We studied 4 patients with steroid-resistant minimal change nephrotic syndrome who developed urinary decoy cells and BK viruria as assessed by PCR. Decoy-cell shedding began at the initial onset of disease in one patient and the other patients were in a frequently relapsing state. All cases were given prednisolone (1∼2mg/kg) and cyclosporine A (CyA). Two patients (cases 1 and 2) were infants, of whom one had non-hemorrhagic cystitis and the other had hemorrhagic cystitis, both with a prolonged period of positive BK viruria and viremia. Case 3 had asymptomatic viruria with a low viral load in the urine and no viremia. Case 4 had prolonged shedding of decoy cells and a high viral load in the urine associated with transient viremia. The risk factors for BKV reactivation were a high trough level of CyA (100∼150μg/l) and a frequent increase in prednisolone dose because of frequent relapses of nephrotic syndrome. A high viral load in the urine in patients with steroid-resistant nephrotic syndrome could progress into viremia resulting in BKV nephropathy. Therefore, viral load in the urine and plasma needs to be carefully monitored.

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 Objective: To evaluate the predictive value of acute Technetium-99m dimercaptosuccinic acid scintigraphy (acute DMSA) and renal ultrasound scanning (US) for high-grade vesicoureteral reflex (VUR) in children with a first urinary tract infection (UTI).
 Materials and Methods: A retrospective analysis of the records of 19 children (14 boys and 5 girls) was performed. Acute DMSA and US were performed within7days from diagnosis, and voiding cysturethrography (VCUG) was performed within 2 months.
 Results: Of 19 children, high-grade VUR (III∼V) was diagnosed in 7 (37%). The detection rate of high-grade VUR by US alone was 28%. But combining acute DMSA and US, we found that the detection rate of high-grade VUR was 100%. If VCUG had been performed only in children with abnormal acute DMSA or US results, 6 VCUGs (32%) could have been avoided.
 Conclusion: VCUG is only indicated when abnormalities are apparent on either acute DMSA or US or both.

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 Aldosterone's main actions are to regulate intravascular volume and serum electrolytes by controlling sodium absorbtion and potassium excretion in the distal nephron.
 Isolated hyperreninemic hypoaldosteronism presenting in infancy is a rare desease caused by aldosterone synthase deficiency resulting in hyponatremia, hyperkalemia and hypovolemia.
 Here, we report a case of infant suspected psedohypoaldosteronism with hyponatremia, hyperkalemia, hypovolemia. During clinical course, plasma aldosterone level remains normal ranges of his age despite high level of plasma rennin activity and fludrocortisone therapy was effective against his hyponatremia and hyperkalemia, thus we diagnosed him as hyperreninemic hypoaldosteronism. He also had absorptive hypercalciuria, renal hypouricemia and high plasma level of 1,25-dihydroxyvitamin D.
 The association between renal hypouricemia and absorptive hypercalciuria has been described in the past, but this is the first case of isolated hyperreninemic hypoaldosteronism associated with absorptive hypercalciuria and temporary renal hypouricemia suggesting possibly new syndrome.

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 PURPOSE: Breakthrough urinary tract infections (UTI) were considered an indication for surgical intervention in children with vesicoureteral reflux (VUR) with the goal of preventing renal scarring. We assessed the influence of reflux grade on the incidence of breakthrough UTI in patients with primary VUR.
 MATERIALS AND METHODS: We retrospectively analyzed 425 (male/female: 281 144, bilateral/unilateral: 229/196) patients with primary VUR. There were 33, 64, 99, 131, and 98 patients with VUR of grade I, II, III, IV, and V respectively.
 RESULTS: Of 425 cases 90 (21.2%) had breakthrough UTI, and 50, 25, 8, 6, and 1 cases had once, twice, thrice, 4times, and 5times of breakthrough UTI respectively. None (0%), 3 (4.7%), 15 (15.2%), 44 (33.6%), and 28 (28.6%) cases had breakthrough UTI in each grade I, II, III, IV, and V group, respectively. Patients with higher grade VUR have more times of breakthrough UTI significantly (p<0.01). Of patients with primary high-grade VUR, 31.4% had experienced breakthrough UTI, while of patients with primary low- and middle grade VUR, 9.2% had experienced breakthrough UTI.
 CONCLUSIONS: Patients with primary high-grade VUR had higher incidence of breakthrough UTI than that with primary low- or middle grade VUR. Our findings may endorse the uselessness of antibiotic prophylaxis as well as continued nonoperative management for the low- or middle-grade VUR.

