Many renal disorders are associated with changes in the size of the kidneys. Ultrasonography has widely replaced the intravenous urogram to evaluate kidney size in children suspected of having urinary tract abnormalities. We examined the kidney length (KL) of 195 children, 105 boys and 90 girls, aged 1 month-15.7 years, without urinary tract abnormalities. Here, we discuss the correlation between KL and age, height, and the distance between the 4th and 5th spinous processes of the lumbar vertebrae (lumbar segment L4-L5). KL showed a linear correlation with these somatic parameters. We noted a mean KL increase of 4.8 mm in boys and 4.6 mm in girls per 10 cm increase in height. The differences between the slopes of the regression lines for the lengths of both the right and left kidneys were also similar. The increase in KL was greater during the first 2 years of life, which mirrors the accelerated body growth during infancy. KL was generally 4-6 times longer than lumbar segment L4-L5. Only 0.5% of the girls, but none of the boys, showed a size that was less than 3.5 times the lumbar segment. We propose the use of the ratio of KL to lumbar segment L4-L5 to evaluate the kidney size as these values are readily available and are simpler to use than any other somatic parameter.

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 With the recent advances in renal transplantation, one of the kidney substitution therapies, the majority of our patients have successfully achieved our goal, living independently their lives similar to the “healthy” people.
 At our institution, we stated renal transplantations in 1987. To date, there are 24 patients aged over 19 who have been followed up since childhood.
 Only one out of them, who requires psychiatric care for depression, spends most of the time at home without working. The jobless rate for 17 patients who graduated from schools is 5.8%. We regard this result acceptable since the complete unemployment ratio for the entire population of this age group is reported 6.4-9.4%. Five patients have obtained some qualifications/licenses for occupation and their works are related to them. Four patients are married, including 2 males as fathers. Renal transplantation for children and adolescents have established medical care and promotes better social activities for the patients with chronic renal insufficiency.

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 Acute renal failure (ARF) induced by anaerobic exercise is an important complication of idiopathic renal hypouricemia. It has been suggested that decreased antioxidant potential in hypouricemia leads to kidney injury caused by reactive oxygen species (ROS). However, the mechanisms involved in the development of exercise-induced ARF, especially in patients without renal hypouricemia, have not been fully clarified. We demonstrated the oxidative imbalance after exercise stress testing in a boy with exercise-induced ARF without hypouricemia.
 A 13-year-old Japanese boy was transferred to our hospital for evaluation of ARF that developed after anaerobic exercise. Routine laboratory tests revealed 5.9 mg/dl of serum creatinine and 12.8 mg/dl of uric acid, respectively. He was diagnosed with exercise-induced ARF. We subjected the patient to a period of strenuous exercise on a treadmill, and compared with a healthy male volunteer. Serum concentrations of ROS and biological antioxidant potentials (BAP) were measured by spectrophotometric methods using commercially available kits (d-ROMs and BAP test, respectively).
 The serum level of BAP in the patient was reduced soon after the initiation of anaerobic stress, whereas that of the volunteer was elevated. Therefore, the ratio of ROS to BAP was increased in the patient (before, 0.20; after, 0.39) but decreased in the volunteer (before, 0.17; after, 0.12).
 These data suggested that an oxidative imbalance resulting from a decreased antioxidant capability is involved in the pathogenesis of exercise-induced ARF. The oxidant imbalance in patients with exercise-induced ARF without hypouricemia may lead to renal vasoconstriction and renal injury.

