Increased risk for dialysis found with HIV infection

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1 CATIE-News CATIE s bite-sized HIV and hepatitis C news bulletins. Increased risk for dialysis found with HIV infection 12 September 2013 In high-income countries such as Canada, Australia and the U.S. and in regions such as Western Europe, the widespread availability of potent combination anti-hiv therapy (commonly called ART or HAART) has greatly reduced deaths due to AIDS-related infections. Furthermore, some researchers are predicting that a young HIV-positive adult who begins ART today and who does not have major co-morbidities such as smoking, co-infection with viral hepatitis, mental health issues, substance use is likely to live for several decades, perhaps, in some cases, even experiencing a near-normal lifespan. Focus on the kidneys Researchers conducting experiments in the lab have found that HIV can infect some cells in the kidney. Studies in HIV-positive people have found that they are at risk for increased kidney injury and, over time, in some cases, impaired functioning of these vital organs. The kidneys perform many important functions, including filtering the blood of wastes and producing urine, regulating blood pressure, monitoring the level of oxygen in the blood and helping convert vitamin D to its active form. The role of treatment In cases where untreated HIV infection causes kidney dysfunction, commencing ART generally results in improvement of overall health and kidney health in particular. There have been reports of an elevated risk of kidney injury and dysfunction among some HIV-positive people who used the older anti-hiv drug indinavir (Crixivan). However, this drug is seldom used in high-income countries today. There have also been reports of kidney injury occurring among some users of the newer anti-hiv medicines atazanavir (Reyataz) and tenofovir (Viread, and found in Truvada, Atripla, Complera and Stribild). More information about these issues appears later in this bulletin as well as in the resources section. New research Researchers in Denmark have been monitoring the health of more than 5,000 HIV-positive people for up to 15 years. They compared data collected from HIV-positive people to that collected from more than 50,000 HIV-negative people of the same age and gender. Over the 15 years of the study the researchers found that there was an increased risk (nearly five-fold) among HIV-positive people of developing serious kidney injury requiring temporary or permanent dialysis compared to HIV-negative people. Further results from this study, including risk factors for serious kidney injury and the possible impact of HIV treatment on kidney health, appear later in this CATIE News bulletin. Study details For some time now, Danish researchers have established a high-quality data set containing health-related information from both HIV-positive and HIV-negative people. This allows researchers to analyse the data for trends in health-related issues. In the present analysis, data from 5,300 HIV-positive people were compared to data from 53,000 HIV-negative

2 people. Specifically, data from each HIV-positive person was compared to data from 10 HIV-negative people of the same age and gender. The average profile of the HIV-positive participants at the start of the study was as follows: gender 76% men, 24% women age 37 years race: white 79%; black 13%; other or unknown race 7% (numbers do not add up to 100 because of rounding) CD4+ count 290 cells Presence of co-morbidities that could impact kidney health: diabetes 2% higher-than-normal blood pressure 4% hepatitis C virus (HCV) infection in people who did not inject street drugs 7% people who injected street drugs 11% (most were likely HCV positive) Kidney function Distribution of egfr (estimated glomerular filtration rate one method for assessing kidney health) where an egfr greater than 90 is considered healthy and less than 60 is considered seriously abnormal: egfr greater than 90 34% egfr between 60 and 90 22% egfr less than 60 1% Note that egfr for 43% of participants at the start of the study was not available. Results During the study, 68 HIV-positive participants required at least temporary dialysis. Among HIV-negative participants, the figure was 182 people. This suggests that HIV-positive people were at nearly five-fold increased risk for serious kidney injury. This difference was statistically significant. The need for dialysis was greatest in the 12 months after an HIV diagnosis. Among the 68 HIV-positive people who required dialysis at least once, 28% had kidney health that grew worse over time and ultimately required dialysis on a regular basis. Results Risk factors Among HIV-positive people, the risk factors for serious kidney injury requiring a round of dialysis were as follows: injection of street drugs higher-than-normal blood pressure having an AIDS-related illness older age Risk factors for needing chronic dialysis were as follows: higher-than-normal blood pressure egfr less than 60 Specific ART In participants who used tenofovir, atazanavir or both drugs, there was no significant impact on kidney health. This was the case even when researchers restricted their analysis to the past decade, when atazanavir and tenofovir became available. Researchers explained that doctors who cared for patients in the study knew about the potential for drugs such as

