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  52nd ICAAC Interscience Conference on
Antimicrobial Agents and Chemotherapy
September 9-12, 2012, San Francisco
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Low-Grade Proteinuria in German HIV Group Tied to Tenofovir, ART Duration
  52nd ICAAC, September 9-12, 2012, San Francisco

Mark Mascolini

More than half of a German HIV group without high-grade proteinuria had low-grade proteinuria detected by spot urine samples [1]. Current tenofovir almost doubled the odds of low-grade proteinuria and taking antiretrovirals for more than 10 years upped the odds 70% in this cohort studied at Munich's Ludwig Maximilians University.

Antiretrovirals and HIV itself heighten the risk of chronic kidney disease. Clinical researchers in Munich hypothesized that low-grade proteinuria may be an easily detected early indicator of kidney trouble in people with HIV and that spotting it could point to modifiable risk factors. To chart rates of low-grade proteinuria (defined as a creatinine level from 100 to 499 mg/g) in adults with HIV, the investigators analyzed spot urine samples collected in an outpatient clinic between January 2009 and February 2011.

The study started with 518 people, 27 (5.2%) of whom had significant proteinuria (at or above 500 mg/g creatinine) and so were excluded from the low-grade analysis. Of the remaining 491 people, 391 (79.6%) were men and 404 (82.3%) Caucasian; 247 people (50.3%) had HIV infection more than 10 years. Median age stood at 45 years (range 20 to 82) and median CD4 count at 500.5.

Among 442 people (90%) taking antiretroviral therapy), treatment had lasted for a median of 7 years (range 0 to 23). More than half of the study group (60.5%) was taking tenofovir at the time of urinalysis. The next most frequently used antiretrovirals were emtricitabine (51.3%), ritonavir (36.5%), efavirenz (30.1%), and lamivudine (25.3%).

While 195 people (39.7%) smoked at the time of urine testing, 305 (62.1%) had ever smoked. Fifty people (10.2%) were taking antibiotics, usually cotrimoxazole. There were 125 people (25.5%) with a mean corpuscular volume above the upper limit of normal.

Urine creatinine levels lay below 100 mg/g in 215 people (43.8% of 491), while 276 (56.2%) had low-grade proteinuria. Univariate analysis identified an association between four antiretrovirals and low-grade proteinuria: tenofovir (odds ratio [OR] 1.684), nevirapine (OR 2.044), ritonavir (OR 1.685), and atazanavir (OR 1.938). In multivariate analysis current tenofovir was the only antiretroviral that independently predicted low-grade proteinuria, as did older age an array of clinical factors:

-- Every additional year of age: OR 1.05, 95% CI 1.03 to 1.07, P < 0.001

-- Current tenofovir: OR 1.89, 95% CI 1.27 to 2.88, P = 0.003

-- Body mass index under 25 kg/m(2): OR 1.62, 95% CI 1.07 to 2.47, P = 0.024

-- Current antibiotics: OR 2.49, 95% CI 1.22 to 5.08, P = 0.012

-- Mean corpuscular volume above upper limit or normal: OR 1.77, 95% CI 1.09 to 2.89, P = 0.022

-- Antiretroviral therapy more than 10 years: OR 1.72, 95% CI 1.11 to 2.67, P = 0.016

-- History of kidney disease: OR 5.69, 95% CI 1.59 to 20.35, P = 0.007

-- CDC stage C (AIDS): OR 1.54, 95% CI 0.990 to 2.39, P = 0.055

-- Anti-HCV EIA positive: OR 1.89, 95% CI 0.966 to 3.70, P = 0.063

The researchers suggested more studies are needed to determine whether switching from tenofovir to another agent will reverse or prevent low-grade proteinuria. They surmised that the univariate association between nevirapine and low-grade proteinuria may reflect more advanced disease in people prescribed nevirapine and its preferred use in people with cardiovascular risk because of its beneficial impact on lipids.

The investigators reminded clinicians that preventing proteinuria involves smoking cessation and substance abuse counseling, as well as review of current medications. Finally, they suggested that "monitoring quantitative spot urine samples may help to detect early renal dysfunction."


1. Zeder AJ, Hilge R, Bogner JR, Seybold U. Prevalence and risk factors of low grade proteinuria in HIV infected patients. 52nd Interscience Conference on Antimicrobials and Chemotherapy (ICAAC). September 9-12, 2012. San Francisco. Abstract H-887.