We performed the survey by questionnare so as to know how the sick children generally feel every day in their schools and society. Patients of chronic renal diseases over 16 were involved in the present investigation.
Ten point nine per cent of patients have been dissapointed by their teachers' underestimation, 6.5% have felt discomfort because of the insufficient communication between schools and hospitals, 16.8% have suffered from misunderstanding, teasing or harassment, and 32.1% have had some troubles or unnecessary restrictions in physical activities after school. Thirty-seven point four percent have been forced to face their own psycholical problems.
  It usually takes so long time for doctors to take care of patients of chronic renal diseases. So we thought these would be very important subjects to give informations of the diseases to schools and society, to re-evaluate physical activities, and to show sincere attitude for the patients' psychologic problems.

View full abstract

  The mechanism of IgA deposition on glomerular mesangial matrix in IgA nephropathy is unknown. We have demonstrated that IgA was incorporated into the extracellular matrix when mixture of IgA and cathepsin D-digested fibronectin fragments was reacted with confluent cell layers of cultured human fibroblasts for 3 hr and was cultured with medium for an additiona1 24 hr. Since we have also demonstrated that IgA 1-associated fibronectin fragments was present in patient's serum, we examined in this paper if patient's IgA obtained by affinity chromatography using jacalin-agarose is able to deposit in extracellular matrix in association with fibronectin, which might be co-purified along with IgA. Samples obtained from serum were applied to the culture system of above described. In all of 10 patients with IgA nephropathy, but not in 10 normal controls, IgA was deposited in extracellular matrix of cultured human fibroblast. The coarse and punctate clusters of IgA staining by immunofluorescence was obtained, and the pattern was similar to that seen in the experiment using mixture of IgA and fibronectin fragments. The staining was abolished by treatment of patients' samples with anti-human fibronectin monoclonal antibodies, suggesting that IgA deposition on extracellular matrix is associated with fibronectin. Furthermore, an addition of cathepsin D-digested fibronectin to the samples from patients augmented the size and the number of IgA deposition on extracellular matrix. When samples were sequentially reacted to the cell layers just after a series of sample application was finished, IgA staining was also augmented. These results suggest that the complex of IgA and fibronectin fragments may co-exist in serum from patients with IgA nephropathy and contribute to IgA deposition onto mesangial matrix through the mechanism of assembly of exogenous fibronectin into extracellular matrix.

View full abstract

  Although the pivotal role of intrarenal renin-angiotensin system (RAS) activation has been demonstrated in the rat model of chronic Cyclosporine (CyA) nephropathy, it is still unclear whether intrarenal RAS activation is responsible for chronic CyA nephropathy in humans. Therefore, the renin distribution of formalin-fixed paraffin embedded renal biopsy specimens obtained from 26 children with idiopathic nephrotic syndrome (NS) treated with long-term moderate dose CyA was examined by immunohistochemistry using rabbit polyclonal anti-human renin antibody. Nineteen patients were steroid-dependent NS and 7 were steroid-resistant NS. However, CyA treatment led all the latter patients into complete remission. All the patients underwent renal biopsies at the start and the end of CyA treatment. Immunoreactivity to renin was mainly detected in the part of arterioles within anatomically well-defined juxtaglomerular apparatus (JGA) in pre-CyA specimells. However, it was also detected in the parts of vessels upstream from JGA in post-CyA specimens. Moreover, the number of renin-positive cells per glomeruli (R-pos-C/G) was significantly increased by long-term CyA treatment (1.26±0.24 vs. 4.30±0.40, p<0.0001). In post-CyA specimens, 11 showed mild or moderate CyA-associated arteriolopathy (CAA), whereas 15 showed no CAA. R-pos-C/G was significantly higher in the specimens with CAA than those without (5.16±0.59 vs. 3.67±0.48, p=0.031). Seven CAA positive patients underwent repeat biopsies 6-12 months after discontinuation of CyA. The specimens after CyA discontinuation showed the improvement of CAA and significantly lower R-pos-C/G compared with the post-CyA specimens (4.18±0.69 vs. 2.10±0.25, p=0,018). In post-CyA specimens, 11 showed mild to moderate interstitial fibrosis, whereas 15 showed no fibrosis. There was no significant difference in immunoreactivity to renin between the specimens with interstitial fibrosis and those without. However, patients having interstitial fibrosis showed significantly longer period of heavy proteinuria during CyA therapy due to steroid-resistant NS or frequent relapses of NS (83±18 vs. 35±12 days, p=0.030). These findings indicate that long-term CyA treatment for idiopathic NS in children may stimulate renin production in arterioles, and suggest that CyA-stimulated intrarenal RAS activation may be responsible for the development of CAA and that CyA-induced interstitial fibrosis may be potentiated by long-term heavy proteinuria, at least in part, independently from CyA-stimulated intrarenal RAS activation.

