Assessment of Urinary and Serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels as Novel Predictors for Vesicoureteral Reflux Diagnosis in Children with Febrile Urinary Tract Infection.

Background: The invasive, expensive, and time-consuming nature of radiological examinations for vesicoureteral reflux (VUR) has compelled researchers to search for new markers to predict VUR. This study was designed to evaluate the usefulness of serum and urine concentrations of neutrophil gelatinase-associated lipocalin (NGAL) in predicting the existence of VUR. Methods: This cross-sectional study involved all patients with a first febrile urinary tract infection (UTI) referred to Ali Asghar Children's Hospital. Each patient included in the study had clinical symptoms of pyelonephritis and a positive urine culture. The patients were divided into 2 groups: VUR and non-VUR. The serum and urinary NGAL levels were calculated in both groups. The receiver operating characteristic (ROC) curve was used to look for serum and urinary NGAL cut-points that differentiated the VUR group from the non-VUR group. Results: Among the 40 children in the study, 23 belonged to the VUR group. The median age was 2.5 years (range, 0.3-8 years), and 35 patients were girls. ROC curve analysis showed that only the urinary NGAL level was significantly related to VUR. There was no association between serum NGAL levels and VUR. According to the ROC curve, a urinary NGAL level cut-off value of 15 ng/mL was likely to be diagnostic of VUR with 82.6% sensitivity and 58.8% specificity. Conclusion: The urinary NGAL level, specifically with a cut-off value of 15 ng/mL, can indicate the existence of VUR in patients with UTI with near-acceptable levels of sensitivity and specificity.

Etiology and Antimicrobial Susceptibility Pattern of Urinary Tract Infection in the First Year after Pediatric Renal Transplantation: A Preliminary Study.

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.

Gastrointestinal Manifestations of Adult Cystinosis in Iran: A Descriptive Study.

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.

Exome sequencing utility in defining the genetic landscape of hearing loss and novel-gene discovery in Iran.

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.

Determination of the value of albumin, anti-thrombin III, fibrinogen and D-dimer factors in the diagnosis of asymptomatic pulmonary embolism in patients with nephrotic syndrome.

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.

Frequency of neurological involvement in patients with/without diarrhea hemolytic uremic syndrome: A Systematic review and meta-analysis.

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.

Whole exome sequencing revealed a novel homozygous variant in the DGKE catalytic domain: a case report of familial hemolytic uremic syndrome.

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_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.

Comparison of tuberculin skin test and interferon gamma release assay for diagnosis of latent tuberculosis infection in pediatric candidates of renal transplantation.

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.

Worldwide view of nephropathic cystinosis: results from a survey from 30 countries.

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.

The prevalence of hypertension in children with renal scars.

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.

Characterising the spectrum of autosomal recessive hereditary hearing loss in Iran.

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.

Are serum and urine neutrophil gelatinase-associated lipocalin predictive of renal graft function in short term?

NGAL is a member of the lipocalin protein family that has diverse function but similar structure. The functions of NGAL are not clear, but it appears to be expressed in stress conditions and in tissues undergoing involution. Varied studies have shown increased levels of plasma or urinary NGAL in diverse renal damages. The aim of this study was the serial measurement of serum and urinary NGAL within the first week after renal transplantation in children to predict immediate and short-term graft function. A total of 27 patients were assessed. These patients were classified into those with rapid reduction in serum creatinine (more than 50% reduction in serum creatinine in the first day after transplantation) and patients with slow reduction in serum creatinine (<50% reduction in serum creatinine). We also assessed the absolute reduction in serum creatinine before and after transplantation. Serum and urinary NGAL on the first day post-transplantation were higher in recipients with slow reduction in serum creatinine (urinary NGAL at the first day: 197 ± 153 [s.e.m.] vs. 22.54 ± 8.5 [s.e.m.], p = 0.04; serum NGAL at the first day: 199 vs. 69.8, p = 0.003). The cutoff point of serum NGAL at the first day after transplantation for prediction of slow creatinine reduction was 174 ng/mL with a sensitivity of 100% and specificity of 95.5%. However, we did not find association between the absolute reduction in serum creatinine before and after transplantation with the amount of serum and urinary NGAL post-transplant. Additionally, we did not find any effect of high serum and urine NGAL concentration on the graft function at the first year post-transplant. Although it is supposed that high serum and urine NGAL may predict ischemia of graft in early phases; however, it appears that this mild ischemic injury to graft without DGF or SGF cannot affect the graft function in short-term period. Further studies are needed using larger transplant recipients in pediatric age group. It is also needed to determine the effects of mild ischemic injuries on the graft function in long-term period in future studies.

Long-Term Outcome of Kidney Transplant Among Iranian Children: A Systematic Review and Meta-Analysis.

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.

Genetic diagnosis of Bartter syndrome in Iranian patients and detection of a novel homozygous CLCNKB mutation.

An Iranian girl with clinical symptoms of Bartter syndrome like hypokalemia, polyuria, polydipsia, hyponatremia, and hypochloremic alkalosis was referred to us in whom the CLCNKB gene was genetically evaluated using Sanger sequencing. A homozygous pathogenic variant of c.1332_1335delCTCT was detected in this patient.

Outcome of renal transplantation in children: a multi-center national report from Iran.

