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Bladder dysfunction in children is common, the most frequent underlying causes are neurologic bladder (NB), dysfunctional voiding syndrome (DVS), and the valve bladder syndrome (VBS). The aim of this study was to determine the 10-y survival rate and the associated morbidities in children with bladder dysfunction. One hundred ninety-nine children were included in the study; 60 with VBS, 75 DVS, and 64 NB. The mean age was 44 mo (CI: 37–50.9) and mean GFR 50.1 (CI 44.6–55.6) mL/min/1.73m2. The 10-y survival rate was 89%. Compared with patients with VBS, the mortality was 11 times higher among patients with NB (p = 0.02) but not significantly higher than patients with DVS (p = 0.2). GFR 5 y) increases mortality risk and/or the need for renal replacement therapy (RRT) by almost 5 times (p = 0.013). It was concluded that the etiology of bladder dysfunction, baseline GFR, and the age at presentation significantly influence the survival rate and morbidities.

Bladder dysfunction in children is common, the most frequent underlying causes are neurologic bladder (NB), dysfunctional voiding syndrome (DVS), and the valve bladder syndrome (VBS). The aim of this study was to determine the 10-y survival rate and the associated morbidities in children with bladder dysfunction. One hundred ninety-nine children were included in the study; 60 with VBS, 75 DVS, and 64 NB. The mean age was 44 mo (CI: 37-50.9) and mean GFR 50.1 (CI 44.6-55.6) mL/min/1.73m

Background and Aims Bladder dysfunction is an important cause of chronic kidney disease (CKD) due to neurogenic causes such as a spinal lesion (SL), Hinman's syndrome, or non-neurogenic neurogenic bladder (NNNB), and valve bladder syndrome (VBS). In this study, we evaluated the outcomes of neurogenic bladder caused by different etiologies. Method Single-center retrospective study of children with neurogenic bladder (NB) over 13 years (2005-2017). Results Totally, 199 children (134 boys, 67.3%) were included and divided into three groups: Group 1 (75, NNNB), Group 2 (64, SL), and Group 3 (60, VBS). Urodynamic examination revealed impaired bladder capacity in 49 children (57.6%), atonic bladder in 1 child (1.1%), and normal bladder compliance in 35 children (41.1%). Additionally, 113 children (56.8%) experienced clean intermittent catheterization (CIC). A significant improvement in the mean estimated glomerular filtration rate and CKD stages was observed among the three studied groups, but the NNNB group showed the least improvement. Children diagnosed and treated during their first year of life had better outcomes than those who presented at a later age. CIC without the need for surgical intervention was associated with improved renal function. Pyelonephritis and hydronephrosis had significant negative impacts on kidney function Conclusion Early diagnosis and management of NB in infancy are associated with better outcome and preservation of renal function. CIC is associated with better preservation of kidney function, while vesicostomy is associated with a worse outcome. Children with NB caused by SL experienced the best kidney function preservation, while those with VBS experienced the worst.

Background and Aims Approximately 50% of children with steroid sensitive nephrotic syndrome (SSNS) will suffer from frequent relapses or steroid dependency, prompting the use of so-called steroid-sparing drugs. In this pilot study, we compare the efficacy and safety of rituximab to oral cyclophosphamide as first-line steroid-sparing medications Method A prospective open label randomized study of children with frequent relapsing or steroid-dependant SSNS. Exclusion criteria were steroid-resistant disease, prescription of immunosuppressive agents other than prednisolone or levamisole, evidence of impaired kidney function, leucopenia or active infection. The recruited children were allocated either to the oral cyclophosphamide (3mg/kg/day for 8 weeks) or intravenous rituximab treatment (two doses of 375 mg/m2/dose, 2 weeks apart) and were monitored for relapses and side effects for 12 months Results 46 subjects were included from two centers; 27 received cyclophosphamide and 19 received rituximab. One-year relapse-free survival was reached in 17 (58.6%) patients treated with cyclophosphamide compared to 16 (84.2%) with rituximab (adjusted HR: 0.36; 95% CI: 0.09 – 1.45; p=0.151). The mean interval to relapse was 6.9 months in the cyclophosphamide group (N=10) and 6.3 months in the rituximab group (N=3). Both treatments were associated with a significant (p=?) reduction in prescribed dose of oral alternate days steroid from 1.02 to 0.36mg/kg (Cyclophoshamide) and 0.86 to 0.08mg/kg (Rituximab). Importantly, a significantly (P = 0.003) higher percentage of patients achieved complete withdrawal of steroid within 3 months of commencing study treatment in the rituximab (73.7%) versus cyclophosphamide (29.6%) group. Transient leucopenia was the most frequent adverse effect observed in the cyclophosphamide group (18.5%) and one patient (3.4%) had acute hepatotoxicity beside severe leucopenia and neutropenia on the 7th week of treatment although she showed complete recovery with withdrawal of cyclophosphamide and maintained remission. A minor infusion related reaction was observed in 1 patient (5%) in the rituximab group. Conclusion Rituximab is non-inferior to cyclophosphamide and safe as a first-line steroid-sparing agent in children with SSNS. A larger multicenter study is required to assess superiority over cyclophosphamide

