Daishi Hirano

Can cranberry juice be a substitute for cefaclor prophylaxis in children with vesicoureteral reflux

Urinary tract infection (UTI) is a common childhood infection. In 30–50% of children with UTI the infections occur recurrently, especially in those with vesicoureteral reflux (VUR), resulting in hospitalizations, and long-term health problems, such as renal scars, hypertension, and end-stage renal disease. To reduce the likelihood of recurrent UTI for children with VUR, antibiotics prophylaxis has been regarded as the therapeutic standard for many years. However, the disadvantage of long-term antibiotic therapy is the potential for development of resistant organisms in the host. Although cranberry juice prophylaxis was found to reduce the frequency of bacteriuria with pyuria in older women, no studies have yet been reported in the literature on children with VUR. The purpose of this study was to examine whether cranberry juice can be substituted for antibiotic prophylaxis in the prevention of UTI in children with VUR.

Low-dose pulse methylprednisolone followed by short-term combination therapy and tonsillectomy for childhood IgA nephropathy

Sirs, We read with great interest the article by Yata et al. concerning the long-term outcome in Japanese children with immunoglobulin (Ig)A nephropathy [1]. These authors found a marked improvement in renal survival since the 2-year combination therapeutic regimen of prednisolone and immunosuppressive agent was first introduced for Japanese children with severe IgA nephropathy [2]; simultaneously, adverse effects, such as growth retardation and aseptic necrosis of the femur, associated with the longterm administration of steroids, were also observed with this combination therapy [2]. Alternatively, Pozzi et al. reported the impressive benefits of treatment with pulse methylprednisolone and short-term prednisolone (6 months) with respect to reducing proteinuria and preventing endstage renal failure in adult patients—without considerable toxicity [3]. Hotta et al. showed that tonsillectomy combined with low-dose pulse methylprednisolone followed by short-term oral prednisolone (12 months), which is regarded as the standard treatment of adulthood IgA nephropathy in Japan, was effective in resolving urinary abnormalities in Japanese adult patients, especially during the earlier course of the disease [4, 5]. We report here the findings of a cohort patients with IgA nephropathy who were treated with low-dose pulse methylprednisolone followed by short-term combination therapy with (n=5) or without tonsillectomy (n=5). Ten consecutive patients (six boys, four girls) with newly biopsy-proven IgA nephropathy and urinary protein excretion of more than 0.5 g/m daily who had been referred to Saitama Children’s Medical Center between 2003 and 2006 were enrolled into the study. Their age at the start of therapy ranged between 6.3 and 14.7 years (mean 10.5 years). The mean urinary protein excretion was 1.2 g/m per day (range 0.5–2.1 g/m per day). The mean percentage of glomeruli showing crescents and segmental sclerosis on renal biopsy in the patients was 32 and 6%, respectively. The treatment regimen consisted of low-dose pulse methylprednisolone (intravenously 15–20 mg/kg/day; maximum 600 mg/day) for three consecutive days weekly for 3 weeks, followed by short-term combination therapy (approximately 12 months) of alternate-day prednisolone (initially 1 mg/kg; maximum 30 mg), mizoribine (5 mg/kg per day)/azathioprine (2 mg/kg per day), and dipyridamole (5 mg/kg per day). The oral prednisolone dosages were tapered off at a dose of 2.5–5 mg every 4–8 weeks on the basis of the reduction in urinary protein excretion. Beginning in 2006, tonsillectomy was additionally performed within 3 months after the initiation of pulse methylprednisolone therapy in five patients. The primary endpoint was the disappearance of protein excretion defined as a morning urinary protein-to-creatinine ratio (mg/ mg) <0.1. The interval between the initial presentation Pediatr Nephrol (2010) 25:563–564 DOI 10.1007/s00467-009-1239-1

Evaluation of kidney dysfunction and angiotensinogen as an early novel biomarker of intrauterine growth restricted offspring rats