View full abstract

  Background: α, α-Trehalase, located on renal proximal tubules, is a glycoprotein which hydrolyses α, α-trehalose to two glucose molecules. Urinary trehalase reflects a renal proximal tubular damage, but its activity has not been routinely measured because of the following two reasons: (1) measurement of the activity is rather complicated, and (2) conventional assays for enzyme activity might not always reflect the whole trehalase protein, because inactivation of the enzyme may occur in various urinary samples. We therefore have developed a new ELISA for quantification of urinary trehalase and tried to assess the extent of renal tubular damages.
  Methods: We have established novel monoclonal antibodies for human trehalase and a sandwich ELISA for quantification of urinary trehalase. Moreover, we have assessed the urinary trehalase level by two methods, i.e. the trehalase quantity by this ELISA and the trehalase activity by a conventional assay. The results of these two methods were compared.
  Results: The ELISA system was more sensitive than the detection of enzyme activity and could detect a subtle difference of trehalase quantity in renal diseases. Highly significant increases in both quantity and activity were seen in patients with nephrotic syndrome (acute phase), Lowe syndrome, and Dent disease. Especially, their enzyme quantity was 200∼260 fold higher than that of the control subjects. The extent of trehalase quantities in chronic glomerulonephritis was larger than the elevation of their enzyme activities compared to the control group. In a patient with acute renal failure, trehalase quantity was 27-fold than the control and yet trehalase activity was similar to control.
  Conclusions: We have established an ELISA system for quantification of urinary trehalase by using novel monoclonal antibodies. Our ELISA system was simpler and sensitive than a conventional activity assay and reflects a whole trehalase protein. This ELISA can be useful as a common tool for clinical assessment of renal proximal tubular damage.

View full abstract

  It has past 25 years since establishment of SUSP in Japan. Every Japanese student (6-14 year old) undergoes their urinary check (proteinuria, hematuria) in SUSP every year (once a year repeatedly). In Chiba city, the total number of two million students underwent SUSP during 20 years (1975-1995). We divided into two groups: A group (1975-1984) the total nnmber of 1,144,685 students (essentially 220,102), B group (1985-1994) the total number of 1,008,314 students (essentially 208,764). In A group, we found some kidney diseases existing subclinically like MPGN, IgA nephropathy (lgAGN), hypolpasia and so on and followed up them without positive therapy except nephrotic cases. There were no differences in the discover rates of each kidney diseases between A and B group. In B group, the patients were treated positively like steroid therapy, anticoaglant therapy, antiplatelet therapy, and so on. In same follow-up period (at 1989 in A group and at 1999 in B group) there were 10 renal failure cases (lgAGN: 3, chronic glomerulo-nephritis: 5, oligomeganephronia: 1, unknown origin: 1) in A goup, only 2 cases (oligomeganephronia: 1, nephronophthisis: 1) in B group. Our positive therapy prevented from proggression of renal failure in the glomerulonephritis. SUSP is valuable for the diagnosis of renal diseases in early stage and the appropriate treatment in early stage of renal diseases prevents from renal failure.

