Nephronophthisis (NPH), an inherited kidney disease with a poor prognosis, is caused by abnormality of an NPHP gene. There are three subtypes of NPH regarding the development of end-stage renal disease, and three different genes responsible for each subtype have been identified. The main pathogenesis of this disease is the dysfunction of primary cilia called ciliopathy. NPHP1 to NPHP13 have been identified as the genes responsible for various types of NPH. NPHP1 and NPHP4 are the main genes responsible for NPH, but this disorder may occur with no abnormality in these genes; other, presently undetermined genes may be involved. The characteristics of Japanese NPH patients are as follows; (1) difficulty of detection by urine mas screening system, (2) high incidence of hypotonic urine (>1.010) and/or low-molecular weight proteinuria, (3) sometimes association with extrarenal findings such as retinitis pigmentosa, (4) NPHP1 abnormality most often by large deletion.

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At least 20% of children with idiopathic nephrotic syndrome develop frequent relapses or steroid dependence under or after the treatment with immunosuppressive agents such as cyclosporine (complicated FRNS/SDNS). To evaluate the efficacy and safety of rituximab in childhood-onset, complicated FRNS/SDNS, a multicenter, double-blind, randomized, placebo-controlled trial was carried out by the Research Group of Childhood-onset Refractory Nephrotic Syndrome (RCRNS) in Japan (RCRNS01). RCRNS01 showed that rituximab is safe and effective for the treatment of childhood-onset, complicated FRNS/SDNS. In 2014, the use of rituximab for patients with complicated FRNS/SDNS was approved, first in the world, by the Ministry of Health, Labour and Welfare, Japan. However, further modification of rituximab therapy, including repeated courses and adjunct immunosuppressive therapies, may be necessary to extend the relapse-free period, as this drug does not cure nephrotic syndrome. In addition, the pathogenesis of idiopathic nephrotic syndrome in children should be clarified to develop a specific and definitive therapy for this disease.

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Pathogenic mechanism of childhood nephrotic syndrome has been investigated for decades, and congenital nephrotic syndrome and early onset steroid resistant nephrotic syndrome has been found to mainly be attributed to podocyte dysfunction. Although many hypotheses regarding the pathogenesis of minimal change nephrotic syndrome (MCNS) including immunological abnormalities and podocyte dysfunction have been proved to be valid, the common definitive cause of MCNS has not been identified. Here, different hypotheses regarding the cause of MCNS are reviewed, and the difficulty in resolving the mechanism is discussed.

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An original method of blood gas analysis was described. This analysis method is composed of the 7 actions based on the paired analysis. The paired factors are, serum sodium and chloride, serum potassium and pH, pH and pCO₂, pCO₂ and HCO₃⁻ and factors for anion gap calculation. How to perform the 7 actions analysis was described in detail. Especially, the fact that the pathophysiology of acid base balance-disorders can partly be estimated by the value of serum (Na–Cl), was emphasized.

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When the Great Eastern Japan Earthquake occurred, people’s lifelines were disturbed markedly due to the earthquake and accompanying tsunami. There was much confusion in people’s daily lives and across healthcare services. In the case of pediatric kidney diseases, children receiving peritoneal dialysis can be affected markedly during large disasters. Peritoneal dialysis requires continuous implementation and a power source for the automated peritoneal perfusion device and supply of commodities, including dialysis fluid. Furthermore, family members must operate peritoneal dialysis. During large disasters, it may become impossible to satisfy these needs, making peritoneal dialysis difficult to continue; however, this can lead to the patient’s death. To avoid such situations, it is important to be prepared for disasters. We will present how children who required peritoneal dialysis were actually managed at the Tohoku University Hospital Department of Pediatrics immediately after the Great Eastern Japan Earthquake, and the challenges faced at that time. It is hoped that details of this experience will provide useful reference information for discussions about the management of children who require peritoneal dialysis during future large disasters.

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Background: Recent studies showed that high-dose mizoribine (MZR) therapy may be effective in the management of children with steroid-dependent nephrotic syndrome (SDNS). However, long-term prognosis of the patients following the immunosuppressive agent remains unclear. Patients and methods: We retrospectively analyzed 12 patients with SDNS who received high-dose MZR prior to cyclosporine (CsA) administration. MZR was initiated at a single daily dose of 5 mg/kg administered after breakfast and adjusted to maintain 2-h post-dose MZR levels of approximately 3-5 μg/mℓ. Results: In all but one patient, treatment with MZR (mean MZR dose, 8.6 mg/kg/day; mean C2, 3.4 μg/mℓ) resulted in significant reduction of the mean prednisolone dose from 0.45 to 0.12 mg/kg/day and the mean relapse rate from 1.86 to 0.40 episodes/12 months. Of six patients who were able to discontinue high-dose MZR therapy, only one patient returned to SDNS and was re-treated with MZR during follow-up periods (median 4.2 years). Conclusion: High-dose MZR therapy may allow many patients with SDNS to avoid further toxic immunosuppressive agents such as CsA in the long term.

