Influence of albumin infusion on the urinary excretion of β2-microglobulin in patients with proteinuria

Most filtered proteins are reabsorbed by the renal proximal tubule by a mechanism that involves binding to the brush border membrane and endocytosis. Under normal conditions the low-molecular-weight protein beta(2)-microglobulin (beta(2)M) which is used to detect tubular injury, is reabsorbed almost completely. However, in proteinuric patients an increased urinary excretion of beta(2)M may not simply reflect tubular damage but might also result from a decreased tubular reabsorption due to competitive mechanisms. To examine the magnitude of such an effect we have studied the renal effects of albumin infusion (40 g in 2 h of a 20% solution) in 10 patients with a glomerular disease and proteinuria >3.5 g/24 h. Before, during and after albumin infusion the GFR (inulin clearance), RPF (PAH clearance), blood pressure and the urinary excretion of albumin, IgG, transferrin and beta(2)M were measured. Albumin infusion resulted in a slight decrease of the GFR (72 +/- 11 ml/min before and 67 +/- 10 ml/min after infusion), an increase of the RPF (379 +/- 66 ml/min before and 445 +/- 83 ml/min after), a decrease of the filtration fraction (0.20 before and 0.17 after), and hemodilution. After infusion the urinary excretion of albumin increased from 4.5 +/- 0.7 to 8.4 +/- 1.6 mg/min (p < 0.05). The urinary excretion of IgG and transferrin increased, probably reflecting a change in glomerular size-selectivity. In contrast, the urinary excretion of beta(2)M did not change significantly (baseline 12 +/- 5 mu g/min, end 13 +/- 6 mu g/min, percentage change 16.8 +/- 11%). To correct for changes in tubular load we calculated the fractional reabsorption of beta(2)M The initial rise in albuminuria during infusion did not affect fractional tubular reabsorption (Delta%: 0.72 +/- 0.52%, median 0.005%). In the period after infusion a slight decrease was noted (median -0.33%, p < 0.01). A decrease in the fractional reabsorption was particularly observed in patients with pre-existing tubular damage. In conclusion: infusion of albumin in proteinuric patients has no clinically relevant effect on the tubular reabsorption of beta(2)M. Therefore, beta(2)M is useful as a parameter to detect tubular injury and alterations in tubular handling of proteins in patients with proteinuria and glomerular diseases.