A role for VAX2 in correct retinal function revealed by a novel genomic deletion at 2p13.3 causing distal Renal Tubular Acidosis: case report.

BACKGROUND: Distal Renal Tubular Acidosis is a disorder of acid-base regulation caused by functional failure of α-intercalated cells in the distal nephron. The recessive form of the disease (which is usually associated with sensorineural deafness) is attributable to mutations in ATP6V1B1 or ATP6V0A4, which encode the tissue-restricted B1 and a4 subunits of the renal apical H(+)-ATPase. ATP6V1B1 lies adjacent to the gene encoding the homeobox domain protein VAX2, at 2p13.3. To date, no human phenotype has been associated with VAX2 mutations. CASE PRESENTATION: The male Caucasian proband, born of a first cousin marriage, presented at 2 months with failure to thrive, vomiting and poor urine output. No anatomical problems were identified, but investigation revealed hyperchloremic metabolic acidosis with inappropriately alkaline urine and bilateral nephrocalcinosis. Distal Renal Tubular Acidosis was diagnosed and audiometry confirmed hearing loss at 2 years. ATP6V0A4 was excluded from genetic causation by intragenic SNP linkage analysis, but ATP6V1B1 completely failed to PCR-amplify in the patient, suggesting a genomic deletion. Successful amplification of DNA flanking ATP6V1B1 facilitated systematic chromosome walking to ascertain that the proband harbored a homozygous deletion at 2p13.3 encompassing all of ATP6V1B1 and part of VAX2; gene dosage was halved in the parents. This results in the complete deletion of ATP6V1B1 and disruption of the VAX2 open reading frame. Later ocular examinations revealed bilateral rod / cone photoreceptor dystrophy and mild optic atrophy. Similar changes were not detected in an adult harbouring a disruptive mutation in ATP6V1B1. CONCLUSIONS: The genomic deletion reported here is firstly, the only reported example of a whole gene deletion to underlie Distal Renal Tubular Acidosis, where the clinical phenotype is indistinguishable from that of other patients with ATP6V1B1 mutations; secondly, this is the first reported example of a human VAX2 mutation and associated ocular phenotype, supporting speculation in the literature that VAX2 is important for correct retinal functioning.

The value of direct radionuclide cystography in the detection of vesicoureteral reflux in children with normal voiding cystourethrography.

BACKGROUND: Vesicoureteral reflux (VUR) is one of the most important risk factors for urinary tract infection (UTI). Diagnosis and treatment of VUR is important to prevent irreversible complications, such as renal scarring and chronic renal failure. This study was conducted to assess the value of direct radionuclide cystography (DRNC) in the detection of VUR in children with UTI and a normal voiding cystourethrography (VCUG). METHODS: DRNC was performed in 35 children with a normal VCUG after an episode of febrile UTI who had hydronephrosis or hydroureter, abnormal acute dimercaptosuccinic acid (DMSA) scan results and/or febrile UTI recurrence. This study was conducted in the nephrology department of Mofid Children's Hospital, Tehran (Iran). RESULTS: The results were statistically analyzed. Among the 70 ureters studied, 33 (49.1 %) were observed to have VUR. Of these, 17 (51.5 %) had mild, 14 (42.4 %) moderate, and 2 (6.1 %) severe reflux. A significant relationship was observed between DRNC results and DMSA renal scan findings (P < 0.05). CONCLUSIONS: Based on our results, we suggest that DRNC may reveal VUR despite a normal VCUG in children with hydronephrosis, abnormal acute DMSA, and/or recurrent febrile UTI.

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.

Renal transplantation in patients with Bardet-Biedl syndrome.