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 Bacterial culture and serum antibody still play main roles to determine infectious pathogens. On the other hand, although gene amplification method s enable to detect small amount of bacterial or viral genes from clinical specimens within several hours, it is highly controversial whether amplified bacteria or virus might be true pathogens or not. The LAMP method (Loop - Mediated Isothermal Amplification) is a novel technique that rapidly amplifies target DNA under isothermal conditions.
 We treated a case of Yersinia pseudotuberculosis (Y. pstb) in which the LAMP method for Y. pstb was helpful to diagnose.
 The patient was a ten year-old female admitted for acute enteritis with hypovolemic acute renal failure. Her laboratory findings was as follows:White blood count 15700/μl, C-reactive protein 9.33mg/dl, blood urea nitrogen 20.8mg/dl, serum creatinine 1.2mg/dl, cystatin C 1.42mg/l, factional excretion of sodium, FENA 0.08%. The symptoms of enteritis and acute renal failure rapidly improved with fluid infusion and antibiotics administration. However, she demonstrated Kawasaki disease-like symptoms (finger membranous desquamation and mild dilation of coronary artery) during her clinical course. These features led us to suspect Y. pstb infection. Stool, blood, and urinary culture yielded no bacterial growth, and various virus antibodies were all negative. The LAMP method detected Y. pstb gene from her stool specimen obtained on admission. Y. pstb infection was confirmed by a significant rise in the serum antibody titer of Y. pstb.
 Y. pstb infection is known to cause acute enteritis with various complications, such as renal failure, Kawasaki disease like symptoms, mesenteric lymphadenitis, and arthritis. Nevertheless, it is quite difficult to make the diagnosis because the isolation rate of Y. pstb. are rare even in low-temperature specified culture due to premedication with antibiotics. Serum antibody titers are assayed only at a few facilities in Japan and these exams require a long time to complete. From this experience, we found that the LAMP method would be very helpful to seek Y. Pstb infection.

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PURPOSE: We examined spontaneous resolution rates in 359 cases with primary vesicoureteral reflux (VUR). Effects of age, laterality and grade of reflux on resolution rate were evaluated.
MATERIALS AND METHODS: Subjects comprised 359 children (239 boys, 120 girls) with primary VUR. Bilateral reflux was seen in 53.2% of cases. Patients were followed-up through a program of repeat voiding cystourethrography (VCUG) observations. Cases with surgical intervention were excluded. Resolution rates were determined for 322 ureters. We evaluated the influence of age, laterality and grade of reflux on the resolution rate.
RESULTS: The spontaneous resolution rates for grade III or less, grade IV and grade V were 72%, 58%, and 40% respectively at the age of 5 years. No significant difference in VUR disappearance could be detected between unilateral and bilateral reflux, but for grade II or less the resolution rate in cases with unilateral reflux tended to be higher than that in cases with bilateral reflux.
CONCLUSIONS: The spontaneous resolution rate for low grade (grades III or less) primary VUR was 72% at the age of 5 years and it seemed that we can expect spontaneous resolution to occur over several years of age.

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 Thin basement membrane nephropathy (TBMN) is characterized by both microscopic hematuria clinically and diffusely thinned glomerular basement membrane pathologically. TBMN has been known to have a good renal prognosis which rarely induces end stage renal disease (ESRD) so far. However, it was reported that heterozygous mutations in COL4A3 and COL4A4, responsible for autosomal recessive Alport syndrome (ARAS), were found in about 40% of TBMN and some of them could progress to ESRD. We report here that two patients with ARAS received living renal transplantation from TBMN donors and heterozygous mutations in COL4A3 or COL4A4 were found in the donors after the transplantation. We confirmed that the kidney function of the donors was good before transplantation, and has been kept good till now. Heredity renal disease patients may have no choice but to receive kidneys from mutation career donors, if they hope living donor renal transplantation. In those cases, we should examine donors carefully, including urinalysis, kidney functions and genome analysis before transplantation, and need careful follow-up after transplantation.