Background Urinary bladder agenesis is a very rare congenital anomaly with very few cases reported in the literature. Case presentation We report a one-month-old baby presenting with ambiguous genitalia and recurrent urinary tract infections. Her clinical course was complicated by renal impairment. Magnetic resonant imaging (MRI) revealed a diagnosis of bladder agenesis with bilateral ectopic insertion of the ureters into the vagina, associated with several other anomalies. The patient underwent bilateral high anterior ureterostomies in an hospital abroad at 5.5 months of age. She then developed ureteral necrosis that had to be corrected with left pyeloplasty and by placing a left nephrostomy tube for drainage. Eventually, the patient’s renal function declined, and she developed chronic kidney disease (CKD).The case with its imaging findings and pathogenesis as well as a review of the literature are presented. Conclusions Urinary bladder agenesis is a rare congenital condition that can be associated with multiple anomalies. Early diagnosis and therapeutic intervention can prevent progression to chronic kidney disease.

The incidence of nephrolithiasis continues to rise. Previously, we showed that a monogenic cause could be detected in 11.4% of individuals with adult-onset nephrolithiasis or nephrocalcinosis and in 16.7-20.8% of individuals with onset before 18 years of age, using gene panel sequencing of 30 genes known to cause nephrolithiasis/nephrocalcinosis. To overcome the limitations of panel sequencing, we utilized whole exome sequencing in 51 families, who presented before age 25 years with at least one renal stone or with a renal ultrasound finding of nephrocalcinosis to identify the underlying molecular genetic cause of disease. In 15 of 51 families, we detected a monogenic causative mutation by whole exome sequencing. A mutation in seven recessive genes ( AGXT, ATP6V1B1, CLDN16, CLDN19, GRHPR, SLC3A1, SLC12A1 ), in one dominant gene ( SLC9A3R1 ), and in one gene ( SLC34A1 ) with both recessive and dominant inheritance was detected. Seven of the 19 different mutations were not previously described as disease-causing. In one family, a causative mutation in one of 117 genes that may represent phenocopies of nephrolithiasis-causing genes was detected. In nine of 15 families, the genetic diagnosis may have specific implications for stone management and prevention. Several factors that correlated with the higher detection rate in our cohort were younger age at onset of nephrolithiasis/nephrocalcinosis, presence of multiple affected members in a family, and presence of consanguinity. Thus, we established whole exome sequencing as an efficient approach toward a molecular genetic diagnosis in individuals with nephrolithiasis/nephrocalcinosis who manifest before age 25 years.

BACKGROUND: Steroid-sensitive nephrotic syndrome (SSNS), the most common form of nephrotic syndrome in childhood, is considered an autoimmune disease with an established classic HLA association. However, the precise etiology of the disease is unclear. In other autoimmune diseases, the identification of loci outside the classic HLA region by genome-wide association studies (GWAS) has provided critical insights into disease pathogenesis. Previously conducted GWAS of SSNS have not identified non-HLA loci achieving genome-wide significance. METHODS: In an attempt to identify additional loci associated with SSNS, we conducted a GWAS of a large cohort of European ancestry comprising 422 ethnically homogeneous pediatric patients and 5642 ethnically matched controls. RESULTS: The GWAS found three loci that achieved genome-wide significance, which explain approximately 14% of the genetic risk for SSNS. It confirmed the previously reported association with the HLA-DR/DQ region (lead single-nucleotide polymorphism [SNP] rs9273542, P=1.59×10-43; odds ratio [OR], 3.39; 95% confidence interval [95% CI], 2.86 to 4.03) and identified two additional loci outside the HLA region on chromosomes 4q13.3 and 6q22.1. The latter contains the calcium homeostasis modulator family member 6 gene CALHM6 (previously called FAM26F). CALHM6 is implicated in immune response modulation; the lead SNP (rs2637678, P=1.27×10-17; OR, 0.51; 95% CI, 0.44 to 0.60) exhibits strong expression quantitative trait loci effects, the risk allele being associated with lower lymphocytic expression of CALHM6. CONCLUSIONS: Because CALHM6 is implicated in regulating the immune response to infection, this may provide an explanation for the typical triggering of SSNS onset by infections. Our results suggest that a genetically conferred risk of immune dysregulation may be a key component in the pathogenesis of SSNS. ispartof: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY vol:30 issue:8 pages:1375-1384 ispartof: location:United States status: published