Background:Few studies have addressed the growing concerns of chronic kidney diseases in children with intrauterine growth restriction (IUGR). Therefore, the purpose of this study was to evaluate long-term kidney dysfunction and determine if urinary angiotensinogen (AGT) was suitable as a novel early biomarker for kidney dysfunction in IUGR offspring.Methods:Pregnant rats underwent bilateral uterine artery ligation, and as a control group, sham surgeries were performed.Results:The birth weight was reduced, the urinary AGT to creatinine ratio was significantly higher at week 20, and urinary protein levels were significantly higher at week 32 in IUGR rats than in control rats. On the other hand, the histological findings at week 32 revealed long-term kidney dysfunction, more severe glomerulosclerosis, and greater glomerular diameters in IUGR rats. Moreover, AGT mRNA expression and immunohistological staining were significantly increased in IUGR rats; this suggests that the intrarenal renin–angiotensin system (RAS) contributes to renal dysfunction of IUGR offspring.Conclusion:Urinary AGT elevation prior to urinary protein levels suggests that AGT is an early biomarker. At week 32, kidney dysfunction was severe in IUGR rats and intrarenal RAS appeared to be one of the causes.

Early identification of steroid dependency in Japanese children with steroid-sensitive nephrotic syndrome undergoing short-term initial steroid therapy

Sirs,We read with great interest the article titled “Early age atdebut is a predictor of steroid-dependent and frequentrelapsing nephrotic syndrome” by Andersen et al. recentlypublished in Pediatric Nephrology [1]. In a retrospectiveanalysis of 54 children (approximately 80% Caucasian)with steroid-sensitive nephrotic syndrome (SSNS), theauthors concluded that young age at presentation and malegender were associated with a high risk of steroiddependency despite prolongation of the steroid course atthe debut of SSNS. In addition, they found a reduction inrelapse frequency in the long-term initial steroid therapygroup (12 weeks) compared with the short-term group(8 weeks).Here, based on our retrospective analysis, we would liketo add to the list of predictive risk factors for steroiddependency with short-term initial steroid therapy inJapanese children with SSNS. Between January 1999 andJune 2007, 72 consecutive patients (51 male, 21 female)with recent-onset SSNS and treated at the Saitama Child-ren’s Medical Center were enrolled in this study. Thesepatients were treated with a short-term steroid treatmentregimen (total 8 weeks) comprising 4 weeks of dailyprednisolone treatment (2 mg/kg or 60 mg/m

Relapsing peritonitis with Corynebacterium aquaticum in a boy receiving automated peritoneal dialysis

Sirs, Corynebacterium species, with the exception of C. diphtheriae, are commonly regarded as contaminants when isolated from clinical specimens because they belong to the normal flora of the human skin and mucous membranes [1]. In immunocompromised patients, however, this organism has been identified as a human pathogen. Corynebacterium aquaticum is an environmental organism, with its natural habitat in fresh water [2]. It has been reported in association with neonatal meningitis and urinary tract infection, septicemia in an elderly patient with diabetes and septic shock in an human immunodeficiency virus (HIV)-infected patient [3–6]. To date, C. aquaticum peritonitis has been reported in only three continuous ambulatory peritoneal dialysis (CAPD) adult patients [7–9]. Here, we describe a boy with relapsing peritonitis caused by C. aquaticum who had received automated peritoneal dialysis (APD). A 17-year-old boy with end stage renal disease due to bilateral hypoplastic kidneys, who had received APD since August 2004, was admitted to our hospital in May 2008 because of persistent fever, abdominal pain and a cloudy peritoneal effluent. His dialysis regimen consisted of six 2.5-L exchanges on the cycler (Baxter Homechoice cycler) for a period of 8 h per night. There was no evidence of immunosuppression in the patient, except for the presence of the PD catheter. Physical examination revealed a temperature of 38.6°C, normal bowel sounds and slight abdominal tenderness, without guarding or rebound. There was no infection at the exit site and tunnel of the peritoneal catheter. A peritoneal fluid analysis showed a total nucleated cell count of 19,300/mm with 50% polymorphonucleated cells. Investigations revealed a peripheral blood white cell count of 8500/mm and a C-reactive protein level of 2.18 mg/dL. Two sets of blood cultures were negative. After dialysate samples of 10 ml were inoculated into both aerobic and anaerobic blood culture vials, the patient was empirically treated with intraperitoneal cefazolin (1 g per day) and ceftazidime (1 g per day). The symptoms and signs subsided, and the peritoneal fluid cleared within 5 days. On the third hospital day, Staphylococcus epidermidis was identified in the dialysate cultures; as this strain was sensitive to all tested antibiotics, including cefazolin, the ceftazidime was discontinued. Despite the treatment with intraperitoneal cefazolin, the patient developed fever and abdominal pain again on day 11. Cultures of the dialysate again resulted in the growth of an aerobic, gram-positive rod. The isolated strain was biotyped using an API Coryne kit (bioMerieux, Japan) and was identified as Corynebacterium aquaticum on day 20. This strain was resistant to cefazolin and ceftazidime, but susceptible to vancomycin: The minimum inhibition concentrations (MICs) were 50 mcg/ml for cefazolin, <100mcg/ml for ceftazidime and 3.13 mcg/ml for vancomycin. Based on the antibiotic susceptibility, cefazolin was stopped and vancoPediatr Nephrol (2009) 24:1253–1254 DOI 10.1007/s00467-008-1059-8