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 Central venous catheters (CVCs) play an important role for the effective and safe extracorporeal blood purification in children. Cuffed tunneled CVCs should be used, if needed for longer than 3 weeks. We retrospectively examined effects of the exit-site of cuffed tunneled dual-lumen CVCs for children treated with the long-term extracorporeal blood purification on catheter-related complications. Nine patients were enrolled in this study, and were divided into two groups according to the exit-site of CVCs. The CVCs were placed into the right jugular vein and the exit-sites were introduced to the front of a chest (group A, N=6) or back of the right side of an ear (group B, N=3). There was a mean of 37.7 extracorporeal blood purification sessions in group A, and 21.3 in group B. Catheter-related complications such as thrombosis and inadequate blood flow rate were observed only in group A and three patients in group A needed to be replaced. Proper placement of CVCs is essential for the effective and safe extracorporeal blood purification in children. It might be useful approach that the CVCs are placed into the right jugular vein and the exit-sites are introduced to the back of the right side of an ear.

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 Autosomal recessive polycystic kidney disease (ARPKD) is known to be quite variable in its clinical presentation and disease progression pattern. We studied the clinical course and outcome of our 10 ARPKD patients. The median age at last follow-up is 9.9 years. All patients were diagnosed within the 1st year of life. The clinical presentations during their neonatal periods were flank mass (80.0%), respiratory insufficiency (50.0%), and hyponatremia (55.6%). Eight of the patients showed hepatic complications such as hepatic fibrosis (100%), and intrahepatic biliary duct dilatation was seen in six out of the eight (75.0%) patients, whereas none of them had cholangitis. Six patients required renal replacement therapy at a median age of 7.6 years, and the five of them subsequently underwent kidney transplantation. Enlarged organs had to be removed, and severe pancytopenia should be corrected by splenectomy before renal transplantation. In conclusion, clinical treatments for kidney and hepatic complications in ARPKD should be designed appropriately depending on individual patient conditions.

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 Objective: To aim of the study was to identify the variables which affect long-term renal outcome in children with pesterior urethral valves (PUV).
 Materials and methods: A retrospective analysis was performed of 46 children presenting our institution with a diagnosis of PUV from 1987 to 2009. The following risk factors for progression to chronic kidney disease (CKD) or end-stage renal disease (ESRD) were analyzed: serum creatinine (sCr) at presentation, hypo/dysplastic kidney at diagnosis, bilateral grade 3 or higher vesicoureteral reflux (VUR) at diagnosis, nadir sCr greater than 1.0mg/dl, recurrent febrile urinary tract infection (UTI), and age at presentation. Patients were divided into two groups:favorable group and poor group.
 Result: The outcome was poor in 5 patients (11%) and was associated with a significantly higher sCr at presentation (P<0.001), with hypo/dysplastic kidney (P<0.001) and higher nadir sCr (P<0.001).
 Conclusions: Poor long-term renal outcome among patients with PUV is associated with initial sCr concentration, presence of hypo/dysplasitc kidney, and nadir sCr concentration after relief of valvular obstruction.

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 Macrophage (MQ) infiltration within the glomerular and interstitial compartments is a common feature in most forms of glomerulonephritis (GN). We have studied role of MQs in the pathogenesis of chronic GN in both human and experimental model of GN, and reported that ‘activation’ of MQ is one of the most important processes during the initiation and the progression of chronic GN.
 During the last decade, it has become clear that macrophages respond to various stimuli to generate phenotypically distinct states of activation. These activation states have been termed ‘classical (pro-inflammatory)’ and ‘alternative’ and represent a range of cellular phenotypes. Pro-inflammatory M1-type MQs (M1) are often associated with tissue damage, whereas alternatively activated M2-type MQs (M2) are usually associated with tissue repair and often involved in fibrosis. Thus, M1 or M2 may explain the underlying differences in pathology of chronic GN. Here we review the main functions of polarized macrophages and discuss the perspectives of this field.