BACKGROUND: Bardet-Biedl syndrome is an autosomal recessive disorder characterized by obesity, polydactyly of hands and feet, retinitis pigmentosa, hypogenitalism, various degrees of intellectual impairment and renal anomalies. Other clinical features include speech disorder, brachydactyly, developmental delay, polyuria/polydipsia, ataxia, poor coordination/clumsiness, diabetes mellitus, left ventricular hypertrophy, hepatic fibrosis, and renal hypoplasia/dysplasia. If spasticity and mental retardation present, it fulfills the criteria for Laurence-Moon-Bardet-Biedl syndrome. METHODS: Between July 1985 and January 2005, 2,282 kidney transplantations were performed at Labbafinejad Medical Center, of whom 262 were children under 15 years of age (61% males). Among children, five (four females) had Bardet-Biedl syndrome who were transplanted preemptively. Kidneys were taken from living unrelated donors. RESULTS: All five patients had retinitis pigmentosa and obesity with body mass index up to 39.33 kg/m(2). The cause of end-stage renal failure was reflux nephropathy in one, neurogenic bladder in one, and renal hypoplasia/dysplasia in three patients. The mean age at transplantation was 11 years (range: 6-17 years). Immunosuppressives administered were prednisolone, cyclosporine, and mycophenolate mofetil. All of them suffered at least one episode of acute rejection shortly after transplantation but reversed with methylprednisolone pulses; in the last follow-up, the mean creatinine was 1.2 (range: 0.6 - 2.3 mg/dL). The mean glomerular filtration rate before transplantation was 10 mL/min/1.73 m(2); in the last follow-up it was 79 (range: 38-137). CONCLUSION: Renal transplantation is a safe and successful procedure and renal replacement therapy of choice in patients with Bardet-Biedl syndrome and end-stage renal failure, but special attention should be paid to body mass index and steroid-free immunosuppression if other suitable drugs, such as sirolimus and basiliximab are affordable.

Microbial sensitivity pattern in urinary tract infections in children: a single center experience of 1,177 urine cultures.

Urinary tract infection is one of the most common diseases in children. Early diagnosis and comprehensive treatment can significantly decrease late serious complications. Knowledge of the sensitivity and resistance pattern of uropathogens in specific geographical locations is an important factor for choosing suitable antibacterial treatment. This study was conducted in order to evaluate the antibacterial resistance of urinary pathogens at Mofid Children's Hospital between March 2000 and August 2001. Positive urine cultures from 1,177 children aged less than 12 years (mean age, 31.7 months; female to male ratio, 2:1) were studied. Cultures were performed on urine samples obtained by sterile urine bags in infants and midstream urine in older children; if samples were contaminated then a suprapubic sample was taken in infants. Sensitivity was measured by the disc diffusion method using the NCCLS protocol. The most prevalent urinary pathogen was Escherichia coli (666 cases, 56.6%). Overall, the lowest resistance rate of microorganisms was that against ciprofloxacin (6.7%) and the highest resistance rate was that against penicillin (83%). A comparison of these data with those of other countries shows that there is considerable geographic variation in bacterial patterns of sensitivity and resistance properties. Therefore, the selection of antibiotics for empiric therapy should be based on the sensitivity and resistance pattern of uropathogens in the respective city.

Effect of N-acetylcysteine on inflammation biomarkers in pediatric acute pyelonephritis: a randomized controlled trial.

INTRODUCTION: This study was designed to investigate the effect of N-acetylcysteine (NAC), as a potent and safe antioxidant, on inflammatory biomarkers of acute pyelonephritis in pediatric patients. MATERIALS AND METHODS: Children (< 15 years old) admitted with a diagnosis of pyelonephritis were recruited in a randomized placebo-controlled trial. They were randomly allocated to 2 groups and recieved placebo or NAC effervescent tablets with daily dose based on their weight, for 5 days. The children were evaluated for serum procalcitonin level, leukocyte count, C-reactive protein (CRP), serum creatinine, and clinical symptoms on the 1st and the 5th days. RESULTS: Seventy patients, 35 in each group, with a mean age of 5.54 ± 3.10 years completed the study. There was no significant difference between the two groups in the amount of changes in procalcitonin levels after 5 days (P = .90). Within-group analysis confirmed CRP reduction in both groups (P < .001); however, between-group analysis did not show significant difference in CRP reductions, either (P = .65). No significant differences were found between the two groups in the day of resolving pyuria (P = .46), day of resolving bacteriuria (P = .81), or reductions in leukocyte count (P = .64) and neutrophil count (P = .49). CONCLUSIONS: A short period of NAC administration with the recommended doses could not lead to a significant decrease in inflammation biomarkers. Studies on higher doses and longer duration of NAC administration along with evaluation of the long-term effects of the intervention by tools such as renal scntigraphy are suggested.

