Pseudohypoaldosteronism type II (PHA II) is a rare autosomal dominant inheritance syndrome characterized by hypertension, hyperkalemia, and high chloride metabolic acidosis. Short stature, malformation of tooth and bone, and developmental and growth delay are occasional complications associated with this syndrome. It is often associated with mutations in WNK4 and WNK1, resulting in increased Na⁺Cl^– reabsorption via thiazide-sensitive Na⁺Cl^– co-transporters and decreased potassium excretion. In 2012, it was discovered that mutations in kelch-like 3 (KLHL3) and cullin 3 (CUL3) cause PHAII. Here, we describe the neonatal case of PHAII caused by KLHL3 gene mutation experienced in our hospital and review the current pathophysiological findings of PHAII.

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1. Children aged 10 years old with normal renal function have about 100 L/day of primitive urine volume, and 1 L/day of urinary output. 2. Creatinine (Cr) is removed from the blood mainly by the kidneys, primarily by glomerular filtration (approximately 70%), but also by proximal tubular secretion (approximately 30%). Therefore, creatinine clearance (Ccr) is approximately 1.4 times of inulin clearance (Cin). 3. Serum Cr level measured by Jaffe method is significantly higher than that by enzymatic method, but urine Cr values measured by these two methods are approximately equivalent. Therefore, Ccr measured by Jaffe method was approximately equal to Cin. 4. In patients with acute kidney injury, length of time it takes for serologic kidney function markers to become stable depends on their distribution volumes. 5. We devised three equations to estimate GFR in Japanese pediatric chronic kidney disease patients, and could evaluate their GFR easily. In addition, we determined reference GFR values of Japanese children. 6. Urine Cr concentrations in younger children are considerably lower than those in older with equivalent renal function because of differences in serum Cr levels.

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MPO-ANCA-associated vasculitis (MPO-AAV) is necrotizing small vessel vasculitis usually involves renal glomeruli with production of MPO-ANCA. Although the pathogenic role of MPO-ANCA has been shown, the mechanism of its production remains unrevealed. A unique cell death of neutrophils, neutrophil extracellular traps (NETs), has recently been discovered. Although NETs are indispensable innate defense system, the disordered NETs could be related to autoimmune diseases, including MPO-AAV. Recently, we have demonstrated that the process of abnormal formation and impaired degradation of NETs induced by antithyroid drug propylthiouracil was involved in the generation of MPO-ANCA and subsequent development of MPO-AAV. On the other hand, IgG eluted from MPO-AAV sera demonstrated high ability for NETs induction, and the ability correlated to the disease activity and was parallel to the ANCA affinity to MPO. In addition, low ability of MPO-AAV serum for NETs degradation was determined. Correspondingly, activity of DNase I, an important physiological regulator of NETs, was generally low in MPO-AAV. Furthermore, the presence of anti-NETs antibodies, which could interfere with the DNase I activity, was demonstrated in some MPO-AAV sera. The collective findings suggest that “NETs-ANCA vicious cycle” could be critically involved in the pathogenesis of MPO-AAV.

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Glomerular diseases associated with monoclonal gammopathy are divided into two subgroups. The first group is characterized by organized deposits, like fibrils (mainly in amyloidosis) or microtubules (cryoglobulinemia and immunotactoid glomerulopathy). The second group represents granular electron dense deposits, and defines entities named monoclonal immunoglobulin deposition disease (MIDD) and proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID). MIDD is characterized by the presence of nodular sclerosing glomerulopathy and other patterns including membranoproliferative glomerulonephritis (MPGN) by light microscopy, monoclonal linear staining along the glomerular basement membranes (GBM) and the tubular basement membranes (TBM) by immunofluorescence, and continuous linear deposits of finely granular electron dense material along the inner aspect of the GBM and along the TBM by electron microscopy. On the other hand, PGNMID is characterized by endocapillary proliferative, membranoproliferative, or membranous features by light microscopy and immune complex type deposits by electron microscopy. The biopsy incidence of PGNMID is about 0.2%. The age was ranged from 20 to 81 years until 2012. Since two pediatric patients with PGNMID have been reported in Japan since 2013, the recognition of PGNMID may be widespread. Recently, cases with PGN with monoclonal other immunoglobulins, including IgA and IgM, have been reported, therefore, we need to reconsider the disease spectrum of PGNMID. It is important for nephrologists to confirm the diagnosis of PGNMID fully using light, immunofluorescence including kappa and lambda light chains, and electron microscopies.

