatinine, renal ultrasound finding of enlarged echogenic kidneys and histology finding of focal segmental glomerulosclerosis. The patient's sociodemographic data, clinical presentation, route of transmission of HIV, laboratory investigations, treatment, and clinical outcome were obtained and analysed using SPSS version 25.0.
RESULTS
There were 112 cases of renal diseases seen during the study period of which 10 (8.9%) had HIVAN. The HIVAN patients were aged between 4-17years. Four (40%) of these HIVAN cases had CKD of which 2 (20%) had ESRD. The route of transmission of HIV was vertical (mother-to-child) in 8 patients and via sexual route in two older male patients aged 17years who were homosexuals. Mortality rate among the HIVAN patients was 30%, with 2 (20%) lost to follow up.
CONCLUSION
There is a rising prevalence of HIVAN among paediatric patients with renal diseases in our environment, with homosexuality being a new route of HIV transmission observed in the older patients.
Topics: AIDS-Associated Nephropathy; Adolescent; Child; Child, Preschool; Female; HIV Infections; Humans; Infectious Disease Transmission, Vertical; Male; Nigeria; Proteinuria
PubMed: 33900708
DOI: No ID Found -
West African Journal of Medicine Apr 2021
Topics: AIDS-Associated Nephropathy; Humans; Kidney Failure, Chronic
PubMed: 33900703
DOI: No ID Found -
PloS One 2021HIV-positive persons of African descent are disproportionately affected by chronic kidney disease (CKD). Deterioration to end-stage kidney disease (ESKD) also occurs in...
BACKGROUND
HIV-positive persons of African descent are disproportionately affected by chronic kidney disease (CKD). Deterioration to end-stage kidney disease (ESKD) also occurs in this population at a higher frequency. There remains a lot to learn about the genetic susceptibility to CKD in HIV positive patients, and the pathophysiology of progression to ESKD.
OBJECTIVES
We will conduct an exploratory genotype-phenotype study in HIV-positive persons with CKD in Aminu Kano Teaching Hospital, Nigeria, to determine blood-based differential gene expression biomarkers in different kidney risk groups according to the KDIGO 2012 criteria.
METHODS
We will consecutively screen 150 HIV-positive adults (≥18 years of age) attending the HIV clinic of Aminu Kano Teaching Hospital, Kano, Nigeria, for CKD based on proteinuria and elevation of estimated glomerular filtration rate. Among these, two separate groups of 16 eligible participants each (n = 32) will be selected in the four (4) KDIGO 2012 kidney risk categories. The groups will be matched for age, sex, viral suppression level and antiretroviral (ARV) regimen. In the first group (n = 16), we will determine differential gene expression markers in peripheral blood mononuclear cells using mRNA-sequencing (RNA-Seq). We will validate the differential expression markers in the second group (n = 16) using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Using a systems-based approach, we will construct, visualize and analyze gene-gene interaction networks to determine the potential biological roles of identified differential expression markers based on published literature and publicly available databases.
RESULTS
Our exploratory study will provide valuable information on the potential roles of differential expression biomarkers in the pathophysiology of HIV-associated kidney disease by identifying novel biomarkers in different risk categories of CKD in a sub-Saharan African population. The results of this study will provide the basis for population-based genome-wide association studies to guide future personalized medicine approaches.
CONCLUSION
Validated biomarkers can be potential targets for the development of stage-specific therapeutic interventions, an essential paradigm in precision medicine.
Topics: AIDS-Associated Nephropathy; Africa South of the Sahara; Biomarkers; Black People; Disease Progression; Genetic Association Studies; Genetic Predisposition to Disease; Glomerular Filtration Rate; Humans; Leukocytes, Mononuclear; Polymorphism, Single Nucleotide; RNA-Seq
PubMed: 33822824
DOI: 10.1371/journal.pone.0249567 -
Cureus Feb 2021Human immunodeficiency virus (HIV) infection occurs due to the HIV virus. It results in an immunodeficient state and multi-organ system infections and malignancy known...
Human immunodeficiency virus (HIV) infection occurs due to the HIV virus. It results in an immunodeficient state and multi-organ system infections and malignancy known as AIDS. HIV-associated nephropathy (HIVAN) is the most common HIV kidney involvement and may present as acute kidney injury (AKI), as well as chronic kidney disease (CKD). HIVAN is a collapsing form of focal segmental glomerulosclerosis (FSGS). HIVAN treatment options include antiretroviral therapy (ART), steroids, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), and hemodialysis (HD). We herein describe the case of a 40-year-old patient with an established diagnosis of HIVAN who has had partial recovery of end-stage renal failure following the initiation of ART.
