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Introduction. Congenital nephrotic syndrome (CNS), an uncommon form of kidney disease, presents during the first year of life and is a diagnostic and therapeutic challenge for the pediatricians as well as pediatric nephrologists. Our study is the first study of Iranian children with CNS in two pediatric nephrology centers in Tehran, Iran. Materials and Methods. We reviewed medical charts of 30 infants diagnosed with CNS from 1990 to 2005. Results. There were 15 boys and 15 girls with CNS (mean age, 1.7 months). The presentation of the disease was nephrotic syndrome in 96.6% of the patients. Eighty percent of the patients presented within 3 months of life and 16 in the neonatal period. The Finnish type of CNS was seen in 43.3% and diffuse mesangial sclerosis in 50%. Preterm labor and low birth weight was seen in 20%. A family history of nephrotic syndrome in infancy was noted for 8 children (26.7%). Numerous complications of nephrotic syndrome occurred in 73.3%. Seventy percent of the patients had 27 episodes of infections. Sepsis was seen in 43.3% of the children, of which 61.5% were caused by gram-negative bacteria and 38.6% were caused by Staphylococcus aureus. Thrombotic complications and hypertension developed in 6.6% and 23.3% of the patients, respectively. The mortality rate of patients was 86.6%. Conclusions. Diffuse mesangial sclerosis is an important cause of CNS. The outcome of our patients was poor and most of our patients died before reaching the age of 5 years old. [ABSTRACT FROM AUTHOR]

Introduction. This study was conducted to evaluate preventive effect of a combination of heparin and aspirin on vascular thrombosis and kidney transplant outcomes of pediatric kidney transplant recipients. Materials and Methods. Twenty-four pediatric kidney transplant recipients received heparin, 50 U/kg, every 8 hours for 7 postoperative days, and aspirin, 5 mg/kg, thrice a week from day 3 of transplantation for 3 months. These patients were compared with a matched group of pediatric kidney allograft recipients in terms of development of thrombosis and serum creatinine level at 1 year postoperation. Results. The mean age of patients was 9.4 ± 3.2 years. No vascular thrombosis was developed among the 24 patients with anticoagulant therapy, while in the control group, 5 grafts (7.9%) developed thrombosis (P = .19). Serum creatinine levels at 1 year were lower in the children with anticoagulant therapy as compared with the controls (P = .02). Conclusions. Our study revealed a reduction in kidney allograft thrombosis incidence in children who received heparin and aspirin after transplantation, which was clinically important although the difference was not statistically significant. Lower serum creatinine levels as compared with a historical cohort group were seen 1 year after transplant surgery. These findings are required to be confirmed by further studies. [ABSTRACT FROM AUTHOR]

Introduction: Some evidence suggest an increase in the prevalence of focal segmental glomerular sclerosis (FSGS) in children. To date, there has been no study of the outcome in children with FSGS and its frequency over several decades in Iran. We aimed to report the changing trend of FSGS incidence and its outcome in a sample of Iranian children.Materials and Methods: Between 1982 and 2008, all 716 kidney biopsies performed in children referred to Ali Asghar Children Hospital were recorded and confirmed cases with FSGS lesions were further evaluated. Baseline and clinical characteristics of all FSGS patients were assessed and the therapies and outcomes were reviewed.Results: The incidence rate of FSGS was 10.1% between 1982 and 1990, which was significantly increased to as high as 20.5% after the year 2000 (P = .001). Among 64 children with FSGS, 20 progressed to end-stage renal disease with a mean survival time of 11.45 years (standard error of mean, 1.34 years). Kidney survival rates were 90.4%, 69%, and 47% at 1, 5 and 10 years of follow-up.Conclusions: Our study demonstrates an increasing trend in FSGS incidence in Iranian children. However, kidney survival rates of our patients were similar to those reported by others in different countries. [ABSTRACT FROM AUTHOR]

INTRODUCTION. Steroid-resistant nephrotic syndrome (SRNS) is uncommon in children, but often leads to ESRD. We report our experience with SRNS and its treatments and outcomes. MATERIALS AND METHODS. We assessed 73 children with SRNS admitted to Ali Asghar Children Hospital in Tehran, Iran. Their clinical presentations, treatment, and disease courses were reviewed. The mean follow-up duration was 6.0 +/- 4.2 years. Moreover, survival times were calculated and the Cox regression method was used to determine variables able to predict survival of the kidneys. Results. Age at the onset of the disease, sex, and hematuria were not predictive of the response to treatment with immunosuppressive drugs in the children with SRNS. The type of resistance (early or late) was associated with the responsiveness to immunosuppressives. Response to any of the immunosuppressive drugs determined the responsiveness to other immunosuppressive drugs. Cyclosporine was more effective than cyclophosphamide as initial therapy. The mean kidney survival time was 11.62 years. Kidney survival rates were 94.6%, 70.0%, 56.0%, and 34.0% at 1, 5, 10, and 15 years, respectively, in patients with initial resistance to steroid, while these were 100%, 100%, 83.0%, and 83.0% in those with late resistance, respectively (P = .03). CONCLUSIONS. We showed that patients with late steroid resistance had better response to immunosuprressive drugs than patients with early resistance. We also showed that resistance to immunosuppressive therapies increased the risk of resistance to other immunosuppressive drugs. Achievement of complete or partial remission with any therapy reduced the risk of ESRD. [ABSTRACT FROM AUTHOR]

