Hyperlipidemia is a well-recognized complication of the nephrotic syndrome and is a factor contributing to the progression of the initial glomerular injury and the development of glomerulosclerosis. Apolipoprotein E (apoE) is a plasma protein and apoE epsilon 4 allele is associated with higher plasma cholesterol levels. With this in mind, we studied apoE phenotypes and alleles in children with nephrotic glomerular diseases (NGD, n=29), including idiopathic nephrotic syndrome (n=16), membranoproliferative glomerulonephritis (n=7), and focal segmental glomerulosclerosis (FSGS, n=6). Children with NGD had a higher epsilon 4 allele frequency (20.7%) than controls (10.8%), and those with FSGS had both higher apoE4/3 (66.7%) and epsilon 4 allele (33.3%) frequencies than controls (20.4% and 10.8%, respectively). In IgA nephropathy (n=30, disease controls), no significant association with specific apoE was found. Further studies are needed to clarify the significance of the observed high frequencies of apoE epsilon 4 allele in children with NGD and apoE4/3 phenotype distribution in FSGS.

The effects of camostat mesilate (CM), a derivative of gabexate mesilate developed for oral use, on primary glomerulonephritis (GN) and chance hematuria and/or proteinuria were evaluated. Fourteen patients (6 males, 8 females) with a mean age of 11 years and 3 months (range 4-16 years) were enrolled. Histological and clinical diagnoses of the 14 patients were as follows: IgA nephropathy 3, non-IgA GN 2, and asymptomatic significant microscopic hematuria [more than 100 red blood cells per high-power field (x400)] with or without proteinuria 9. They were consecutively treated with oral CM (100 mg twice a day) when they were confirmed to have continuous significant microscopic hematuria and/or proteinuria after a few months of observational follow-up. Urinary findings were normalized in 10 of the 14 patients (85.7%) between 1 month 1 week and 10 months (mean 4 months) after administration of CM. Hematuria cleared in 11 of 13 patients, and proteinuria disappeared in 4 of 5 patients. The mean duration of CM administration was 21.7 +/- 9.1 months (range 4-37 months). At present, 3-12 years after discontinuation of CM therapy, their urinary findings remain normal at 9 years 10 months to 26 years 6 months of age. In conclusion, there appears to be an association between the oral use of CM and reduction in significant microscopic hematuria and/or proteinuria. Oral CM therapy could represent a practical primary care approach to chance hematuria and/or proteinuria in children.

We studied the relationship between plasma α₂-macroglobulin (α₂M) and depressed cell-mediated immunity in idiopathic nephrotic syndrome (INS). Plasma α₂M concentrations (μmol/l) were increased during relapses of INS; however, the proteinase inhibitory activity, measured using bacterial thermo-lysin, was significantly decreased when calculated per 1 mol of α₂M, implying a reduced proteinase-inhibiting capacity of α₂M. The decreased proteinase-inhibiting capacity of α₂M was associated with the inhibitory activity of plasma on normal lymphocyte blastogenesis. Purified α₂M, when complexed with chymotrypsin, intensively inhibited normal lymphocyte blastogenesis induced by concanavalin A, as compared with the free form of α₂M. From these results it is suggested that, although the amount of α₂M protein has increased in the plasma of INS patients during relapse, its binding capacity to proteinases has relatively decreased. The results of this study may provide speculation for both the well-known high plasma α₂M concentrations and the immunodepres-sion, both of which have been observed in INS patients in the past few decades.