Glomerular permselectivity is dependent on adequate serum concentrations of orosomucoid

Abstract

Orosomucoid, or α1-acid glycoprotein, a serum protein known to be an 'acute phase reactant' has recently been shown to be needed for the maintenance of normal capillary permeability in skeletal muscle and mesentery. Therefore, we were interested in studying whether the glomerular capillary wall is affected by orosomucoid as well. For this purpose, left and right kidneys from nine rats (group A) were isolated and perfused in situ and in parallel using separate solutions of human albumin (1.8% in Tyrode), differing in their content of orosomucoid, one containing 0.21 g/liter, the other less than 0.005 g/liter. The temperature was kept at 8°C in order to minimize tubular reabsorption of fluid and albumin. The two kidneys showed identical and stable vascular resistances during the experiments. Also the glomerular filtration rates (GFR) were stable between 30 and 33 ml/min/100 g kidney. Initially, the two kidneys showed similar fractional albumin clearance (Θ) values of approximately 0.003. However, in the 'absence' of orosomucoid Θ increased to become four- to fivefold higher in the test kidney than in the control kidney at the end of the 1 1/2 hour experiment. This difference was observed in all rats, suggesting that orosomucoid is needed also for the maintenance of the glomerular permselectivity. In a separate group of eight animals (group B), orosomucoid-containing albumin solutions were used in parallel with horse serum solutions to perfuse the two kidneys of each rat, at 8°C. The same protocol as above was used, but no differences could be observed between the two perfusates, indicating that serum proteins other than albumin and orosomucoid are less important for the maintenance of normal capillary permeability. Orosomucoid probably exerts its action on the capillary wall by interacting with the capillary charge barrier. The results indicate that the glomerular barrier has major similarities with that of other capillary beds. Furthermore, the notion that the glomerular permselectivity can be modulated by a serum protein may have pathophysiological implications.