INTRODUCTION. Congenital nephrotic syndrome may be caused by mutations in NPHS1 and NPHS2, which encode nephrin and podocin, respectively. Since the identification of the NPHS2 gene, various investigators have demonstrated that its mutation is an important cause of steroid-resistant nephrotic syndrome. We aimed to evaluate frequency and spectrum of podocin mutations in the Iranian children with steroid-resistant nephritic syndrome. MATERIALS AND METHODS. We examined 20 children with steroid-resistant nephritic syndrome referred to Ali Asghar Children's Hospital, in Tehran, Iran. Mutations in the 5th and 7th exons of NPHS2 were assessed. The mutational analysis of NPHS2 was performed by DNA sequencing. RESULTS. The mean age at the onset of proteinuria was 6.4 +/- 3.6 years. None of the children had mutations in the exons 5 or 7. CONCLUSIONS. Our study suggests that NPHS2 mutations in exons 5 and 7 are not seen in our children. Therefore, we cannot recommend NPHS2 (exons 5 and 7) mutation for screening in Iranian children with steroid-resistant nephritic syndrome. Other exons of podocin or other podocyte proteins in Iranian children may play a role in pathogenesis of steroid-resistant nephritic syndrome. [ABSTRACT FROM AUTHOR]

Severe hyperuricemia accompanied by the other comorbidities such as anuria, fluid overload, calcium-phosphate imbalance, and/or tumor lysis syndrome is one of the indications for dialysis in the setting of acute kidney injury. Rasburicase is used in different clinical conditions such as tumor lysis syndrome and uric acid nephropathy. Among referred patients to our center from 2008 to 2010, there were 3 patients who had an indication for dialysis because of hyperuricemia. Contributing factors to the acute kidney injury were multi-organ dysfunction, rapidly progressive glomerulonephritis, and spontaneous tumor lysis syndrome. None of the patients showed any response to treatment with bicarbonate and hydration. After rasburicase administration, serum uric acid level declined, and urine output increased. Treatment with a single low dose of rasburicase would be effective to decrease the serum uric acid level and reverse kidney injury secondary to uric acid nephropathy. [ABSTRACT FROM AUTHOR]

Purpose: To determine the prevalence, outcome and prognostic factors in children with hemolytic uremic syndrome (HUS) who underwent laparotomy. Materials and Methods: The medical records of 104 patients with HUS who presented to our center between 1986 and 2003 were reviewed retrospectively. Data were analyzed using Student′s t test for comparing means, Fisher′s exact test for frequencies and Pearson′s correlation for finding the correlations. Results: 78% of cases presented with vomiting and diarrhea. Seven out of 104 needed surgical exploration. The indications of surgery were acute abdomen, severe abdominal distention and the sign of peritonitis. The findings at laparotomy were intussusceptions, perforation (colon, ileum), gangrene of entire colon, rectosigmoidal tearing, duodenal obstruction and toxic megacolon. Pathological findings were transmural infarction in two cases in which staged surgical management was performed (cecostomy, resection, later anastomosis). Four out of seven patients died because of pulmonary failure, coma and multiple organ failure ( P< 0.05) compared to those who did not need laparotomy. The patients requiring surgery were young (< 3 years), had high leukocyte count (>20000 mm 3 ) and low albumin level (< 3g/dl) ( P< 0.05). Conclusion: Surgical complications of HUS are rare but are assorted with high mortality due to respiratory failure and multiple organ failure. Early decision of laparotomy associated with intensive care, including mechanical ventilation, adequate dialysis and ultrafiltration, are recommended.

Introduction. Atypical hemolytic uremic syndrome (HUS) is accompanied by a poor prognosis and high mortality rate. We investigated the predictive value of severity of renal involvement, as evaluated by pathologic examination, for long-term outcome of atypical HUS. Materials and Methods. Kidney biopsies of 29 children diagnosed with atypical HUS between 1992 and 2005 were reviewed. The severity of glomerular, vascular (arteriolar and arterial), interstitial, and tubular involvement were determined. Scores of renal involvement were determined by re-evaluating kidney specimens. The outcome measures were death, chronic kidney disease (CKD), hypertension, and proteinuria. Results. After a mean of 3.7 years of follow-up, 24.1% of the patients had normal kidney function and blood pressure, 24.1% showed proteinuria, and 41.4% had CKD, and 10.3% had unknown prognosis. Overall, 24.1% of the patients died due to emergent hypertension with or without CKD. The existence of arteriolar and arterial thrombosis attributed to severe CKD (risk ratio, 3.67; 95% confidence interval, 1.63 to 8.2). Presence of thrombosis in the vessels, and thickening of the arterial medial and intimal layers had brought about a significantly higher mortality rate. Chronic kidney disease was more frequent in the children with vascular scores higher than 0.14 and a final score of more than 0.2. Conclusions. The severity of renal pathological involvement, especially the degree of vascular damage, is a good predictor of long-term outcome of patient with atypical HUS. [ABSTRACT FROM AUTHOR]

