VITAMIN D DEFICIENCY AGGRAVATES TENOFOVIR INDUCED METABOLIC SYNDROME AND RENAL FAILURE

Abstract

Introduction and Aims:Vitamin D deficiency (VDD) is highly prevalent among HIV-infected individuals. Tenofovir disoproxil fumarate (TDF), a widely used component of antiretroviral regimens for HIV treatment, has been associated with comorbidities, some of which have been attributed to renal toxicity and metabolic syndrome. The aim of the study was to investigate the effect of VDD on TDF treated rats. Methods:Wistar rats were randomly divided into four groups: control (C, n = 9), receiving a standard diet for 60 days; VDD (n = 6), receiving a free-vitamin D diet for 60 days; TDF (n = 9), receiving a standard diet for 60 days with the addition of TDF (50 mg/kg food) for the last 30 days; and VDD+TDF (n = 7) received a free-vitamin D diet for 60 days with the addition of TDF (50 mg/kg food) for the last 30 days. We measured inulin clearance (GFR, mL/min/100g); blood pressure (BP, mmHg), renal blood flow and calculated renal vascular resistance (RVR, mmHg/mL/min); serum levels of 25-hydroxyvitamin D (25(OH)D, ng/mL), cholesterol (mg/dL) and triglycerides (mg/dL); urinary sodium excretion (UVNa,mEq/24h). In renal tissue, we immunoblotted for angiotensin II (AII), endothelial nitric oxide synthase (eNOS) and vitamin D receptor (VDR). Data are expressed as mean ± SEM. Results:Vitamin D levels were similar in C (15.4±1 ng/mL) and TDF (14.8±1.3 ng/mL) groups and <1.5 ng/mL in VDD groups. Body weight, water intake and food ingestion were not different among the 4 groups. Treatment with TDF led to impaired renal function, hypertension, higher RVR and dyslipidemia. Administration of TDF also increased protein expression of AII and VDR. Association of TDF and VDD exacerbates TDF nephrotoxicity, as well as metabolic syndrome. Furthermore, VDD+TDF group showed urinary sodium retention. The increased VDR protein expression in TDF groups may represent a compensatory effect to decrease renal injury. Conclusions:VDD aggravates renovascular effects and TDF-induced renal failure at least in part due to the involvement of renin-angiotensin-aldosterone system. Therefore, the assessment of vitamin D is important in HIV patients receiving TDF.