Recently, the authors reported that the ratio of serum IgA to C3 (serum IgA/C3 ratio) is a good marker to distinguish patients with IgA nephropathy from non-IgA nephropathy patients together with serum IgA levels using an international reference preparation (IFCC/CRM470). In this study, the authors investigated whether the serum IgA/C3 ratio might be an indicator of prognostic grading in patients with IgA nephropathy. Two hundred and thirteen patients with IgA nephropathy and 96 other glomerular diseases including diffuse or focal mesangial proliferative glomerulonephritis without mesangial IgA deposition (non-IgA PGN), membranous nephropathy and thin basement membrane syndrome were examined. The levels of serum IgA and C3 in these patients were adjusted by the specified formula to those using international standard serum (IFCC/CRM470) in this study. The results of this study showed the highest levels of IgA/C3 ratio in patients with IgA nephropathy. The serum IgA/C3 ratio appears to gradually increase according to the prognostic grading of this disease. Therefore, measurement of the serum IgA/C3 ratio may be useful for prediction of diagnosis and prognostic grading in patients with IgA nephropathy.

The production of hydrogen peroxide (H2O2) by neutrophilic polymorphonuclear leukocytes (PMN) after stimulation and the infiltration of PMN in glomeruli were determined in 20 patients with primary IgA nephropathy. The H2O2 production of PMN after the stimulation was measured with a spectrophotometer using horseradish peroxidase as substrate. The results were as follows: 1) when PMN were pretreated with cytochalasin B, H2O2 production after stimulation with heat-aggregated IgG (IgG) or serum-treated zymosan (STZ) was significantly higher in patients with IgA nephropathy than in controls, and 2) there was an increased amount of PMN localized in glomeruli in patients with IgA nephropathy using immunofluorescence of monoclonal anti-PMN antibody. It appeared that the increased renal infiltration of PMN which have a high potential for production of reactive oxygen species might induce the glomerular injuries in patients with IgA nephropathy.

Correlations between the steady-state mRNA levels of extracellular matrices using specific cDNA probes for the alpha 1 chain of type IV collagen (alpha 1 (IV) chain); laminin A, B1, and B2 chains; and heparan sulfate proteoglycan (HSPG); and glomerular injuries in ddY mice were evaluated. Eight-, sixteen- and forty-week-old ddY mice were used in this study. ICR mice of the same age served as control. Extracted total RNA of pooled kidneys was fixed on a filter and then hybridized with the cDNA probes. Renal cryostat sections were incubated with rabbit anti-mouse type IV collagen, laminin, and HSPG antisera and then stained with FITC-labeled goat anti-rabbit IgG antiserum. The sections were also stained with FITC-labeled goat anti-mouse IgA, IgM, IgG, and C3 antisera. In light microscopy, the average number of glomerular cells was calculated at each age. Increased expression of extracellular matrices genes for the alpha 1(IV) chain; laminin A, B1, and B2 chains; and HSPG was found in renal tissues of ddY mice. Staining of type IV collagen, laminin, and HSPG was observed in renal tissues of ddY mice at each age. Increased proteinuria in 40-week-old ddY mice might be related to the decrease in glomerular basement membrane HSPG which acts as the anionic sites in such areas. Marked proliferation and or expansion of glomerular cells and mesangial matrices were observed in 40 week-old-ddY mice. The intensity of IgA and C3 deposits in the glomeruli was parallel to the levels of mRNA for such components.(ABSTRACT TRUNCATED AT 250 WORDS)

Levels of glomerular nonenzymatic glycosylation and lipid peroxide in streptozotocin (STZ)-induced diabetic rats were examined. Isolation of glomeruli was performed using a sieving technique. The levels of nonenzymatic glycosylation in the glomeruli of these rats were measured by the thiobarbituric acid (TBA) method. Measurement of lipid peroxide, i.e., malondialdehyde (MDA), levels in the renal cortex, medulla and isolated glomeruli was performed by the TBA test. Light-microscopic and immunofluorescent examinations were also performed. An increase in nonenzymatic glycosylation in the glomeruli was observed in the early phase, i.e. after 4 and 12 weeks, in STZ-induced diabetic rats. The levels of MDA in the renal cortex of 12-week-old STZ-induced diabetic rats were also significantly increased compared with those of control rats at the same age. Levels of MDA in the glomeruli of 12-week-old STZ-induced diabetic rats were slightly increased compared with those of control rats, but there was no statistical significance. In immunofluorescence, IgG or IgM was deposited in the glomerular mesangial areas and capillary walls in 12-week-old diabetic rats. However, there was no significant change in renal tissues after 4 and 12 weeks in STZ-induced diabetic rats. It was concluded that glomerular nonenzymatic glycosylation and lipid peroxide were already increased in the early phase of STZ-induced diabetic rats prior to the appearance of marked histologic alterations.

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