INTRODUCTION. Cystinosis is an autosomal recessive disorder which is characterized by both renal and extrarenal symptoms. Gastrointestinal dysfunction has been reported in adolescent with cystinosis, and it is rarely considered in the infants. The present case series reviewed gastrointestinal manifestations of these patients. MATERIALS AND METHODS. Gastrointestinal signs and symptoms of 23 children aged 5.99 +/- 0.50 years (range, 1.0 to 12.5 years) on average with cystinosis, admitted to our department of nephrology between 1996 and 2005, were retrospectively reviewed. The inclusion criteria were the presence of the crystals of cystine in bone marrow aspiration and corneal deposition detected by slit lamp examination. Results. Gastrointestinal signs and symptoms were as follows: vomiting in 16 patients (69.6%), hepatomegaly in 8 (34.8%), diarrhea in 6 (26.1%), splenomegaly in 5 (21.7%), constipation in 4 (17.4%), anorexia in 4 (17.4%), abdominal pain in 3 (13.0%), nausea in 2 (8.7%), and ascites in 2 (8.7%). Height below the 3rd percentile in was seen in 16 patients (69.6%) and weight below the 3rd percentile, in 17 (73.9%). Fifteen patients (65.2%) had both low weight and low height. Esophagogastroduodenoscopy had been performed in 6 cases and chronic inactive gastritis with H pylori infection was detected in 2 patients (8.7%). CONCLUSIONS. Our study revealed a wide spectrum of gastrointestinal disturbances in young patients with cystinosis. Such findings should lead to greater awareness of the presence of gastrointestinal dysfunction in these children, encourage prompt gastrointestinal evaluation, and encourage treatment of more severely affected patients. [ABSTRACT FROM AUTHOR]

Introduction: Management of frequently relapsing steroid-responsive or steroid-resistant idiopathic nephrotic syndrome (NS) in children has been a clinical challenge for pediatric nephrologists. In addition, adverse effects of long-term corticosteroids and cyclosporine administration emerge seeking a safe and effective treatment. The purpose of this study was to evaluate the safety and efficacy of mycophenolate mofetil (MMF) in these patients.Materials and Methods: This study reviewed the outcomes of children with frequently relapsing or steroid-resistant idiopathic NS who were treated with MMF.Results: A total of 36 patients (23 boys and 13 girls) were included. Their mean age at the time of diagnosis of NS was 61.94 ± 43.9 months. Of the children, 91.6% of those who had frequent relapses and 8.3% of those with steroid-resistant NS responded to MMF significantly (P < .001), with no significant association between age and gender with response to MMF. The treatment was well tolerated with no significant complications.Conclusions: In children with frequently relapsing NS, MMF was a safe and useful drug for maintaining remission, while it was of low value in children with steroid-resistant NS. [ABSTRACT FROM AUTHOR]