Congenital and infantile nephrotic syndrome (CNS and INS) are rare inherited defects in glomerular filtration involving a variety of gene mutations. This study aimed to analyze all genetic mutations associated with congenital and infantile nephrotic syndrome treated at our institution. We also discussed our different approach secondary to culture and resources. A retrospective single-center study of all children diagnosed as NS before the age of 1 year over a duration of over one decade. Twenty-nine children (12 boys) were included in the study. Their median age (range) was 2.4 (0.1–12) months (20 CNS and 9 INS). Consanguinity was present in 90% of children. The genetic analysis’ results were only available for 20 children. An underlying causative homozygous mutation was detected in 18 children (90%): NPHS1 (9), NPHS2(2), LAMB2(3), PLCE1(1), WT1(1), and ITSN1 novel mutation (2). One child had heterozygous mutation of NPHS2 and another child had heterozygous mutation of NPHS1 which could not explain the disease. All CNS cases were all managed with intermittent intravenous albumin infusion, ACEi, diuretics, and indomethacin. None of the children were managed by nephrectomy followed by peritoneal dialysis (PD) because of limited resources. Only one child achieved partial remission, while 15 children died at a median (range) age of 5.8 (1.25–29) months. The remaining 14 children were followed up for an average of 36 (3.9–120) months. Three children progressed to end-stage kidney disease and PD was performed in only two children. NPHS1 is the main underlying cause of CNS and INS in our study population. CNS and INS were associated with high morbidity and mortality.

Obstructed hemivagina and ipsilateral renal agenesis (OHVIRA) is a rare congenital urogenital anomaly, which usually presents after menarche. We report a 3-month-old infant who presented with recurrent urinary tract infections (UTI) and had an abdominal lump. Radiological investigations revealed absent right kidney, hydronephrotic left kidney, and a cystic pelvic mass. Exploratory laparotomy revealed hydrometrocolpos which was evacuated. During 1-year follow-up, hydronephrosis decreased, there were no further UTI, and kidney function remained normal. Our case illustrates that OHVIRA syndrome may present in early infancy with UTI, renal anomalies, and pelvic mass.

BACKGROUND AND OBJECTIVES: Mutations in several genes are known to cause steroid-resistant nephrotic syndome (SRNS), most commonly in NPHS1, NPHS2, and WT1. Our aims were to determine the frequency of mutations in these genes in children with SRNS, the response of patients with SRNS to various immunosuppressants, and the disease outcome, and to review the predictive value of genetic testing and renal biopsy result. DESIGN AND SETTINGS: A retrospective review was performed of the medical records for all children with SRNS who were treated and followed-up in the Pediatric Nephrology Unit of King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia from 2002–2012. PATIENTS AND METHODS: We retrospectively reviewed the medical records of children above 1 year of age, who presented with SRNS to KAUH, Jeddah, Saudi Arabia, in the 10-year interval from 2002–2012 and for whom the results of genetic testing for NPHS1, NPHS2, and WT1 were available. We compared the clinical phenotype, including response to treatment and renal outcome to genotype data. RESULTS: We identified 44 children with a clinical diagnosis of SRNS in whom results of genetic testing were available. Presumably disease-causing mutations were detected in 5 children (11.4%) of which 3 (6.8%) had NPHS2 mutation and 2 (4.5%) had NPHS1 mutation. Renal biopsy revealed minimal change disease (MCD) or variants in 17 children, focal segmental glomerulosclerosis (FSGS) in 23 children, membranoproliferative changes (MPGN) in 2 children, and IgA nephropathy in another 2 children. Children with MCD on biopsy were more likely to respond to treatment than those with FSGS. None of those with an identified genetic cause showed any response to treatment. CONCLUSION: The frequency of identified disease-causing mutations in children older than 1 year with SRNS presented to KAUH was 11.4%, and these patients showed no response to treatment. Initial testing for gene mutation in children with SRNS may obviate the need for biopsy, and the use of immunosuppressive treatment in children with disease due to NPHS1 or NPHS2 mutations. Renal biopsy was useful in predicting response in those without genetic mutations.