The outcome of pediatric renal transplantation was previously reported by a single-center study at the year 2006. Therefore, we aimed to evaluate and report the characteristics and outcome of renal pediatric renal transplantation in a multi-center nationwide study. In this nationwide report, medical records of 907 children (≤18yr) with renal transplantation in eight major pediatric transplant centers of Iran were recorded. These 907 patients received a total of 922 transplants. All children who failed to follow-up were excluded. Rather than baseline characteristics, graft and patient outcomes were considered for survival analysis. For further analysis, they were divided into two groups: patients who had graft survival time more than 10yr (n=91) and the ones with graft survival time of equal or less than 10yr (n=831). Of 922 recipients, 515 (55.8%) were boys and 407 (44.2%) were girls with the mean age of 13.10 (s.d.=3.54) yr. DGF and AR were occurred in 10% and 39.5% of the transplanted children, respectively. Transplantation year, dialyzing status before transplantation, DGF, and AR were significant enough to predict graft survival in cox regression model (overall model: p<0.001). Nowadays, there is a successful live donor pediatric renal transplantation in Iran. Graft survival has improved in our recipients and now the graft survival rates are near to international standards.

Evaluation of combined left ventricular function using the myocardial performance index in children with chronic kidney disease.

BACKGROUND: Myocardial dysfunction that complicates the initial stages of chronic kidney disease (CKD) has not been yet fully characterized in young patients. We aimed to assess the clinical usefulness of myocardial performance index obtained by pulsed-wave Doppler method (PWD-MPI) in predicting early disturbances of global left ventricular (LV) function in children with CKD stages 2-4. In addition, we evaluated the clinical utility of tissue Doppler imaging (TDI) as a tool for calculating MPI in comparison with the conventional method. METHODS: Standard echocardiography was performed in 34 patients aged 3-18 years and for 35 age-matched healthy control subjects. PWD-MPI was calculated from Doppler spectra of mitral inflow and LV outflow. To obtain TDI-MPI, time intervals were measured from mitral annulus. RESULTS: The mean values of both PWD-MPI and TDI-MPI of the patients were significantly different from those of the control subjects. Using receiver operating characteristics curve analysis, TDI-MPI yielded a better predictive discrimination for separating patients with versus those without myocardial dysfunction than PWD-MPI. Using a PWD-MPI >0.36 as the cutoff value, myocardial dysfunction was found with a sensitivity of 64.7% and specificity of 97%. The sensitivity and specificity of TDI-MPI >0.34 in identification of LV dysfunction were 91% and 82%, respectively. TDI-MPI was correlated with that measured by PWD (P < 0.004, r = 0.57). CONCLUSIONS: Subtle abnormalities of LV function develop early when renal insufficiency is mild to moderate. MPI, measuring by PWD and TDI, are appropriate indicators of overall LV function in young patients with CKD.

Short-term and long-term effects of slow graft function on graft survival in pediatric live donor renal transplantation.

SGF generally has early and long-term consequences for allograft survival. Limited studies have been performed on SGF and its complications in pediatric renal transplantation. Therefore, 230 children who received transplants between 1985 and 2005 in Labafi Nejad hospital were included in this study. SGF was defined if the serum creatinine level increased, remained unchanged, or decreased by <10% per day immediately after surgery during three consecutive days in the first week after transplantation. The children were divided into two groups: 183 children in group A (non-SGF) and 47 patients in group B (SGF). The impact of SGF on renal function within the first year, long-term graft survival and post-transplantation complications were analyzed and compared using logistic regression model and Kaplan-Meier survival analysis. The incidence of graft failure at the end of follow-up period was significantly more common in SGF group (53.2% vs. 22.4%, p < 0.001). The median survival time was 140.25 (s.e.m. = 19.35) months in group A (non-SGF) and 60 (s.e.m. = 17.90) months in group B (SGF) (p < 0.001). The graft survival rate was 94.9%, 91.9%, 83.9%, 79.2%, and 72% at one, three, five, seven, and twelve yr after transplantation in children without SGF vs. 75.6%, 53.2%, 47.2%, 40% at one, three, five, and seven yr after transplantation in patients with SGF. The results of our study showed that slow graft function could remarkably affect graft survival and worsen both short-term and long-term transplantation outcomes. Thus, the prevention of SGF is one of the most important issues in graft survival improvement.

Whole Exome Sequencing Reveals a XPNPEP3 Novel Mutation Causing Nephronophthisis in a Pediatric Patient

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_022098.2: c.719_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.

Changes in body mass index after pediatric renal transplantation.

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/m2, 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.

Outcome of living donor renal allograft survival in children with focal segmental glomerulosclerosis.

FSGS is the most frequent GN that may recur in a renal allograft. Compared with adults, the impact of FSGS on graft survival appears to be more significant in children. Thus we decided to assess graft survival and complications after renal transplantation in children with FSGS. Outcome of renal transplantation in 25 children with FSGS who received a renal transplant at Labafi Nejad Hospital was studied and compared with 75 patients as a control group. The mean follow-up duration was 68.16 (s.d. = 41.93) months. Other than demographics, variables such as DGF, acute rejection, number of acute rejection episodes, and graft failure in both groups were evaluated. Acute rejection was seen in 22/25 (88%) of FSGS group, compared to 40/75 (53.3%) in the control group. This difference was statistically significant (p = 0.001). DGF was seen in 4/25 (16%) and 13/75 (17.3%) in the FSGS and control groups, respectively (p = N.S.). The mean graft survival time was 115.61 (s.e.m. = 12.56) and 155.56 (s.e.m. = 7.16) month in FSGS and control group, respectively (p = N.S.). We demonstrated that graft function and survival were not significantly different in the FSGS and control patients. However, acute rejection episodes were more common in FSGS patients but without a significant impact on graft survival.