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For acute blood purification therapy in neonates, the principal modality used has been peritoneal dialysis (PD). With the development of equipment and apparatus, extracorporeal blood purification has become available for neonates and low-birth-weight infants. In Japan, we can use blood purification equipment of low blood flow rates (1 ml/min), small volume modules, and anticoagulant with low risk of hemorrhage. Guidelines for acute extracorporeal blood purification in neonates were made based on mainly the case reports and expert opinions in Japanese neonates. This guideline may help to save the lives and improve the prognoses of neonates with serious conditions. It is necessary to obtain evidence using apparatus appropriate for neonates.

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IgA nephropathy (IgAN) is most frequently found in chronic glomerulonephritis (CGN) in childhood, followed by Henoch-Schönlein purpura nephritis (HSPN), focal segmental glomerulosclerosis, and membranoproliferative glomerulonephritis. Recently, it has been reported that the pathogenesis of IgAN and HSPN may be associated with the circulation of defective forms of IgA1 or the presence of in situ immune complexes, and the onset and progression of inflammation are thought to be associated with complement components, activated macrophages and mesangial cells. To control these inflammations, the most beneficial treatment was chosen according to the severity of each disease. For children with severe CGN, the long-term prognosis was improved by multi-drug combination therapy including steroid and immunosuppressive drugs, plasmapheresis and LDL-apheresis. It is important to control CGN activity by minimum doses of steroids and immunosuppressive drugs. To establish the best treatment for the management of CGN, randomized control studies are required to provide evidence.

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Urinary tract infection (UTI) is one of the most common infections encountered by pediatricians. UTI can occur either as bladder infections (lower UTI) or infections involving the kidneys (upper UTI). Upper UTI can be an important cause for end stage renal failure as it may lead to renal scarring without inappropriate management. Therefore, we should have high index of suspicion that all febrile infants without evident focal signs have upper UTI. To make a correct diagnosis of upper UTI, urine samples for culture should be obtained by bladder catheterization before administration of antimicrobial agents. Furthermore, bacteriuria should be screened using KOVA slide immediately for the prompt treatment which alleviate the risk of renal scarring. In order to prevent recurrent UTI, all infants with first upper UTI should be screened for underlying conditions predisposing to UTI, such as vesicoureteral reflux (VUR) or lower urinary tract dysfunctions by voiding cystourethrography (VCUG). If he/she has high grade VUR by VCUG, they should receive continuous antibiotic prophylaxis for recurrent UTI based on the recent findings from the RIVUR (Randomized Intervention for Children With Vesicoureteral Reflux) trial.

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Children with nephrotic syndrome frequently have a chronic clinical course resulting in various difficulties in both daily and school life. However, few studies discuss these children's school life. Therefore, we studied the level of satisfaction with school life in 45 children with nephrotic syndrome by self-completed questionnaire. Approximately 90% of the children experienced hospitalization after beginning elementary school, but teaching assistance was not always adequate. A generalized linear model showed that high satisfaction level was significantly related to higher age (p=0.04); no concomitant disease or severe adverse effects of treatment (p=0.012); fewer relapses during the preceding year (p=0.05); no immunosuppressant therapy in the preceding year (p=0.003); supplementary study support after discharge (p=0.07); and peer support (p=0.05). High level of satisfaction with school life in children with nephrotic syndrome requires not only better treatment, but appropriate environment and study support appropriate to their disease and particular problems.

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The residual renal function is often discussed in patients with a solitary kidney, such as those with a multicystic dysplastic kidney or after nephrectomy. We analyzed the changes in the serum creatinine (sCr) and serum cystatin C (sCysC) levels in six patients (four males and two females) who were receiving follow-up for a solitary kidney, and examined their renal function. As a result, the sCysC level was found to be higher than normal, while the sCr was within the normal range. Furthermore, we found a difference in the estimated glomerular filtration rate (eGFR), as well as a declining trend in the eGFR obtained from sCysC, especially beginning around the time of puberty. For the follow-up of a pediatric patient with a solitary kidney, we believe that a more accurate evaluation of the renal function will be possible by using a combination of the commonly-used sCr and sCysC values, which are less susceptible to changes resulting from the age and body type of the patient.

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A 12-year-old girl with nephrotic syndrome since 7 years old, repeated recurrence despite administration of prednisolone (PSL) and cyclosporine A (CyA). Her blood concentration levels of CyA have been monitored regularly. But the level was relatively low (C0 70 ng/ml, C2 500 ng/ml) considering the dose (7.7 mg/kg/day in two divided doses), and unstable. We found out that her medication was always after meal and the timing was irregular. She was advised to take CyA at a fixed time 30 minutes before meals. As a result, her blood concentration levels of CyA elevated markedly and stabilized. Consequently, she has succeeded in reducing dosage of CyA. It is important not only to monitor blood concentration regularly but also to check on the medication status of a patient, and advise appropriate oral medication.

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