CLEARANCE RATIOS OF AMYLASE ISOENZYMES AND IGG SUBCLASSES - DO THEY REFLECT GLOMERULAR CHARGE SELECTIVITY

The clearance ratios of endogenous plasma proteins with the same size but a different charge, such as the amylase isoenzymes and the immunog lobulin (Ig) G subclasses, have been used to assess glomerular charge selectivity in man, These proteins are, however, subject to tubular re absorption, In this study we measured the IgG subclass/IgG clearance r atios for IgG1 (pI 8.0-9.5), IgG2 (pI 7.0-7.5) and IgG4 (pI < 6) in 6 healthy volunteers. Our results suggested a selective influence of tub ular reabsorption: the IgG1/IgG clearance ratio was 0.68 +/- 0.14 (mea n +/- SD) and lower than IgG2/IgG (2.02 +/- 1.06, p less than or equal to 0.01), IgG4/IgG was 0.89 +/- 0.39. In addition, we studied the cle arance ratios of pancreatic (PA, pI 7.0) and salivary amylase (SA, pI 5.9-6.4) and of IgG1 and IgG2 in 8 patients with minimal change nephro tic syndrome (MCNS), 11 patients recovering from acute tubular necrosi s (ATN) and 9 healthy volunteers (controls), In MCNS glomerular charge selectivity is lost, while in recovering ATN tubular function is seve rely disturbed. The PA/SA clearance ratio was 3.25 +/- 0.89 in control s, reflecting intact glomerular charge selectivity. In MCNS patients t he PA/SA clearance ratio had decreased to 1.21 +/- 0.23 (p less than o r equal to 0.001). In ATN patients the PA/SA clearance ratio was reduc ed as well: 1.55 +/- 0.41 (p less than or equal to 0.001), although th e aselective nature of the proteinuria and the modest albuminuria indi cated intact. glomerular charge selectivity, The IgG1/IgG2 clearance r atio was 0.54 +/- 0.15 in controls, again suggesting preferential tubu lar reabsorption of IgG1. In MCNS patients the IgG1/IgG2 clearance rat io was 0.16 +/- 0.10 (p less than or equal to 0.001); this probably re flects the relatively increased glomerular sieving of IgG2 when glomer ular charge selectivity is lost. In ATN patients the IgG1/IgG2 clearan ce ratio was 1.07 +/- 0.37 (p less than or equal to 0.001), which sugg ests a partial loss of preferential reabsorption of IgG1, It was concl uded that the PA/SA clearance ratio is influenced by loss of tubular f unction and therefore does not reflect glomerular charge selectivity s pecifically, The IgG1/IgG2 ratio cannot be used to assess glomerular c harge selectivity either because of the interference of selective tubu lar reabsorption of the subclasses, These findings put the assessment of glomerular charge using endogenous proteins in a new light and brin g forward the necessity to interpret these ratios with the outmost cau tiousness.