To evaluate the social consequences of dialysis on children and their parents.From January through June 2012 short structured interviews with parents or caregivers of children on peritoneal dialysis (PD) or hemodialysis (HD) who were followed up at King Abdulaziz University Hospital, King Faisal Specialty Hospital and Research Center, or the Kidney Center at King Fahad Hospital were conducted. Data were analyzed using the Statistical Package for the Social Sciences.Thirty six children (20 boys and 16 girls [corrected] ) and their families were included. The mean (SD) age of the children was 11.5±6.87 y, and the mean (SD) duration of dialysis was 28±11.32 mo. Only one third of the families had the opportunity to choose the modality of dialysis. Both modalities of dialysis had a negative effect on fathers' jobs in over 50% of the cases. Similarly, both modalities of treatment had a considerable impact on the quality of care provided by the mothers to other family members. There was no difference between the two modalities on the frequency of admissions.Both PD and HD had a negative impact on fathers' jobs and on the level of care provided by mothers to the rest of the family.

Aim We aimed to examine the social impact of clean intermittent catheterization (CIC) on children with a neurogenic bladder and to compare the impact of urethral CIC with Mitrofanoff catheterization. Methods Questionnaires containing 29 questions about the social impact of CIC on the children and their families were administered with their parents or caregivers of 50 children (34 boys and 16 girls) using CIC. The mean (standard deviation [SD]) age of the children was 9.6 (4.32) years and duration on CIC was 6.1 (3.97) years. Results Seventeen children were using Mitrofanoff catheterization (group I) and 33 children urethral catheterization (group II). Of the respondents, 54% respondents reported that their children accept the use of CIC, 30% respondents reported that they do not like it, and 16% respondents reported that they always refuse and resist it. There was no difference in the level of acceptance between the two groups. Both groups reported that children were social (90%) and had close friends (88%). However, 50% felt that CIC affected mood, with 30% of the children displaying bad temper. Mitrofanoff catheterization was associated with fewer episodes of frequent urinary tract infection (p = 0.004) and greater adherence. All children from group I, who were older than 6 years, were attending school compared with 78% from group II. School performance was significantly better in group I (p = 0.022). Conclusion There was acceptance of CIC by most children but Mitrofanoff catheterization seemed to have a lower social impact in terms of school performance, adherence to therapy, and complications.

Background: Renal cystic diseases are important causes of chronic kidney disease (CKD). Objectives: We report the pattern of renal cystic disease in children and evaluate the outcome of children with multicystic dysplastic kidney (MCDK). Patients and Methods: Retrospective study of all children with cystic kidney diseases at King Abdulaziz University hospital from 2006 to 2014. Results: Total of 55 children (30 males); 25 MCDK, 22 polycystic kidney diseases (PKD), 4 nephronophthises and 4 renal cysts. Consanguinity was positive in 96.2%. MCDK and simple renal cyst patients had good renal function while PKD and nephronophthisis developed renal impairment. Most MCKD were diagnosed ante-natally, 16 of them were followed up for 3.4 (1.97) year. Their last creatinine was 33.9 (13.5) umol/L. MCDK was spontaneously involuted at mean age of 2.6 (1.3) years in 56%. Conclusions: MCDK is the commonest cystic renal disease and diagnosed ante-natally in the majority of cases. It has a good prognosis.