The Synergistic Effect of Mizoribine and a Direct Renin Inhibitor, Aliskiren, on Unilateral Ureteral Obstruction Induced Renal Fibrosis in Rats

PURPOSE Renal fibrosis, the major histopathological change in various renal disorders, is closely related to renal dysfunction. Unilateral ureteral obstruction is a well established model of experimental renal disease that results in tubulointerstitial fibrosis. Previous studies showed that aliskiren and mizoribine ameliorated unilateral ureteral obstruction induced renal fibrosis. However, to our knowledge the protective effect of combination therapy with aliskiren and mizoribine against renal fibrosis is unknown. We investigated the synergistic effects of aliskiren and mizoribine combination therapy on unilateral ureteral obstruction induced fibrosis in rats. MATERIALS AND METHODS Male Sprague Dawley® rats underwent unilateral ureteral obstruction followed by aliskiren and/or mizoribine treatment. Kidney samples were fixed for histopathology and immunohistochemistry of myofibroblasts (α-SMA) and macrophages (ED-1). Real-time quantitative reverse transcription-polymerase chain reaction was performed to measure α-SMA, TGF-β1, osteopontin, MCP-1 and renin expression. RESULTS After unilateral ureteral obstruction the tubular dilatation, interstitial volume and α-SMA expression scores were significantly decreased by combination therapy compared with monotherapy with aliskiren or mizoribine. Combination therapy caused a significant decrease in the number of ED-1 positive cells and in TGF-β1 gene expression compared with monotherapy with either drug (each p <0.05). Combination therapy also decreased OPN and MCP-1 gene expression (p <0.05). CONCLUSIONS Aliskiren and mizoribine combination therapy provides increased renal protection against renal fibrosis and unilateral ureteral obstruction induced inflammation.

Risk factors for early relapse during maintenance therapy after a single infusion of rituximab in children with steroid-dependent nephrotic syndrome

