Akio Furuse

Clinicopathological Correlation of IgA Nephropathy in Children

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.

Developmental changes in carbonic anhydrase II in the rat kidney

Abstract. 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.

Glomerular IgA1 and IgA2 Deposits in IgA Nephropathies

IgA1 and IgA2 deposits in the renal glomeruli were studied in 29 biopsy specimens from 17 children with IgA nephropathy and 12 children with anaphylactoid purpura nephritis. IgA1 and IgA2 were detected with the indirect immunofluorescence method, using various combinations of dilutions of sheep antihuman IgA subclass antisera and fluorescein isothiocyanate conjugated rabbit antisheep IgG antiserum. The glomeruli of all the 29 specimens studied were strongly positive for IgA1, while only twelve specimens were positive for IgA2. Ten specimens without IgM deposits were all negative for J chain. These results indicate that the glomerular IgA deposits consist mainly of monomeric IgA1, with a minor share for IgA2. The serum IgA in normal individuals consists of about 90% IgA1 and 10% IgA2. Therefore, it was assumed that the serum IgA is deposited irrespective of subclass in the glomeruli of the patients with IgA nephropathies.

Epidemiologic Survey of Children with End‐Stage Renal Disease

We performed an epidemiologic study on the basis of a questionnaire survey of 162 children with end‐stage renal disease (ESRD). Sixty‐nine (43%) of our 162 children, including 25 detected at mass screening of urine, were found by chance hematuria and/or proteinuria. The three major causes of ESRD in our children were chronic glomerulonephritis (CGN) in 56, congenital anomalies of the urinary tract in 30, and nephrotic syndrome (NS) in 27. The renal pathology in 39 children with CGN or NS was focal glomerular sclerosis in 15, diffuse mesangial GN in 7, IgA GN in 5, membranoproliferative GN in 3, membranous GN in 3, and unclassified in 6. Forms of dialysis initiated were hemodialysis in 91 children, continuous ambulatory peritoneal dialysis (PD) in 66, and intermittent PD in 5. Renal transplantation was performed on 38 children, and the graft and the patient survival rates were 76% and 89%, respectively. The survival rate of our 162 children for a mean follow‐up of 8.1 years was 77%. In conclusion, an integrated program of maintenance dialysis and transplantation provides a favorable life for children with ESRD.

Renal tubular differentiation in mouse and mouse metanephric culture. II. Na-K-ATPase activity.

Sodium-potassium adenosine triphosphatase (Na-K-ATPase) activity was measured by microassay, and the surface density of basolateral membranes was measured morphometrically in postglomerular segments of single tubules isolated from normally developing, intact mouse kidneys and from transfilter metanephric cultures. Proximal tubule Na-K-ATPase activity was 1092±480 pmol/mm per hour in newborn mice, increasing to 2462±258 in 1-week-old and 3470–578 pmol/mm per hour in adult mice. The Na-K-ATPase activity in newborn mice was approximately one-third of the activity in adult mice. Tubular Na-K-ATPase in transfilter metanephric culture was 972±536 pmol/mm per hour, a mean value almost identical to that in newborn mice. The surface density of basolateral cell membranes was 1.36±0.60 μm2/μm3 in newborn mice and 1.34±0.45 μm2/μm3 in 1-week-old mice, increasing to 2.70±0.98 μm2/μm3 in 4-week-old mice and 2.89±0.51 μm2/μm3 in adult mice. The surface density of tubular basolateral cell membranes in transfilter metanephric culture was 1.13±0.51 μm2/μm3, not significantly different from the surface density in newborn mice. The calculated mean surface area of basolateral membranes per unit tubular length was greater in cultures than in newborns, however, because total epithelial volume per unit length was significantly larger in the cultured tubules. Membrane surface area in intact mice increased with age, the surface area per unit length of tubule in adults being 4.6 times the area in newborn animals. The ratio of enzyme activity to membrane surface area more than doubled in the 1st week of life without any increase in the density or surface area of basolateral membranes. The ratio fell thereafter, as membrane area increased with maturation, to a value in the adult animal three-fourths of that in the newborn. The early postnatal increase in enzyme activity, beginning almost immediately after birth, possibly relates to an increased density of enzyme sites on the membrane. The postnatal spurt in enzyme activity, without a corresponding increase in membrane area, suggests that tubules have considerable functional reserve in generating a complement of sodium pumps. The studies of proximal tubules grown in metanephric culture show that the basolateral membranes and the sodium pump are initiated independently of renal blood flow and tubular fluid flow, presumably as inherent characteristics. The functional data confirm the similarity, already shown by morphometric studies, between natural tubules and those grown in culture.

Presence of HBe Antibody in Glomerular Deposits in Membranous Glomerulonephritis Is Associated with Hepatitis B Virus Infection

The specificity of IgG on the glomerular capillary wall was investigated in 3 patients with hepatitis B virus associated membranous glomerulonephritis. The immune deposits on the capillary walls were stained by immunofluorescent antibody against HBe antigen and IgG. The eluted fluid (0.02 M citrate buffer, pH 3.2) from renal biopsy slices contained significant activity of HBe antibody, but not of HBs and HBc antibodies. After elution, the disappearance of IgG on the capillary walls was confirmed by immunofluorescence. Heterologous complement activation with fresh guinea pig complement was positive in the glomerular capillary walls from all 3 patients. Our observations support the notion that this disease is caused by HBe antigen-anti-HBe immune complexes.

The Nature and Molecular Weight of the Circulating Immune Complex in Glomerulonephropathy Associated With Hepatitis B Virus Infection

Circulating immune complex (CIC) in patients with hepatitis B virus associated glomerulonephropathy was fractionated into two parts by sucrose gradient ultracentrifugation. A CIC of higher molecular weight (more than 900,000 daltons) consisted of hepatitis B virus surface antigen (HBsAg), and one of lower molecular weight (between 900,000 and 66,000 daltons) consisted of hepatitis B virus e antigen (HBeAg). The patients with membranous glomerulonephropathy (MGN) had much more CIC of higher than of lower molecular weight, while deposits in the glomerular basement membrane were stained with anti‐HBeAg but not with anti‐HBsAg. A patient with minimal changes had only higher molecular weight CIC and no deposits in the kidney. Our results suggest that lower molecular weight CIC containing HBeAg may play an important role in the development of MGN.

A new variant of Lowe oculocerebrorenal syndrome

A case is reported of a 5-year-old boy with Lowe syndrome. The patient was unusual in that he had only mild and transient acidosis with no rickets. The corneal opacities in the parents suggest that this disease might be autosomal recessive.

IgA Nephropathy Indicating Nephrotic Pattern in Childhood

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.