3 atazanavir and tenofovir to cause kidney injury and dysfunction. These doctors, the researchers argued, would not have been likely to prescribe atazanavir or tenofovir (or both) to patients with kidney dysfunction. Furthermore, should kidney dysfunction have appeared, doctors would have discontinued these drugs. These practices may have helped reduce the risk of kidney injury and the need for dialysis among patients who took those medicines. Race, HIV and the kidneys Several other studies have found a connection between an increased risk of HIV-related kidney damage and being of African ancestry. This increased risk has been linked to the gene called Apol1, which is more commonly found in people of West and Central African ancestry. In the Danish study, most (70%) of black people were of East African descent. This could be one possible reason why the present study did not find any significant link between being black and serious kidney disease. AIDS-related illnesses The initial decrease in kidney function seen during the first year of an HIV diagnosis may have been related to the poor health of participants when they sought care. HIV infection causes inflammation, which can impair the functioning of the kidneys (and other organ-systems). Also, participants with an AIDS-related illness may have been weak, dehydrated and exposed to certain medicines (antibiotics, antifungal agents and so on) that could have injured the kidneys. All of these factors likely contributed to the poor state of kidney health and the need for at least temporary dialysis among some patients during their first year after an HIV diagnosis. After this time, the risk of dialysis was generally reduced, likely because use of ART improved overall health and kidney function. Bear in mind Although this was a cohort study, some of the findings from the Danish researchers have been seen in larger data sets in the European Union. Also, the fact that Danish researchers were able to compare data from each HIVpositive person to 10 HIV-negative people of the same age and gender was one of the strengths of this study. The Danish study s findings are important and underscore factors that can be addressed to improve the health of HIVpositive people and reduce the risk of developing serious kidney injury. These factors include the following: frequent testing for HIV (and other sexually transmitted infections) in sexually active adults so that this infection can be uncovered and treatment initiated before serious organ damage has developed and the immune system becomes weak screening HIV-positive patients for mental health issues and providing the psycho-social support to assist recovery from depression, anxiety and other issues that can lead to substance use and addiction screening HIV-positive patients for higher-than-normal blood pressure and treating this when found Resources Risk factors for kidney dysfunction TreatmentUpdate 195 Ask the Experts: Kidney Health The Positive Side Here s Lookin at You, Kidneys The Positive Side REFERENCES: Sean R. Hosein 1. Fierer DS, Klotman ME. Kidney and central nervous system as reservoirs of HIV infection. Current Opinion in HIV/AIDS Mar;1(2): Marras D, Bruggeman LA, Gao F, et al. Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy. Nature Medicine May;8(5): Winston JA, Bruggeman LA, Ross MD, et al. Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. New England Journal of Medicine Jun 28;344(26): Helleberg M, Afzal S, Kronborg G, et al. Mortality attributable to smoking among HIV-1-infected individuals: a nationwide, population-based cohort study. Clinical Infectious Diseases Mar;56(5): Simmons R, Ciancio B, Kall M, et al. Ten-year mortality trends among persons diagnosed with HIV infection in

4 England and Wales in the era of antiretroviral therapy: AIDS remains a silent killer. HIV Medic ine. 2013; in press. 6. Gustafson R, Montaner J, Sibbald B, et al. Seek and treat to optimize HIV and AIDS prevention. Canadian Medical Association Journal Dec 11;184(18): Sabin C. Review of life expectancy in people with HIV in settings with optimal ART access: what we know and what we don t. In: Program and abstracts of the 11th International Congress on Drug Therapy in HIV Infection, November 2012, Glasgow, UK. Abstract O May M, Gomples M, Sabin C, et al. Impact on life expectancy of late diagnosis and treatment of HIV-1 infected individuals: UK Collaborative HIV Cohort Study. In: Program and abstracts of the 11th International Congress on Drug Therapy in HIV Infection, November 2012, Glasgow, UK. Abstract O Lohse N, Hansen AB, Pedersen G, et al. Survival of persons with and without HIV infection in Denmark, Annals of Internal Medicine Jan 16;146(2): Lohse N, Hansen AB, Gerstoft J, et al. Improved survival in HIV-infected persons: consequences and perspectives. Journal of Antimicrobial Chemot herapy Sep;60(3): Søgaard OS, Lohse N, Østergaard L, et al. Morbidity and risk of subsequent diagnosis of HIV: a populationbased case control study identifying indicator diseases for HIV infection. PLoS One. 2012;7(3):e Rasch MG, Helleberg M, Feldt-Rasmussen B, et al. Increased risk of dialysis and end-stage renal disease among HIV patients in Denmark compared with background population. Nephrology, Dialysis, Transplantation. 2013; in press. 13. Harris RC, Neilson EG. Chapter 278. Adaption of the Kidney to Renal Injury. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison s Principles of Internal Medicine. 18 th ed. New York: McGraw- Hill; Bargman JM, Skorecki K. Chapter 280. Chronic Kidney Disease. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison s Principles of Internal Medicine. 18 th ed. New York: McGraw-Hill; Waikar SS, Bonventre JV. Chapter 279. Acute Kidney Injury. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison s Principles of Internal Medicine. 18 th ed. New York: McGraw-Hill; Ryom L, Mocroft A, Kirk O, et al. Exposure to antiretrovirals (ARVs) and risk of renal impairment among HIVpositive persons with normal baseline renal function: the D:A:D study. Journal of Infectious Diseases May 1;207(9): Fine DM, Gallant JE. Nephrotoxicity of antiretroviral agents: Is the list getting longer? Journal of Infectious Diseases May 1;207(9): Scherzer R, Estrella M, Li Y, et al. Association of tenofovir exposure with kidney disease risk in HIV infection. AIDS Apr 24;26(7): Jaffe JA, Kimmel PL. Chronic nephropathies of cocaine and heroin abuse: a critical review. Clinical Journal of the American Society of Nephrology Jul;1(4):

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