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   <subfield code="a">Clearance rate of immunoglobulins and diabetic nephropathy</subfield>
   <subfield code="h">[Elektronische Daten]</subfield>
   <subfield code="c">[U. Di Mario, R. Romano, S. Morano, P. Pietravalle]</subfield>
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   <subfield code="a">The interaction between the electrostatic charge of macromolecules and the fixed charges of glomerular basement membrane pores is of importance in protein permselectivity in addition to a number of other factors. In normal conditions anionic proteins are filtered to a lesser extent than cationic proteins of similar size and shape. In the early stages of diabetic nephropathy there are biochemical changes in the glomerulus, i.e. a decrease in glomerular fixed anionic charges, which lead to an increased vascular permeability to macromolecules. Attention has been focused on methods for detecting the initial permselectivity defects, to monitor the early preclinical stages of diabetic nephropathy over time. A promising methodological approach is the parallel evaluation of the clearance of two proteins similar in all main characteristics but differing in their electrostatic charge, i.e. the different subclasses of immunoglobulins. A preferential excretion of anionic molecules would be expected when a diabetic loss of charge selectivity is present. Studies have been performed in normal subjects and in type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetic patients both in basal conditions and after pharmacological challenges. In normal subjects in basal state anionic and cationic immunoglobulins were found to be excreted in a ratio of about 1 : 10 and the anionic/cationic ratio could be only minimally influenced by orthostatism or physical exercise. In diabetic patients of both type 1 and 2 the clearance of anionic immunoglobulins and the anionic/cationic immunoglobulin ratio were clearly increased in several randomly selected patients; in particular several normoalbuminuric patients showed enhanced immunoglobulin G4 clearances. The acute intravenous administration of an angiotensin-converting enzyme inhibitor in diabetic patients induced marked modifications of kidney haemodynamics and quantitative alterations of protein permselectivity, together with a selective decrement of anionic immunoglobulins in comparison with the excretion of total immunoglobulins. In conclusion, disproportions in the anionic/cationic immunoglobulin G ratio which are present in microalbuminuric and in a number of normoalbuminuric patients appear to detect initial abnormalities in diabetic kidney disease.</subfield>
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   <subfield code="a">Kidney permselectivity</subfield>
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