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 Background: Retinoic acid-inducible gene-I (RIG-I) is a putative RNA helicase involved in immune reactions against RNA viruses and various inflammatory and autoimmune diseases. The purpose of the present study was to investigate the role of RIG-I in glomerular diseases.
 Methods: We treated human mesangial cells (MC) in culture with interferon-γ (IFN-γ), a potent Th1 type cytokine, and polyinosinic-polycytidylic acid (poly IC), which is an authentic double-stranded RNA and analyzed the expression of RIG-I, interferon regulatory factors (IRF) 1 and 7, CC chemokine ligand 5 (CCL5) and IFN-β by western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR), or enzyme-linked immunosorbent assay (ELISA). To elucidate the RIG-I-mediated signaling pathway, we subjected the cells to RNA interference (RNAi) against RIG-I, nuclear factor-κB p65, IFN-β or toll-like receptor (TLR) 3. Further, we studied the effects of IFN-β receptor blocking.
 Results: IFN-γ was found to induce the expression of RIG-I in human mesangial cells in culture. Knockdown of RIG-I inhibited the IFN-γ-induced upregulation of IRF7, a transcriptional factor involved in immune and inflammatory reactions. Poly IC induced the expression of RIG-I and CCL5 in human mesangial cells, and RNAi against RIG-I inhibited this poly IC-induced CCL5 expression. Poly IC-induced RIG-I expression was also inhibited by RNAi against IFN-β and by an antibody against the IFN-β receptor. The knockdown of TLR3 abolished poly IC-induced RIG-I expression.
 Conclusions: The IFN-γ/RIG-I/IRF7 and TLR3/IFN-β/RIG-I/CCL5 signaling pathways may be involved in the pathogenesis of glomerulonephritis, and also suggesting the role of this pathway in the aggravation of glomerulonephritis due to viral infection.

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 In children, hemolytic uremic syndrome (HUS) is mainly caused by the Shiga toxin (Stx) produced by pathogenic Escherichia coli O157: H7. It is well known that infants and toddlers are more prone to develop HUS than adult though its precise mechanism remains unknown. Recent studies postulate that reactive oxygen species (ROS) and reactive nitrogen species including nitric oxide (NO) play some role in the development of HUS.
 In this review, we firstly make a brief summary of the literature regarding the ROS in HUS, and secondly, introduce our result of the study investigating the amounts of NO produced by neutrophils stimulated by Stx.
 Previous reports and our interim results showing less NO production in toddlers than in adult strongly suggest a protective role of ROS and RNS in the pathogenesis of HUS.

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 Although the favorable therapeutic effects of LDL apheresis (LDL-A) have been widely reported in pediatric patients with steroid resistant and refractory nephrotic syndrome, the mechanism by which LDL-A benefits patients with SRNS is obscure. To clarify the exact mechanism of LDL-A, we analyzed the gene expression of peripheral blood mononuclear cells (PBMC) from LDL-A effective patients, using cDNA microarrays and real-time reverse transcription-polymerase chain reaction (RT-PCR). We conducted the extraction of the genes that are specifically related with favorable effects of LDL-A through the comparing of the gene expressions between nephrosis and complete remission phases, and GZMB encoding granzyme B was extracted out of the candidate genes. For further examination, polychromic flow cytometric analysis was performed to evaluate the expression of granzyme B in pan T cells from patients with steroid resistant nephrotic syndrome (SRNS), steroid sensitive nephrotic syndrome (SSNS) and healthy subjects. The percentage of granzyme B-positive T cells in SRNS patients was significantly higher than those in SSNS and healthy controls. In recent years, emerging clinical and biochemical evidence has shown that perforin-independent extracellular granzyme B may have a pathogenic role in several kinds of diseases. Our results indicated the possibilities that granzyme B expressed in circulating T cells might have pathogenic role for SRNS through the involvement of the glomerular filtration barrier and that a favorable regulation of granzyme B over-expression in T cells by LDL-A might be associated with a remission of steroid resistant and refractory nephrotic syndrome.

