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Chronic, Acute, and Reactivated HIV Infection in Humanized Immunodeficient Mouse Models
Published on: December 3, 2019
HIV and chronic kidney disease
Saraladevi Naicker1, Sadaf Rahmanian, Jeffrey B Kopp
1Division of Nephrology, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa, and Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Insights
Chronic kidney disease (CKD) is a significant complication of HIV infection. Early detection and access to antiretroviral therapy (ART) improve kidney health and survival rates in HIV patients.
Area of Science:
- Nephrology
- Infectious Diseases
- Genetics
Background:
- Chronic kidney disease (CKD) affects 3.5-48.5% of individuals with HIV infection.
- Kidney disease in HIV is multifactorial, involving the virus, host genetics (e.g., APOL1 variants), and co-infections.
- HIV-associated nephropathy (HIVAN) and HIV-immune complex disease are key renal manifestations.
Purpose of the Study:
- To review the epidemiology, pathogenesis, and management of CKD in HIV-infected individuals.
- To highlight the impact of antiretroviral therapy (ART) on HIV-associated kidney disease.
- To discuss factors influencing CKD progression and renal survival in the context of HIV.
Main Methods:
- Literature review of studies on HIV-associated nephropathy and CKD.
- Analysis of factors contributing to HIV-CKD, including genetic predisposition and co-morbidities.
- Evaluation of the role of ART, dialysis, and kidney transplantation in HIV-CKD management.
Main Results:
- ART has reduced HIVAN incidence but focal segmental glomerulosclerosis is increasing.
- ART initiation improves kidney function in HIV-CKD patients.
- High-grade proteinuria, reduced eGFR, co-infections, and glomerulosclerosis predict worse renal outcomes.
Conclusions:
- CKD is a complex complication of HIV requiring multifactorial management.
- Early screening for kidney disease and prompt ART initiation are crucial for improving outcomes.
- Renal survival is enhanced by renin-angiotensin system blockers and viral suppression.
Abstract:
Chronic kidney disease (CKD) is a frequent complication of HIV infection, occurring in 3.5 - 48.5%, and occurs as a complication of HIV infection, other co-morbid disease and infections and as a consequence of therapy of HIV infection and its complications. The classic involvement of the kidney by HIV infection is HIV-associated nephropathy (HIVAN), occurring typically in young adults of African ancestry with advanced HIV disease in association with APOL1 high-risk variants. HIV-immune complex disease is the second most common diagnosis obtained from biopsies of patients with HIV-CKD. CKD is mediated by factors related to the virus, host genetic predisposition and environmental factors. The host response to HIV infection may influence disease phenotype through activation of cytokine pathways. With the introduction of antiretroviral therapy (ART), there has been a decline in the incidence of HIVAN, with an increasing prevalence of focal segmental glomerulosclerosis. Several studies have demonstrated the overall improvement in kidney function when initiating ART for HIV CKD. Progression to end stage kidney disease has been reported to be more likely when high grade proteinuria, severely reduced eGFR, hepatitis B and/C co-infection, diabetes mellitus, extensive glomerulosclerosis, and chronic interstitial fibrosis are present. Improved renal survival is associated with use of renin angiotensin system blockers and viral suppression. Many antiretroviral medications are partially or completely eliminated by the kidney and require dose adjustment in CKD. Certain drug classes, such as the protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, are metabolized by the liver and do not require dose adjustment. HIV-infected patients requiring either hemo- or peritoneal dialysis, who are stable on ART, are achieving survival rates comparable to those of dialysis patients without HIV infection. Kidney transplantation has been performed successfully in HIV-infected patients; graft and patient survival appears to be similar to that of HIV-uninfected recipients. Early detection of kidney disease by implementation of screening on diagnosis of HIV infection and annual screening thereafter will have an impact on the burden of disease, together with access to ART to those who require it. Programs for prevention of HIV infection are essential to prevent this lethal disease.
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