Influence of urine pH on accurate urinary protein determination in Sprague-Dawley rats.

Abstract

BACKGROUND: Rat urinary protein concentration is commonly measured during safety assessment studies to evaluate potential drug-induced nephrotoxicity. It has been reported that impregnated reagent test strips (dipsticks) can yield false-positive urinary protein results for alkaline urine samples. OBJECTIVE: The objective of this study was to determine if urinary dipsticks accurately assess protein concentrations, especially in alkaline rat urine. METHODS: Ten male Sprague-Dawley rats were treated with 2% sodium bicarbonate and 2% ammonium chloride to alkalinize and acidify the urine, respectively. Urine pH was measured in treated and control rats using a pH meter and urinary dipsticks with the Clinitek 500. Quantitative urinary protein results were compared to urinary dipstick protein evaluations obtained with the Clinitek 500 and sulfosalicylic acid precipitation test methods. RESULTS: The urinary dipstick pH measurement had a very high correlation (r = .98) with the pH meter technique. Samples with alkaline pH (>or=7.5) analyzed for protein by dipstick analysis were in complete agreement 34.7% of the time with the quantitative technique, which was very similar to the 39.3% agreement for samples with neutral and acidic pH (<or=7.0). Samples with alkaline pH analyzed by the sulfosalicylic acid method were in agreement 0% of the time with the quantitative technique, compared to 7.1% of the time with samples with neutral or acidic pH. CONCLUSION: The urine dipstick method does not lead to gross overestimation of urinary protein concentration in alkaline urine and provides a rapid and reasonably accurate way of determining the presence or absence of urinary protein in rats.