We retrospectively analyzed 20 prepubertal children with steroid-dependent nephrotic syndrome (SDNS) who had been treated with cyclophosphamide (CPM: 1.5-2.5 mg/kg per day) for 12 weeks (cumulative dose within 200 mg/kg) as first-line therapy of immunosuppressive agents. Mean duration of follow-up was 36.2 (range 9-72) months. Twelve of 20 children (responders: 60%) showed a long-term remission or infrequent relapsing NS, while 8 of 20 (non-responders: 40%)developed relapses again when the dose of prednisolone (PSL) tapered to 0.5 mg/kg per alternate days and were subsequently treated with cyclosporine (CsA). Furthermore, we analyzed patient's steroid threshold, (i.e. the dose of PSL at which the relapses occurred) before the initiation of CPM using 1 mg/kg per alternate days as a cut-off points. The patients of responders whose PSL threshold levels were less than 1 mg/kg per alternate days responders were significantly higher than those of non-responders (p=0.025). In conclusions, CPM as first-line therapy of immunosuppressive agents may be tried if prepubertal patients develop steroid dependency. If possible, we recommend that CsA is given only to midpubertal children with SDNS.

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  A14-year-old girl with idiopathic nephrotic syndrome showed decoy cells in urine sediments. BK virus is a human polyomavirus that infects nearly 80% of the general population. BK virus is associated with interstitial nephritis and ureteral stenosis in renal allograft recipients. The virus affects tubular epithelial cells that show characteristic intranuclear inclusion bodies. Latent BK virus infection of the renal epithelium is reactivated by immunosuppression, leading to viruria. Inclusion bearing cells sloughed into the urine can be detected in urine cytology. Those cells were named ‘decoy cells’. The detection of decoy cells estimates the likelihood of BK viruria. At the time of the detection of abundant decoy cells, the patient was on prednisolone and cyclophosphamide. We detected BK virus DNA in the urine from this patient by quantitative real-time polymerase chain reaction methods. BK virus DNA excretion disappeared three weeks later without the reduction of immunosuppressive therapy. The results showed that the patient was diagnosed with BK viruria. It is suggested that we need to monitor BK virus nephropathy in pediatric patients receiving immunosuppressive therapy.

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  It has been reported that pediatric patients with renal disease require a higher dosage of mizoribine (MZR) than that of adult patients to obtain an effective serum concentration. Although the major factor regarding this issue might be responsible for different pattern of pharmacokinetics of MZR between children and adults, a little information has yet been available on this difference. Here, we investigate the difference using the pharmacokinetic parameters of MZR in 10 patients with pediatric-onset renal diseases and 7 adult patients with rheumatic arthritis, for which data were previously reported. As a result, there was a negative correlation between age and distribution volume (correlation coefficient, -0.44; p-value, 0.0042); however, there was no correlation between age and urinary excretion rate (correlation coefficient, 0.14; p-value, 0.41). Because MZR is mainly excreted from the kidneys, its urinary excretion rate strongly reflects its absorption rate. From the data obtained in this study, it is suggested that the difference in distribution volume between children and adults, but not the difference in the absorption rate of MZR, is strongly correlated to the difference in the dose of MZR required, when it is corrected for body weight. If the distribution volume of MZR is high, the dose of MZR should be increased, after the dose is corrected for body weight.

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  We measured serum cystatin C (CysC) in 82 pateints consisting of 28 renal disease, 10 neurological disease (cerebral palsy), 35 endocrine disease (diabetes, obesity), and 9 cardiovasucular disease (congenital heart disease). All of then showed normal renal function assessed by estimated GFR more than 90 ml/min/1.73m² by Schwartz formula. The mean serum CysC was renal disease 0.79±0.13 mg/L, neurological disease 0.66±0.14 mg/L, endocrine disease 0.79±0.15 mg/L, cardiovasucular disease 0.79±0.15 mg/L. Neurological disease was significantly low value as compared with renal disease and endocrine disease. There were 13 patients of serum CysC 0.9-1.0 mg/L and 7 patients of those were obesity. In degree of obesity, serum CysC was non-obesity (degree of obesity<20%) 0.75±0.16 mg/L, mild obesity (degree of obesity 20-30%) 0.76±0.11 mg/L, moderate obesity (degree of obesity 30-50%) 0.77±0.13 mg/L, severe obesity (degree of obesity<50%) 0.93±0.14 mg/L. The severe obesity patients was significantly high value as compared with other patients. Serum CysC was suggested to show low value in the nervous system disease (cerebral palsy) and high value in the severe obesity.

