We created a small volume circuit (36ml) suitable for safety monitoring devices of blood purification and tried to use the circuit in rabbits. Healthy Japanese white rabbits weighing about 3kg were divided into hemodialysis (n=8) and control groups (n=5). Autologous whole blood collected previously was used for priming the circuit, with heparin for anticoagulation and bicarbonate solution for dialysate. On the hemodialysis setting, flow rates for blood and dialysate were both 10ml/min, but ultrafiltration was not performed. Dialysis was performed for 6h, with vital signs monitored hourly. Blood was sampled at baseline, 1, 4, and 6h for blood counts, blood chemistries, and blood gases. Hemodialysis was maintained using the safety monitoring devices in all cases. However, body temperature in the hemodialysis group was lower than control group after the start of hemodialysis. In the hemodialysis group, blood pressure was lower after 5h than at baseline. We conclude that this circuit offers hemodialysis with good safety monitoring in rabbits. However, care should be taken to maintain body temperature and blood pressure at the time of performing hemodialysis in infants.

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 Although combination therapy with intravenous cyclophosphamide (IVCY) and pulse methylprednisolone has been reported to be effective for patients with severe lupus nephritis, its long-term use significantly causes considerable toxic effect. Mizoribine (MZB) has been applied without serious adverse effects in the treatment of lupus nephritis. However its clinical efficacy was reported to be limited in patients with mild case of lupus nephritis.
 We treated four children with severe lupus nephritis by triple therapy with low-dose IVCY (500mg/m², cumulative dose of 3g/m²), oral MZB (4-5mg/kg/day) and steroids (2-3 courses of pulse methylprednisolone followed by oral prednisolone) who achieved complete remission with renal histological improvements in a short period of time, and without significant adverse effects.
 From these findings, the triple therapy could be an alternative to achieve remission in children or adolescents with severe lupus nephritis, but long-term study is needed to confirm our preliminary findings.

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 There exist only limited longitudinal data on patients who had abnormal urinalysis findings at the 3-year-old routine check up. We examined the results of routine urinalysis of 3-year-olds at 7 public health centers and branches in Kyoto City, and the follow-up results from those with abnormal findings who visited Kyoto City Hospital. Routine urinalysis was done on 53,294 children at the 3-year-old check up and 4,450 children were reexamined at 7 public health centers and branches in Kyoto City because their first urinalysis showed some abnormality. Of them, 683 children (1.28% of the original group) were referred to hospitals for more detailed testing. Over the past 10 years, 394 children consulted the pediatric department of Kyoto City Hospital due to abnormal urinalysis results at the 3-year-old routine urinalysis. Out of 394, 181 showed normal urinalysis, 157 showed microhematuria, 50 showed asymptomatic hematuria, 3 showed asymptomatic proteinuria and 3 were tentatively diagnosed with nephritis at the hospital. We investigated 271 children who had follow up information collected when they became 6 years old. We found that 24 of the children had changed hospitals, 116 quit visiting the hospital, 51 were determined to have normal urinalysis and stopped coming, 49 had normal urinalysis, 22 showed microhematuria, 3 showed asymptomatic hematuria, 3 showed asymptomatic proteinuria and 2 were diagnosed with non-IgA mesangium proliferative glomerulonephritis.

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 Collapsing variant (CV) of focal segmental glomeruoscrelosis (FSGS) is characterized by collapse of the glomerular tuft with marked proliferation of overlying glomerular visceral epithelial cells. Idiopathic FSGS-CV has been known to display black racial predominance, a higher serum creatinine, more severe features of nephrotic syndrome and a rapidly progressive course to renal failure. It has been clinically refractory for various treatment modalities. Thus, the optimal therapy for this variant is unknown.
 We report three cases of this variant, without clinical or serological evidence of HIV-1 infection. All patients clinically showed severe hypertension and steroid resistance at the conventional dose, but two of them attained complete remission after methylprednisolone pulse therapy combined with ciclosporin A. At that time, the improvement of severe hypertension that was achieved by the use of enalapril, losartan, continuous intravenous infusion of nicardipine chloride and timely removal of excess fluid using peritoneal dialysis, was necessary to avoid hypertensive encephalopathy and perform safely the therapy.
 In Japan, few cases of this type of FSGS have been reported. However, the incidence of CV has progressively increased over the past two decades at a single center in the United States. So, in the near future we might be confronted with many cases of FSGS-CV and need the optimal therapy.