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 We studied long-term clinicopathologic analysis of 258 pediatric patients with idiopathic nephrotic syndrome started in childhood, especially of 50 patients who carried over (CO) the disease to adulthood. This study has been done from 1980 to 2010 by our institute and National Hospital Organization Okayama Medical Center. The propotion of the carry over the disease to adulthood was approximately 20% of the patients. The characteristics of CO were 1) the onset of the disease was slightly younger than non-CO and 2) the type of relapse was mainly frequent type. Furthermore, the more younger the onset, more likely with the clonicity. The patients with idiopathic nephrotic syndrome tended to show complete remission until their puberty period. And even the carry over occurred, renal function did not become worse and response to steroid-sensitivity to relapse was still fine and stable. Another problem regarding CO is certainly impairment of social adjustment for the patients.

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 Patients with refractory nephrotic syndrome, such as steroid-dependent, frequently-relapsing or steroid-resistant nephrotic syndrome, are frequently complicated with serious adverse effects of steroid therapy caused by long-term use. In particular, bone complications such as failure to thrive (short height), osteoporosis, osteonecrosis of the femoral head and vertebral bone fractures are irreversible and compromise the patients' quality of life.
 We administered rituximab to four patients with refractory nephrotic syndrome who suffered from osteonecrosis or vertebral bone fractures. After the rituximab therapy, all four patients were able to discontinue steroid therapy, thereby preventing new bone complications. Their bone mineral density had remarkably improved. In addition, the patients recovered the ability to walk without assistance or a stick. No severe adverse effects of rituximab were experienced.
 Rituximab is a hopeful agent for children with severe bone complications. However, we should be aware of any risks of rituximab therapy.

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 We conducted an open-label, single-arm multicenter study to evaluate the efficacy, safety and pharmacokinetics of MMF in Japanese pediatric renal allograft recipients, comparing with historical data in United Sates pediatric and Japanese adult renal allograft recipients. The primary efficacy outcome was the proportion of patients experiencing a biopsy-proven acute rejection episode within the first 6 months post-transplantation. Secondary efficacy outcomes were the proportion of patients who lost their graft by 12 months, the proportion of patients who died at 12 months.
 25 patients (2 to < 18 years) received MMF 300-600 mg/m² b.i.d. concomitantly with calcineurin inhibitor and corticosteroids with or without antilymphocyte antibody induction. Six patients (25%) experienced a biopsy-proven (Banff grade borderline or higher) acute rejection episode within the first 6 months post-transplantation. One year after transplantation, patient and graft survival were 100% and 100%, respectively. Seventeen patients (68%) experienced adverse events. The most common adverse events related to MMF involved the infection associated with cytomegalovirus virus. Withdrawal of MMF due to adverse event was necessary in two patients. All adverse events associated with MMF were acceptable. The dosing regimen of MMF 300-600 mg/m² b.i.d. achieved the targeted in the first 3 months post-transplantation MPA 12-h area under concentration-time curve (AUC_0-12) of 48.7 ± 27.6 μg hr/ml. This was similar with AUC_0-12 of Japanese adult renal transplant recipients treated with MMF 2,000 mg b.i.d. The time course of estimated AUC_0-12 showed no clinically difference with that of United Sates pediatric renal allograft recipients treated with MMF 600mg/m² b.i.d.
 Administration of MMF 300-600mg/m² b.i.d. may be effective in prevention of acute rejection and be tolerant in Japanese pediatric renal transplant recipients, although this study has the limitation of study design and small patients' numbers. This dosing regimen provided predictable pharmacokinetics, too.

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 Blood priming is required for extracorporeal continuous renal replacement therapy in neonates. However, blood is thought to release the hypotension-inducing agent bradykinin while passing through the polyacrylonitrile membranes used as low-volume hemofilters under acidic conditions. We examined bradykinin generation in blood-primed circuits and determined the performance of different purification modalities. Bradykinin was measured at 5-min intervals without blood purification in a closed circuit (n=3). Thereafter, the blood was purified using hemodialysis (dialysate flow rate, 2 L/h), hemofiltration (filtration rate, 0.5 L/h) or hemodiafiltration (dialysate flow and filtration rates, 1.5 and 0.5 L/h, respectively). Bradykinin, pH, bicarbonate, electrolytes and citric acid were measured at defined intervals during these processes (n=6). The bradykinin concentration significantly increased from 42.6 ± 12.4 to 145.0 ± 9.5 pg/mL (means ± SD) after blood priming and decreased in all modalities, but fell below 100 pg/mL at 30 min in all purifications using hemodiafiltration. The residual ratio of bradykinin at 10 min of blood purification was significantly lower in hemodiafiltration than in hemodialysis. Hemodialysis and hemodiafiltration were superior to hemofiltration in terms of other measured parameters. Hemodiafiltration might eliminate bradykinin more effectively from blood-priming circuits with polyacrylonitrile membranes than either hemodialysis or hemofiltration.