Serum and Urine Leptin Concentrations in Children Before and After Treatment of Urinary Tract Infection.

INTRODUCTION: Urinary tract infection (UTI) among children is sometimes associated with anorexia and sometimes failure to thrive. Appetite-regulating hormones may be a causative factor. Leptin regulates appetite, food intake, and body weight via hypothalamic melanocortin-4 receptor. Leptin is also a potential cytokine for inflammation. The aim of this study was to evaluate serum and urine leptin before and after treatment of children with UTI. MATERIALS AND METHODS: In this before-after study, serum and urine leptin were measured in 40 patients with UTI at admission and 5 days after treatment. Pyelonephritis was suggested by signs and symptoms and confirmed with positive urine culture and dimercaptosuccinic acid renal scintigraphy. Other measurements included urinalysis, urine culture, urine creatinine level, complete blood count, erythrocyte sedimentation rate, C-reactive protein level and serum levels of urea, creatinine, glucose, cholesterol, and triglyceride. RESULTS: The mean serum leptin level was 6.85 ± 18.90 ng/mL before the treatment and 8.29 ± 18.30 ng/mL after the treatment, the difference of which was not significant (P = .64). There were significant correlations between serum leptin and age, weight, and C-reactive protein. Urine leptin levels were reduced significantly from 0.75 ± 0.82 ng/mL to 0.46 ± 0.27 ng/mL after the treatment (P = .03). A significant correlation was observed between urine leptin level with age and weight. CONCLUSIONS: Serum leptin level did not change significantly after treatment of UTI, but urine leptin significantly decreased. Serum leptin level was higher in patients with anorexia in comparison with children with normal appetite; however, the difference was not significant.

Effects of interleukin 2 receptor blockers on patient and graft survival in renal-transplanted children.

BACKGROUND: Monoclonal antibodies block interleukin-2 receptors on alloantigen-reactive T-Lymphocytes and induce selective immunosuppression. It is postulated that induction therapy with these agents in pediatric transplantation may decrease acute rejection and improve graft survival with no significant side effect or increase in the incidence of viral infections. OBJECTIVES: The aim of this study was to examine the effects of interleukin 2 receptor blockers on patient and graft survival in renal-transplanted children. PATIENTS AND METHODS: One hundred and eighty six children aged 7-13 years who received renal transplantation in university-affiliated hospital between 2003 and 2012 were enrolled in the study. All patients received prednisolone, cyclosporine and mycophenolate mofetil or azathioprine as basic immunosuppressive therapy. Patients were divided into two groups according to receiving induction therapy with IL2-receptor blockers. We investigated for acute rejection episodes, Cytomegalovirus (CMV) and BK virus infection and one and three year's survival of the patients and the grafts. RESULTS: From 186 renal-transplanted children included in this study, 36 patients were in treated group (group 1) and 150 patients in control group (group 2). The mean age of the patients was 10.4 ± 2 years and 55.6% were males. In first six months of transplantation, eight patients in group one had one episode of acute rejection and no one had two episodes. Early acute rejection rate was 8.36 (22%). In the control group, 37 patients had one episode and three patients had two episodes of acute rejection (rejection rate 28.6%). Therefore, early acute rejection rates were lower in group one. Late acute rejection rates did not show any difference in group 1 and group 2 (27.7% vs. 27.3% respectively). There was lower prevalence of steroid-resistance rejection in group 1 patients (5.5%) compared with 6.6% in group 2, but it did not reach statistical significance. None of the patients in IL2-R blocker group died at one year follow-up (patient survival 100%). However, in control group, four (2.6%) patients died toward the end of first year (patient survival 97.4%). When patients in group 1 and group 2 were age and sex matched with equal number the difference was significant (P < 0.05). CONCLUSIONS: Induction therapy with IL2-R blockers reduced the rate of early acute rejection, but had no effect on late acute rejections. Patient and graft survival were better in treated group, but did not reach statistical significance. A longer period of follow-up may be required to discern a clear advantage for induction therapy with these agents.

