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      HIV and kidney diseases: 35 years of history and consequences

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          Abstract

          Kidney diseases in human immunodeficiency virus (HIV)-infected patients are often misdiagnosed. Despite reductions in morbidity and mortality owing to widespread use of highly effective combination antiretroviral therapy (cART), acute kidney injury (AKI) and chronic kidney disease (CKD) are still more common in these patients than in the general population, and are associated with poor health outcomes. HIV-associated nephropathy and HIV immune complex kidney diseases are the more recognizable HIV-related kidney diseases. However, a broad spectrum of kidney disorders related or not directly related with HIV infection can be observed, including cART-induced AKI, CKD, proximal tubular dysfunction, crystalluria and urolithiasis, among others. This review summarizes the major epidemiologic studies of kidney diseases in HIV-infected patients, discusses novel approaches that may potentially limit nephrotoxicity such as the use of tenofovir alafenamide, and outlines current screening measures for early diagnosis of kidney dysfunction or tubular damage, and for accurate detection of increased risk for acute or chronic kidney diseases.

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          Causes of death among persons with AIDS in the era of highly active antiretroviral therapy: New York City.

          Lucia V Torian, R Pfeiffer, Judith E Sackoff … (2006)
          Monitoring the full spectrum of causes of death among persons with AIDS is increasingly important as survival improves because of highly active antiretroviral therapy. To describe recent trends in deaths due to HIV-related and non-HIV-related causes among persons with AIDS, identify factors associated with these deaths, and identify leading causes of non-HIV-related deaths. Population-based cohort analysis. New York City. All adults (age > or =13 years) living with AIDS between 1999 and 2004 who were reported to the New York City HIV/AIDS Reporting System and Vital Statistics Registry through 2004 (n = 68,669). Underlying cause of death on the death certificate. Between 1999 and 2004, the percentage of deaths due to non-HIV-related causes increased by 32.8% (from 19.8% to 26.3%; P = 0.015). The age-adjusted mortality rate decreased by 49.6 deaths per 10,000 persons with AIDS (P < 0.001) annually for HIV-related causes but only by 7.5 deaths per 10 000 persons with AIDS (P = 0.004) annually for non-HIV-related causes. Of deaths due to non-HIV-related causes, 76% could be attributed to substance abuse, cardiovascular disease, or a non-AIDS-defining type of cancer. Compared with men who have sex with men, injection drug users had a statistically significantly increased risk for death due to HIV-related causes (hazard ratio, 1.59 [95% CI, 1.49 to 1.70]) and non-HIV-related causes (hazard ratio, 2.54 [CI, 2.24 to 2.87]). Compared with autopsy and chart review, death certificates may lack specificity in the underlying cause of death or detailed clinical and treatment-related information. Non-HIV-related causes of death account for one fourth of all deaths of persons with AIDS. Cardiovascular disease, non-AIDS-defining cancer, and substance abuse account for most non-HIV-related deaths. Reducing deaths from these causes requires a shift in the health care model for persons with AIDS from a primary focus on managing HIV infection to providing care that addresses all aspects of physical and mental health.
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            Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America.

            Gregory Lucas, Michael J Ross, Peter Stock … (2014)
            It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
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              Tenofovir nephrotoxicity: acute tubular necrosis with distinctive clinical, pathological, and mitochondrial abnormalities.

              Vivette D. D'Agati, Sumit Mohan, M. Stokes … (2010)
              Tenofovir, a widely prescribed antiretroviral medication for treatment of HIV-1 infection, is infrequently associated with renal dysfunction and biopsy findings of acute tubular necrosis. We examined the clinical and pathological findings in 13 cases of tenofovir nephrotoxicity (7 men and 6 women, mean age of 51.1±9.6 years). Patients received tenofovir therapy for a mean of 19.6 months (range, 3 weeks to 8 years; median 8 months). Nine patients presented with acute kidney injury, and four had mild renal insufficiency with subnephrotic proteinuria. Mean baseline serum creatinine was 1.3±0.3 mg/dl, reaching 5.7±4.0 mg/dl at the time of biopsy, with mean proteinuria of 1.6±0.3 g/day. Glycosuria was documented in seven patients, five of whom were normoglycemic. Renal biopsy revealed toxic acute tubular necrosis, with distinctive proximal tubular eosinophilic inclusions representing giant mitochondria visible by light microscopy. Electron microscopy showed mitochondrial enlargement, depletion, and dysmorphic changes. Clinical follow-up after tenofovir discontinuation was available for 11 of 13 patients (mean duration 13.6 months). Significant recovery of renal function occurred in all patients, including four who required transient hemodialysis. Our study shows that tenofovir nephrotoxicity is a largely reversible form of toxic acute tubular necrosis targeting proximal tubules and manifesting distinctive light microscopic and ultrastructural features of mitochondrial injury.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Kidney J
                Journal ID (iso-abbrev): Clin Kidney J
                Journal ID (publisher-id): ckj
                Journal ID (hwp): ndtplus
                Title: Clinical Kidney Journal
                Publisher: Oxford University Press
                ISSN (Print): 2048-8505
                ISSN (Electronic): 2048-8513
                Publication date (Print): December 2016
                Publication date (Electronic): 25 October 2016
                Publication date PMC-release: 25 October 2016
                Volume: 9
                Issue: 6
                Pages: 772-781
                Affiliations
                [1 ]Nephrology Department, Hospital Fernando Fonseca, Lisbon, Portugal
                [2 ]IIS-Fundación Jiménez Díaz, School of Medicine, UAM and IRSIN, Madrid, Spain
                [3 ]Iberoamerican CKD Research Network (IBERERC), Madrid, Spain
                [4 ]Chronic Diseases Research Center-CEDOC-FCM, Nova Medical School, Lisbon, Lisbon, Portugal
                Author notes
                Correspondence and offprint requests to: Karina Soto; E-mail: ksoto.nefro@ 123456gmail.com
                Article
                Publisher ID: sfw104
                DOI: 10.1093/ckj/sfw104
                PMC ID: 5162418
                PubMed ID: 27994853
                SO-VID: b9e934c8-cd9d-42cd-9e5a-2e4102dbbed0
                Copyright © © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                Date received : 29 April 2016
                Date accepted : 15 September 2016
                Page count
                Pages: 10
                Categories
                Subject: Systemic Disease and the Kidney

                ScienceOpen disciplines: Nephrology
                Keywords: acute kidney injury,antiretroviral,chronic kidney disease,hiv,nephropathy
                Data availability:
                ScienceOpen disciplines: Nephrology
                Keywords: acute kidney injury, antiretroviral, chronic kidney disease, hiv, nephropathy

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