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]
Summary
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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