Introduction. Chronic kidney failure was suggested to have a protective effect against Helicobacter pylori infection in adults. However, data about this effect in children is lacking. This study was designed to ascertain the prevalence, endoscopic findings, and histopathological features accompanying the Helicobacter pylori infection in children with end-stage renal disease. Materials and Methods. Data were collected from 117 children with end-stage renal disease aged 5 to 18 years that underwent routine upper gastrointestinal endoscopy before kidney transplantation between 1998 and 2009. The specimens that were taken from the antrum were stained with hematoxylin-eosin and Giemsa to detect Helicobacter pylori. Results. Gastrointestinal symptoms were reported in 12% of the patients. Helicobacter pylori was detected in 24% of the children. The prevalence of Helicobacter pylori infection was high in children with abnormal endoscopic findings (P = .02). There was no correlation between Helicobacter pylori infection and gender, dialysis status, duration of dialysis, underlying diseases, and gastrointestinal symptoms. Helicobacter pylori infection had a significant correlation with histopathological features (P = .005), age older than 10 years (P = .003), and upper gastrointestinal endoscopic findings (P = .001). Conclusions. In this study, Helicobacter pylori infection had a high prevalence in children with end-stage renal disease, especially in older ones. The majority of children with Helicobacter pylori infection were asymptomatic, while they had abnormal findings on upper gastrointestinal endoscopy and chronic active gastritis features in histopathological assessment. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infection (UTI) is common after pediatric renal transplantation, and the emergence of multidrug-resistant (MDR) bacteria causing UTI is a therapeutic challenge in this regard. The main purpose of this study was to determine the UTI frequency, its etiologic agents, and the antibiotic susceptibility pattern in the first year following renal transplantation in Iranian pediatric recipients. Methods: In a retrospective cohort study, all of the 81 children who had undergone renal transplantation in Hazrat Rasoul Akram Hospital between 2012 and 2017 were enrolled. Confirmed episodes of UTI during the first year following renal transplantation were analyzed. The pattern of antibiotic resistance was determined for the causative agents of UTI. The data were analyzed using the IBM SPSS Statistics software (version 20). and the P < 0.05 was considered significant. Results: Totally, from 81 enrolled cases, 37(44.7%) cases were in the age group of 11-15 years. Overall, 19, 10, and 3 UTI episodes had occurred in the first month, from the first to sixth month, and between the sixth month and one year after transplantation, respectively. The four most common isolated bacteria were Escherichia coli ( E. coli ; 31.2%), Pseudomonas aeruginosa ( P. aeruginosa ; 25%), Enterococci (21.9%) and Klebsiella pneumoniae ( K. pneumoniae ; 12.5%). The highest rate of resistance was reported to trimethoprim/sulfamethoxazole (TMP/SMX), cephalosporins, and fluoroquinolones among gram-negative bacteria. However, none of the Enterococci isolates were resistant to linezolid and nitrofurantoin. Conclusion: Resistance to antibiotics is increasing among the pathogens causing UTI in pediatric renal transplanted cases. It is suggested to stop the administration of TMP/SMX and third-generation cephalosporins for empiric treatment of UTI in Iranian pediatric renal transplant recipients. Ciprofloxacin might be administered cautiously secondary to the increasing rate of antibiotic resistance in this group., Competing Interests: The authors declare that they have no competing interests., (© 2023 Iran University of Medical Sciences.)

Objectives: End-stage kidney disease has dramatic health effects and life consequences in children. Presently, kidney transplant has been globally accepted as a treatment of choice for end-stage kidney disease in both children and adults, leading to better quality of life and longer patient survival. Because of lack of comprehensive information on the outcome of kidney transplant among children in Iran, we aimed to present a proper vision of pediatric kidney transplant in Iran by systematically reviewing the current literature., Materials and Methods: Major databases were searched, including Medline, Web of Knowledge, Google Scholar, Scopus, Cochrane, and the Iranian Scientific Information Database for all eligible studies in accordance with specific keywords. The inclusion criteria forthe retrieved studies were determination of graft survival, patient survival, and reasons for graft failure. The exclusion criteria were as follows: (1) a lack of clearresults; (2) non-English or non-Persian language format; (3) lack of access to the full-text manuscripts; and (4) case reports, case series, and review papers. A total of 115 studies were initially assessed based on the keywords; of these, 8 met inclusion criteria and were considered for final analysis; these were published between 2005 and 2017., Results: According to our results, 1-year graft survival rates were overall 89.7%, and 5-year graft survival rates were 65.4%. The 1-year patient survival rates were estimated to be 97.1%, and 5-year patient survival rates were estimated to be 89.8%. Acute rejection, dialysis status before transplant, and inappropriate immunosuppression were the main risk factors., Conclusions: Our systematic review and meta-analysis indicated a high success rate of childhood kidney transplant in Iran according to long-term graft and patient survival rates.

Background: Cystinosis is a multisystemic disease caused by the accumulation of cystine crystals in the kidney and many other organs. This disease most often involves children. Recent developments in the treatment procedures have improved the chance of patients surviving as long as puberty. This study discusses the importance of immediate diagnosis and early treatment of the disease with cystagon, which reduces gastrointestinal complications in such patients. Methods: This descriptive study was performed on 19 adult patients (over 18 years old) with cystinosis who were observed by nephrologists from medical universities throughout Iran. Gastrointestinal complications were studied in the patients. Data were analyzed using SPSS Version 22. Results: The mean age of patients at the time of enrollment was 23.89 ± 5.06 years. Seventeen (89.4%) patients of this group had received renal replacement therapy (3 dialysis, 14 renal transplantation) due to end-stage renal disease and 2 (10.5%) of them were in stages 2 and 3 of chronic kidney disease. Three patients (15.7%) had hepatomegaly and splenomegaly; liver enzymes were normal in all patients. One patient (5.2%) had increased portal vein flow velocities, 2 of the patients (10.5%) underwent percutaneous endoscopic gastrostomy implantation due to severe dysphagia and eventually died. Most gastrointestinal symptoms in patients were nausea and abdominal pain. Conclusion: Early diagnosis and treatment with the proper dose of cystagon can increase life expectancy, reduce complications, and improve the patient's quality of life., Competing Interests: The authors declare that they have no competing interests., (© 2022 Iran University of Medical Sciences.)