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 The development of thromboembolism exist on several disease, each arterial and venous thromboembolism have their own different basic disease and pathology. And many factors tend to complicate for the development of that. Thromboembolic disease is an important complication, venous thrombosis is well known. It occurs by an increased hyperviscosity and decreased factors of anti-coagulation. This article include a case report of the recurrence of nephrotic syndrome with arterial thromboembolism on two organs, propose the prospective issues of pathology and its treatment.

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 Renal lymphangiectasia is a very rare disorder in pediatric cystic renal disease. We report a case of renal lymphangiectasia in an 8-year-old boy who presented high-renin hypertension, growth hormone deficiency and polycytemia with increased erythropoietin production. Abdominal ultrasonography showed enlarged kidney with increased echogenicity and poorly defined corticomedullary junctions. MRI reveals low signal intensity on T1-weighted images, which were compatible with the peripelvic cysts. These images are typical of renal lymphangiectasia. This is the first case report that revealed these typical images persistent for 6 years.

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 We reported a case study of nephronophthisis in a boy who was detected during anemia treatment. The patient was 9-years-old boy without having been noted renal disease. Even past urine analysis has not been noted abnormality either. He was detected at anemia by chance. He was diagnosed iron-deficiency anemia and treated by iron supplement for two years. He was discovered renal function degeneracy by drawing blood examination for anemia close inspections (BUN67mg/dL, Cr3.5mg/dL). We performed renal biopsy and were confirmed with nephronophthisis. We started peritoneal dialysis because his renal function is CKDstage5. Nephronophthisis has difficulty with a diagnosis, but it is important for the prevention of the complication to be diagnosed.

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 Neonatal hemochromatosis is a severe, often fatal multiorgan disorder of iron metabolism. We report a case of neonatal hemochromatosis associated with bilateral renal hypoplasia. The patient also had congenital intestinal atresia and meconium peritonitis. The radical operation was performed for congenital intestinal atresia at one-day-old. After surgery, oliguria occurred and renal disorder progressed to chronic renal failure. Subsequently, liver dysfunction and hyperferritinemia appeared. Bilateral hypoplastic kidney was diagnosed by CT scan, and MRI demonstrated abnormal iron deposition in the liver, pancreas and renal cortex at 2-month-old, indicating hemochromatosis. The hemochromatosis slowly improved by withdrawal of blood and oral vitamin E. Peritoneal dialysis was initiated for chronic renal failure at 10-month-old.
 We conclude that this is a very rare case of renal hypoplasia complicated with neonatal hemochromatosis.

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  Methotrexate (MTX), a classic antifol, is one of the most widely prescribed anticancer agents in children. The high-dose MTX therapy (over 1.0 g/m²), may induce renal dysfunction that exacerbates other toxicities of MTX, because of delayed MTX excretion. Several studies reported that it is effective the dialysis-based methods of MTX removal. A 12-year-old boy who had Burkitt lymphoma, after third high-dose MTX therapy (3 g/m²), occurred MTX-induced renal dysfunction (serum creatinine 2.47 mg/dl) and his plasma MTX concentrations elevated to 18.8 μmol/l (48-hour-value). We treated him with one session of high-flux hemodialysis (HD) for 4 hours and two sessions of charcoal hemoperfusion. The plasma MTX concentration was significantly decreased. The clearance of plasma MTX in one session is 64.9% in HD, 72.2% and 65.3% in hemoperfusion. His creatinine levels recovered to normal range. After then, additional MTX (0.5 g/m²) was administered him without recurrence of renal dysfunction. Now he is in a clinical complete remission of Burkitt lymphoma. We successfully treated the patient with MTX-intoxication by high-flux HD and charcoal hemoperfusion. We report the timing of introduction of the blood purification therapy and the comparative efficacy of MTX removal methods.