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Voiding dysfunction is not well known in infants with Down syndrome (DS). Herein, we report two cases with DS who presented with acute urinary retention due to voiding dysfunction. Both cases (Case 1: a 2-year-old girl; Case 2: a 6-year-old girl) developed pyelonephritis accompanied by acute urinary retention resulting in acute kidney injury, which was resolved by fluid replacement, antibiotics and urinary catheterization. In Case 1, voiding dysfunction was assumed to have been latent before the acute urinary retention, because she subsequently required long-term clean intermittent catheterization (CIC) to prevent renal damage. In Case 2, megaureter and vesicoureteral reflux had been previously detected at the age of 3 years, and voiding dysfunction had been identified by a urodynamic study at 5 years of age. She had suffered from frequent urinary tract infections that had caused renal scarring and damage requiring the eventual initiation of CIC. Both cases were diagnosed with non-neurogenic neurogenic bladder due to the absence of structural abnormalities in the spinal cord and urethra. Continuous observation for symptoms of voiding dysfunction after birth is warranted for infants with DS.

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Thromboembolism is one of the serious complications of pediatric idiopathic nephrotic syndrome (NS). We report the case of a 4-year-old boy suffering from steroid-resistant NS complicated with posterior reversible encephalopathy syndrome (PRES), acute kidney injury and multiple vein thrombosis. Although his symptoms with PRES subsequently improved by antihypertensive therapy, his renal dysfunction persisted requiring peritoneal dialysis. And then, intestinal thromboembolism caused sepsis and intestinal necrosis as a result. Despite thrombolytic and antibiotic therapy, his condition with sepsis and massive diarrhea caused by intestinal necrosis didn’t improve. Since his electroencephalogram suggested poor neurologic prognosis, we discontinued active treatments with fully informed consent of his parents and he died 93 days after onset. Adequate anticoagulation to prevent thromboembolism should be considered in treatment of the severe NS in children.

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Renal coloboma syndrome is a disease caused by mutations in the PAX2 gene, and is characterized by optic nerve dysplasia and renal malformations. We experienced treating an 11-year-old male who was diagnosed as having renal coloboma syndrome, with afebrile convulsions as the chief complaint. He exhibited proteinuria in his urinalysis that year for the first time, and a family history of renal disease (abnormal urinalysis findings, renal failure) was noted. Following afebrile tonic convulsion with respiratory depression during sleep, the patient was transported by ambulance to our hospital. We detected hematuria, proteinuria, and mild renal dysfunction. In addition to an increase in the echogenicity of the renal parenchyma detected by ultrasonography, focal glomerulosclerosis was observed by renal histopathological analysis. We also detected congenital nystagmus, right divergent strabismus, and optic disc coloboma. In the second episode of his afebrile convulsions, EEG showed abnormal findings. On the basis of these abnormal findings, he was diagnosed as having localization-related epilepsy. For which he was administered an anticonvulsant agent. We found a new mutation (c.58_64dup) by PAX2 gene analysis. Over 4 years, his renal dysfunction progressed gradually. A careful follow-up of future progress is needed for this patient.

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We treated a case of concurrent obstructive lower urinary tract disease and esophageal atresia for which oligohydramnios was not observed until the third trimester of pregnancy. The patient was a 1-year-old boy in whom severe bilateral hydroureteronephrosis and bladder distension were detected at 21 weeks of intrauterine life, raising suspicion of lower urinary tract obstruction. However, amniotic fluid volume was maintained, so follow-up observations were conducted with no active treatment. From 36 weeks of gestation, oligohydramnios was observed, and the patient was delivered at 37 weeks after labor induction. Postnatally, he was diagnosed with esophageal atresia and urethral hypoplasia was suspected due to a pinhole-shaped urethral meatus. Postnatal imaging revealed severe bilateral hydroureteronephrosis and vesicoureteral reflux. Failure of the functioning of the right kidney was also observed. In fetuses with nephrourinary malformations, oligohydramnios suggests renal failure and is an indicator for terminating pregnancy. In the present case, concurrent esophageal atresia delayed the onset of oligohydramnios, and the renal failure may have progressed because the period for pregnancy termination had been exceeded. When determining renal function in fetuses with the possibility of lower urinary tract obstruction, concurrent esophageal atresia and gastrointestinal obstruction should also be considered.

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Unilateral and segmental localized polycystic kidney disease is a rare, non-familiar, non-progressive renal disorder in other organs. Few cases have been reported in the literature. It is benign nonsurgical condition. Therefore it should be ruled out differential diseases such as autosomal dominant polycystic kidney disease, cystic nephroma, multicular cystic nephroma. To resolve this diagnostic problem needed to perform long-term follow-up. We report a case of a 16 year-old male who detected microscopic hematuria by school urinary screening. He didn’t have any loin pain and abdominal mass and any family history of kidney disease. Ultrasonography showed polycystic kidney at right upper pole kidney, and contralateral kidney was normal. His urine analysis showed microscopic hematuria and his kidney function tests were with in normal range. Computerized tomography showed that there weren’t any disorder in other organs. He has been followed with US study and blood exam for 5 years without surgery. Until now, he was admitted to our hospital because of cyst hemorrhage. We continue following him with Echoic study.

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