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 Recently, the frequency of congenital renal disease of hypoplasia is increasing as causes of worsening renal functional deterioration in pediatric nephrology despite the treatment for chronic glomerularitis has been advanced. Secondary causes are involving contracted kidney causes some kinds of glomerularitis, reflux nephropathy. Renal hypoplasia causing reduced functional nephron number developes glomerular hyperfiltration, resulting in glomerular sclerosis. Histologic findings of patients with oligonephronia show fewer nephrons, enlarged glomeruli, and glomerular sclerosis. We analyze the histologic findings of five cases with oligonephronia and secondary glomerular disease. Two cases with glomerular sclerosis show reduced significantly nephron number, and the others show minor abnormalities. All cases show glomerular hypertrophy.

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 Serious infection, especially spontaneous bacterial peritonitis, can complicate idiopathic nephrotic syndrome (INS). Though pathogenesis of susceptibility to bacterial infection remains unknown, multiple predisposing factors including defective opsonisation, altered T cell function, altered IgG concentrations have been proposed.
 Recent observation revealed that serum albumin plays an important role in the host defense mechanism as it is one of the important antioxidants.
 In this review, firstly, oxidative stress caused by decreased antioxidants in INS is discussed. Secondly, an importance of albumin as a most abundant antioxidant in plasma showing the mechanisms how it works against reactive oxygen species is demonstrated. Finally, we show that our preliminary finding regarding the anitioxidant potentials of albumin suggesting low serum albumin concentrations contribute to a declined immunity in INS.

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 To determine the efficacy of tonsillectomy for childhood IgA nephropathy, we evaluated the 31 patients with IgA nephropathy who underwent tonsillectomy. We evaluated the alteration of clinical and pathologic findings before and after tonsillectomy. The magnitude of proteinuria and the frequency of sudden macroscopic hematuria after upper respiratory infection were significantly improved. However, serum IgA concentration and glomerular IgA deposition did not change after tonsillectomy. The efficacy of tonsillectomy was more prominent in patients who underwent tonsillectomy within 3 years after discovery of urinary abonormalities. Glomerular complement C3 and the number of myeloid-related protein (MRP-8) positive macrophage infiltrating glomeruli were significantly decreased after tonsillectomy. However, the glomerular number of CD163 macrophage did not show obvious change after tonsillectomy. These finding could indicate that tonsillectome for intractable childfood IgA nephropathy is potential intervention for ameliorating clinical and pathologic findings through reduction of complement C3 and activated macrophage.

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 Alport syndrome (AS) and benign familial hematuria (BFH) are both familial inherited nephropathies. Gene mutations in COL4A5 located on Xq22 are believed to be causative in most patients with AS, while homozygote or compound heterozygote mutations and heterozygote mutations in COL4A3 gene or COL4A4 gene located on chromosome 2 are known to be associated with autosomal recessive AS and BFH, respectively.
 Accumulated knowledge, however, in regard to genotype- phenotype correlation has revealed that there is no one-to-one correspondence between genetic mutations and clinical pictures as in other gene mutaions. We experienced a family with BFH caused by COL4A5 mutation suggesting that COL4A5 should be added to the list of causative genes for BFH, and, we therefore propose a new concept of “type IV collagen associated nephropathies” which involve both AS and BFH diagnosed by clinical findings and can be used for diseases caused by abnormal configuration of glomerular basement membrane due to mutations in COL4A3, COL4A4 and COL4A5.

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 The classical renin-angiotensin system (RAS) is a circulating regulatory system for sodium balance, intravascular volume, and therefore blood pressure. There is increasing evidence that local RAS is situated in many organs, including kidney where it is involved in renal development, renal function and the progression of chronic kidney disease. This article briefly reviews the history and new development of RAS and indicates the importance of the research performed by physicians.

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 I described my own view concerning medical educational training method in the field of pediatric nephrology based on my accumulative experiences. I commented bout ongoing skill-up seminar and future ideal studies in this field. I sincerely hope that many fresh doctors would have interest in pediatric nephrology through feeling the attraction of pediatric nephrology and considering carrier design for continuous professional training of pediatric nephrology in future.