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  We experienced an extremely rare case of a 15-year-old boy with minimal change nephrotic syndrome who turned out steroid-resistant 12 years after the onset. The patient first suffered from nephrotic syndrome at the age of 3 in November in 1996. He has been treated with prednisolone (PSL) and cyclosporine A (CyA) because of frequent relapses. The renal biopsies held three times revealed minimal-change nephrotic syndrome. He was diagnosed with steroid-resistant nephrotic syndrome for the first time in February in 2009. The fourth renal biopsy at this points showed minimal change and no evidence of cyclosporine nephropathy. According to the protocol of Japanese Study Group of Renal in Children (JSRDC), two series of methylprednisolone pulse therapy (MPT) were performed in April in 2009, and then proteiurea gradually decreased. Since then, he has kept complete remission. Frequent relapsers of nephrotic syndrome who require long-term observation have a risk of changing steroid-sensitivity from sensitive to resistant though it rarely happens. For that reason, we have to pay attention to the timings of both renal biopsy and the introduction of methylprednisolone pulse therapy.

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  Adrenocorticotrophic hormone (ACTH) has been used as a first-line therapy to treat West syndrome. Among the potential side-effects of ACTH therapy, nephrocalcinosis (NC) or urolithiasis cannot be ignored. The etiologies of NC in ACTH-treated patients are multifactorial. Possible causes include increased urine calcium (Ca) and phosphorous (P) excretion, osteoporosis, and/or abnormal levels of parathyroid hormone.
  Zonisamide (ZNS) is an antiepileptic agent that is widely used in Japan, sometimes concomitant with ACTH therapy. ZNS is also known to be associated with urolithiasis. It is speculated that ZNS has weak carbonic anhydrase inhibitor effects resulting in alkalized urine and increased urine calcium excretion, which, in turn, cause urolithiasis.
  We report 5 children who developed NC or urolithiasis with West syndrome treated with ACTH (NC group).
  To examine the risk factors for NC, duration of ACTH therapy, total dose of ACTH, usage of ZNS, serum Ca level, serum P level, serum alkaline phosphatase (ALP) level, urine Ca/Cr ratio, %TRP and urine pH during ACTH therapy were examined retrospectively.
  For the purpose of comparison, we examined those parameters in 4 other patients who had developed neither NC nor urolithasis during treatment using ACTH (non-NC group).
  All patients with NC group had been treated with ZNS as opposed to only one in non-NC group. Total dose of ACTH was higher in the NC group than in the non-NC group. (NC 0.37±0.10 mg/kg, non-NC 0.26±0.01 mg/kg, p=0.07). Duration of ACTH therapy was significantly longer in the NC group. (NC 41.8±9.4 days, non-NC 27.5±2.6 days, p=0.02).
  No remarkable changes were seen in serum Ca levels during ACTH therapy. Urine Ca/Cr ratio increased, with a much higher mean peak level in the NC group (NC 2.0±0.7, non-NC 0.7±0.6, p=0.03). One patient who did not developed NC despite administration of ZNS expressed normal urine Ca/Cr ratio during ACTH therapy.
  Serum P levels and %TRP decreased, but no significant difference was seen between the NC and non-NC groups. Serum ALP level decreased in all except one patient with preexisting hyperalkaline phosphatemia. Urine pH did not show any particular tendency.
  In our study, patients with West syndrome on ACTH therapy were in the risky environment for urolithialis:urine Ca and P excretion increased, turnover of the bone lowered (decreased serum Alp). Risk factors for NC were 1) administration of ZNS, 2) high dose and long duration of treatment with ACTH, and 3) high urine Ca/Cr ratio. During ACTH therapy, particularly in combination with ZNS, renal echo-sonography and urine Ca/Cr ratio have to be monitored closely. Thiazide therapy or changing to antiepileptic agents other than ZNS can be alternative management if any abnormalities are detected.

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 Dent disease is characterized by progressive proximal renal tubulopathy with hypercalciuria, low-molecular-weight proteinuria, and nephrocalcinosis. While nearly 60% of cases are reported to be caused by mutations in CLCN5 gene located on Xp11.22 and 10∼15% of cases are caused by mutations in OCRL1 gene located on Xq26.1, causes of the remaining 25∼30% of cases are still unknown.
 We here report the case of sibling with Dent disease having no mutations of OCRL1 and CLCN5 and suggest an autosomal fashion of inheritance of this disease.
 Case report: A 13 year-old brother and his 10-year-old sister were referred to us for further evaluation of asymptomatic tubular proteinuria detected at school screening program in Japan. Their past medical histories and family history were unremarkable. They were the first and the third products of the five siblings by healthy unrelated Japanese parents. Their physical examinations at referral revealed no abnormal findings whereas their urinary findings demonstrated increased concentrations of β₂-microglobulin (β₂MG) without significant hematuria or hypercalciuria. Blood tests showed normal values including serum creatinine, electrolytes, and proteins and ultrasound examinations did not detect any abnormal findings on their urinary tracts. Urinary levels of β₂MG in their mother and other siblings were also within normal values.
 Based on these findings, the diagnoses of Dent disease were made on them. They have been followed-up periodically for 3 years by now to check their values of urinary β₂MG which revealed consistent abnormal values: the brother demonstrated the values between 560μg/L and 1,830μg/L (normal: 30∼340μg/L) while the sister's values varied from 317μg/L to 23,550μg/L. Their sequence analyses of CLCN5 and OCRL1 did not show any mutations. Thus, we suggest that some patients with Dent disease show autosomal inheritance.

