Measurement of glomerular charge selectivity in non-diabetic renal disease.

Background: Until now, the renal clearance index of IgG to IgG4 (IgG/IgG4) as well as pancreatic to salivary amylase (PA/SA) were separately used as parameters of renal charge selectivity in diabetic and non-diabetic albuminuria. The suitability of the IgG index may be questioned because 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 albumin. We questioned whether IgG/IgG4 and PA/SA reflect renal charge selectivity in a comparable way in subjects with non-diabetic albuminuria over 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 normo-albuminuria (UAE 4 [3-17] micrograms/min), six with micro-albuminuria (UAE: 147[36-200] micrograms/min), and 20 with macro-albuminuria (UAE: 2301 [608-13611] micrograms/min).

Results: Macro-albuminuria is associated with a reduced IgG/IgG4 and PA/SA, whereas micro-albuminuria is only associated with a reduced IgG/IgG4 compared to normo-albuminuria. A reduction 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). IgG/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 subjects with macro-albuminuria. Multiple regression analysis revealed IgG clearance to be the variable which contributes to the variance of albuminuria clearance for the greater part in our population.

Conclusion: Both charge selective indices do not appear to correlate in micro-albuminuria. In addition, the presence of a size selective defect has a opposing effect on both charge selective indices. Although the reduction of IgG/IgG4 and PA/SA with increasing albuminuria suggests a progressive charge selective defect, albuminuria in our population is almost entirely explained by urinary loss of IgG. These data seriously question whether either one or both charge selective indices IgG/IgG4 and PA/SA do specifically reflect glomerular charge selectivity.