Chronic Kidney Disease in Iran: First Report of the National Registry in Children and Adolescences.

PURPOSE: Knowing the epidemiological aspects of chronic kidney disease (CKD) in children is crucial for early recognition, identification of reversible causes, and prognosis. Here, we report the epidemiological characteristics of childhood CKD in Iran. MATERIALS AND METHODS: This cross-sectional study was conducted during 1991 - 2009. The data were collected using the information in the Iranian Pediatric Registry of Chronic Kidney Disease (IPRCKD) core dataset. RESULTS: A total of 1247 children were registered. The mean age of the children at registration was 0.69 ± 4.72 years (range, 0.25 -18 years), 7.79 ± 3.18 years for hemodialysis (HD), 4.24 ± 1.86 years for continuous ambulatory peritoneal dialysis (CAPD), and 3.4±1.95 years for the children who underwent the renal transplantation (RT) (P < .001). The mean year of follow-up was 7.19 ± 4.65 years. The mean annual incidence of CKD 2-5 stages was 3.34 per million age-related population (pmarp). The mean prevalence of CKD 2-5 stages was 21.95 (pmarp). The cumulative 1-, 5-, and 10-year patients' survival rates were 98.3%, 90.7%, and 84.8%, respectively. The etiology of the CKD included the congenital anomalies of the kidney and urinary tract (CAKUT) (40.01%), glomerulopathy (19.00%), unknown cause (18.28%), and cystic/hereditary/congenital disease (11.14%). CONCLUSION: The incidence and prevalence rate of pediatric CKD in Iran is relatively lower than those reported in Europe and other similar studies. CAKUT was the main cause of the CKD. Appropriate management of CAKUT including early urological intervention is required to preserve the renal function. Herein, the long-term survival rate was higher among the children with CKD than the literature.

MEFV mutations in Iranian Azari Turkish patients with Henoch-Schönlein purpura.

BACKGROUND/AIM: The aim of the current study was to screen the rate of MEFV mutations in Henoch-Schönlein purpura (HSP) and to investigate the association of these mutations plus clinical symptoms with HSP disease in the Iranian Azari Turkish ethnic group. MATERIALS AND METHODS: The study groups included 40 unrelated HSP patients and 200 apparently healthy people without any kind of inflammatory diseases as a control group. Molecular screening was performed for eight main mutations, namely M694V, M694I, M680I, V726A, E148Q, R761H, P396S, and R408Q, using polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and sequencing. RESULTS: Out of the 40 studied patients, 27 subjects (67.5%) did not show any mutation, whereas 10 patients (25%) were heterozygotes for one of the following mutations: M694V, M680I, V726A, E148Q. Moreover, three patients (7.5%) were compound heterozygotes for P369S and R408Q. The significant differences between the patient and control groups for M680I, V726A, E148Q, P396S, and R408Q were P = 0.0043, P = 0.0324, P = 0.0145, P = 0.0043, and P = 0.0043, respectively. Furthermore, no significant difference in clinical manifestations was observed between the two groups of patients with and without mutations. CONCLUSION: Based on the results, MEFV mutations could be considered effective genetic factors for development of HSP in the Iranian Azari Turkish ethnic group.

Chemokine MCP1/CCL2 gene polymorphism influences Henoch-Schönlein purpura susceptibility in Iranian Azeri-Turkish patients.

BACKGROUND: Henoch-Schönlein purpura (HSP) is the most common small-vessel vasculitis and mainly affects children. Although its pathophysiology is unknown, several studies have indicated the possible involvement of infections and genetic factors in the development of HSP. The human leukocyte antigen (HLA) gene family and several other genes involved in the inflammatory system have been studied. The CCL2 gene, encoding chemokine monocyte chemo-attractant protein 1 (MCP-1/CCL2), is one of several cytokine genes clustered on chromosome 17. The encoded protein displays chemotactic activity for monocytes. METHODS: This is a case-control study comparing 36 children diagnosed with HSP within the Iranian Azeri-Turkish ethnic population and 50 healthy adults from the same ethnic group. CCL2, C-2518T polymorphism genotypes were determined by polymerase chain reaction and by PVUII restriction enzyme analysis and subsequent agarose gel electrophoresis. RESULTS: Our results showed a significant association between the allelic and genotypic frequency of this gene and HSP disease in this cohort. The results of this study indicate that frequencies of the T allele of CCL2 (P = 0.015) and the TT genotype (P = 0.004) are significantly higher in HSP patients. A comparison of clinical symptoms and laboratory data with CCL2 C-2518T polymorphism showed that patients with the TT genotype presented a higher clinical score and more severe clinical features. CONCLUSIONS: MCP1/CCL2 C-2518T gene polymorphism is associated with susceptibility to HSP. This is the first study to report a significant association between MCP1/CCL2 C-2518T and a susceptibility to HSP in this population.