PubMed: 33717725
DOI: 10.7759/cureus.13181 -
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 -
Arteriosclerosis, Thrombosis, and... Jan 2021To determine the effects of HIV serostatus and disease severity on endothelial function in a large pooled cohort study of people living with HIV infection and HIV-...
OBJECTIVE
To determine the effects of HIV serostatus and disease severity on endothelial function in a large pooled cohort study of people living with HIV infection and HIV- controls. Approach and Results: We used participant-level data from 9 studies: 7 included people living with HIV (2 treatment-naïve) and 4 had HIV- controls. Brachial artery flow-mediated dilation (FMD) was measured using a standardized ultrasound imaging protocol with central reading. After data harmonization, multiple linear regression was used to examine the effects of HIV- serostatus, HIV disease severity measures, and cardiovascular disease risk factors on FMD. Of 2533 participants, 986 were people living with HIV (mean 44.4 [SD 11.8] years old) and 1547 were HIV- controls (42.9 [12.2] years old). The strongest and most consistent associates of FMD were brachial artery diameter, age, sex, and body mass index. The effect of HIV+ serostatus on FMD was strongly influenced by kidney function. In the highest tertile of creatinine (1.0 mg/dL), the effect of HIV+ serostatus was strong (β=-1.59% [95% CI, -2.58% to -0.60%], =0.002), even after covariate adjustment (β=-1.36% [95% CI, -2.46% to -0.47%], =0.003). In the lowest tertile (0.8 mg/dL), the effect of HIV+ serostatus was strong (β=-1.90% [95% CI, -2.58% to -1.21%], <0.001), but disappeared after covariate adjustment. HIV RNA viremia, CD4+ T-cell count, and use of antiretroviral therapy were not meaningfully associated with FMD.
CONCLUSIONS
The significant effect of HIV+ serostatus on FMD suggests that people living with HIV are at increased cardiovascular disease risk, especially if they have kidney disease.
Topics: AIDS Serodiagnosis; AIDS-Associated Nephropathy; Adolescent; Adult; Aged; Brachial Artery; Cardiovascular Diseases; Case-Control Studies; Endothelium, Vascular; Female; HIV Infections; HIV Seronegativity; HIV Seropositivity; Heart Disease Risk Factors; Humans; Male; Middle Aged; Predictive Value of Tests; Risk Assessment; Severity of Illness Index; Vasodilation; Young Adult
PubMed: 33327750
DOI: 10.1161/ATVBAHA.120.315435 -
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 -
Internal Medicine (Tokyo, Japan) May 2021Objective A kidney biopsy is generally performed in diabetic patients to discriminate between diabetic nephropathy (DN) and non-diabetic kidney disease (NDKD) and to...
Objective A kidney biopsy is generally performed in diabetic patients to discriminate between diabetic nephropathy (DN) and non-diabetic kidney disease (NDKD) and to provide more specific treatments. This study investigated the impact of anemia on the renal pathology and the clinical course in patients who underwent a kidney biopsy. Methods We reviewed 81 patients with type 2 diabetes who underwent a percutaneous kidney biopsy. Patients were classified into two groups: isolated DN (DN group, n=30) and NDKD alone or concurrent DN (NDKD group, n=51) groups. The laboratory and pathological findings and clinical courses were investigated. Results In the NDKD group, membranous nephropathy was the most common finding (23.5%), followed by IgA nephropathy (17.6%) and crescentic glomerulonephritis (13.7%). In the logistic regression analysis, the absence of severe hematuria and presence of anemia were significantly associated with a diagnosis of DN. Akaike's information criterion (AIC) and net reclassification improvement (NRI) analyses revealed improved predictive performance by adding anemia to the conventional factors (AIC 100.152 to 91.844; NRI 27.0%). The tissues of patients in the DN group demonstrated more severe interstitial fibrosis and tubular atrophy (IF/TA) than those in the NDKD group (p<0.05) regardless of the rate of global glomerulosclerosis, and IF/TA was related to the prevalence of anemia (odds ratio: 7.31, 95% confidence interval: 2.33-23.00, p<0.01) according to a multivariable regression analysis. Furthermore, the isolated DN group demonstrated a poorer prognosis than the NDKD group. Conclusion DN is associated with anemia because of severe IF/TA regardless of the renal function, and anemia helps clinician discriminate clinically between isolated DN and NDKD.
Topics: Anemia; Biopsy; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Glomerulonephritis, IGA; Humans; Kidney
PubMed: 33250462
DOI: 10.2169/internalmedicine.5455-20