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 Clean intermittent catheterization in combination with oral anticholinergic agents (oxybutynin chloride) is the present standard therapy for children with neurogenic bladder dysfunction and detrusor overactivity. The mechanism of action of oxybutynin chloride involves its antimuscarinic properties that relax bladder smooth muscle. However, well-known complications arising from systemic anticholinergic effects may interfere with clinical use. When these side effects supersede therapeutic efficacy or this therapy fails to decrease bladder pressure to levels that protect the upper urinary tract, more invasive options are used, such as augmentation cystoplasty. We report here our experience with the intravesical oxybutynin chloride for neurogenic bladder in children.

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 In 1986, nitric oxide (NO) was identified as a powerful vasodilating agent in the cardiovascular system. This was a revolutionary finding because it had never been shown that a gaseous molecule could function as a messenger or an effector in the body. The importance of NO's role in our understanding of human health and disease was recognized in 1998 when the Nobel Prize in Physiology or Medicine was awarded to three scientists who made fundamental contributions to our understanding of this remarkable molecule. As a molecule with a myriad of activities, NO may be involved in the development and progression of pediatric kidney diseases. However, the “NO status” in young subjects and appropriate methods for its measurement remain to be defined. This review attempts to highlight the recent progress in our understanding of the cellular and molecular pathways of NO that has led to current or potential future therapies involving NO. It also suggests the direction of future researches that can be recommended for Japanese pediatricians.

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[in Japanese]

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 It is generally considered that the intensity of the pharmacological effects and adverse effects of drug is determined by drug concentration in blood (plasma or serum) or the amount in the body. The therapeutic objective is to maintain a proper concentration of drug at the site of action during therapy. In addition, individual dosage adjustment based on targeted drug concentration in blood can prevent or minimize adverse effects of drug.
 To administer drugs optimally, therefore, knowledge is needed not only of the mechanisms of drug absorption, distribution, metabolism and elimination but also of the kinetics of these processes, that is, pharmacokinetics. The pharmacokinetics is the study of the time course of the drug absorption, distribution, metabolism and excretion. If we can obtain the pharmacokinetic data (parameters) of drug following a single dose, the plasma concentration or amount of drug in the body at any dosing schedules can be mathematically estimated by the pharmacokinetic models. Knowing the pharmacokinetics of the drug aids the clinician in anticipating the optimal dosage regimen for individual patients and in predicting the pharmacological effects and adverse effects.
 The most commonly used approach to the pharmacokinetic characterization of a drug is to represent the body as a compartment, and to assume that the rate of transfer between compartments and the rate of drug elimination from compartments follows the first-order kinetics. The one-compartment model, which represents the body as a single and kinetically homogeneous unit, is particularly useful for the pharmacokinetic analysis of drug.
 In conclusion, basic pharmacokinetic theory in patients receiving drug therapy provides useful information to dosage adjustment for individual patients. This article describes about the application of therapeutic drug monitoring (TDM) in drug therapy, focusing upon the foundation of the pharmacokinetics of drug fitted to one-compartment model.

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 The frequency of the obese children are increasing in the recent years, due to the change of lifestyle such as poor exercise, a fat highly-content diet and so on. Recently we encountered three pediatric cases with Obesity-Related Glomerulopathy(ORG). All of these patients showed moderate proteinuria associated with high glomerular hyperfiltration rate, mild hypertension and the enlargement of glomerula size. However, focal glomerular sclerotic change was observed only in one patient. The principal of the therapy for ORG is base on the normalization of GFR by reducing over-weight through adequate diet and exercise, but sometimes it likely to difficult. Therefore ACE-I and ARB are sometimes administered to these patients, and mostly showed effectiveness. Among the obese children with the asymptomatic proteinuria and/or histologically minor glomerular abnormality, ORG could be included.

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 As for that actual condition, a child membranous nephropathy is not clear though it is the minority from the viewpoint of epidemiology. This time, the case of idiopathic Membranous Nephropathy on two years old girl was experienced. We performed renal biopsy due to macrohematuria and massive proteinuria. Treatment by the steroid was started in accordance with minimal change nephrotic syndrome protocol, because microscopic views showed slight change. It was left behind, all except for IgA and IgM were stained with the line-shaped in the fluorescent antibody and Electron Dense Deposit was recognized in electron microscope on a basal lamina, so it became a definite diagnosis. Fortunately effect on a decrease in urine albumin by the steroid is seen, and a proteinuria becomes negative in about six weeks, and future progress is smooth, too. We report about the case progress, renal pathology and the treatment.

