Important to monitor kidney function in HIV patients doing well

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The prevalence of impaired kidney function is low among white HIV-positive individuals with an undetectable viral load, Danish investigators report. However, the rate was still double that seen in closely matched HIV-negative controls (4% vs 2%), and as a risk factor for impaired kidney function, infection with HIV was on a par with diabetes. Older age accentuated the risk of renal impairment for people with HIV.

The authors believe their research is especially important as it focused on people with HIV who had an otherwise low risk of renal impairment, underlining the importance of monitoring kidney function as part of routine HIV care.

“This is the first study of its kind to compare prevalence and associated risk factors for renal impairment in a group of virologically suppressed people living with HIV with few confounding renal risks and a matched general population,” note the authors from department of infectious diseases, viro-immunology research unit, Rigshospitalet, Copenhagen, Institute for Global Health, UCL, London, Hvidovre Hospital, Copenhagen, University of Copenhagen and Herlev and Gentofte Hospital, Copenhagen. “Prevalence was still twice as high as that seen in the matched general cohort.”

Kidney disease is an increasingly important cause of serious illness and death among people with HIV. The exact reasons are unclear, but may include the inflammatory effects of untreated HIV infection, a high prevalence of traditional risk factors such as diabetes and hypertension, and possibly the side-effects of some antiretroviral drugs.

Previous research suggests that up to a third of people with HIV may have impaired kidney function. But a team of investigators in Copenhagen led by Dr N Petersen noted that for the most part these studies had included large numbers of people with additional risk factors for declining kidney function. These include ongoing HIV replication, co-infection with hepatitis C, injecting drug use and black race.

To untangle the association between HIV infection and impaired kidney function, Petersen and colleagues designed a cross-sectional study involving white HIV-positive, antiretroviral-treated patients in Copenhagen, all of whom had an undetectable viral load. Each person with HIV was matched with four individuals from the general population of the same age and sex.

The investigators compared the prevalence of impaired kidney function – estimated glomerular filtration rate < 60mL/min/1.73m2 – between the two populations. Socio-demographic data were collected from the participants’ notes, as was information on diabetes and hypertension. For the HIV-positive participants, the authors also collected data on current and nadir CD4 cell count, duration of infection with HIV and the use of antiretroviral drugs associated with kidney impairment.

Most of the participants were male (89%) and the median age was 51 years. Three-quarters of the HIV-positive participants were gay and bisexual men. The median current CD4 cell count was 700 cells/mm3 and the median time since diagnosis with HIV was 14 years. Approximately two-thirds of the HIV-positive people were taking tenofovir disoproxil fumarate (TDF), a drug associated with an increased risk of renal impairment. As regards traditional risk factors for declines in kidney function, the prevalence of hypertension was lower in the HIV-positive group compared to the controls (46% vs 57%), but the prevalence of diabetes was comparable between the two populations (5% vs 4%).

The prevalence of renal impairment was twice as high among the people with HIV than the controls (3.7% vs 1.7%, p = 0.001).

Even after taking into account potential confounders, infection with HIV was associated with a more than threefold increase in the risk of renal impairment (OR = 3.4; 95% CI, 1.8-6.3). The authors emphasise that this elevation in risk is comparable to the increase associated with diabetes (OR = 2.9; 95% CI, 1.3-6.7), a well-established risk factor for kidney disease.

Other risk factors included older age (a more than fivefold increase in risk per decade) and female sex (OR = 5.0; 95% CI, 2.5-9.8).

Having HIV accentuated the effects of age on the risk of renal impairment, in some cases tripling the odds seen in older HIV-negative participants compared to HIV-negative individuals of a similar age (OR 16 vs 5).

Separate analysis of the HIV-positive participants showed that no HIV-related factor, including treatment with TDF, was associated with kidney impairment.

“HIV status itself remains independently associated with impaired renal function, which suggests a pathway other than immunosuppression, ongoing viraemia and coinfections are driving the pathogenesis of renal impairment,” write the authors. “Impaired renal function, albeit relatively rare in virologically suppressed people living with HIV, therefore remains a concern requiring attention and monitoring.”

Abstract
Objectives: While renal impairment is reported more frequently in people living with HIV (PLWH) than in the general population, the PLWH samples in previous studies have generally been dominated by those at high renal risk.
Methods: Caucasian PLWH who were virologically suppressed on antiretroviral treatment and did not have injecting drug use or hepatitis C were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) study. Sex- and age-matched controls were recruited 1:4 from the Copenhagen General Population Study up to November 2016. We defined renal impairment as one measurement of estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2 , and assessed associated factors using adjusted logistic regression models. The impact of HIV-related factors was explored in a subanalysis.

Results: Among 598 PLWH and 2598 controls, the prevalence of renal impairment was 3.7% [95% confidence interval (CI) 2.3-5.5%] and 1.7% (95% CI 1.2-2.2%; P = 0.0014), respectively. After adjustment, HIV status was independently associated with renal impairment [odds ratio (OR) 3.4; 95% CI 1.8-6.3]. In addition, older age [OR 5.4 (95% CI 3.9-7.5) per 10 years], female sex [OR 5.0 (95% CI 2.6-9.8)] and diabetes [OR 2.9 (95% CI 1.3-6.7)] were strongly associated with renal impairment. The association between HIV status and renal impairment became stronger with older age (P = 0.02 for interaction). Current and nadir CD4 counts, duration of HIV infection and previous AIDS-defining diagnosis were not associated with renal impairment among virologically suppressed PLWH.
Conclusions: The prevalence of renal impairment is low among low-risk virologically suppressed Caucasian PLWH, but remains significantly higher than in controls. Renal impairment therefore remains a concern in all PLWH and requires ongoing attention.

Authors
Petersen N, Knudsen AD, Mocroft A, Kirkegaard-Klitbo D, Arici E, Lundgren J, Benfield T, Oturai P, Nordestgaard BG, Feldt-Rasmussen B5, Nielsen SD, Ryom L

Aidsmap material HIV Medicine abstract

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