View full abstract

  IgA nephropathy is characterized by prominent and diffuse IgA deposits in the glomerular mesangium on immunofluorescent microscopy. Clinical manifestation of IgA nephropathy varies and ranges from asymptomatic urinary abnormalities to acute renal failure. Most of the patients show microscopic hematuria and/or asymptomatic proteinuria and some of the patients present with an acute nephritic syndrome and/or nephrotic syndrome.
  We describe a 5-year-old girl with an acute onset IgA nephropathy with nephrotic syndrome and macrohematuria. She was initially treated with steroid, anticoagulant and thrombolytic agents and her proteinuria was decreased. However. her proteinuria was not decreased to less than 1.0 g/day. Then she was additionally treated with angiotensin converting enzyme inhibitor (ACEI) and her proteinuria was completely disappeared in 4 months. The renal specimens obtained at her acute phase revealed thin and irregular segments of the glomerular basement membrane (glomerular membranolysis), and IgA deposits in the mesangial region and in the glomerular capillary wall. Repeat biopsy after 1 year remission showed an improvement of those pathological changes. Administration of ACEI is considered to induce alteration in glomerular circulatory dynamics leading to improve the damage of size selectivity and charged barrier of the basement membrane. Most of the patients with an acute onset IgA nephropathy have favourable prognosis, however a part of the patients have poor prognosis and its characteristic pathologic feature of membaranolysis is one of the indicators of poor outcome in IgA nephropathy. Considering a pathognomonic change in IgA nephropathy and the pharmacological effects of ACEI, ACEI therapy would be recommended to prevent and/or improve the basement membrane damage in the patients with an acute onset IgA nephropathy.

View full abstract

  We report on a 7-year-old Japanese boy who presented with bilateral cryptorchism and renal insufficiency. Although the patient had fair visual acuity, he was found to have bilateral optic nerve coloboma with partial retinal detatchment. We identified a Guanine 619 insertion in exon 2 of PAX2 gene in this patient. Human PAX2 mutation syndrome or Renal-coloboma syndrome (RCS), resulting from autosomal dominant mutations in the PAX2 gene, has recently been characterized. In addition to renal hypoplasia and optic nerve coloboma, the clinical features of patients with this syndrome are vesico-ureteral reflux (VUR), high frequency hearing loss, and central nervous system (CNS) anomalies. Our patient had bilateral small kidneys with renal insufficiency which currently progressed to end stage renal failure at the age of 15. The pathological diagnosis of kidney biopsy in our patient at the age of eight was mild mesangial proliferative glomerulonephritis. This pathological findings have been well described with RCS and may be one of the characteristic features of the syndrome. On the other hand, the patient had bilateral cryptorchism which has not been described in RCS.

View full abstract

  We treated a lupus nephritis patient refractory to conventional therapy with mycophenolate mofetile (MMF). She was diagnosed as systemic lupus erythematosus (SLE) at age 4 and soon involved nephritis. Renal histopathological diagnosis made two years later was WHO class IV. She received oral administration of prednisolone, cyclophosphamide, mizoribine, azathioprine, and cyclospoline as well as intravenous pulse therapy of methylprednisolone and cyclophosphamide. However, all failed to control her nephritis or disease activity of SLE. Before treatment with MMF, urinary protein excretion was 11.6 g/day, serum albumin 2.4 g/dl, C3c 37.4 mg/dl, and anti ds-DNA antibody 38 IU/ml. After initiation of MMF, proteinuria began to decrease within 3 weeks and has been below 1 g/day since 10 weeks. Serum activity indices of lupus; C3c and anti ds-DNA antibody, also improved to normal levels. We believe MMF should be used for refractory lupus nephritis with conventional therapy.