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 Microscopic polyangiitis is a type of antineutrophil cytoplasmic antibody (ANCA) associated vasculitis characterized by inflammation of small vessels. Although myeloperoxidase (MPO)-ANCA is usually positive in microscopic polyangiitis, we report the first case of ANCA-negative microscopic polyangiitis associated with streptococcal infection in a 12-year-old boy. He was admitted to our hospital for fever, skin rash, abdominal pain, nephrotic range proteinuria, gross hematuria and renal insufficiency. Subsequent oliguric renal failure, acute pancreatitis and arthritis were observed, and continuous hemodaiafiltration was initiated. He was diagnosed with vasculitis syndrome due to multiple organ symptoms. Laboratory findings revealed negative results for MPO-ANCA and proteinase 3 (PR3)-ANCA. Elevation of antistreptokinase (ASK) titer was observed, but there was no hypocomplementemia. Skin biopsies showed leukocytoclastic vasculitis without IgA and other immunoglobulin deposition. Renal histopathology revealed diffuse endocapillary hypercellularity and mesangial proliferation with mesangiolysis. Crescentic formation was not observed. Severe inflammatory cell infiltration was observed in the entire interstitium with tubulitis. Small-sized vessels, such as afferent arterioles, revealed fibrinoid necrotic angitis with swelling of endothelium. Immunofluorescence studies revealed only a few C3 deposits. Nephritis-associated plasmin receptor (NAPlr), nephritogenic streptococcal antigen, and plasmin activity were seen in the renal biopsy specimens. A diagnosis of ANCAs-negative microscopic polyangiitis with pauci-immune rapidly progressive glomerulonephritis was made and subsequent steroid therapy was initiated which proved to be very effective. Immediate improvement of clinical symptoms and abnormal laboratory findings were seen with complete recovery of renal function.
 We report the first case of ANCAs negative MPA accompanied with pauci-immune rapidly progressive glomerulonephritis which may have been caused by streptococcal infection due to elevated ASK titers and positive NAPlr and plasmin activity in renal specimens.

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 Adenovirus cystitis is a rare complication of hematopoietic stem cell transplantation and rarely induces inflammation of the upper urinary tract and hydronephrosis. Obstruction of the urinary tract may cause renal impairment. Herein, we describe the case of a 7-year-old boy who developed hydronephrosis and ureteritis due to adenovirus hemorrhagic cystitis following umbilical cord blood transplantation for Philadelphia-acute lymphoblastic leukemia (Ph-ALL). Although he completely recovered from the clinical symptoms of cystitis, MAG3 renoscintigraphy revealed obstruction pattern of right kidney.
 The patient was diagnosed as having Ph-ALL at 7 years of age;he underwent umbilical cord blood transplantation after chemotherapy. Conditioning regimen included total body irradiation (12 Gy), etoposide, and cyclophosphamide. Successful graft preservation was noted at the 20^th day after transplantation. The patient showed fever, macrohematuria, and progressive micturition pain at the 43^rd day after transplantation. He received supportive care, but the symptoms persisted. Serum creatine level increased gradually. At the 52^nd day of transplantation, abdominal ultrasonography and abdominal computed tomography showed bilateral hydronephrosis, dilatation of the right ureter, and wall thickening of the whole bladder. Adenovirus was isolated from the urine sample at the 44^th day after transplantation. Imaging study and culture test suggested hemorrhagic cystitis and ureteritis due to adenovirus infection. At the 73^rd day of transplantation, the patient showed complete recovery from the clinical symptoms, and his serum creatine level returned to normal as the number of lymphocytes increased. However, right hydronephrosis remained. MAG3 renoscintigraphy revealed obstruction pattern of right kidney. The patient did not receive invasive therapy because of the expectancy of spontaneous relief of obstruction and the risk of infection. Currently, his renal function is being closely observed.

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[in Japanese]

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[in Japanese]

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[in Japanese]

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