Sepsis is considered a systemic inflammatory response syndrome that is activated by an invasive infection. Pro- and anti-inflammatory hypercytokinemia plays a pivotal role in sepsis pathophysiology, by contributing to the dysregulation of the host immune system, inflammatory response, and coagulation system. As the modulation of these responses may translate to improved outcomes, extracorporeal cytokine removal has been performed as a non-renal indication in septic patients. Over the last two decades, high-volume hemofiltration and polymyxin B hemoperfusion have been attempted as non-renal indications in patients with sepsis. Additionally, continuous hemodiafiltration with a cytokine-absorbing column including a polymethyl methacrylate membrane hemofilter has been preferred and often performed by Japanese intensivists for patients with severe sepsis. However, no evidence is available regarding the efficacy of these therapies for mortality of patients with sepsis. There are some concerns regarding hemodynamic instability and abnormal blood coagulation with blood purification therapy, particularly in children with severe sepsis. To minimize problems with blood purification therapy, sufficient experience with pediatric intensive care and the therapy is desired unless there is solid evidence for the therapy. In addition, efforts to accumulate evidence for the effect of extracorporeal cytokine removal on survival in children with severe sepsis are needed.

The hypothesis of the Developmental Origins of Health and Disease (DOHaD) reports that environmental factors acting during fetal and infantile life are risk factors for some chronic diseases. It suggests that premature birth and low birth weight affect renal function. However, little information in this regard has been reported in Japanese children. This study examined the estimated glomerular filtration rate (eGFR) and serum creatinine levels in 151 children born before 35 weeks of gestation.

The results showed that eGFR at 2 years of age was significantly correlated with the birth weight and gestational age. Approximately 12% of the researched children showed a low eGFR (<90 ml/min/1.73 m²) without clinical symptoms, and abnormal urine examination. These children showed high serum creatinine levels at Day 7 after birth and showed a delayed rate of recovery of these levels in the first month after birth.

These data show that low gestational age and low birth weight directly affect the renal function in young children. High serum creatinine level at Day 7 after birth is one of the risk factors for chronic kidney disease in children.

Objectives: Nocturnal enuresis (NE) significantly affects self-esteem both emotionally and behaviorally, and can impact the quality of life of patients and their families. However few reports have assessed social and school functioning among children with NE. Methods: We enrolled 242 children aged 5 to 12 years who presented with NE at our outpatient department. The patients and their parents were assessed in person and they separately completed the Japanese language version of the PedsQL during the first presentation at our clinic. Results: Among the 242 children, 164 and 78 had of monosymptomatic (MNE) and non-monosymptomatic (NMNE) nocturnal enuresis, respectively. The quality of life according to the Child Self-Reports was significantly worse in terms of total score (p=0.020), physical subscale (p=0.047), emotional (p=0.024) and school (p=0.028) functioning scores for patients with NMNE than with MNE. However, the Parent Proxy-Reports of the PedsQL did not significantly differ between children with NMNE and those with MNE. Conclusion: These results indicated that parents dismissed the lower emotional and school functioning in their children with NMNE. Therefore, support is needed in school and in society as well as in medical settings.

There have been few studies on continuous antibiotic prophylaxis (CAP) with cefaclor (CCL) for urinary tract infections (UTIs) in children. Therefore, we examined CAP with CCL for preventing the recurrence of UTIs in children in a multicenter study. From April 2004 to March 2013, 126 febrile patients with UTIs were admitted to Showa University Northern Yokohama Hospital, Showa University Fujigaoka Hospital, or St. Marianna University School of Medicine Hospital and were followed up for over 6 months. The patients were divided into two groups: the CAP group and the non-CAP group. The presence or absence of vesicoureteral reflux (VUR) was examined in 114 patients who underwent voiding cystourethrography (VCUG). No significant differences in patient characteristics were found between the two groups. However, the recurrence of UTIs was significantly less frequent in the CAP group. In addition, among the 114 patients who underwent VCUG, the recurrence of UTIs was significantly less frequent in patients with VUR in the CAP group. Thus, it is possible to prevent the recurrence of UTIs by CAP with CCL (12% vs 67%, p<0.01).

