A Study on the CLCN5 Gene in Iranian Patients: A Report of Novel and Recurrent Mutations.

INTRODUCTION: Dent's disease is an X-linked inherited renal tubular disorder characterized by proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, rickets, and end-stage renal disease. Almost 60% of patients have causative mutations in the CLCN5 gene (Dent 1), and 15% of affected individuals have mutations in the OCRL1 gene (Dent 2). The aims of this study are to identify CLCN5 mutations in Iranian families with Dent's disease and to characterize the associated clinical syndromes. METHODS: We studied 14 patients from 13 unrelated Iranian families with a clinical diagnosis of Dent's disease. Proteinuria was detected in all patients. Nephrolithiasis was found in 5 patient, and hematuria in 2 patients. Most of the affected individuals had nephrocalcinosis. PCR-sequencing for the CLCN5 gene was performed in all 14 patients. Next-generation sequencing (NGS) has also been performed in one patient who we did not find causative mutation. RESULTS: We identified four different CLCN5 mutations including one missense mutation (c.731C>T), one nonsense mutation (c.100C>T), and two novel mutations, consisting of one frameshift mutation (c.1241_1242dupAA) and one splicing mutation (c.805-2A>G). We also identified one OCRL1 mutation, one splicing mutation (c.1466 + 1G>A), using NGS. CONCLUSION: This is the first report to characterize mutations in the CLCN5 gene in Iranian patients with Dent's disease and expands the spectrum of CLCN5 mutations by reporting two novel mutations, c.1241_1242dupAA and c.805-2A>G.

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.

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.

Risk factors of renal scars in children with acute pyelonephritis.

OBJECTIVE: The aim of this study was to determine the association between previously documented risk factors such as recurrent pyelonephritis with the incidence of renal scarring after acute pyelonephritis in children. MATERIAL AND METHODS: Children with acute pyelonephritis who were admitted to the Department of Pediatrics of a teaching hospital during 2007-2009 were enrolled in this study. DMSA scans were obtained 4-6 months after the last episode of pyelonephritis in all patients. RESULTS: A total of 80 children with acute pyelonephritis were enrolled in this study. Most of them were girls (77.5%), with a median age of 12 months. Nearly half of the children (n = 44; 55%) had one or more renal scars. The distribution of gender, CRP level and leukocytosis did not differ significantly regarding the absence or presence of renal scars (p > 0.05). Most of the scars occurred in children who had presented with bilateral pyelonephritis (69.4% vs. 18.2%, p = 0.001). Most of the patients with renal scars had a positive history of vesicoureteral reflux (VUR) (75% vs.13.6%, p = 0.001). The significant roles of recurrent pyelonephritis and presence of VUR were further confirmed by multivariate analysis. CONCLUSIONS: According to our findings, presence of VUR and recurrent pyelonephritis are independently associated with a higher incidence of renal scarring.

Risk factors of renal scars in children with acute pyelonephritis

OBJECTIVE: The aim of this study was to determine the association between previously documented risk factors such as recurrent pyelonephritis with the incidence of renal scarring after acute pyelonephritis in children. MATERIAL AND METHODS: Children with acute pyelonephritis who were admitted to the Department of Pediatrics of a teaching hospital during 2007-2009 were enrolled in this study. DMSA scans were obtained 4-6 months after the last episode of pyelonephritis in all patients. RESULTS: A total of 80 children with acute pyelonephritis were enrolled in this study. Most of them were girls (77.5 percent), with a median age of 12 months. Nearly half of the children (n = 44; 55 percent) had one or more renal scars. The distribution of gender, CRP level and leukocytosis did not differ significantly regardingthe absence or presence of renal scars (p > 0.05). Most of the scars occurred in children who had presented with bilateral pyelonephritis (69.4 percent vs. 18.2 percent, p = 0.001). Most of the patients with renal scars had a positive history of vesicoureteral reflux (VUR) (75 percent vs.13.6 percent, p = 0.001). The significant roles of recurrent pyelonephritis and presence of VUR were further confirmed by multivariate analysis. CONCLUSIONS: According to our findings, presence of VUR and recurrent pyelonephritis are independently associated with a higher incidence of renal scarring.