MEASUREMENT OF GLOMERULAR CHARGE SELECTIVITY IN NONDIABETIC RENAL-DISEASE

Background. Until now, the renal clearance index of IgG to IgG4 (IgG/I gG4) as well as pancreatic to salivary amylase (PA/SA) were separately used as parameters of renal charge selectivity in diabetic and non-di abetic albuminuria. The suitability of the IgG index may be questioned becuase urinary loss of IgG rather reflects a size selective defect. In contrast, the amylase index seems more appropriate to reflect renal charge selectivity because its molecular size is comparable to albumi n. We questioned whether IgG/IgG4 and PA/SA reflect renal charge selec tivity in a comparable way in subjects with non-diabetic albuminuria o ver a wide range. Methods. Renal fractional clearances of albumin, IgG , IgG4, PA and SA were estimated from ambulatory 24-h urine samples in 12 subjects with normoalbuminuria (UAE 4 [3-17] mu g/min), six with m icroalbuminuria (UAE: 147 [36-200] mu g/min), and 20 with macro-albumi nuria (UAE: 2301 [608-13611] mu g/min). Results. Macro-albuminuria is associated with a IgG/IgG4 and PA/SA, whereas microalbuminuria is only associated with a reduced IgG/IgG4 compared to normo-albuminuria. A r eduction of IgG/IgG4 (r = -0.75, P < 0.001) and PA/SA (r = -0.52, P < 0.001) correlates with an increased albuminuria. In addition, IgG/IgG4 correlates with PA/SA in the total population (r = 0.49, P < 0.01). I gG/IgG4 (r = 0.51, P < 0.05) correlates with the size selective index IgG/albumin in an opposite way to PA/SA (r = -0.52, P < 0.05) in 20 su bjects with macroalbuminuria. Multiple regression analysis revealed Ig G clearance to be the variable which contributes to the variance of al buminuria clearance for the greater part in our population. Conclusion . Both charge selective indices do not appear to correlate in micro-al buminuria. In addition. the presence of a size selective defect has a opposing effect on both charge selective indices. Although the reducti on of IgG/IgG4 and PA/SA with increasing albuminuria suggests a progre ssive charge selective defect, albuminuria in our population is almost entirely explained by urinary loss of IgG. These data seriously quest ion whether either one or both charge selective indices IgG/IgG4 and P A/SA do specifically reflect glomerular charge selectivity.