Background: Diarrhea-associated-hemolytic-uremic-syndrome (D+HUS) is a common from of HUS. Central-nervous-system (CNS) involvement is one of the most common extrarenal organ involvements in children with D+HUS. This systematic review and meta-analysis aim to recognize the frequency of neurological complications in pts with HUS. Methods: Databases of PubMed, Embase, and Web of Science were searched systematically to find the papers on neurological involvement in HUS pts. Two researchers independently assessed the papers' quality and extracted data. CMA v. 2.2.064. was used for data analysis. Heterogeneity was evaluated using the I-squared (I2) test, and a fixed/random-effects model was used when appropriate. Results: In this review, 21 studies including 2,189 participants with a median age between 1.3-40-year-old, entered the meta-analysis. The meta-analysis in D+HUS patients indicated 27.0% with neurological complications (95% CI, 22.0%-32.6%), 25.5% of symptoms weren't categorized (95% CI, 15.9%-38.3%), 20.8% of them developed the seizures (95% CI, 2.3%-74.4%). In D-HUS pts, 20.8% of them were presented neurological symptoms (95% CI, 17.9%-24.0%), of which 29.0% weren't categorized (95% CI, 19.2%-41.2%), 17.5% of pts got into coma (95% CI, 9.6%-29.7%), 5.6 % showed hemiparesis (95% CI, 2.8%-10.9%), 17.2% experienced lethargy (95% CI, 5.2%-44.1%), 30.5% developed the seizures (95% CI, 18.2%-46.2%), 7.4% manifested speech abnormalities (95% CI, 0.2%-7.22%), 6.4% of D-HUS pts presented visual-disturbances (95% CI, 3.4%-11.6%). Conclusion: This systematic review and meta-analysis indicated more than one-fourth of both D+HUS and D-HUS patients were presented with neurological symptoms, and the most prevalent symptoms were seizures, which can lead to an epilepsy sequel., (© 2021 Iran University of Medical Sciences.)

Hearing loss (HL) is one of the most common sensory defects affecting more than 466 million individuals worldwide. It is clinically and genetically heterogeneous with over 120 genes causing non-syndromic HL identified to date. Here, we performed exome sequencing (ES) on a cohort of Iranian families with no disease-causing variants in known deafness-associated genes after screening with a targeted gene panel. We identified likely causal variants in 20 out of 71 families screened. Fifteen families segregated variants in known deafness-associated genes. Eight families segregated variants in novel candidate genes for HL: DBH, TOP3A, COX18, USP31, TCF19, SCP2, TENM1, and CARMIL1. In the three of these families, intrafamilial locus heterogeneity was observed with variants in both known and novel candidate genes. In aggregate, we were able to identify the underlying genetic cause of HL in nearly 30% of our study cohort using ES. This study corroborates the observation that high-throughput DNA sequencing in populations with high rates of consanguineous marriages represents a more appropriate strategy to elucidate the genetic etiology of heterogeneous conditions such as HL., (© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Background: Thromboembolism is one of the most important and dangerous complications of nephrotic syndrome. This study aimed to determine the value of albumin, anti-thrombin III, fibrinogen and D-dimer factors in the prediction of asymptomatic pulmonary embolism in patients with nephrotic syndrome in non-remission period., Methods: Plasma levels of albumin, anti-thrombin III, fibrinogen and D-dimer were assessed in 30 nephrotic children in non-remission period (including new case-patient or relapse period), and the results were compared with chest X-ray and lung perfusion scintigraphy (Q scan)., Results: The mean age of patients was 6.22 ± 3.5 years (range 2-12 years). Of patients, 23.3% had abnormal findings in perfusion scan suggestive of pulmonary emboli despite absence of any respiratory manifestations. Median plasma albumin and anti-thrombin III levels in patients with asymptomatic pulmonary embolism were lower than in patients without pulmonary embolism. Also, median fibrinogen and D-dimer levels in patients with asymptomatic pulmonary embolism were higher than in patients without pulmonary embolism, with no statistically significant differences between sex, age, hemoglobin and hematocrit of patients and lung perfusion scan results., Conclusion: Patients with abnormal blood levels of albumin (< 3.5 g/dl), anti-thrombin III (< 80 ml/dl), fibrinogen (> 400 ml/dl) and D-dimer (> 0.5 μg/dl) underwent CXR/Q scan and were treated with heparin if there was pulmonary embolism.

Background: Nephronophthisis (NPHP) is a progressive tubulointestinal kidney condition that demonstrates an AR inheritance pattern. Up to now, more than 20 various genes have been detected for NPHP, with NPHP1 as the first one detected. X-prolyl aminopeptidase 3 (XPNPEP3) mutation is related to NPHP-like 1 nephropathy and late onset NPHP., Methods: The proband (index patient) had polyuria, polydipsia and chronic kidney disease and was clinically suspected of NPHP. After the collection of blood sample from proband and her parents, whole exome sequencing (WES) was performed to identify the possible variants in the proband from a consanguineous marriage. The functional importance of variants was estimated by bioinformatic analysis. In the affected proband and her parents, Sanger sequencing was conducted for variants’ confirmation and segregation analysis., Results: Clinical and paraclinical investigations of the patient was not informative. Using WES, we could detect a novel homozygous frameshift mutation in XPNPEP3 (NM&#95;022098.2: c.719&#95;720insA; p. Q241Tfs*13), and by Sanger sequencing, we demonstrated an insertion in XPNPEP3., Conclusion: The homozygous genotype of the novel p.Q241Tfs*31 variant in XPNPEP3 may cause NPHP in the early childhood age.