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 CKD-MBD (chronic kidney disease-mineral and bone disorders) is characterized by abnormal metabolism of calcium and phosphate, ectopic calcification, bone deformity and growth retardation in patients with impaired kidney function. FGF23, wich maintains serum phosphate levels, is secreted from osteocytes in bone. This means physiological interaction between kidney and bone, and this interaction is called bone-kidney axis. FGF23 requires FGF receptor type 1 and klotho to exert its effects. Hyperphosphatemia is one of clinical manifestations of CKD-MBD, and increases mortality risk and coronary artery events by accelerated ectopic calcification. Adequate protein intake and phosphate binders help to keep normal serum phosphate levels and to prevent CKD-MBD.

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 We present a 17-day-old male infant who developed renal rupture and urinary ascites secondary to posterior urethral valves (PUV). He had a normal vaginal delivery at 38 weeks of gestation. No abdominal cystic lesions and no oligohydramnios were observed on prenatal ultrasound scans during pregnancy. Abdominal distention, electrolyte imbalance, and an elevated BUN/serum creatinine were noted at the time of hospitalization. The levels of serum creatinine promptly returned to normal after establishment of urinary catheter drainage.
 In our case, the developement of ascites secondary to PUV, which can serve as a “pop-off” mechanism to buffer high pressure in the urinary tract, appears to provide a protective effect on renal function.

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 We report a case of septic shock due to urinary tract infection successfully treated with polymyxin B hemoperfusion. An 18 year-old man undergoing a living-related renal transplantation 34 months ago, was admitted to our hospital with a diagnosis of urinary tract infection. A few hours later after admission, he developed severe shock with sepsis. Despite administration of heavy volume of fluid for initial resuscitation, he remained anuric with low level of blood pressure. He received polymyxin B hemoperfusion in combination with continuous hemodialysis filtration, and one hour later his blood pressure had significantly increased with an improvement of general condition.
 We consider polymyxin B hemoperfusion to be an effective alternative therapy for septic shock refractory to fluid resuscitation.

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 Mutation of the OCRL1 gene has been reported to be found in 10-15% of patients with Dent disease. It is noteworthy that the OCRL1 gene is involved in the pathogenesis of at least two different diseases: Dent disease and Lowe syndrome. The common features between these two diseases include the OCRL1 gene mutation, proximal tubular dysfunction (increased U-β2 MG), and increased serum levels of enzymes such as GOT, LDH and CPK; however, the two diseases have distinct extrarenal findings, such as ocular involvement and neurological symptoms (developmental delay) in Lowe syndrome. We identified the OCRL1 gene mutation in two patients: one patient with Lowe syndrome had a missense mutation of exon 10, and the other, with Dent-2 disease, had a frame shift of exon 5. Abnormal nonsense mutation and frame shift in exons 4 to 7 have been reported in all Dent-2 disease patients seen until date, except one, which indicates that these genetic abnormalities are important for the distinct manifestations of the disease.

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 Continuous hemodiafiltration was initiated for two children with severe hemophagocytic lymphohistiocytosis (HLH) that was unresponsive to immunosuppressive therapy. Case 1 involved a 6-year-old boy who relapsed into HLH during the course of juvenile idiopathic arthritis. He showed hypotension and renal impairment despite immunosuppressive therapy. Case 2 involved a 14-year-old girl who relapsed into Epstein-Barr virus-associated HLH. She presented with hypotension, renal impairment, and intravascular coagulopathy after treatment with methylprednisolone, cyclosporine, and etoposide. In these 2 cases, symptoms and laboratory abnormalities improved after continuous hemodiafiltration. Continuous hemodiafiltration may be effective for the treatment of children with severe HLH unresponsive to immunosuppressive therapy.

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