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.

Acute kidney injury in Hemiscorpius lepturus scorpion stung children: Risk factors and clinical features.

Acute kidney injury (AKI) is frequently seen in Hemiscorpius lepturus scorpion stung children. We have previously reported several victims with hemolytic uremic syndrome (HUS) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency. Hence, we conducted this study to identify predictive factors and clinical features of AKI in H. lepturus scorpion stung patients. We included all 215 H. lepturus scorpion stung children with no previous renal diseases in two groups (with and without AKI) and compared them based on their clinical and laboratory findings. AKI was found in 27.4% of patients, they were significantly younger and with lower body weight (P = 0.006, P = 0.011, respectively). There was a significant difference between groups with and without AKI in findings such as fever (P = 0.003), hypertension (P <0.001), hemolytic anemia (P <0.001), thrombocytopenia (P <0.001), massive proteinuria (P <0.001), hemoglobinuria (P <0.001), pyuria (P <0.001), and hematuria (P = 0.004). HUS was in 5.5% and disseminated intravascular coagulation in 14.6% which had a significant association with AKI (P <0.001).There were several independent predictors for AKI in a multivariate regression model including thrombocytopenia (P = 0.002), pyuria (P = 0.01), proteinuria (P =0.01), and fever (P = 0.02). Hemodialysis was performed in four patients but kidney function improved in all patients and there was no findings of renal impairment after three months follow-up. We found several predictors for AKI in children following H. lepturus scorpion sting including younger age, delay in receiving medical care, pigmenturia, microangiopathic hemolytic anemia, proteinuria, and pyuria.

Prevalence of Escherichia coli O157:H7 in Children with Bloody Diarrhea Referring to Abuzar Teaching Hospital, Ahvaz, Iran.

INTRODUCTION: Escherichia coli O157: H7 are recognized as important aetiological agents of diarrhea in children, particularly in developed countries. AIM: The aim of the study was to determine the rates of detection of E. coli O157: H7strains among children in Ahvaz, Iran. MATERIALS AND METHODS: From June 2010 to December 2010, 137 diarrheal stool samples of children were collected. E.coli was identified by standard microbiological techniques. O157 or O157:H7 subtypes discerned by serological tests. RESULTS: Of the 137 E. coli isolates, enteropathogens were found in 53 (38.7%) of the patients as follow: Shigella spp. (75.5%), EPEC (enteropathogenic E. coli) (16.9%), Campylobacter spp. (3.8%) and Salmonella spp. (3.8%). None of the isolated E. coli was O157:H7 serotype. CONCLUSION: This shows that non-O157:H7 E. coli are the major cause of paediatric infections in this region of Iran.

Predisposing factors for infantile urinary calculus in south-west of Iran.

INTRODUCTION: Urinary calculi in infants are relatively infrequent, but their incidence has increased in the recent decades. The aim of this study was to investigate the clinical presentation, metabolic risk factors, and urinary tract abnormalities in infants suffering from kidney calculus. MATERIALS AND METHODS: A total of 152 infants were admitted between 2009 and 2012 with ultrasonography-proven urolithiasis. A Foley catheter was fixed and 24-hour urine samples were analyzed for calcium, citrate, oxalate, uric acid, and magnesium. For detecting cystinuria, qualitative measurement of urinary cystine was done by nitroprusside test. Urinary tract structural abnormalities were also evaluated. RESULTS: The mean age at the diagnosis of kidney calculus was 5.46 months (range, 15 days to 12 months). The most common clinical findings were restlessness and urinary tract infection. A family history of calculi was found in 67.1% of the patients and 68.4% were born to consanguineous marriages. Metabolic abnormalities and urinary tract abnormalities were found in 96.1% and 15.1% of children, respectively. Urinary tract abnormalities were more common in girls. The most common metabolic risk factors were hypercalciuria (79.6%) and hypocitraturia (40.9%). Hyperoxaluria and hypomagnesuria were found in about 28% of patients, both of which were associated with bilateral urolithiasis. CONCLUSIONS: These findings show that urinary metabolic abnormalities are very common in infants with urolithiasis. Appropriate evaluation of urinary metabolic parameters can lead us to proper diagnosis and treatment.

