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Kidney International Oct 2022Four decades after the first cases of HIV were reported, kidney disease remains an important comorbidity in people with HIV (PWH). Both HIV-associated nephropathy and... (Review)
Review
Four decades after the first cases of HIV were reported, kidney disease remains an important comorbidity in people with HIV (PWH). Both HIV-associated nephropathy and immune complex kidney disease were recognized as complications of HIV infection in the early years before treatment was available. Although the introduction of effective antiretroviral therapy in the late 1990s resulted in dramatic improvements in survival and health in PWH, several commonly used antiretroviral agents have been associated with kidney injury. HIV infection and treatment may also promote the progression of comorbid chronic kidney disease due to traditional risk factors such as diabetes, and HIV is one of the strongest "second hits" for the high-risk APOL1 genotype. Unique considerations in the management of chronic kidney disease in PWH are largely related to the need for lifelong antiretroviral therapy, with potential for toxicity, drug-drug interactions, and polypharmacy. PWH who develop progressive chronic kidney disease are candidates for all modalities of kidney replacement therapy, including kidney transplantation, and at some centers, PWH may be candidates to serve as donors for recipients with HIV. Transplantation of kidney allografts from donors with HIV also offers a unique opportunity to study viral dynamics in the kidney, with implications for kidney health and for research toward HIV cure. In addition, HIV-transgenic animal models have provided important insights into kidney disease pathogenesis beyond HIV, and experience with HIV and HIV-related kidney disease has provided important lessons for future pandemics.
Topics: AIDS-Associated Nephropathy; Animals; Anti-Retroviral Agents; Antigen-Antibody Complex; Apolipoprotein L1; HIV Infections; Humans; Renal Insufficiency, Chronic
PubMed: 35850290
DOI: 10.1016/j.kint.2022.06.021 -
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 -
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 -
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 -
Journal of Infection and Public Health 2015This paper reviews the current literature and information on the combination drug Complera(™) (rilpivirine/emtricitabine/tenofovir disoproxil fumarate) that was... (Review)
Review
This paper reviews the current literature and information on the combination drug Complera(™) (rilpivirine/emtricitabine/tenofovir disoproxil fumarate) that was approved by the Food and Drug Administration (FDA) in August 2011. PubMed, Cochrane and Embase (2001-2014) were searched for primary and review articles on rilpivirine, emtricitabine, and tenofovir disoproxil fumarate, individually or in combination. Data from drug manufacturer and product label was also used. Clinical trial reports were selected, extracted and analyzed to include relevant and recent ones. Selected English-language trials were limited to those with human subjects and included both safety and efficacy outcomes. Results from two phase 3 randomized double blind trials (ECHO and THRIVE) showed that rilpivirine is non-inferior to efavirenz in suppressing viral load below 50 copies/mL in anti-retroviral therapy (ART) naïve human immunodeficiency virus (HIV) infected patients. In addition, psychiatric disturbances, rash and increase in lipid levels occurred less frequently with rilpivirine when compared to efavirenz. However, virological failure and drug resistance were higher with rilpivirine in patients with baseline viral load >100,000 copies/mL. Rilpivirine showed cross resistance to efavirenz and etravirine. Efavirenz, on the other hand, did not demonstrate cross resistance to rilpivirine and etravirine, leaving the latter drugs as options for use in case of virological failure with efavirenz. Complera(™) remains an acceptable alternative treatment to Atripla(™) in ART naïve patients who have a pre-ART plasma HIV RNA <100,000 copies/mL and CD4 count >200 cells/mm(3) with non-inferior efficacy and better safety and tolerability.
Topics: AIDS-Associated Nephropathy; Adult; Anti-HIV Agents; Drug Resistance, Viral; Emtricitabine; Emtricitabine, Rilpivirine, Tenofovir Drug Combination; HIV Infections; HIV-1; Humans; Rilpivirine; Tenofovir
PubMed: 26001757
DOI: 10.1016/j.jiph.2015.04.020 -
Transplantation Jul 2021HIV-positive patients had been successfully transplanted for the last 15 y and the donor pool had successfully been expanded to also include HIV-positive donors. (Review)
Review
BACKGROUND
HIV-positive patients had been successfully transplanted for the last 15 y and the donor pool had successfully been expanded to also include HIV-positive donors.
METHODS
We aimed to evaluate the effectiveness of transplantation in HIV-positive patients and highlight some of the important issues reported in the literature. We pooled clinical data from different cohorts to show some of the common issues encountered in HIV-positive transplantation. Furthermore, we searched MEDLINE via PubMed, EMBASE, Cochrane CENTRAL to create a comprehensive table for current evidence for different issues currently encountered when transplanting HIV-positive patients.
RESULTS
We included data from 19 cohort studies and reported on outcomes of the current HIV-positive transplant programs. We made recommendations based on personal experience as well as the experience reported in the literature regarding rejection, opportunistic infection, and HIV-associated nephropathy. Opportunistic infections and malignancies are not a major problem for this population group.
CONCLUSIONS
HIV-positive patients encounter very specific issues after transplantation, specifically related to drug interactions and higher rejection rates. When utilizing HIV-positive donors, the recurrence of HIV-associated nephropathy in the graft kidney is an issue which can be important. Despite some issues with high rejection rates, HIV-positive patients have similar results to HIV-negative patients posttransplantation.
