Although indirect, our data suggest the existence of a vascular isoform of podocin with a different molecular mass. We propose that examination of podocin expression may help differentiate MCD from FSGS.

Familial idiopathic low-molecular-weight proteinuria (FILMWP) is a renal proximal tubulopathy that occurs predominantly in males. FILMWP is characterized by mild proteinuria consisting of low-molecular-weight proteinuria, aminoaciduria and relatively conserved renal function, but without rickets. To determine whether FILMWP is related to the CLCN5 gene, which is responsible for Dent's disease and two related disorders, we analyzed the CLCN5 gene from four Japanese families with FILMWP. We identified two novel mutations: one was a single base insertion at codon 520 serine in exon 10 and the other was a single base deletion at codon 403 tyrosine in exon 8. These mutations caused a shift in the reading frame, resulting in synthesis of truncated CLC5 proteins that lacked 220 (29%) and 314 (42%) amino acids, respectively. These mutations were demonstrated to cosegregate with the disease in two families, respectively. We conclude that the CLCN5 gene is responsible for this proximal renal tubulopathy in some Japanese families and that FILMWP is possibly a variant of Dent's disease.

No abstract

22 patients with IgA nephropathy aged 7–16 years, 15 of whom were found by mass urine screening of school children, were divided into three groups based on the degree of their proteinuria at admission: group A (n = 6) below 0.5 g/day of urine protein, group B (n = 7) between 0.6 and 3.0, and group C (n = 9) above 3.0 g/day of urine protein. The degree of proteinuria seemed to be related to the severity of pathological changes of the glomerular basement membrane; most severe in group C, moderate in group B, and minimal in group A. IgA deposits in the mesangial area were found in all groups of patients, but those in the capillary walls were most frequently found in group C. In addition to electron-dense deposits in the mesangial area, which was found in all groups of patients, the subendothelial and subepithelial deposits were the most remarkable changes found in group C. During the clinical observation period, which was between 2.0 and 7.1 years, no patient belonging to group A progressed to groups B or C. 4 cases in group C developed chronic renal failure, but none in the other groups did. The amount of urine protein might be used as a valuable parameter of the pathological damage of the glomerulus in children with IgA nephropathy.

Urinary abnormalities combined with positive serum hepatitis B virus surface antigen (HBsAg) were found in 9 children. Most of these patients were found by mass urine screening of school children. Renal biopsy findings revealed 6 cases of membranous glomerulonephropathy (MGN) and 3 cases of minimal change disease. Immune deposits consisting of hepatitis B virus e antigen (HBeAg), IgG and C₃ were detected in the glomerular capillary walls by immunofluorescent study in patients with MGN. Circulating immune complex was positive at a rate of 67% (6/9 cases) by the C_1q-binding assay and at a rate of 56% (5/9 cases) by the protein-A precipitation test in patients with persistent urinary abnormalities and hepatic dysfunction.

In 16 patients with mucocutaneous lymph node syndrome (MCLS) during the first 2 weeks after the onset (acute phase) and 1 month after the onset (remission phase), measurement of the circulating immune complex (CIC) was performed by a C1q-binding assay (C1q-B.A.) and/or a Protein-A precipitation test (protein-A P.T.). Seven out of 12 samples and four out of nine samples were shown to have raised levels of CIC in the acute phase with the C1q-B.A. and Protein-A P.T. test. In the remission phase, on the other hand, positive results were found in one out of six samples with the C1q-B.A. test and in three out of nine samples with the Protein-A P.T. test. High levels of CIC and disease activity were parallel. Our finding of a higher incidence of positive CIC in MCLS supports the possibility of the immunopathological mechanism.

We examined the distribution and maturational changes of carbonic anhydrase I (CAI) and carbonic anhydrase II (CAII) in microdissected nephron segments of Sprague-Dawley rats. CAI and CAII proteins were measured by enzyme-linked immunosorbent assay. CAI was not detected in any nephron segment in 7-week-old rats. CAII was present in the collecting ducts, proximal tubules, and thick ascending limbs of loop of Henle in 7-week-old rats. CAII contents were significantly higher in the early proximal tubules (S1) than in second (S2) and late (S3) portions of the proximal tubules, while the contents in S1 were less than in cortical collecting ducts (CCD), outer stripe and inner stripes of the outer medullary collecting ducts (OMCDo and OMCDi). CAII content in each of S1, CCD, and OMCD of 1-week-old rats was only 14% or less of that of adults, but increased steeply during the 2nd and 3rd weeks of life, reaching almost 40% at 3 weeks of age and 97% at 7 weeks. Our results indicate that CAII is present throughout the entire nephron of the rat, and that CAII content in S1, CCD, and OMCD increases exponentially during the first 7 weeks of life. Our data suggest that the immature low levels of CAII may explain, at least in part, the limited capacity of urinary acidification during neonatal life. Further studies are necessary to establish the role of such changes in CAII content in acid-base homeostasis during neonatal life.

During the last 4 years, we had the opportunity to examine 11 patients of IgA nephropathy in childhood, in whom stainning of IgA and Cs in mesangium area was a common finding by immunofluorescent study. Urinary analysis indicated persistent microscopic hematuria and proteinuria in all cases. 8 cases among them showed macroscopic hematuria attack during the observation period. The levels of proteinuria were usually above 1 g/day. 4 cases had massive proteinuria, hypoalubminemia and hyperlipidemia, indicating nephrotic syndrome.By the light microscopic observation, the glomerular lesions of the disease with nephrotic syndrome were (1) increasing of mesangium cells and mesangium matrix, (2) creascent formation, (3) marked mononuclear cells infiltration and (4) fibrosis of interstitial area.The electron microscopic findings of them were not only showing deposits in mesangium area, but also intramembranous and subendotherial deposits. These findings suggest that there is positive correlation between the degree of proteinuria and alteration of glomerular lesion.In 3 cases of nephrotic syndrome, steroid and/or immunosuppresant therapy were employed, but no significant effect was obtained. Acta Paed. Jap, (Japanese Ed.) 83: 365-373, 1979.