Diagnostic accuracy of renal pelvic dilatation in determining outcome of congenital hydronephrosis.

INTRODUCTIONS: The widespread use of prenatal ultrasonography results in increased recognition of congenital hydronephrosis, a therapeutic and diagnostic challenge. This study was conducted to investigate the natural course of prenatal hydronephrosis and the accuracy of postnatal APD in determining the outcome. MATERIALS AND METHODS: All newborns with prenatal hydronephrosis were followed up by ultrasonography after birth. Voiding cystoureterography, diethylene triaamine pentaacetic acid renal scintigraphy, and dimercaptosuccinic acid renal scintigraphy were done if indicated. The receiver operating characteristic curve was plotted to determine the best cutoff for the anterior-posterior pelvic diameter (APD) to distinguish surgical from spontaneously resolving group. RESULTS: Of 178 neonates, 42 (23%) required surgery. The area under the curve for APD to predict the need for surgery was 0.925 with an APD cutoff of 15 mm. The diagnostic value of APD for determining the need for surgery was determined by sensitivity and specificity of 95.2% and 73.5%, respectively. CONCLUSIONS: Postnatal APD on ultrasonography has a valuable diagnostic accuracy for requiring surgery and provides a useful guide for parental counseling.

Urinary endothellin-1 level in children with pyelonephritis and hydronephrosis.

Hydronephrosis is a common finding in patients with urinary tract infection (UTI). Endothellin-1 (ET-1) is a potent vasoactive peptide that has vasoconstrictive effects. It has been shown that urinary ET-1 increases in urinary obstructions. In this study, we measured the urinary ET-1 level in patients with UTI and hydronephrosis of various causes. In this case-control study, we evaluated the urinary ET-1 level in 45 patients who had UTI and hydronephrosis, serving as a case group, and 45 patients who had UTI without hydronephrosis, serving as a control group. Urinary ET-1 was quantified using enzyme-linked immunosorbent assay and urinary creatinine (Cr) by Jaffe method. To rule out the effect of urinary flow rate, the urinary ET-1 to Cr correlation was considered for analysis of the results. The mean age of the patients in the case and control groups was 36.5 ± 27.2 and 26.2 ± 15.5 months, respectively (P >0.01). The mean urinary ET-1 was 89.6 ± 41.7 pg/dL in the case group and 29.3 ± 26 pg/dL in the control group, P <0.001. The mean urinary ET-1 was 121 ± 55.4 pg/dL in patients who had grade 4 hydronephrosis. We conclude that urinary ET-1 was significantly higher in the obstructed than in non-obstructed cases. Urinary ET-1 could be a useful marker that can be utilized in young children for diagnosis of hydronephrosis, especially obstructive cases.

Urinary adrenomedullin level in children with acute pyelonephritis before and after treatment.