Sir,We readwith great interest the article “Long-term outcome ofchildren treated with rituximab for idiopathic nephrotic syn-drome” by Tellier et al., which was recently published inPediatricNephrology [1].Inaretrospectivemulticenterstudyincluding18Frenchchildrentreatedwithrituximab(RTX)forsteroid-dependent nephrotic syndrome (SDNS), they recom-mendedregularandrepeatedtreatmentwithRTX,arelativelysafe biological agent, with the aim of inducing a long-lastingB-cell depletion period (at least 18–24 months in the Frenchprotocol). However, it remains unclear whether all patientsshouldbere-treatedbecausesomepatientsmaintainremissioneven after B-cell recovery. Furthermore, it is impossible toperform vaccinations during long-term B-cell depletion,which is a critical issue when treating children. In contrast,resultsfromrecentJapaneseprospectivestudieshaverevealedthat maintenance therapy with cyclosporine (CsA) or myco-phenolate mofetil (MMF) following a single infusion of RTXmay eliminate the need to repeat RTX infusions and, conse-quently, decrease the side effects associated with repeateddoses [2, 3]. However, early relapse of NS after RTX therapyis noted in some patients, despite this therapeutic protocol.Onthebasisofourexperienceinasinglecenter,wewouldlike to comment on the risk factors that predict early relapseafterinitialsingle-doseRTXtherapyfollowedbymaintenancetherapy in Japanese children with severe SDNS. BetweenSeptember 2007 and April 2012, a study was conducted atthe Saitama Children’s Medical Center which comprised 37patients (26 boys, 11 girls; mean age 11.7±4.9 years) withpersistent SDNS despite treatment with multiple immunosup-pressive agents who had been initially treated with single-doseRTX (375 mg/m

Tolvaptan in a pediatric patient with diuretic-resistant heart and kidney failure.

Despite conventional diuretic therapy, volume overload persists in many patients with decompensated heart failure. Adverse effects of diuretics are common, including worsening kidney function and electrolyte disturbance. Furthermore, decreased kidney function also affects the response to diuretics and is associated with an increased risk of mortality. A 10‐year‐old boy with congestive heart failure (CHF) complicated by advanced chronic kidney disease (CKD) presented with oliguria and generalized edema. He was being treated with furosemide and spironolactone, and these doses were increased to 3 mg/kg/day after admission. Although edema decreased temporarily, the symptoms worsened and furosemide resistance developed 2 months later. Tolvaptan (0.1 mg/kg/day) was started, resulting in a gradual increase in the plasma sodium level and adequate decongestion of the volume overload state. Cardiac function also improved. The use of tolvaptan should be considered in pediatric cases of conventional diuretic‐resistant CHF, even when complicated by advanced CKD.

Two dosing regimens for steroid therapy in nephrotic syndrome

regimen depended on the treating physician. The age of the children at onset varied from 1.0 to 11.4 (median 4.0) years. Although there were no significant differences between the two groups in terms of gender ratio, age, serum albumin at onset, time to response to initial therapy, or proportion of adverse events, the onset time for relapses after initial therapy was significantly shorter for children in the BW-based dosing group than for those in the BSA-based group (2.0 vs. 6.0 months; p<0.05). Further, the proportion of steroiddependent NS was also significantly higher among children in the BW-based dosing group than among those in the BSA-based group (53.3 vs. 12.5 %; p<0.05). Our study, although retrospective in nature, indicates that for children with idiopathic NS, BW-based and BSA-based steroid dosing are not equivalent if the child’s BW is <30 kg. In conclusion, our findings are in agreement with the simulation study by Saadeh et al. [1] that BW-based dosing might lead to “underdosing.” Based on our retrospective analysis, we would like comment that in order to enable accurate comparisons between trials, consistent dosing regimens should be used in future trials involving children with idiopathic NS.

Nephronophthisis Cannot Be Detected by Urinary Screening Program

Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease and is the most frequent genetic cause for end-stage renal disease (ESRD) in Western countries. In contrast, the actual incidence of NPHP in Japan remains unclear because details of only about 30 Japanese patients have been reported so far. Till date, mutations in 9 NPHP genes (NPHP1-9) have been identified in NPHP subtypes 1 to 9. The first identified NPHP gene NPHP1, which is localized on chromosome 2q13, encodes nephrocystin. Based on the timing for ESRD, the following 3 clinical variants have been described: infantile, juvenile, and adolescent. Of these, juvenile NPHP (NPHP1) is the most common form, which accounts for 5% to 10% of ESRD cases in Caucasian children. To our knowledge, only 2 previous studies have reported on Japanese patients with NPHP in whom genetic diagnosis was made. Here, we report on a girl with NPHP1 who initially visited a local hospital because of general fatigue and was referred to our hospital as she demonstrated anemia associated with chronic renal insufficiency. However, no abnormal findings had been noted during annual school urinary screenings conducted over a long period of time.