A charge selectivity impairment in protein permselectivity is present in type 2 diabetes

Abstract

A possible loss in kidney charge permselectivity of proteins before any manifestation of nephropathy has been sought in type 2 (non-insulin-dependent) diabetes by assessing the clearances of proteins differing in charge and/or size (anionic and cationic immunoglobulins, albumin). Eighty-five consecutive outpatients with type 2 diabetes were studied and compared with 101 normal subjects. Of the patients, 14.1% wree microalbuminuric and 2.3% macroalbuminuric. A significant increase in protein clearances was observed in diabetic patients in comparison with normal subjects: the median of albumin clearance was 0.09 ml/min, interquartile range (IR) 0.04–0.31 (P<0.01 vs normals); that of anionic immunoglobulins (IgG4) 0.02 ml/min, IR 0.01–0.05 (P<0.005 vs normals); and that of neutral/cationic immunoglobulins (IgG) 0.13 ml/min, IR 0.07–0.19 (P<0.01 vs normals). The anionic/cationic immunoglobulin ratio median was 0.22, IR 0.11–0.43, and exceeded the upper limit of normal values in 29.4% of all patients. IgG4 clearance was positively correlated with albumin clearance (r=0.72) and with IgG clearance (r=0.98). Nevertheless anionic immunoglobulin clearance was increased in a number of patients (17.3%) with normal IgG excretion and even in patiens (15.1%) with normal albumin clearance. Clearances of IgG4 and IgG, but not that of albumin, were correlated with the duration of diabetes. Thus, an increased anionic/cationic IgG ratio in type 2 diabetes highlights a charge selectivity defect in protein permselectivity; this selective proteinuria may reflect more accurately than does microalbuminuria an early kidney abnormality in this form of diabetes.