Shinnyo Karashima

Sclerosing encapsulating peritonitis in pediatric peritoneal dialysis patients

Abstract The aim of this study was to define the incidence and characteristics of sclerosing encapsulating peritonitis (SEP) in pediatric peritoneal dialysis (PD) patients in Japan. A questionnaire was sent to all dialysis units with at least two pediatric PD patients. Among 687 patients registered, 11 cases (1.6%) of SEP were diagnosed. The mean age of patients with SEP at the start of PD was 9.7±3.6 years and at SEP diagnosis, 19.1±3.8 years. All patients had undergone PD for more than 5 years, and the mean PD duration was 9.6±3.3 years. SEP was diagnosed in 6.6% and 12% of patients dialyzed for >5 years and >8 years, respectively. The incidence of peritonitis among patients with SEP was not different from that among the Japanese pediatric registry. All patients had virtually no residual urine volume and 9 had impaired peritoneal ultrafiltration. Peritoneal calcification was the most-frequent radiological finding. Peritoneal biopsy was performed in 7 patients and confirmed sclerotic peritonitis in all. Ten patients transferred to hemodialysis, and only 1 patient underwent surgery. Three patients died. We recommend that patients on PD for more than 5 years who have impaired peritoneal ultrafiltration or peritoneal calcification should be carefully managed as presumptive cases of SEP.

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.

Another autosomal recessive form of focal glomerulosclerosis with neurological findings

Abstract. We report four patients in a consanguineous family with focal segmental glomerulosclerosis (FSGS), early onset nephrotic syndrome, eventual end-stage renal failure, psychomotor retardation, seizures and microcephaly or brain atrophy without hiatus hernia. Other characteristic dysmorphic features were convergent strabismus and narrow forehead. One patient had enamel hypoplasia of the upper incisors and deviation of bilateral thumbs to palm side. We could not detect an NPHS2 mutation in this family. We propose that this may be another autosomal recessive syndrome with FSGS and neurological findings.

Splicing Mutations in the COL4A5 Gene in Alport's Syndrome: Different mRNA Expression Between Leukocytes and Fibroblasts

The COL4A5 gene from 40 patients with Alports syndrome was examined using single-strand conformation substitution at the acceptor site (-2) of intron 50 and a G-to-C substitution at the donor site (+1) of intron 47, respectively. The transcript in peripheral leukocytes from the former had a 10-nucleotide deletion. This shortened transcript was derived from abnormal splicing in a cryptic acceptor site within exon 51. This could be translated into a protein with an alteration of three amino acids followed by premature termination, which eliminated 23 amino acids from the carboxyl end. Gene tracking revealed that the mother and a brother carried the mutant allele. In the latter, the transcript in leukocytes was normal, but that in cultured skin fibroblasts showed skipping of exon 47, the result being that 71 amino acids were absent. Glomerular basement membrane from the patient did not react with the anti-alpha 5(IV) antibody. His maternal grandmother, mother, and a sister, all with abnormal urinalysis, carried the mutant allele. Thus, the appearance of exons of the COL4A5 gene in leukocytes may differ from that in fibroblasts. If kidney mRNA is not available, mRNAs from cultured skin fibroblasts, in addition to leukocytes, can be used for gene analysis in subjects with Alports syndrome.

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.