No 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% were 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 0.04-0.05 (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 patients (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.

To investigate the role of protein charge in early diabetic proteinuria, the clearance of proteins differing in charge and/or size (anionic and cationic Igs, albumin) was evaluated in 98 insulin-dependent (type I) diabetic patients selected as a representative sample of the 418 patients attending our clinics. Of the patients, 12.9% were microalbuminuric and 4.8% were macroalbuminuric. Anionic and total IgG clearances were significantly increased in 30.6 and 12.2% of patients and were correlated with duration of disease. Anionic IgG4 clearances were increased in patients (9.2%) with normal IgG excretion, suggesting that charge-selectivity impairment is responsible for protein loss. Anionic Ig clearances were also higher in some patients (14.3%) with normal albumin clearance, probably as a result of different glomerular filtration and/or tubular reabsorption. The anionic-cationic IgG clearance ratio tended to increase in parallel with albumin clearance, but once above macroalbuminuric levels, it tended to fall again, indicating the concomitant presence of size-selectivity loss. The anionic IgG clearance and the anionic-cationic IgG ratio, in addition to albumin excretion, may be valuable in assessing early kidney protein charge-selectivity impairment and better characterizing normoalbuminuric patients and those in the preclinical stage of diabetic nephropathy.

No abstract

Renal protein charge permselectivity is impaired in 40% of patients with IBD with no overt proteinuria. Our data suggest that altered IgG(4) clearance may represent a subclinical marker of renal involvement in IBD.