Glycemic Control Reverses Increases in Urinary Excretions of Immunoglobulin G and Ceruloplasmin in Type 2 Diabetic Patients with Normoalbuminuria

Abstract

To examine whether urinary excretions of plasma proteins with molecular radii of 45-55 A and different isoelectric points such as IgG (pI = 7.4) and ceruloplasmin (pI = 4.4) increase selectively in normoalbuminuric type 2 diabetic patients, urinary albumin excretion rate (AER), renal clearances of IgG, ceruloplasmin and alpha2-macroglobulin, and creatinine clearance (Ccr) were studied in timed overnight urine samples of 36 diabetic outpatients and 16 control subjects. Furthermore, to examine effect of glycemic control on these urinary protein excretions, the same analysis was performed before and after glycemic control in 17 diabetic inpatients admitted for glycemic control. Renal clearances of IgG and ceruloplasmin were significantly higher in diabetic outpatients than in the control group, whereas AER and renal clearance of alpha2-macroglobulin did not differ. Glycemic control caused significant decreases in renal clearances of IgG and ceruloplasmin, accompanied with tendency for Ccr to decrease (p = 0.055). The present results, together with our previous finding of selectively increased urinary excretions of 45-55 A sized plasma proteins in parallel with enhanced glomerular filtration rate after acute protein loading, led us to conclude that enhanced intraglomerular hydraulic pressure may cause increases in clearances of IgG and ceruloplasmin, and that this change can be reversed by strict glycemic control in normoalbuminuric diabetic patients.

Increased Urinary Excretions of Immunoglobulin G, Ceruloplasmin, and Transferrin Predict Development of Microalbuminuria in Patients With Type 2 Diabetes

“…Parallel increases in these urinary proteins in timed overnight urine samples were found in patients with impaired glucose tolerance (15) and in type 2 diabetic patients with normoalbuminuria (3,9). Furthermore, strict glycemic control reversed increases in these urinary proteins without change in albuminuria (3). Given the finding that hyperglycemia induces an increase in intraglomerular hydraulic pressure (16 -18) in early stages of diabetic nephropathy, parallel increases in these urinary proteins likely reflect increased intraglomerular hydraulic pressure, and increased intraglomerular hydraulic pressure does not produce increase in albuminuria.…”

“…However, several studies have shown that increases in certain urinary proteins (immunoglobin G [IgG] [1][2][3], transferrin [Tf] [4 -7], and ceruloplasmin [CRL] [3,8]) were found in normoalbuminuric diabetic patients. Recently, we reported that in normoalbuminuric diabetic patients, there was a strong linear correlation among these urinary proteins (9).…”

Parallel Increase in Urinary Excretion Rates of Immunoglobulin G, Ceruloplasmin, Transferrin, and Orosomucoid in Normoalbuminuric Type 2 Diabetic Patients

“…Sixty-one patients were asked to collect exactly timed overnight urine samples on three different occasions according to the procedure previously reported (4). Concentrations of six different SPPs (albumin, IgG, ceruloplasmin, ␣ 2 -macroglobulin, transferrin, and orosomucoid) were measured to determine urinary excretion rates (albumin, IgG, ceruloplasmin, ␣ 2 -macroglobulin, transferrin, and orosomucoid excretion rates, respectively) of these substances.…”

“…Early recognition of renal changes increases the chance of preventing the development of diabetic nephropathy. Although microalbuminuria is generally recognized as the best available noninvasive predictor of diabetic nephropathy, several studies including ours have shown that increased urinary excretions of some kinds of plasma proteins with different molecular radii Ͻ55 Å and different isoelectric points (pIs) such as IgG (2-4), transferrin (5)(6)(7)(8), ceruloplasmin (4,9), and orosomucoid (10) may precede the development of microalbuminuria in diabetic patients. Kazumi et al (11) reported that increased urinary transferrin excretion could predict the development of microalbuminuria in type 2 diabetic patients.…”

Non enzymatic glycosylation of IgG and their urinary excretion in patients with diabetic nephropathy

“…Urinary IgG excretion, which reflects the combination of selectivity and magnitude of proteinuria, thus measuring urinary IgG excretion, may be of help in guiding the treatment of these patients. Several studies have shown that increased urinary excretion of some kinds of plasma proteins with different molecular radii <55A and different isoelectric points such as IgG (4,7), transferrin (8), ceruloplasmin (7,9) and orosomucoid (10) may precede the development of microalbuminuria in diabetic patients.…”