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia caused by small vessel thrombosis, thrombocytopenia, and renal failure. The common cause of aHUS is a dysregulation in the alternative complement pathway. Mutations in none complement genes such as diacylglycerol kinase epsilon (DGKE) can also result in this syndrome., Case Presentation: Here, we report on a 19-year-old female with the clinical diagnosis of aHUS, who has unaffected consanguineous parents and an older sibling who was deceased from aHUS when she was seven months old. We performed whole exome sequencing (WES) followed by evaluation of detected variants for functional significance, using several online prediction tools. Next, in order to confirm the detected pathogenic variant in proband and segregation analysis in her family, Sanger sequencing was done. The novel variant was analyzed in terms of its impact on the protein 3-dimensional structure by computational structural modeling. The results revealed that the proband carried a novel homozygous missense variant in DGKE located in exon 6 of the gene (NM&#95;003647.3, c.942C > G [p.Asn314Lys]), and in silico analysis anticipated it as damaging. Protein computational study confirmed the influence of potential pathogenic variant on structural stability and protein function., Conclusion: We suggest that some variations in the catalytic domain of DGKE like p.Asn314Lys which can cause alterations in secondary and 3-D structure of protein, might lead to aHUS.

Significant weight gain following renal transplantation is common in adult and pediatric recipients and mostly depends on receiving higher doses of steroids, changes in mood and feelings, as well as their level of physical activities. This study was performed to evaluate body weight and body mass index (BMI) before and after kidney transplantation in children and adolescents. In this cross-sectional study, 71 pediatric renal transplant recipients (42 boys and 29 girls) were included. World Health Organization criteria were used for comparing Z-score BMI for age in our cases. Overweight was defined as Z-score BMI >+1 SD (standard deviation) and obesity as >+2 SD. At the time of transplantation, the mean age was 10.8 ± 3 years (5-16 years) and based on BMIZ-score, the patients were found to be thin (BMIZs <-2 SD) in 16.9%, normal (BMIZs = -2 to +1 SD) in 67.6%, overweight (>+1 SD to +2 SD) in 9.9%, and obese (BMIZs >+2 SD) in 5.6%.The mean follow-up duration after transplantation was 3.57 ± 1.68 years (1-7 years) and at the time of reevaluation after transplant, their mean age was 14.4 years (6-18 years). The mean BMI was 22 ± 5.3 kg/m 2 , and for BMI grouping, the patients were thin in 7%, normal in 54.9%, overweight in 21.1%, and obese in 17%. Pretransplant thinness (BMIZs <-2 SD) was found in 12 patients (16.9%), equally in boys and girls, and in most of them (83.3%), BMIZs changed to normal or even >+1 SD after transplant. Chronic continuous decrease of glomerular filtration rate (CCD/GFR) was found in 27 cases (38%); 74.1% were male (P = 0.045), hypertriglyceridemia was found in 74.1% (P = 0.023%), hypercholesterolemia in 63% (P = 0.032),and obesity in 18.5% (p = 0.5). The incidence of obesity has tripled after kidney transplantation. It was not a risk factor for graft or patient survival in our experience, whereas pretransplant obesity had some effects on long-term graft outcome.

Introduction: Central nervous system (CNS) involvement is the most common extrarenal involvement in hemolytic uremic syndrome (HUS). There are limited reports on clinical cause of chronic neurologic problems in HUS. We evaluated residual neurologic involvement in children with HUS., Materials and Methods: This cross-sectional study was conducted on 58 patients with a diagnosis of HUS referred to 2 tertiary pediatric centers. Neurological examinations was performed on all of the patients and they were followed up between 2001 and 2015. Data including demographic variables, type of HUS, neurological symptoms, and other complications were recorded. Neurological involvements that occurred after 6 months from the acute phase of HUS were considered as chronic neurological involvement., Results:  Among 58 patients who were included in the study, 31 (53.4%) had neurological manifestations (31 with acute and 19 with chronic complications). There was no significant difference in acute neurological manifestations between typical and atypical HUS, while chronic neurological manifestations were more frequents in patients with atypical HUS (P = .05). The most common presentations were seizure and decreased level of consciousness. Chronic neurologic problems were found in follow-up visits of 11 patients with acute and 8 without acute involvement. Hypertension was associated with chronic manifestations (P = .01)., Conclusions: According to our results, residual neurological problems were not infrequent in HUS and they were more related with atypical form of disease. Evidence of hypertension is a significant variable for persistence of neurologic problems.