INTRODUCTION: Adrenomedullin (AM) is a 52-amino acid peptide that causes vasodilatation by increased synthesis of nitric oxide. Its production by different cells such as cardiac myocytes, smooth muscle, endothelial, and oncogenic cells is stimulated by inflammatory processes. It has been shown that in the presence of inflammation in the urinary system, concentration of AM increases. In this study, we measured urinary AM in children with acute pyelonephritis before and after treatment and compared its level with that in healthy children. MATERIALS AND METHODS: In a case-control study, 31 children with clinical and paraclinical documentation of pyelonephritis (case group) and 30 healthy children without pyelonephritis or other infections (control group) were studied. Urinary AM were measured on spot urine samples by high-performance liquid chromatography, and creatinine was measured by spectrophotometry to report the AM-creatinine ratio. RESULTS: Urinary AM-creatinine ratios were 61.3 +/- 119.4 pg/mg and 4.26 +/- 11.4 pg/mg, respectively, in the case and control groups (P = .01). After treatment of pyelonephritis in the patients of the case group, this ratio decreased to 13.1 +/- 21.9 (P = .048). The coefficient correlation between urinary AM and leukocytes count was 0.252 (P = .17). Urinary AM levels were 1896 +/- 1748 pg/dL and 391 +/- 477 pg/dL in the patients with 4+ versus negative C-reactive protein levels, respectively (P = .008). CONCLUSIONS: Urinary AM increases in the course of pyelonephritis and decreases significantly after treatment.

Protective effect of heparin and aspirin against vascular thrombosis in pediatric kidney transplants.

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.

Biochemical risk factors for stone formation in healthy school children.

Prevalence of urolithiasis in childhood is increasing. The wide geographic variation in the incidence of lithiasis in childhood is related to climatic, dietary, and socioeconomic factors. Many children with stone disease have a metabolic abnormality. In Southeast Asia, urinary calculi are endemic and are related to dietary factors. The main aim of this study was to determine the prevalence of renal stone, urine metabolic abnormality, control of blood pressure and demographic character in elementary school children of Qom. A cross sectional study was performed on 110 primary school children (56 girls and 54 boys) aged 7 to 11 years old. Demographic data such as age, height, weight were gathered, and systolic and diastolic blood pressure, Urine analysis and culture, urinary levels of calcium, creatinine, phosphorus, magnesium, sodium, potassium, uric acid, cystine, citrate, oxalate, protein and sonographic findings were evaluated. The mean (±SD) of age was 8.85±1.51 years. Only one child had renal stone (1%), but the prevalence of abnormal renal sonography was 7%. The most prevalent urine metabolic abnormalities were hypercalciuria (23%) and hypocitraturia (100%). 11.2% of children had positive urine culture that all were female. The prevalence of high blood pressure was 7.1% for girls and 11.1% for boys. The prevalence of renal stone in children in this study was 1%, which means the accurate judgment about the prevalence of renal stone in Qom city needs more comprehensive studies. Similar to other studies in Iran this study shows that the prevalence of hypercalciuria is significantly higher comparing to other countries, it may be associated with excessive intake of sodium.

Role of vitamin A in preventing renal scarring after acute pyelonephritis.

INTRODUCTION: The role of vitamin A in re-epithelialization of the damaged mucosal surfaces has been documented. The aim of this study was to evaluate the role of vitamin A in preventing renal scaring after acute pyelonephritis in children. MATERIALS AND METHODS: This clinical trial study was conducted in children with acute pyelonephritis in Mofid Children Hospital (Tehran, Iran). Patients were randomly divided into two groups to receive ceftriaxone and vitamin A or ceftriaxone only. Dimercaptosuccinic acid (DMSA) renal scintigraphy was performed before the start of the treatment and 6 months later. Results were compared for renal scaring between the two groups. RESULTS: Seventy-six patients (11 boys and 65 girls) were enrolled. The mean age was 25 ± 24 months and 54 patients (71.1%) were under 2 years old. The average vitamin A level was 71 ± 24 microg/dL in the treatment group and it was 62 ± 18 µg/dL in the control group. Baseline DMSA scans were comparable between the two groups in terms of scarring (P = .53), but the second DMSA scans showed a significant change in progression of the renal injury and scaring in the control group compared to those treated with vitamin A as well as antibiotic (P < .001). CONCLUSIONS: We found administration of the vitamin A was useful in decreasing the amount of the injury and scarring following the pyelonephritis. Based on our study, vitamin A can be used in conjunction with other treatments in the management of acute pyelonephritis in children.

Distal renal tubular acidosis and its relationship with hearing loss in children: preliminary report.