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  Minimal change nephrotic syndrome (MCNS) is the major type of idiopathic nephrotic syndrome in children. Glucocorticoids and immunosuppressive agents are used for the treatment of MCNS. Although proteinuria resolves with glucocorticoids therapy in 90% of patients, the disease relapses in about 70% of them with the recurrence of proteinuria. Therefore, some children with MCNS need long-term glucocorticoid therapy.
  Growth failure is common during long-term treatment with glucocorticoids, although the cause of this complication is unknown. Since long-term glucocorticoid therapy is often required to treat nephrotic syndrome, growth retardation occurs in some patients.
  The growth of 75 patients with steroid-dependent nephrotic syndrome treated at our institution was evaluated. In6patients with growth retardation, serum levels of growth hormone and insulin-like growth factor were measured. Growth hormone deficiency was detected in 5 of them, and they were diagnosed as having glucocorticoid-induced growth failure. Recombinant growth hormone (GH) was administered to 4 of these 5 patients.
Case 1: A 9-year-old girl, who had developed nephrotic syndrome at the age of 2 years, with a height of 118.0 cm (-2.30 SD) was treated with GH for 6 years, and her height increased to 152.4 cm (-1.10 SD).
Case 2: A 14-year-old boy, who had developed nephrotic syndrome at the age of 3 years, with a height of 144.2 cm (-3.17 SD) was treated with GH for 3 years, and his height improved to 168.6 cm (-0.38 SD).
Case 3: A 15-year-old boy, who had developed nephrotic syndrome at the age of 5 years, with a height of 144.4 cm (-3.67 SD) was treated with GH for 26 months, and his height increased to 170.3 cm (-0.05 SD).
Case 4: An 11-year-old boy, who had developed nephrotic syndrome at the age of 3 years, with a height of 124.3 cm (-2.83 SD) was treated with GH for 66 months, and his height improved to 163.6 cm (-1.16 SD).
  Thus, all patients showed an increase of growth and reached the target range.
  The mean duration of glucocorticoid therapy before diagnosis of glucocorticoid-induced growth failure was, 107, months and all patients displayed GH deficiency. This implies that GH deficiency is the cause of glucocorticoid-induced growth failure and we suggest that GH therapy is effective for the treatment of growth retardation.

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  We measured serum concentration of mizoribine in 16 children with chronic renal deseases. Mizoribine was administered orally at a dose of 5mg/kg (range, 4.3-5.9 mg/kg) as a single daily dose before breakfast. The relationship between pharmacokinetic parameters of mizoribine and clinical parameters, such as sex, age, and the predonisolone dose was examined. Tmax was 1.67±0.50 hours, Cmax was 2.70±1.13 μg/ml, and AUCinf was 13.80±5.58 μg·h/ml. There was a positive correlation between age and AUCinf (r0.64, P=0.0074). There was a negative correlation between PSL dosage and Cmax (r-0.55, p=0.0287) and AUCinf (r-0.51, p=0.0421). It is necessary to investigate factors which has an influence on pharmacokinetics of mizoribine.

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  We performed management 55 pediatric patients with renal transplant between 20 years. Character of the pediatric renal-transplant recipient is to have much congenital disorder, and therefore many patients were necessary for urological treatments.
  The graft survival rate at 1 and 5 year after transplantation was 100 and 97%, respectively. Pediatric renal transplant in itself is established medical care recently. However, there are grave complications such as infection diseases, post transplantation diabetes mellitus and lymphoproliferative disease, and there is the problem that was must overcome in future.
  We experienced six renal graft loss cases. The half of those was a non-compliance case and might be able to avoid graft loss. Beside it, we experienced seven non-compliance patients. The non-compliance is character of adolescents and young adults.
  There are the problem that pediatric child elsewhere. The renal graft function gradually worsens, so we must always think about next treatment. As well as it, we must be able to cope about finding employment, a marriage, gestation, and childbirth.
  Pediatric renal transplant medical care is to be team approach, and it is necessary to examine children for all men.

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Purpose: The purpose of this study is to provide an introduction to evaluating the effectiveness of cystatin C (Cys-C) which is a new marker of renal function.
Patients and methods: The study population consisted of forty-three children including 21 males and 22 females ranging from 1 to 19 years of age. We evaluated their Cys-C, creatinine clearance (CCr), and serum creatinine (S-Cr) at the same time.
Results: Both the relationship of Cys-C to CCr and S-Cr showed strong correlation among all patients. But among children whose Glomerular Filtration Rate (GFR) was < 70 ml/min, the correlation of Cys-C to CCr was significantly greater than the correlation with S-Cr. Although S-Cr blood concentrations increase with aging, Cys-C blood concentrations are almost stable regardless of age. The Cystatin C-based formula is more accurate at detecting mild renal failure than the CCr and Schwartz formulae.
Conclusion: Cys-C is more effective and accurate for evaluating renal function than the existing markers of renal function.