Usefulness of serum procalcitonin level for prediction of vesicoureteral reflux in pediatric urinary tract infection.

INTRODUCTION: Procalcitonin is a sensitive biomarker for bacterial infections. Recent studies show a correlation between serum procalcitonin level and vesicoureteral reflux (VUR). The aim of this study was to evaluate the predictive value of procalcitonin in diagnosis of VUR in children with febrile urinary tract infection. MATERIAL AND METHODS: One hundred and eight children aged 2 month to 12 years with febrile urinary tract infection were evaluated. Serum procalcitonin was measured before initiation of antibiotics. Standard voiding cystourethrography (VCUG) was performed in all children as the gold standard for detection of VUR. Sensitivity and specificity of a high procalcitonin level was evaluated using the receiver operating characteristic curve. RESULTS: Forty-eight patients (44%) had VUR at least in one kidney, including grade 1 to 2 in 12 patients (11.1%), grade 3 in 16 (14.8%), and grade 4 to 5 in 20 patients (18.5%). Procalcitonin level ranged from 0.05 ng/mL to 13.6 ng/mL. Procalcitonin level was significantly higher with increasing the grading of reflux. Comparing procalcitonin levels with VCUG results, a sensitivity of 97% and a specificity of 75% was obtained at a procalcitonin level of 0.59 ng/mL for diagnosis of VUR. There was a significant correlation between procalcitonin level and leukocytosis, erythrocyte sedimentation rate, and C-reactive protein. CONCLUSIONS: A high procalcitonin level may be used for prediction of all grades of VUR in children with febrile urinary tract infection. A low procalcitonin level may be used for avoidance of unnecessary VCUG in some low-risk patients.

Steroid response pattern and outcome of pediatric idiopathic nephrotic syndrome: a single-center experience in northwest Iran.

AIMS: Characteristics of nephrotic syndrome (NS) in children varies in different geographical areas based on genetic and environmental factors. The aim of this study is to evaluate the steroid response pattern and outcome of idiopathic NS (INS) in a pediatric referral hospital in northwest Iran. METHODS: Medical records of all admitted children under 14 years of age with INS in the Children's Hospital of Tabriz, Iran, from 1999 to 2010 were studied retrospectively. Demographics, pattern of response to medications, recurrence rate, histopathology, and outcome were documented. RESULTS: A total of 165 patients with INS, with a mean age of 4.98 ± 2.61 years were studied. Male to female ratio was 2:1. Duration of follow-up was 5.36 ± 2.2 years (1-10 years). A total of 124 patients (75.2%) responded to steroids, and 41 patients (24.8%) were steroid resistant. Frequency of hematuria (P = 0.01) and steroid resistance (P = 0.005) in girls was significantly higher than boys. Patients with steroid resistance had a higher frequency of hematuria (P = 0.001) and a higher mean age (P = 0.017) in comparison with steroid responders. Renal biopsy carried out in 49 patients (29.7%) revealed minimal change in NS in 20 (40.8%), focal segmental glomerulosclerosis in 16 (32.7%), and mesangial proliferation in 11 (22.5%) patients. Twenty-two steroid resistant patients (13%) achieved remission with other immunosupressives. Nineteen patients (11.5%) were resistant to all treatment modalities; of these, nine (5.4%) progressed to end-stage renal disease, and 10 (6%) continued nephrotic range proteinuria. Seven patients (4.2%) died. Of the 146 patients who achieved remission with any one of the treatment modalities, 91 patients (62.3%) experienced at least one recurrence episode, 15 patients (10.3%) were frequent relapsers, and 12 patients (8.2%) were steroid dependent. Higher age at onset of NS was associated with lower relapse rate (P = 0.04). CONCLUSION: Demographics, histological features, and outcome of INS in our area were similar to western countries. In the present study, risk of steroid resistance was higher in girls than boys.