INTRODUCTION: In autosomal recessive distal renal tubular acidosis (DRTA), a substantial fraction of the patients have progressive bilateral sensorineural hearing loss. This coexistence is due to the mutations of a gene expressed both in the kidney and in the cochlea. The aim of this study was to assess the correlation between hearing loss and DRTA. MATERIALS AND METHODS: In this study, 51 children diagnosed with renal tubular acidosis were evaluated. Diagnosis of DRTA was based on clinical manifestations and detection of normal anion gap metabolic acidosis, urine pH higher than 5.5, and positive urinary anion gap. Audiometry was performed in children with DRTA and sequencing of the ATP6V1B1 gene was done for those with sensorineural hearing loss. RESULTS: Twenty-seven patients (52.9%) had DRTA, of whom 51.9% were younger than 1 year old, 55.6% were boys, and 44.4% were girls. Eleven patients (40.7%) had bilateral sensorineural hearing loss, consisting of 5 of 15 boys (33.3%) and 6 of 12 girls (50.0%). There was no correlation between hearing loss and gender. Three patients with hearing loss had mutation in the ATP6V1B1 gene (11.1% of patients with DRTA and 27.3% of patients with DRTA and hearing loss). CONCLUSIONS: This study indicated that a significant percentage of the children with DRTA had sensorineural hearing loss and mutation in ATP6V1B1 gene. It is recommended to investigate hearing impairment in all children with DRTA.

Technetium Tc 99m dimercaptosuccinic acid renal scintigraphy in children with acute pyelonephritis: correlation with other imaging tests.

INTRODUCTION. Urinary tract infection is the most common serious bacterial infection in children. The aim of this study was to compare the value of different laboratory and imaging techniques in detecting renal involvement in acute pyelonephritis. MATERIALS AND METHODS. In a cross-sectional study of patients 1 month to 14 years of age diagnosed with urinary tract infection were examined with systemic inflammatory markers, renal ultrasonography, voiding cystourethrography (VCUG), and technetium Tc 99m dimercaptosuccinic acid ((99m)Tc-DMSA) renal scintigraphy. A total of 1467 pediatric patients were eligible for treatment of pyelonephritis. Evaluations included a complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), urinalysis, urine culture, and measurement of serum blood urea nitrogen and creatinine levels. RESULTS. The results of (99m)Tc-DMSA scans were normal in 20.2%, mild decreased cortical uptake in 45.0%, moderate decreased cortical uptake in 12.3%, severe decreased cortical uptake in 12.0%, and decreased cortical function plus irregularity or scar formation in 10.5%. Voiding cystourethrography showed vesicoureteral reflux in 25.9%. The sensitivity of (99m)Tc-DMSA for prediction of vesicoureteral reflux was 84.1% with a negative predictive value of 80.6%. Significant differences were found in the level of blood leukocyte count (P = .03), urine leukocyte count (P = .003), ESR (P = .008), and age (P = .04) between patients with normal and abnormal (99m)Tc-DMSA scan results. CONCLUSIONS. We found that in patient with clinical signs of pyelonephritis, (99m)Tc-DMSA renal scintigraphy can detect pyelonephritis more accurately than the other inflammatory and imaging tests.

Senior-Loken syndrome in an Iranian family.

Senior-Loken syndrome is a rare entity that combines familial juvenile nephronophthisis with retinal dystrophy. Herein, we report Senior-Loken syndrome in six members of an Iranian family with progressive blindness and renal failure since childhood. Although, this syndrome was reported from other parts of the world, report of six members of one family with this syndrome is rare. To the best of our knowledge, this is the first report from Iran.

Diagnostic potential of urinary tumor necrosis factor-alpha in children with acute pyelonephritis.