Topics: AIDS-Associated Nephropathy; Anti-HIV Agents; Drug Interactions; Graft Rejection; HIV Infections; Humans; Immunosuppressive Agents; Kidney Transplantation; Recurrence; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 33044431
DOI: 10.1097/TP.0000000000003485 -
Nature Reviews. Nephrology Oct 2020Reports of collapsing glomerulopathy in patients of African ancestry and high-risk genotype infected with SARS-CoV-2 have emerged during the COVID-19 pandemic. This new... (Review)
Review
Reports of collapsing glomerulopathy in patients of African ancestry and high-risk genotype infected with SARS-CoV-2 have emerged during the COVID-19 pandemic. This new entity, which we term COVID-19-associated nephropathy (COVAN), may particularly impact individuals in some regions of the world. Awareness of this potentially ominous complication of COVID-19 must be raised.
Topics: AIDS-Associated Nephropathy; Apolipoprotein L1; Betacoronavirus; COVID-19; Coronavirus Infections; DNA; Global Health; Humans; Incidence; Pandemics; Pneumonia, Viral; Polymorphism, Single Nucleotide; SARS-CoV-2
PubMed: 32753739
DOI: 10.1038/s41581-020-0332-3 -
Advances in Chronic Kidney Disease Sep 2014APOL1 kidney disease is a unique case in the field of the genetics of common disease: 2 variants (termed G1 and G2) with high population frequency have been repeatedly... (Review)
Review
APOL1 kidney disease is a unique case in the field of the genetics of common disease: 2 variants (termed G1 and G2) with high population frequency have been repeatedly associated with nondiabetic CKDs, with very strong effect size (odds ratios 3-29) in populations of sub-Saharan African descent. This review provides an update on the spectrum of APOL1 kidney disease and on the worldwide distribution of these kidney risk variants. We also summarize the proper way to run a recessive analysis on joint and independent effects of APOL1 G1 and G2 kidney risk variants.
Topics: AIDS-Associated Nephropathy; Africa South of the Sahara; Apolipoprotein L1; Apolipoproteins; Black People; Gene Frequency; Genetic Predisposition to Disease; Genetics, Population; Glomerulosclerosis, Focal Segmental; Haplotypes; Humans; Lipoproteins, HDL; Lupus Nephritis; Renal Insufficiency, Chronic
PubMed: 25168832
DOI: 10.1053/j.ackd.2014.06.005 -
PloS One 2022Racial disparities are known in the occurrence of kidney disease with excess risks found among people of African descent. Apolipoprotein L1 (APOL1) gene variants G1 and...
INTRODUCTION
Racial disparities are known in the occurrence of kidney disease with excess risks found among people of African descent. Apolipoprotein L1 (APOL1) gene variants G1 and G2 are associated with kidney disease among HIV infected individuals of African descent in the USA as well as among black population in South Africa. We set out to investigate the prevalence of these high-risk variants and their effects on kidney disease among HIV infected patients in Northern Nigeria with hitherto limited information despite earlier reports of high population frequencies of these alleles from the Southern part of the country.
METHODS
DNA samples obtained from the whole blood of 142 participants were genotyped for APOL1 G1 and G2 variants after initial baseline investigations including assessment of kidney function. Participants comprised 50 HIV positive patients with no evidence of kidney disease, 52 HIV negative individuals with no kidney disease and 40 HIV positive patients with chronic kidney disease (CKD) evidenced by persistent proteinuria and/or reduced eGFR, who also had a kidney biopsy. All the HIV positive patients were newly diagnosed and treatment naïve.
RESULTS
The distribution of the APOL1 genotypes among the study participants revealed that 24.6% had a G1 risk allele and 19.0% a G2. The frequency of the High Risk Genotype (HRG) was 12.5% among those with CKD compared to 5.8% in the HIV negative group and zero in the HIV positive no CKD group. Having the HRG was associated with a higher odds for developing HIV Associated Nephropathy (HIVAN) (2 vs 0 risk alleles: OR 10.83, 95% CI 1.38-84.52; P = 0.023; 2 vs 0 or 1 risk alleles: OR 5.5, 95% CI 0.83-36.29; P = 0.07). The HRG was also associated with higher odds for Focal Segmental Glomerulosclerosis (FSGS) (2 vs 0 risk alleles: OR 13.0, 95% CI 2.06-81.91; P = 0.006 and 2 vs 0 or 1 risk alleles: OR 9.0, 95%CI 1.62-50.12; P = 0.01) when compared to the control group.
CONCLUSION
This study showed a high population frequency of the individual risk alleles of the APOL1 gene with higher frequencies noted among HIV positive patients with kidney disease. There is high association with the presence of kidney disease and especially FSGS and HIVAN among treatment naive HIV patients carrying two copies of the HRG.
Topics: AIDS-Associated Nephropathy; Apolipoprotein L1; Apolipoproteins; Genetic Predisposition to Disease; Genotype; Glomerulosclerosis, Focal Segmental; HIV Infections; Humans; Lipoproteins, HDL; Nigeria; Renal Insufficiency, Chronic; Risk Factors
PubMed: 36227935
DOI: 10.1371/journal.pone.0275949