Plasma OLC is elevated in mild experimental uremia but is not associated with hypertension

Background: Little is known about the renal handling of endogenous ouabain-like compound (OLC). The aim of this study was to determine the normal renal clearance of OLC and the effect of mild experimental uremia on plasma OLC and its clearance. Methods: Male Wistar rats were studied 8 weeks after subtotal (5/6th) nephrectomy (n = 8) and compared with a control sham-operated group (n = 8). Results: Plasma creatinine and OLC were higher in uremic animals compared with controls (creatinine 76 ± 5.6 μmol/L v 45 ± 9.6 μmol/L, respectively, P< .00005; OLC 195 ± 62 pmol/L v 121 ± 62 pmol/L, P< .02). Creatinine clearance and OLC clearance were lower in uremic animals compared with controls (creatinine 1.06 ± 0.12 mL/min v 1.58 ± 0.32 mL/min, respectively, P< .002; OLC 23.6 ± 10.4 μL/min v 33.2 ± 11.4 μL/min, P< .05). There were no significant differences (all P> .05) between the uremic and control groups in the fractional clearance of OLC (uremic 2.3% ± 1.0% v control 2.2% ± 1.0%), OLC excretion rate (uremic 6.2 ± 2.4 pmol/24 h v control 5.0 ± 1.1 pmol/24 h) or in the mean systolic blood pressure (BP) (uremic 132 ± 13 mm Hg v control 126 ± 3 mm Hg). The amount of OLC excreted per unit of functioning nephron mass was 78% higher in uremic animals than in controls. The rate of tubular absorption varied linearly with filtered load, did not differ between groups, and showed no evidence of saturation. Conclusions: The kidneys are an important excretion route for plasma OLC and moderate but significant increases may occur without inducing hypertension in the short term. The low fractional clearance of OLC is most likely due to tubular absorption and/or catabolism.