Indications for voiding cystourethrography (VCUG) tend to be limited in recent management guidelines for urinary tract infection (UTI), causing a concern that patients with severe vesicoureteral reflux (VUR) may be overlooked. We elucidated the clinical characteristics of patients with severe VUR among UTI patients at 3 institutions and examined patients indicated for VCUG. The subjects were 168 patients who were hospitalized in the Department of Pediatrics of Showa University Fujigaoka Hospital, Showa University Northern Yokohama Hospital, and St. Marianna University Hospital for initial febrile UTI and underwent VCUG between April 2004 and March 2013. We compared the patients by classifying them into the severe (grade IV or higher VUR) and non-severe VUR groups. VUR was found in 59 patients (35.1%), of whom 18 had severe VUR. No significant difference in the baseline characteristics of the patients were found between the two groups. In the severe VUR group, abnormal ultrasonographic findings (p<0.05) and bacteria other than Escherichia coli as causative bacteria were significantly more prevalent (p<0.05). VCUG should be considered in patients with initial UTI with abnormal ultrasonographic findings and whose UTI is not caused by E. coli, with the possibility of concurrent severe VUR in mind.

It is reported that recurrence of urinary tract infection (UTI) may contribute to renal scarring. Though previous studies have evaluated risk factors of recurrent UTI, the risk factors were unclear. In this study, we investigated the risk factors of UTI in children according to a multicenter study of UTI cases. From April 2004 to March 2013, the initial febrile UTI patients admitted to St. Marianna University School of Medicine Hospital, Showa University Fujigaoka Hospital and Showa University Northern Yokohama Hospital were studied. Seventy two patients who could be followed over 6 months and were not administrated prophylactic antibiotics were enrolled in this study. The patients were divided into two groups with the recurrent and non-recurrent group. In these 72 patients, there were no significant differences in sex and age between the two groups. The numbers of UTI caused with non-E.coli in the recurrent group was significantly higher than the non-recurrent group (p<0.01). Futhermore, the numbers of high grade hydronephrosis and existence of vesicoureteral reflux (VUR) in the recurrent group were significantly higher than the non-recurrent group (p<0.01). This study suggests that the risk factors of recurrent UTI in children may be concerned with non-E.coli infection, high grade hydronephrosis and VUR.

Although influenza virus (flu) vaccines or infections can precipitate the relapse of idiopathic nephrotic syndrome (NS) in children, no data are available on the backgrounds of NS patients. We report six pediatric cases who experienced NS relapses associated with flu vaccines or infections. The patients were all males. Three experienced NS relapses associated with flu vaccination (vaccine relapse patients), and three relapsed following flu infections (infection relapse patients). In all three vaccine relapse patients, the period from vaccination to disease onset or the last relapse was less than 6 months, whereas it was less than 6 months in only three of 15 vaccines in the control group. In all three infection relapse patients, the period between infection and disease onset or the last relapse was less than 6 months, whereas this period was more than 6 months in all three infected patients in the control group. Flu infections or vaccines may precipitate the relapse of NS, and this may be affected by the disease severity in each child. A prospective multicenter study of NS relapse associated with flu infection or vaccination is required.

Alport-leiomyomatosis syndrome (A-LS) is a rare disease, in which diffuse leiomyomatosis occurs in patients with Alport syndrome. Here, we report on a case of A-LS incidentally detected by radiographic examination performed for symptoms of the common cold. The case was a boy who was undergoing follow-up observation in the outpatient department after being diagnosed with Alport syndrome from a result of the detection of complete deficiency of the type IV collagen alpha 5 chain via renal biopsy performed at the age of 6. An abnormal shadow was observed on a chest x-ray performed for symptoms of the common cold at the age of 10. Follow-up examination indicated diffuse leiomyomatosis in the esophagus and he was diagnosed with A-LS. The fact that leiomyoma was observed in the rectum as well as the esophagus made this a rare case. Genetic analysis revealed extensive deficiency from COL4A5 to COL4A6, which was the same gene loss pattern as reported in previous studies. This case was considered sporadic because no gene mutation was detected in the patient’s mother. This case was considered sporadic due to this result. Due to the possibility that leiomyomatosis may occur in multiple organs in the future, this case requires continued observation.

Acute poststreptococcal glomerulonephritis (APSGN) is the most common postinfectious glomerulonephritis in childhood. In some cases, urinary findings are clear or very subtle. Such cases are known as extrarenal symptomatic APSGN.

A 9-year-old boy had suffered from abdominal distention and loss of appetite for 3 days, and came to our hospital. Physical examination revealed body weight gain, hypertension, edema, and hepatosplenomegaly. Although urinary findings were almost clear and there were no symptoms of antecedent infection, laboratory data showed elevated antistreptolysin O level and hypocomplementemia, so we diagnosed extrarenal symptomatic APSGN. Supportive care was provided, and the patient was discharged without any lasting effects on the 11th hospital day. At subsequent examinations, neither hypocomplementemia nor any recurrences of glomerulonephritis have been seen.

Extrarenal symptomatic APSGN is one of the important differential diagnoses involving edema and hypertension in children.

PAX2 mutation causes CAKUT and renal coloboma syndrome (RCS). We are presenting an infant with renal hypo/dysplasia which showed pseudo-Bartter syndrome during the course of treatment.