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  Posterior reversible encephalopathy syndrome (PRES) is a relatively new clinico-radiological entity first described as reversible posterior leukoencephalopathy syndrome in 1996. Originally, it denoted a reversible predominantly posterior leukoencephalopathy in patients who had renal insufficiency or hypertension or were immunosuppressed. Since then, there have been various reports on this syndrome in a variety of clinical settings, including pediatric patients.
  In this review, we most emphasize the significance of early and precise diagnosis of PRES. Although its clinical and radiological courses have been reported as benign and reversible, a significant effect of early management on the prognosis of neurological function is suggested.
  Classic neuroimaging applied to patients shows edema involving the white matter in the posterior portions of the cerebral hemispheres, especially bilaterally in the parietooccipital regions. We have shown, however, radiological abnormalities extended to the gray matter, frontal and temporal lobes, and even the cerebellum. Thus, posterior reversible encephalopathy syndrome should be suspected in pediatric kidney transplant recipients and patients with kidney disease if they have a sudden episode of neurological symptoms, even if imaging findings are not restricted to the subcortical white matter of the occipital region.
  We also review the management of PRES, including the treatment of hypertension and seizures as well as the discontinuance and re-administration of calcineurin inhibitors.

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  Resent advances in podocyte biology indicated that the main cause of the heavy proteinuria in nephrotic syndrome (NS) is a dysfunction of slit diaphragm. On the other hand, we need to consider the theory of charge selective barrier dysfunction of glomerular capillary wall (GCW) in NS, at the same time, because the charge selective barrier is not likely to have a place in slit diaphragm. Therefore we re-evaluated the charge selective barrier function in NS and chronic glomerulonephritis using recently established charge selectivity index (CSI) in comparison with Dent disease. CSI is a clearance ratio of IgG and IgA. In order to evaluate the CSI of normal glomerular filtrate, we measured the CSI of Dent disease. The urine of Dent disease is considered to be a concentrate of filtered protein from normal glomerulus, without having a process of tubular protein reabsorption. 35 patients with podocyte diseases, 72 patients with chronic glomerulonephritis and8patients with Dent disease, were analyzed. CSI (mean±SD) of Podocyte disesses, chronic glomerulonephritis and Dent disease was 1.12±0.25, 0.42±0.31 and 0.16±0.06 respectively. The results indicated that the charge selective barrier of GCW is working strongly in normal glomerulus, less strongly in podocyte diseases and not working in chronic glomerulonephritis. Taking into account for the known dysfunction of slit diaphragm in nephrotic syndrome, the true cause of nephrotic syndrome may affect to both slit diaphragm and GCW resulting in heavy proteinuria showing some degree of charge selectivity.

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  A 5-year-old girl with red urine was referred to our hospital with proteinuria, hematuria and chylous serum. Urine appeared whitish red in color and gave strong positive results for protein, glucose, occult blood and ketone bodies. Since urinary sediment showed many isomorphic red blood cells and fatty balls, hematochyluria was diagnosed. Laboratory data revealed increased levels of blood glucose (430 mg/dl), HbA1C (16.9%), triglycerides (19,910 mg/dl), VLDL (551.6 mg/dl) and apo C-II (28.6 mg/dl). Urinary levels of C-peptide were below detection limit. Lipoprotein lipase activity and apo E genotype were normal. Type1diabetes mellitus and secondary type V hyperlipidemia were thus diagnosed. Lymphoscintigraphy demonstrated leakage from lymphatic vessels to the bladder. Based on these findings, hematochyluria might have been caused by marked hypertriglyceridemia, resulting in stasis of the lymphatics and rupture of lymphatic vessels into the bladder.

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  We herein describe a 6-year old girl with focal segmental glomerulosclerosis (FSGS) who was complicated with familial Denys-Drash syndrome and successfully responded to treatment with Angiotensin II receptor blocker (ARB). She was diagnosed to have Denys-Drash syndrome and a Wilms tumor in the bilateral kidney at 8 months of age and thereafter underwent a tumor extirpation. Later, proteinuria appeared at 1 year and 8 months of age and the patient's urinary protein excretion thereafter gradually showed a marked increase. A renal biopsy was performed at 6 years of age, and FSGS was thus diagnosed based on a renal histopathological study. As a result, ARB was administered and she rapidly showed a good response and thereafter a marked decrease in urinary protein excretion. One and a half years later, the patient's proteinuria disappeared. This case demonstrates the efficacy of ARB in a patient with FSGS who is complicated with Denys-Drash syndrome.
  Her father was also diagnosed to have Denys-Drash syndrome and a Wilms tumor in his left kidney at 1 year of age and a left nephrectomy and tumor expiration were thus performed. In the father, intermittent proteinuria and hematuria appeared at 6 years of age and his renal function also gradually deteriorated since 26 years of age. He therefore began to undergo hemodialysis at 31 years of age.
  The WT1 gene in both the girl and her father showed the same nonsense mutation R390X in exon 9. However, their clinical courses differed somewhat from each other, even though they demonstrated the same nonsense mutation, thus indicating a diversity in the phenotype of WT1gene mutations.

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[in Japanese]

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[in Japanese]

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[in Japanese]

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