Abstract

BackgroundRisk factors for and optimal surveillance of renal dysfunction in patients on tenofovir disoproxil fumarate (TDF) remain unclear. We investigated whether a urine protein-osmolality (P/O) ratio would be associated with renal dysfunction in HIV-infected persons on TDF.MethodsThis retrospective, single-center study investigated the relationship between parameters of renal function (estimated glomerular filtration rate (eGFR) and P/O-ratio) and risk factors for development of kidney dysfunction. Subjects were HIV-infected adults receiving TDF with at least one urinalysis and serum creatinine performed between 2010 and 2013. Regression analyses were used to analyze risk factors associated with abnormal P/O-ratio and abnormal eGFR during TDF therapy.ResultsPatients were predominately male (81%); (65%) were Caucasian. Mean age was 45.1(±11.8) years; median [IQR] TDF duration was 3.3 years. [1.5–7.6]. Median CD4+ T cell count and HIV viral load were 451 cells/μL [267.5–721.5] and 62 copies/mL [0–40,150], respectively. Abnormal P/O-ratio was not associated with low eGFR. 68% of subjects had an abnormal P/O-ratio and 9% had low eGFR. Duration of TDF use, age, diabetes and hypertension were associated with renal dysfunction in this study. After adjustment for age, subjects on TDF > 5 years had almost a four-fold increased likelihood of having an abnormal P/O-ratio than subjects on TDF for < 1yr (OR 3.9; 95% CI 1.2–14.0; p = 0.024).ConclusionAbnormal P/O-ratio is common in HIV-infected patients on TDF but was not significantly associated with low eGFR, suggesting that abnormal P/O-ratio may be a very early biomarker of decreased renal function in HIV infected patients.

Highlights

  • Chronic kidney disease in persons infected with HIV is an important part of the changing epidemiology of the disease

  • Duration of tenofovir disoproxil fumarate (TDF) use, age, diabetes and hypertension were associated with renal dysfunction in this study

  • Increasing age was significantly associated with abnormal renal function on TDF as determined by P/O-ratio and estimated glomerular filtration rate (eGFR), which corresponds with findings from previous studies that TDF-containing regimens should be used with caution in older subjects or those with diabetes. [4, 15]

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Summary

Introduction

Chronic kidney disease in persons infected with HIV is an important part of the changing epidemiology of the disease. [3, 6,7,8] The proposed mechanism of renal injury is an independent direct cytotoxic effect by proximal tubular accumulation of the drug and prevention of organic acid transport.[6, 9] After ingestion, TDF undergoes rapid plasma metabolism to TFV, which is subsequently phosphorylated to its active form TFV-diphosphate within cells. It is the circulating plasma TFV which undergoes both glomerular filtration and tubular secretion in the kidneys by the organic acid transporters (OAT). We investigated whether a urine protein-osmolality (P/O) ratio would be associated with renal dysfunction in HIV-infected persons on TDF.

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