INTRODUCTION: Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of the inflammatory response in serious bacterial infections. The aim of this study was to evaluate the potential of urinary TNF-alpha for diagnosis of acute pyelonephritis in children. MATERIALS AND METHODS: This study was conducted from March 2006 to December 2007 on children with confirmed diagnosis of acute pyelonephritis. They all had positive renal scintigraphy scans for pyelonephritis and leukocyturia. The ratios of urinary TNF-alpha to urine creatinine level were determined and compared in patients before and after antibiotic therapy. RESULTS: Eighty-two children (13 boys and 69 girls) with acute pyelonephritis were evaluated. The mean pretreatment ratio of urinary TNF-alpha to urinary creatinine level was higher than that 3 days after starting on empirical treatment (P = .03). The sensitivity of this parameter was 91% for diagnosis of acute pyelonephritis when compared with demercaptosuccinic acid renal scintigraphy as gold standard. CONCLUSIONS: Based on our findings in children, the level of urinary TNF-alpha-creatinine ratio is acute increased in pyelonephritis and it decreases after appropriate therapy with a high sensitivity for early diagnosis of the disease. Further research is warranted for shedding light on the potential diagnostic role of urinary TNF-alpha in pyelonephritis in children.

Urinary N-acetyl-beta-D-glucosaminidase as a diagnostic marker of acute pyelonephritis in children.

INTRODUCTION: Prompt diagnosis and localization of pyelonephritis are of great importance in children. The urinary excretion of enzymes, and in particular N-acetyl-beta-D-glucosaminidase (NAG), is considered a simple noninvasive marker for detection of renal tubular dysfunction due to pyelonephritis. This study was performed to determine the diagnostic value of urinary NAG in acute pyelonephritis. MATERIALS AND METHODS: In a quasi-experimental study conducted on 72 children with confirmed pyelonephritis, we measured urinary NAG, creatinine, and NAG-creatinine ratio before and after the treatment. Diagnostic values of these parameters were evaluated by considering the patients before and after the treatment as disease-positive and disease-negative groups, respectively. RESULTS: The patients were 18 boys (25.0%) and 54 girls (75.0%) with a mean age of 43.0 +/- 39.0 months. The mean levels of urinary NAG were 12.20 +/- 6.14 U/L and 5.46 +/- 7.98 U/L before and after the treatment, respectively (P < .001). The sensitivity and specificity of urinary NAG-creatinine ratio for diagnosis of pyelonephritis were 73.6% and 77.3%, respectively, with a cutoff point of 10.16 U/g (area under the curve = 0.76, 95% confidence interval, 0.67 to 0.76). Significantly higher levels of urinary NAG were found in those who had a negative urine culture at diagnosis (8.8 +/- 10.4 U/L) compared to those with a positive urine culture (4.5 +/- 8.7 U/L). CONCLUSIONS: We concluded that urinary NAG is elevated in children with pyelonephritis and it can be considered as a further criterion in the diagnosis of upper urinary tract infection.

Urinary interleukin-8 in acute pyelonephritis of children: a before-after study.

INTRODUCTION: The aim of this study was to assess urinary interleukin-8 (IL-8) levels in pyelonephritis and its relation with the clinical course of the infection and of inflammatory changes detected by renal scintigraphy. MATERIALS AND METHODS: In this quasi-experimental before-after study, we evaluated 91 children aged 1 to 144 months (mean 34.4 +/- 35.2 months) with pyelonephritis. Inflammatory markers including erythrocyte sedimentation rate, C-reactive protein, leukocyte count, and urinary IL-8, together with the results of ultrasonography, voiding cystourethrography, and dimercaptosuccinic acid renal scintigraphy were evaluated in these children. The ratios of urinary IL-8 to creatinine (IL-8/C) before and after the treatment were compared with each other. RESULTS: Urinary IL-8/C levels were significantly higher after the empirical treatment in comparison with those before the treatment (0.19 +/- 0.21 versus 0.51 +/- 0.53, P < .001). No correlation was found between the urinary IL-8 levels and leukocyturia, urine culture results, other inflammatory markers, or findings of imaging examinations. CONCLUSIONS: We found high urinary IL-8 levels in children with pyelonephritis. We also documented its increasing after the treatment. We conclude that evaluation of urinary IL-8 can be a noninvasive test for diagnosis of upper urinary tract infection and its response to treatment.