High frequency of acquired ADAMTS13 deficiency after hemolysis in Hemiscorpius Lepturus (scorpion) stung children.

OBJECTIVE: To estimate the frequency of acquired ADAMTS13 deficiency in severe cases of Hemiscorpius lepturus stung patients and the frequency of acute kidney injury (AKI) in these patients. METHODS: Sixty scorpion stung children who were referred with severe hemolysis and hemoglobinuria were studied. None of them had received blood products and no one had a past medical history of renal failure. RESULTS: Plasma levels of ADAMTS13 and ADAMTS13 antibody (IgG) were measured using ELISA. ADAMTS13 was decreased in 91.7 % of patients and the anti-ADAMTS13 antibody (Ab) was increased in 98.3 %. ADAMTS13 decreased in all of the patients with acute kidney injury and none of those with normal levels of ADAMTS13 developed renal failure; all patients with AKI had also increased levels of ADAMTS13Ab. Acute kidney injury was found in 23.3 % and had significant association with severe anemia, thrombocytopenia, pyuria, hematuria and considerable proteinuria (p < 0.001). Disseminated intravascular coagulation (DIC) and Hemolytic uremic syndrome (HUS) developed in 6.7 % and 10 % respectively. CONCLUSIONS: The index findings demonstrate that Hemiscorpius lepturus sting is usually associated with ADAMTS13 deficiency, and increased ADAMTS13 autoantibody. These combined mechanisms may contribute to scorpion sting-induced coagulopathies and may predispose patients to develop DIC and HUS.

The first molecular genetics analysis of individuals suffering from nephropatic cystinosis in the Southwestern Iran.

OBJECTIVE: Nephropatic Cystinosis (NC) is a rare metabolic disorder due to mutation in the CTNS gene in which more than 90 different mutations have already been reported so far. This study was performed to investigate mutations of the CTNS gene and its promoter in a number of Iranian patients with NC. METHODS: Polymerase chain reaction and direct sequencing were performed for molecular characterization of the CTNS gene in 25 patients from 24 unrelated Iranian families with NC. RESULTS: None of the patients showed the 57 kb deletion in heterozygous or homozygous manner. One was homozygous for a novel mutation, which was termed as "c.153-155insCT", while one of the cases was homozygous and another was compound heterozygous for the second novel mutation c.923G>A. Moreover three known mutations c.18-21delGACT, c.1017G>A, and c.681G>A in 11 of the patients were detected. No apparent mutation was observed in the rest of patients (44%, n=11). CONCLUSION: The present data exhibit a fundament for molecular carrier detection and prenatal diagnosis of a relatively large percentage of Iranian patients suffering from NC, at least in the Southwestern Iran, where Arab ethnicity is one of the common ethnicities of the region.

Clinical correlation between hypercalciuria and nocturnal enuresis.

Hypercalciuria may present with dysuria, urinary incontinence and nocturnal enuresis (NE). To determine the frequency of hypercalciuria in NE patients and normally continent children, we studied 122 consecutive pre- school children with NE referred to our nephrology clinic during two years, from September 2007 to August 2009. We measured the 24- hour urinary calcium. Furthermore, we compared the response to nasal desmopressin in hypercalciuric and normocalciuric patients. Hypercalciuria was found in 26 (21.3 %) of the NE patients as compared with five (4.5%) of 110 continent children [(P < 0.001), OR = 5.68 (95% CI, 2.1-15.4)]. In addition, the mean 24- hour urine calcium/body weight ratio (24h- U- Ca/Bw) was higher in NE patients, 3.04 ± 1.54 vs. 2.57 ± 0.9, respectively (P = 0.005). Wet nights per week in both NE patients with and without hypercalciuria at the first visit ranged from two to seven (median: 6 and 7, respectively), and the mean overall success rate of the nasal desmopressin therapy was 83.3% and 90%, respectively (P > 0.05). The response to desmopressin above 90% occurred within one month of therapy without a significant change in the levels of hypercalciuria. We conclude that these results suggest that hypercalciuria has a significant association with NE and does not interfere with the desmopressin therapy.