Auditory brain stem response and otoacoustic emission results in children with end-stage renal disease.

BACKGROUND: Abnormalities in auditory system are frequent in patients with end stage renal disease (ESRD). There is not yet any consensus for the effect of renal failure and hemodialysis on auditory complications. The aim of this study was to evaluate the auditory abnormalities in pediatric ESRD patients undergoing long term hemodialysis and compare the results with those of nondialytic chronic renal failure (CRF) children and controls. METHODS: Children aged 1-16 years were evaluated in three groups: 25 ESRD patients undergoing hemodialysis, 25 nondialytic patients with CRF, and 25 age and sex-matched normal counterparts. Patients with history of otological diseases, ear trauma, diabetes mellitus, receiving ototoxic drugs and syndromes with hearing abnormalities were excluded. The auditory brainstem response (ABR) and otoacoustic emission (OAE) were tested in all subjects. Frequency of cases with abnormal findings was compared between the groups. RESULTS: The ABR testing was abnormal in 11 (44%) dialytic patients with normal results in all nondialytic CRF cases and controls (p<0.001). The OAE testing was abnormal in all dialytic patients with abnormal ABR testing results (44%), in 1 (4%) nondialytic CRF patient and in no controls (p<0.001). There ware no significant differences with regard to age, gender, height, weight, blood pressure, serum levels of blood urea nitrogen (BUN), creatinine, sodium, and potassium, glomerular filtration rate (GFR), duration of dialysis and dialysis adequacy between dialytic patients with and without abnormal results of ABR/OAE testing. CONCLUSION: Sensorineural hearing loss is rare among nondialytic pediatric patients with CRF but very common in ESRD children undergoing long term dialysis.

Acute kidney failure in neonatal period.

INTRODUCTION: Acute kidney failure (AKF) is a common clinical problem in neonatal intensive care units and is usually associated with a contributing condition such as sepsis, asphyxia, and heart failure. The aim of this study was to determine the types, frequency of associated contributing conditions, and short-term outcome of neonatal AKF. MATERIALS AND METHODS: Medical records of neonates with a diagnosis of AKF from March 2003 to September 2006 were studied in a tertiary care children's hospital in Tabriz, Iran. RESULTS: Of 6042 hospitalized neonates, 151 with documented AKF (100 boys and 51 girls) were reviewed in the study. Ninety-one patients (60.3%) had been referred from other cities. Fifty-seven patients (37.7%) developed AKF following a surgery. Causes of AKF were intrinsic kidney failure in 52.3%, prerenal in 42.4%, and postrenal in 5.3%. Oliguria was observed in 72.2% of the patients. Perinatal asphyxia was present in 29.8% of the neonates, sepsis in 28.5%, respiratory distress syndrome in 25.2%, dehydration in 24.2%, and heart failure in 21.2%. Most patients (85.4%) had more than 1 associated contributing condition. Mortality rate was 20.5%. Most patients (76.2%) were discharged with normal kidney function and 3.3% with diminished kidney function. Initial admission to NICU, female sex, septicemia, and the need for mechanical ventilation were associated with a higher mortality rate. CONCLUSIONS: The frequency of associated contributing conditions and short-term outcome of neonatal AKF in our institution is comparable with other studies; however, intrinsic kidney failure comprises the most common form of AKF in our patients.

Fatty liver in children.

AIMS: The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran. METHODS: In this cross-sectional study all subjects aged between six months to 15 years that were referred to the sonography unit, were investigated for fatty liver from March 2005 to August 2006. Patients with fatty liver change underwent detailed clinical and laboratory evaluation. RESULTS: From 1500 children who were investigated, 34 subjects with sonographic evidence of fatty liver were enrolled in this study (2.3%). The mean age was 6.53 +/- 3.07 years. Elevated aspartate aminotransferase and alanine aminotransferase was detected in 38.2% and 47.1% of patients, respectively. The mean level of cholesterol was 461 +/- 182.23 mg/dl and 94.1% of patients had hypercholesterolemia. Total cholesterol level and serum aminotransferase levels had a significant positive correlation with severity of fatty liver (p < 0.05). Mean body mass index was significantly higher in patients with severe fatty liver (p < 0.05). CONCLUSION: The epidemiology of pediatric NAFLD should inform future attempts to develop evaluated screening protocols. Moreover, these data should guide efforts to delineate the pathophysiology of fatty liver in children.