IGRA has been approved as an alternative in vitro test to diagnose Mycobacterium TB infection. This study aimed to assess the diagnostic value of TST in comparison with QFT assay to detect LTBI among Iranian children candidate for renal transplantation. This cross-sectional study was performed on 31 children who were candidate for renal transplantation admitted to Ali Asghar Children's Hospital and Rasoul Akram Hospital, Tehran, Iran, from 2013 to 2014. TST and QFT were performed for all patients. QFT was negative in all patients, while TST was positive only in one case. Both tests results were negative in 30 patients, yielding an accuracy rate of 96.7% for TST to diagnose LTBI when compared to QFT. In conclusion, compared to QFT, TST is still a valuable diagnostic tool with high accuracy rate for diagnosis of LTBI in children candidates for renal transplantation and can still be used as an accurate test for screening Mycobacterium TB infection., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: There is evidence of the effectiveness of rituximab in treatment of nephrotic syndrome in children. The present study aimed to assess safety and the therapeutic effectiveness of rituximab in steroid- and cyclosporine-resistant pediatric nephrotic syndrome., Materials and Methods: Forty-three children with steroid- and cyclosporine-resistant or steroid- and cyclosporine-dependent noncongenital nephrotic syndrome were included in the study to receive intravenous rituximab, 375 mg/m2/wk, for 4 weeks. The children were followed up for 2 years. Effectiveness was defined as remission of proteinuria in response to rituximab. Side effects of rituximab were monitored., Results: Overall, 23 (57.1%) of the children had steroid- and cyclosporine-resistant nephrotic syndrome, of whom 8 (34.8%) revealed complete response and 3 (13%) revealed partial response. Seven children (16.7%) had late-resistant nephrotic syndrome, of whom 6 (85.7%) revealed complete response and none revealed partial response. Ten children (26.2%) had steroid- and cyclosporine-dependence all of whom revealed complete response to rituximab. Complete response rate was significantly higher in those with drug-dependent pattern than the other groups (P = .002). There was no association between response to rituximab and pathological basis of disease. Side effects were found in 4 patients as leukopenia in 2, alopecia in 1, and eosinophilia in 1., Conclusions: Rituximab is effective for children with nephrotic syndrome with high efficacy and well tolerability, especially in those with steroid- and cyclosporine-dependent nephrotic syndrome.

Background: Nephropathic cystinosis is a rare inherited metabolic disorder leading to progressive renal failure and extra-renal comorbidity. The prognosis relies on early adherence to cysteamine treatment and symptomatic therapies. Developing nations [DiN] experience many challenges for management of cystinosis. The aim of this study was to assess the management characteristics in DiN compared with developed nations [DeN]., Methods: A questionnaire was sent between April 2010 and May 2011 to 87 members of the International Pediatric Nephrology Association, in 50 countries., Results: A total of 213 patients were included from 41 centres in 30 nations (109 from 17 DiN and 104 from 13 DeN). 7% of DiN patients died at a median age of 5 years whereas no death was observed in DeN. DiN patients were older at the time of diagnosis. In DiN, leukocyte cystine measurement was only available in selected cases for diagnosis but never for continuous monitoring. More patients had reached end-stage renal disease in DiN (53.2 vs. 37.9%, p = 0.03), within a shorter time of evolution (8 vs. 10 yrs., p = 0.0008). The earlier the cysteamine treatment, the better the renal outcome, since the median renal survival increased up to 16.1 [12.5-/] yrs. in patients from DeN treated before the age of 2.5 years of age (p = 0.0001). However, the renal survival was not statistically different between DeN and DiN when patients initiated cysteamine after 2.5 years of age. The number of transplantations and the time from onset of ESRD to transplantation were not different in DeN and DiN. More patients were kept under maintenance dialysis in DiN (26% vs.19%, p = 0.02); 79% of patients from DiN vs. 45% in DeN underwent peritoneal dialysis., Conclusions: Major discrepancies between DiN and DeN in the management of nephropathic cystinosis remain a current concern for many patients living in countries with limited financial resources.

Background: Hypertension (HTN) is a late outcome of congenital or acquired renal scar. We used ambulatory blood pressure to assess the early blood pressure abnormalities in children with history of urinary tract infection with various degrees of renal scars., Methods: Between 2009 and 2011, 60 (45 females, 15 males) children aged 5-15 years and height equal or more than 120 cm with previous history of febrile urinary tract infection were entered into the study. All children went on 24-hour ambulatory blood pressure monitoring (24-H ABPM). Updated classification of 24-H ABPM was used to interpret the results., Results: Masked hypertension was detected in 5% of cases, hypertension in 8.4%, and white coat hypertension in 11.7%. Pre-hypertension was seen in 23.3% of children. There was significant correlation between abnormal blood pressure and the severity of renal parenchymal scar (r=0.39, P value=0.004), vesicoureteral reflux (r= 0.34, P value=0.009), microalbuminuria (r= 0.39, P value=0.004), and carotid intima media thickness (r=0.41, P value=0.006)., Conclusions: This study revealed the utility of 24-H ABPM in early detection of hypertension and pre-hypertension in children with severe renal scars and past history of urinary tract infection.