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 Two girls with C1q nephropathy were reported. Both patients had moderate proteinuria without nephrotic syndrome. Renal biopsy specimens of both showed predominant mesangial C1q deposition and mesangial electron dense deposits. However, one showed focal segmental sclerosis in light microscopy with minimal deposition of IgG and C3 by immunofluorescence and another showed minor glomerular abnormalities associated with significant immunoglobulins, C3 and C4, so called full house pattern. In the literature light microscopic classification of C1q nephropathy is composed of three categories; minor glomerular abnormalities (MGA), proliferative glomerulonephritis and focal segmental sclerosis. The difference in the category of pathological findings should reflect on the difference of clinical features. The patients with C1q nephropathy must be divided into three groups by light microscopic findings to clarify the pathogenesis and to evaluate the prognosis of C1q nephropathy.

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A four-year-old boy visited our clinic with abdominal distension, pretibial pitting edema, hypoalbuminemia without any abnormal findings in urinalysis. One week prior to the onset, he had an episode of Influenza B infection treated with Oseltamivir phosphate. As the hypoalbuminemia improved without treatment, we could not specify the pathogenesis of his symptom. However, he returned to our clinic with typical Nephrotic syndrome with proteinuria one and a half months later. A conventional steroid therapy for Nephrotic syndrome succeeded in prompt improvement such as edema and proteinuria. He has not experienced a relapse so far. Because the clinical course and the laboratory findings of both episodes resembled to each other except for proteinuria, we speculate that the first episode may have represented the convalescent process of Nephrotic syndrome.

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 This report describes a 11-year-old girl with diffuse mesangial proliferative glomerulonephritis without IgA deposition (diffuse non-IgA MesPGN). She was refered to our hospital because of evaluation for hematuria and proteinuria in 7-year old. First renal biopsy showed diffuse non-IgA MesPGN with focal interstitial fibrosis. The estimation of histological renal injuri was expressed as G (2.3) and S (2.3) according to the histological grading and staging classification by Shigematsu (G-S system). She was treated with prednisolone, azathioprine, warfarin and dipyridamole for 2 years. Second renal biopsy performed after the 2 year treatment showed the estimation of histological injuri expressed as G (1.3) and S (0.5), which indicated the reduction of the renal histological injury. In conclusion, combined therapy with prednisolone and cytotoxic may be the usuful treatment for the reduction of histological lesion in children with diffuse non-IgA MesPGN.

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 ARC syndrome is an autosomal recessive multisystem disorder characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and cholestasis. We report a female case of the disease. The patient was born at 38weeks' gestation, weighing 2,466g. The pregnancy had been uncomplicated, and the family history was unremarkable. At birth, arthrogryposis was found in bilateral ankle joints. At 1month of age she was transferred to our hospital because of jaundice and acholic stool. Liver function tests showed a total bilirubin of 4.7mg/dl, a direct bilirubin of 3.5mg/dl, normal transaminase level, and normal γ-glutamyl transpeptidase level. There was no evidence of bile duct atresia or neonatal hepatitis. Urinalysis showed proteinuria, glycosuria, and aminoaciduria. The blood urea nitrogen level was 6.4mg/dl, the creatinine 0.4mg/dl and the total cholesterol 109mg/dl. Additional findings were dysgenesis of the corpus callosum, polymicrogyrus, and nerve deafness. In spite of sufficient feeding, her growth was severely impaired. Jaundice gradually increased. At 12months of age her body weight was 2,658g, and the total bilirubin level was 19.2mg/dl with 70% direct. She died at 15months of pneumonia. ARC syndrome is a rare genetic disorder. To our knowledge, this is the second reported case of the disease in Japan.

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 A 7-year-old boy had undergone renal transplantation at the age of 2years and 2months. However, because of infection and thrombotic microangiopathy due to Tacrolimus hydrate the kidney was removed soon after the transplantation and hemodialysis was started. After the initiation of hemodialysis he had no cardiomegaly and no hypotension for 4years and echocardiography revealed that left ventricular diastolic dimension was 101% of normal value. On the process of fitting his dry weight to his growth, cardiothoracic ratio developed to 57% during the last one year. Therefore, his dry weight was decided to be decreased. But cardiothoracic ratio did not remarkable change and he became hypotensive. Echocardiography showed normal left ventricular systolic function, contractility and cardiac output. However, left ventricular diastolic dimension was decreased to 91% of normal value and suggested that the hypotension was due to decreased preload. So his dry weight was increased. As a result left ventricular diastolic dimension was increased to 98% of normal value, and hypotension was disappeared. And no cardiomegaly was shown on the chest rentogenogram. Assessing of left ventricular preload was difficult only using chest rentogenogram. Echocardiographic study was effective on the decision of dry weight.

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