The outcome of Iranian children on continuous ambulatory peritoneal dialysis: the first report of Iranian National Registry.

BACKGROUND: Continuous ambulatory peritoneal dialysis is not a very common modality to treat Iranian children with end-stage renal disease; however, there is sometimes no choice but to offer this therapy to salvage the patient. Obviously, promotion in each program needs re-evaluation to find the pitfalls. Therefore, a nation-wide survey on pediatric continuous ambulatory peritoneal dialysis was conducted to find the cause of death or termination of dialysis. METHODS: All children, younger than 14 years old, treated by continuous ambulatory peritoneal dialysis in nine main pediatric nephrology wards in Iran between 1993 and 2006 were included in this historical cohort study. Patient and technique survival rates were determined. Kaplan-Mayer and Cox-regression analysis were used to compare the survival. 2 x 2 table was used to calculate the risk ratio. A P<0.05 was considered significant. RESULTS: One hundred twenty children with a mean age of 47.6 months were on continuous ambulatory peritoneal dialysis. The most frequent cause of renal failure was hereditary-metabolic-cystic disease. One hundred eighty-two peritoneal dialysis catheters were inserted surgically. The median first catheter exchange was 0.74 year (95%CI: 0.5 - 0.98). The most frequent cause of catheter replacement was catheter outflow failure due to displacement, adhesion, and infection (persistent peritonitis or tunnel infection). The mean patient survival was 1.22 years (95%CI: 0.91 - 1.53). The mortality rate was 55% before 1997, and 60% between 1998 and 2001, which declined to 23% after 2002 (P<0.05). Young age (<24 months) was the only independent factor that predicted mortality (P<0.05). The outcome of children was as follows: recovery of renal function (6.7%), renal transplantation (8.3%), switch to hemodialysis (16.7%), still on continuous ambulatory peritoneal dialysis (23.3%), death (43.3%), and lost to follow-up (1.7%). CONCLUSION: The mortality is still high among Iranian children on peritoneal dialysis. Young age is the most important factor influencing on survival and mortality.

Endoscopic findings and Helicobacter pylori in children on long-term hemodialysis.

The aim of this study is to evaluate the prevalence of GI symptoms, endoscopic abnormalities, histologic gastritis and Helicobacter pylori infection in children with End Stage Renal Disease (ESRD) undergoing maintenance hemodialysis. Upper endoscopy and gastric biopsy were performed in 31 consecutive ESRD children from 2002-2007, before renal transplantation. H. pylori status was determined by urease test and histology. The mean age of patients was 11 +/- 3.3 years (4-16 year). The mean duration of dialysis was 12.4 +/- 11 months (1.5-54 months). Seventeen patients (54.8%) were symptomatic. Twenty patients (64.5%) had endoscopic abnormalities. Antral erythema, esophagitis, antral nodularity and diffuse gastritis were common endoscopic findings. Endoscopic abnormalities were more common in symptomatic patients than asymptomatic patients (p < 0.05). Twenty patients (64.5%) were H. pylori positive. There was no statistical correlation between age, sex, serum creatinine level, presence of any symptoms and endoscopic abnormalities with H. pylori positivity. The mean duration of dialysis in H. pylori negative patients was significantly longer in comparison with H. pylori positive patients. High prevalence of eodoscopic abnormalities and H. pylori infection in both symptomatic and asymptomatic patients emphasize the necessity of upper GI evaluation in ESRD children before renal transplantation.

Asymptomatic intracardiac thrombus in a child with nephrotic syndrome.

Nephrotic patients are at risk of developing venous and arterial thromboses. Various organ manifestations have been reported. Intracardiac thrombi associated with multiorgan thrombosis have been reported in autopsy in the earlier literature, but there is only one case report in living patients with nephrotic syndrome. Here we report a 9-year-old boy with steroid-resistant nephrotic syndrome who developed an asymptomatic but potentially hazardous large intracardiac thrombus.