Purpose: In this report, we document the CTNS gene mutations of 28 Iranian patients with nephropathic cystinosis age 1-17 years. All presented initially with severe failure to thrive, polyuria, and polydipsia., Methods: Cystinosis was primarily diagnosed by a pediatric nephrologist and then referred to the Iran University of Medical Sciences genetics clinic for consultation and molecular analysis, which involved polymerase chain reaction (PCR) amplification to determine the presence or absence of the 57-kb founder deletion in CTNS, followed by direct sequencing of the coding exons of CTNS., Results: The common 57-kb deletion was not observed in any of the 28 Iranian patients. In 14 of 28 patients (50%), mutations were observed in exons 6 and 7. No mutation was detected in exon 5, and only one (3.6%) patient with cystinosis showed a previously reported 4-bp deletion in exon 3 of CTNS. Four patients (14.3%) had a previously reported mutation (c.969C>A; p.N323K) in exon 11, and five (18%) had novel homozygous deletions in exon 6 leading to premature truncation of the protein. These deletions included c.323delA; p.Q108RfsX10 in three individuals and c.257-258delCT; p.S86FfsX37 in two cases. Other frame-shift mutations were all novel homozygous single base pair deletion/insertions including one in CTNS exon 9 (c.661insT; p.V221CfsX6), and four (14.3%) in exon 4, i.e., c.92insG; p.V31GfsX28 in two and c.120delC; p.T40TfsX10 in two. In total, we identified eight previously reported mutations and eight novel mutations in our patients. The only detected splice site mutation (IVS3-2A>C) was associated with the insertion mutation in the exon 9., Conclusion: This study, the first molecular genetic analysis of non-ethnic-specific Iranian nephropathic cystinosis patients, may provide guidance for molecular diagnostics of cystinosis in Iran., (Copyright © 2017 Sociedad Española de Nefrología. All rights reserved.)

Background: Countries with culturally accepted consanguinity provide a unique resource for the study of rare recessively inherited genetic diseases. Although hereditary hearing loss (HHL) is not uncommon, it is genetically heterogeneous, with over 85 genes causally implicated in non-syndromic hearing loss (NSHL). This heterogeneity makes many gene-specific types of NSHL exceedingly rare. We sought to define the spectrum of autosomal recessive HHL in Iran by investigating both common and rarely diagnosed deafness-causing genes., Design: Using a custom targeted genomic enrichment (TGE) panel, we simultaneously interrogated all known genetic causes of NSHL in a cohort of 302 GJB2-negative Iranian families., Results: We established a genetic diagnosis for 67% of probands and their families, with over half of all diagnoses attributable to variants in five genes: SLC26A4, MYO15A, MYO7A, CDH23 and PCDH15. As a reflection of the power of consanguinity mapping, 26 genes were identified as causative for NSHL in the Iranian population for the first time. In total, 179 deafness-causing variants were identified in 40 genes in 201 probands, including 110 novel single nucleotide or small insertion-deletion variants and three novel CNV. Several variants represent founder mutations., Conclusion: This study attests to the power of TGE and massively parallel sequencing as a diagnostic tool for the evaluation of hearing loss in Iran, and expands on our understanding of the genetics of HHL in this country. Families negative for variants in the genes represented on this panel represent an excellent cohort for novel gene discovery., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Introduction: Mutations of the anion exchanger 1 (AE1) gene encoding the kidney anion exchanger 1 can result in autosomal dominant or autosomal recessive form of distal renal tubular acidosis (DRTA). This study aimed to report deletion mutations of the AE1 and its impact on Iranian children with DRTA., Materials and Methods: Twelve children with DRTA referred to Ali Asghar Children Hospital were investigated for all AE1 gene exons through polymerase chain reaction amplification, DNA sequencing, and bioinformatics analysis., Results: Eleven of 12 patients (91.7%) showed an alteration in AE1 gene with a real hot spot in its exons 11 or 15. Homozygote and heterozygote deletions were confirmed in exon 15 in 5 (41.7%) and 3 (25.0%), respectively. Two patients (16.7%) showed homozygote deletions in exon 11 of AE1 gene, and 1 patient (8.3%) showed point mutation in exon 11. The 3-dimensional structures of the native and these mutant kidney AE1 proteins were determined by the multitemplate method using the Phyre and Hidden Markov Model algorithms., Conclusions: Parents' consanguinity of these patients reveals that cousins are at a high risk for DRTA. This study is considered as a pilot study showing the importance of AE1 mutations in Iranian children with DRTA and further studies is recommended in this geographic region of the world. These models suggest that alteration in the structures leads to alteration in function and change in the current role of AE1.