We aimed to investigate the effect of single, high-dose intramuscular cholecalciferol on vitamin D3 and intact parathyroid hormone (iPTH) levels in children with chronic kidney disease (CKD). Between January 2012 and June 2012, we conducted a prospective, uncontrolled study at the Pediatric Nephrology Unit of King Abdulaziz University Hospital, Jeddah, to investigate the effect of single, high-dose intramuscular vitamin D3 on 25(OH)D3 and iPTH levels in vitamin D insufficient/deficient children with CKD. Serum vitamin D3, iPTH, calcium, phosphate, alkaline phosphatase (ALP), and creatinine levels were measured before intramuscular vitamin D3 (300,000 IU) administration, and these were subsequently repeated at 1 and 3 months after treatment. Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA). Nineteen children fulfilled the criteria. At 3 months after treatment, vitamin D3 levels were significantly higher than at baseline (p

Posterior urethral valves (PUV) are a common cause of end-stage renal failure in childhood. Our aim was to describe a cohort of patients with PUV and to investigate the predictors of renal impairment. We performed a retrospective chart review of children with PUV who were followed at King Abdulaziz University hospital between 2002 and 2011. The cohort comprised 68 boys. There was a significant difference in the duration of follow-up (p = 0.024), nadir serum creatinine (p

Rituximab has been used over the last decade as a rescue therapy for refractory cases of nephrotic syndrome (NS). Here we report the use of rituximab in four children with idiopathic steroid-resistant nephrotic syndrome (SRNS) with various histological backgrounds (two cases with focal segmental glomerulosclerosis, one case with IgM nephropathy, and one case with minimal change disease), who failed to respond to other immunsuppressions. Their median age (range) was 10 (8–11) years. NPHS2 genetic mutation was negative in all of them. All patients received a single dose of rituximab (375 mg/m2) and achieved complete B cell depletion as CD19 was

A 15-year-old Saudi Arabian boy presented with painless hard subcutaneous swellings inhis fingerswith intact overlying skin (Fig. 1a). These lesions had developed over severalmonths.He had widespread bone pain and was unable to walk for 1 year. He presented in end-stage kidney disease (ESKD) of unknown etiology at 1 year of age and received peritoneal dialysis for 3 years. Due to repeated episodes of peritonitis, Fig. 1 a X-rays of both hands. b X-ray of left hip. c Non-contrast head CT scan

Aim: This study aimed to identify the differences between primary and secondary vesicoureteric reflux (VUR) and the effect of associated bladder abnormalities on kidney function. Patients and Methods: We retrospectively reviewed the medical records of children with VUR who were followed up at King Abdulaziz University Hospital from January 2005 to December 2010. The review included results of radiological investigations and kidney function tests. We used Chi-square test for statistical analysis and paired t -test to compare group means for initial and last creatinine levels. Results: Ninety-nine children were included in this study. Twenty (20.2%) had primary VUR, 11 had high-grade VUR, while 9 had low-grade reflux. All children with low-grade VUR had normal dimercaptosuccinic acid (DMSA). Renal scars were present in 72% of the children with high-grade VUR. The mean creatinine levels (initial and last) for both groups were normal. Seventy-nine (79.8%) children had secondary VUR, which was due to posterior urethral valves (PUV) (46.8%), neurogenic bladder caused by meningomyelocele (25.3%), non-neurogenic neurogenic bladder (NNB) (21.5%), or neurogenic bladder associated with prune belly syndrome (6.3%). Children with NNB, meningomyelocele and PUV had high creatinine at presentation with no considerable worsening of their kidney functions during the last visit. Renal scars were present in 49.4% of the children with secondary VUR. Conclusion: Children with primary VUR and normal bladder had good-functioning kidneys, while those with secondary VUR associated with abnormal bladder caused by NNB, spina bifida or PUV had abnormal kidney functions. DMSA scans were useful in predicting higher grades of VUR in children with primary reflux.

The cases are reported of two young children who developed insulin-dependent diabetes mellitus (IDDM) within 2 weeks of receiving a diagnosis of nephrotic syndrome. Neither patient responded to 8 weeks of daily prednisolone. The first patient presented at 2 years and 9 months of age. Her renal biopsy showed mesangial proliferation. The second child presented with steroid resistant nephrotic syndrome at 18 months of age and developed IDDM 2 weeks later. He achieved partial remission with cyclosporine therapy. His initial renal biopsy at 3 years of age showed minimal change disease and follow-up renal biopsy at 5 years of age showed early diabetic glomerulosclerosis. Tests for NPHS2 and WT1 genetic mutations were negative in both patients. To our knowledge this is the first report of steroid resistant nephrotic syndrome with almost simultaneous onset of IDDM in young children.