Effect of renal insufficiency on the concentration of free retinol-binding protein in urine and serum

Abstract

The concentration of retinol-binding protein (RBP) in urine was determined in 20 healthy individuals and 119 patients with various renal diseases involving tubular or glomerular dysfunction. The sera from 4 healthy individuals and 33 patients were chromatographed on Sephadex G-75 to measure the concentration of free (i.e. not prealbumin-bound) RBP. In healthy individuals, the mean concentration of free RBP in serum was 5.8 mg/l and represented 14% of total RBP; the renal clearance and the fractional tubular uptake of free RBP averaged 0.032 ml/min and 99.97%, respectively. In patients, the concentration of free RBP and the percentage of free RBP in serum were on logarithmic scales inversely correlated with the endogenous creatinine clearance ( r = −0.80 and −0.76) and increased in parallel with the serum creatinine ( r = 0.67 and 0.66) and β 2-microglobulin concentrations (β 2-m, r = 0.76 and 0.89). The semi-logarithmic plot of urine versus serum concentration of free RBP suggests a renal threshold for the tubular reabsorption of this protein at a concentration of about 25 mg/l in serum. The existence of this threshold is confirmed by the relationship between urinary RBP and serum β 2-m showing that urinary excretion of RBP is invariably high when the serum level of β 2-m exceeds 5 mg/l. The latter value corresponds precisely to the renal threshold for the tubular reabsorption of β 2-m. The corresponding value for free RBP derived from the relationship between both proteins is 24 mg/l. These renal thresholds for the tubular reabsorption of free RBP and β 2-m are reached when the endogenous creatinine clearance is reduced by > 70% (serum creatinine around 177 μmol/l or 20 mg/l). From this stage of renal insufficiency, the urinary excretion of both proteins cannot be used any more for the assessment of renal tubular function.