Increased Glomerular Hydrostatic Pressure is Associated with Tubular Creatinine Reabsorption in Healthy Subjects

<b><i>Background:</i></b> Cr is secreted by the proximal tubules and thus Cr clearance (<i>C</i>_cr) can overestimate inulin clearance (<i>C</i>_in). However, in some cases, <i>C</i>_cr can even underestimate <i>C</i>_in. This suggests that Cr could be reabsorbed in the tubuli. We examined the clinical parameters that are associated with tubular Cr reabsorption. <b><i>Methods:</i></b> In 80 kidney donor candidates (53.9 ± 13.2 years, 29 males), <i>C</i>_in and para-aminohippuric acid clearance were measured simultaneously. Intrarenal hemodynamic parameters were calculated by Gomez’s formulae. To quantify the secretory component of <i>C</i>_cr (SF_cr), it was calculated as follows: SF_cr = (<i>C</i>_cr − <i>C</i>_in)/<i>C</i>_cr. <b><i>Results:</i></b> Twenty-five subjects (31.3%) showed SF_cr values &#x3c;0. SF_cr that correlated significantly and negatively with efferent arteriolar resistance (<i>R</i>_e) and glomerular hydrostatic pressure (<i>P</i>_glo) (<i>R</i>_e: <i>r</i> = −0.30, <i>p</i> = 0.008; <i>P</i>_glo: <i>r</i> = −0.28, <i>p</i> = 0.025). In multiple regression analyses, <i>R</i>_e and <i>P</i>_glo were significantly and negatively associated with SF_cr after adjustment for other confounders. <b><i>Conclusions:</i></b> These findings suggest that tubular reabsorption of Cr can occur in some cases. Intrarenal glomerular hemodynamic burden may be related to tubular creatinine reabsorption, which possibly leads to lower <i>C</i>_cr values.

Dietary protein affects urea transport across rat urothelia

Recent evidence suggests that regulated solute transport occurs across mammalian lower urinary tract epithelia (urothelia). To study the effects of dietary protein on net urothelial transport of urea, creatinine, and water, we used an in vivo rat bladder model designed to mimic physiological conditions. We placed groups of rats on 3-wk diets differing only by protein content (40, 18, 6, and 2%) and instilled 0.3 ml of collected urine in the isolated bladder of anesthetized rats. After 1 h dwell, retrieved urine volumes were unchanged, but mean urea nitrogen (UN) and creatinine concentrations fell 17 and 4%, respectively, indicating transurothelial urea and creatinine reabsorption. The fall in UN (but not creatinine) concentration was greatest in high protein (40%) rats, 584 mg/dl, and progressively less in rats receiving lower protein content: 18% diet, 224 mg/dl; 6% diet, 135 mg/dl; and 2% diet, 87 mg/dl. The quantity of urea reabsorbed was directly related to a urine factor, likely the concentration of urea in the instilled urine. In contrast, the percentage of instilled urea reabsorbed was greater in the two dietary groups receiving the lowest protein (26 and 23%) than in those receiving higher protein (11 and 9%), suggesting the possibility that a bladder/urothelial factor, also affected by dietary protein, may have altered bladder permeability. These findings demonstrate significant regulated urea transport across the urothelium, resulting in alteration of urine excreted by the kidneys, and add to the growing evidence that the lower urinary tract may play an unappreciated role in mammalian solute homeostasis.