Evaluation of glomerular filtration rate in HIV-1-infected patients before and after combined antiretroviral therapy exposure*

Abstract

The prevalence and factors associated with an increased risk of renal dysfunction in HIV-infected patients receiving or not receiving antiretroviral therapy (ART) have been poorly evaluated in observational settings. MethodsPatients in the ICONA Foundation cohort with at least two creatinine values available while still ART-naïve were enrolled in the study. A logistic regression analysis was performed to identify predictors of an estimated glomerular filtration rate (eGFR)o90 mL/min/1.73 m 2 at baseline. The incidence and predictors of a 420% reduction in eGFR from pre-combination ART (cART) levels (or a decrease from ! 90 to o90 mL/min/1.73 m 2 ) were evaluated by Poisson regression. ResultsA total of 1505 patients were included in the study; 363 (24%) had eGFRo90 mL/min/1.73 m 2 at baseline. Older patients [odds ratio (OR) 1.58 per 10 years older; Po0.00001], female patients (OR 2.41 vs. male patients; Po0.00001), those who had diabetes and/or hypertension (OR 2.36 vs. neither; Po0.03) and patients with higher baseline CD4 count (OR 1.06 per 100 cells/mL higher; Po0.03) showed a greater risk of eGFRo90 mL/min/1.73 m 2 . Ninety-six patients experienced an eGFR decrease of 420% from pre-cART levels (6.8 per 100 person-years). Older age [relative risk (RR) 1.41 per 10 years older; P 5 0.005], female gender (RR 2.25 vs. male; P 5 0.003) and current exposure to didanosine (ddI), tenofovir and protease inhibitors were the major determinants. ConclusionsWe observed a relatively high rate of mild renal dysfunction in the absence of ART. In addition to traditional risk factors such as older age and diabetes/hypertension, female gender and current use of ddI, tenofovir and protease inhibitors were associated with a greater risk of decreased renal function as measured by eGFR.Keywords: antiretroviral exposure, estimated glomerular filtration rate (eGFR), renal impairment [7][8][9][10][11], there are a number of other factors potentially influencing the onset of renal disorders through different mechanisms, whose prevalence may be different in an HIV-positive population compared with the general population. Indeed, patients' longer survival following the introduction of cART may be considered as an additional risk for renal dysfunction, as long-term toxic events associated with the prolonged used of ART have been observed (e.g. metabolic alterations, diabetes, hypertension and cardiovascular events) [12][13][14]. It has been hypothesized that antiretroviral medications may have a direct effect in increasing the risk of renal dysfunction, and a variety of cART-related effects, including proteinuria, renal tubular damage, interstitial nephritis and overall declines in glomerular filtration rates, have been noted [15][16][17][18][19][20][21][22][23].The potential role of tenofovir in renal toxicity is a current clinical research question. As a consequence of its tolerability, convenient dosing and efficacy, this nucleoside reverse transcriptase inhibitor (NRTI) has been widely used as a component of cART regimens. There are...

High Prevalence of Signs of Renal Damage Despite Normal Renal Function in a Cohort of HIV-Infected Patients: Evaluation of Associated Factors

“…Results from European cohorts show a prevalence of kidney disease (eGFR < 60 mL/ min/1.73 m 2 ) to be 2-5%. [21][22][23] The relatively low median age (48 years) of our patients likely explains this finding. However, the high prevalence of patients with signs of renal damage, most of whom had an eGFR > 60 mL/min/1.73 m 2 is similar to other results recently reported elsewhere, 21 and, contrary, is lower than others regarding the proportion of proteinuria detected.…”

“…However, the high prevalence of patients with signs of renal damage, most of whom had an eGFR > 60 mL/min/1.73 m 2 is similar to other results recently reported elsewhere, 21 and, contrary, is lower than others regarding the proportion of proteinuria detected. 23 Interestingly, these others signs of renal damage (no only AUC or UPC altered) could appear earlier than proteinuria in the case of renal alteration, and this is a possible explanation of the differences in the results regarding the distinct parameters evaluated. it should be take in consideration in order to early detect and manage this alterations, even when a normal eGFR is present.…”

Simulating the development and progression of Chronic Kidney Disease and osteoporosis in people living with HIV

“…The incidence of HIV-associated kidney disease markedly decreased after the introduction of ART and any increase in the incidence of kidney disease may be attributed to aging and traditional associated risk factors like diabetes and hypertension [5] and as a side effect of ARTs themselves [6][7][8]. ARTs are recommended for all symptomatic patients and those asymptomatic with CD4 cell count below 350/μL [9].…”

“…Therefore, renal function assessment before and after initiation is critical; and in patients with renal dysfunction, tenofovir is better avoided [9]. This safety concern was observed to a lesser extent with other ARTs [6][7][8], yet more studied and confirmed with tenofovir [13][14][15]. In clinical practice, another problem arises regarding assessing the long term renal safety of tenofovir due to higher discontinuation rates with decreasing eGFR [7].…”

“…Five HIV-specific CKD risk factors were identified in the literature and incorporated in the model basing on the results of comparative studies: -PLHIV versus HIV-uninfected people [14]; -Late-stage HIV infection versus non-AIDS PLHIV [14]; -ART versus treatment-naïve PLHIV [14]; -Nucleoside reverse transcriptase inhibitors (NRTIs) pair: -specific for each drugs [6]; -including vs not including tenofovir [13]. -Third drug prescription [6].…”