View full abstract

  We encountered four cases of congenital nephrotic syndrome (CNS). The treatment schedule for CNS was planned as follows; (1) Albumin was administered by a central venous catheter (CVC). (2) Hemi-nephrectomy was performed at three to four months of age in each patient and peritoneal dialysis (PD) was started after the removal of the residual kidney around one year of age when weaning was completed. (3) The kidney transplantation was done around five years of age.
  Although one patient died due to severe infection, the other three completed the kidney transplantation successfully as planned. Ten episodes of catheter infection occurred during the total 1,782 days of CVCs use. Four episodes of PD-associated peritonitis occurred during the total 4,927 days of PD treatment. There was no occlusion of mid or large sized veins due to complications of CVC placement. The surviving patients show normal height and mental development to date. We report the details of the successful treatments and the courses in patients with CNS, a disease that was previously described as having a poor prognosis.

View full abstract

  We have experienced of 8 children who were hospitalized in Hirakata city hospital because of acute focal bacterial nephritis (AFBN). Imaging studies such as sonography, enhanced CT, and ^99mTc-DMSA renoschintigraphy are useful method to make a diagnosis of AFBN. It is generally thought that Vesicoureteral reflux (VUR) is concemed with etiology of AFBN in childhood, but there is only one case which complicated with VUR in our cases. In cases of fever of unknown origin, although there is no evidence of urinary tract infection, we should keep AFBN in mind and imaging studies are necessary for diagnosis.

View full abstract

  We reported a case of acute renal failure associated with Salmonella infection. Seven year-old-girl was suffering from high fever, vomiting and severe diarrhea from September 14, 1999 and received a medical examination of a doctor of an around. Her illness was diagnosed as acute gastroenteritis and she received medication. The symptom mentioned above continued on September 16 and she was referred to our hospital because of her bad condition. Her paleness and low systolic blood pressure of 88mmHg on admission showed that she was a shock state. Because of origuria and elevation of musculogenic enzyme, blood urea nitrogen and creatinine, we diagnosed that she had acute renal failure with rhabdomyolysis. Hemodialysis therapy was started, and renal function was improved gradually after twice of hemodialysis. During her medication, she was also complicated with disseminated intravascular coagulation (DIC), but she recovered from it and discharged our hospital on the 32nd day of her illness. Salmonella typhimurium was isolated from her fecal samples. We think that various factors such as DIC and a rhabdomyolysis or advanced dehydration are piled up in this case, and that the acute renal failure did departure from symptom. Such a case was rare, so we reported with consideration of some documents.

View full abstract

  A 11-year-old girl was refered to our hospital due to continuous fever. As results of laboratory data (high titer of anti-SS-A antibody, etc), lip biopsy (infiltration of inflammatory cells into salivary grand) and sintinograhy (dysfunction of parotid and mandibular glands), she was diagnosed Sjögren syndrome. Oral predonisolone treatment (0.5 mg/kg/day) was begun. Her temperature decreased to normal and initial abnormal laboratory data was changed to normal. After 6 month, dose of predonisolone was decreased to 7.5 mg every other day. Her younger sisiter's laboratory data (anti-SS-A antibody, etc) was also abnormal. Therefore, lip biopsy and sintinography were performed. She was also diagnosed Sjögren syndrome. However, she had no clinical symptom. She was given predonisolone (1 mg/kg/day). Her laboratory data was changed to normal. After 6 month, dose of predonisolone was decreased to 7.5 mg every other day. We have experienced that oral steroid therapy for sisters suffered from Sjögren syndrome has been controlled effectively. Long period study to compare steroid therapy with other therapy for Sjögren syndrome should be done. We will try to follow their clinical condition and laboratory data continuously.

View full abstract

  We aimed to investigate, by means of dimercaptosuccinic acid (DMSA) scan, the relations between a degree of vesicoureteral reflux (VUR) and renal scar formation. Twenty-six children with VUR, 22 boys and 4 girls (mean age at the diagnosis of VUR; 67 months), were enrolled in the study.
  Results are as follows; (1) a significant correlation was found between split renal uptake in DMSA scan and grade of VUR. (2) DMSA renoscintigraphy revealed that 15% (1/6) of the kidneys with low grade VUR (I-II) and 34% (14/41) of the kidneys with high grade VUR (III-V) had renal damage. (3) Anti-reflux operation improved split renal uptake significantly.

View full abstract