A female born in the 41st gestational week, weighing 3,116 g. On the 4th day of life she was pointed out 11% weight loss, and instructed additional milk with breastfeeding at discharge. Since she did not drink milk from nursing bottle, mother brought up her by breastfeeding only. On the 2 month of age, she pointed out failure to thrive and referred to our hospital. On the 78th day after birth, her weight was 3,930 g. Blood examination showed urea nitrogen 23.1 mg/dl, creatinine 0.57 mg/dl, and ultrasonography revealed bilateral small and echogenic kidneys. We diagnosed renal hypo/dysplasia. On ocular examination, no abnormalities were pointed out in the fundus. On the 6 months of age, she showed metabolic alkalosis, hypokalemia and hypercalciuria, so Bartter syndrome was suspected. We analyzed the genes, those associated with Bartter syndrome or CAKUT. Next-generation sequencing analysis with CAKUT revealed PAX2 gene mutation. One base insertion on exon2 of PAX2 gene(NM_003987.3:c.76dupG, p.Val26Glyfs*28) was detected. We re-examined ocular funds and found a mild optic papilla abnormality. We diagnosed this patient as RCS.

A 13-year-old girl developed a fever, and on the second day of illness was prescribed an antibacterial agent and Loxoprofen. Despite two changes of the antibacterial agent, intermittent fever persisted for 16 days, necessitating admission to our hospital. Laboratory data indicated anemia, and elevation of both the leukocyte count and total serum IgE level. All tests for infections and autoantibodies gave negative results. Urinalysis revealed sterile pyuria, with mild increases in the urinary protein/creatinine ratio and β₂-microglobulin level. A midstream urine culture was negative. Gallium-67 scintigraphy gave a false-negative result in both kidneys. However, abdominal contrast-enhanced computed tomography demonstrated multiple spherical filling defects in both kidneys and diffusion-weighted magnetic resonance imaging showed patchy abnormal high intensity in the bilateral renal parenchyma. Therefore, we performed percutaneous renal biopsy, and acute tubulointerstitial nephritis was diagnosed. The patient had taken all of the antibacterial agents prescribed several times, whereas Loxoprofen had been taken twice for the first time. A drug lymphocyte stimulation test for Loxoprofen showed a positive response. Abdominal diffusion-weighted magnetic resonance imaging may be very useful for early diagnosis and treatment of NSAIDs-induced acute tubulointerstitial nephritis.

We experienced two cases showing the clinical usefulness of deviation from the normal difference between Na and Cl (Na-Cl=36) in the serum, raising suspicion of acid-base balance disorders and thus prompting blood gas analysis. Case 1, a 3-year-old girl, had developed a brain tumor at age 3 months and received multimodal therapy. When she developed gastroenteritis at age 3 years, she was diagnosed as having drug-induced Fanconi syndrome because of hypophosphatemia, low-molecular-weight proteinuria, metabolic acidosis and, rickets. Her serum Na-Cl levels were consistently 30 or lower, suggesting prolonged metabolic acidosis. Case 2, a 19-year-old woman, had suffered rhabdomyosarcoma at age 9 months and received multimodal therapy. After the end of treatment, her serum magnesium levels had gradually decreased. At age 19 years, she was diagnosed with hypocalcemia, hypokalemia, and metabolic alkalosis. While her serum magnesium levels decreased, her serum Na-Cl levels were consistently 40 or higher, suggesting prolonged metabolic alkalosis. When blood gas analysis is not performed, deviation from the Na-Cl=36 in the serum appears to be clinically useful as it raises suspicion of the presence of acid-base balance disorders.

Here, we report two patients diagnosed with tubulo-interstitial nephritis and uveitis (TINU) syndrome. One patient was a 14-year-old girl, admitted to our hospital because of prolonged fever and fatigue. Her urine examination revealed high level of urinary β₂ microglobulin, and ophthalmological findings revealed features of uveitis. The other patient, a 13-year-old girl, complained of redness of right eye only, and was diagnosed with uveitis by an ophthalmologist. She was referred to our hospital under the suspicion that she was suffering from systemic inflammatory response syndrome. Renal biopsies were performed in both patients, showing the findings of tubulo-interstitial nephritis, and they were diagnosed with TINU syndrome. Oral prednisolone was prescribed to treat uveitis in both of the cases; however, following dose reduction of prednisolone, uveitis relapsed in both of them. Subsequent addition of mizoribine with oral prednisolone led to satisfactory management of uveitis without relapse in both cases. Hence, we suggest that uveitis associated with TINU syndrome, which is recurrent in nature and runs a chronic course, can be effectively managed by mizoribine along with prednisolone.