Renal tubular dysfunction in pediatric patients with beta-thalassemia major.

To evaluate the prevalence of renal tubular dysfunction in children with ß-thalassemia (ß-T) major, we studied the glomerular and tubular function in 140 children with ß-T major and compared them to a healthy control group at our center from May 2007 to April 2008. Fresh first morning samples were collected from each patient and analyzed for sodium, potassium, calcium (Ca), protein, uric acid (UA), creatinine (Cr), urine osmolality and urinary N-acetyl-ß-D-glucosaminidase (UNAG) activity. Blood samples were also collected for complete blood count, blood urea nitrogen (BUN), fasting blood sugar, serum creatinine (SCr), electrolytes, and ferritin before transfusion. Among the study patients, 72 were males, and the mean age was 11.5 (ranging 7-16) years. SCr levels were all within normal limits and all of them had normal glomerular filtration rate (GFR). The mean UNAG was 17.8 IU/L in the study patients (normal 0.15-11.5 IU/L) and 3.2 IU/L in the control group (P < 0.001). Of the 82 study patients who had elevated level of UNAG, 58 (62.4%) had high blood levels of ferritin also (r = 0.2, P < 0.001) and 13 (15.9%) patients had hypercalciuria also (UCa/UCr > 0.21) (P = 0.006). Nine (6.4%) thalassemic patients with a mean age of 12 years had proteinuria (Upr/UCr > 0.2). Sixty-nine (49.3%) out of the 140 patients and 45 (65.2%) of the patients having UNAG had uricosuria also (UUA/UCr > 0.26). Ten (7%) patients had microscopic hematuria and 10 (7%) patients with a mean age of 13.5 years had glucosuria or diabetes mellitus. We conclude that tubular dysfunction is a relative common complication of the ß-T major; UNAG and its index are the best to detect renal tubular dysfunction in these patients. Currently, periodic measurement of UCa/UCr and UUA/UCr ratios as well as urinalysis are recommended.

Renal function in transfusion-dependent pediatric beta-thalassemia major patients.

PURPOSE: In this study, the relationship between glomerular and tubular function and creatinine, glomerular filtration rate (GFR) and urine NAG in thalassemia major patients aged 7-16 years was investigated. DESIGN AND SETTING: This is a case-control study comprising 280 individuals [144 (51·4%), males; 136 (48·6%), females]. MATERIALS AND METHODS: Patients were divided in groups of 14 individuals and age groups of 7-16 years. Sodium excretion fraction, fraction excretion of potassium, calcium-to-creatinine and uric acid-to-creatinine ratios, and duration of specific blood transfusion were determined in all age groups receiving deferoxamine. RESULTS: GFR decreased with increasing age, but the correlation was not statistically significant. There was no significant correlation between the ferritin levels and the GFR changes. The mean value of NAG activity between thalassemic patients and controls has no significant difference. The difference in mean age of the groups with high NAG activity and normal NAG activity was statistically significant. Thirty-seven patients (52·1%) in the group with normal NAG activity, and 45 patients (6·25%) in the group with NAG activity above normal were observed with uricosuric effects with no significant difference. Four patients (6·9%) in the group with normal NAG activity and six patients (7·3%) in the group with NAG activity above normal were shown to have hematuria with no significant difference. The results show that the increase in serum ferritin is significantly correlated with the increase in NAG activity (P<0·001, r = 0·2). Of patients with normal NAG activity 1 (1·7%) and with NAG activity higher than normal, 13 (15·9%) cases experienced hypercalciuria that significant difference was existing. The data also indicated that the NAG changes do not correlate with GFR changes. CONCLUSION: The results showed that kidney dysfunction in thalassemia increases with increasing age, duration, and levels of blood transfusion and hypercalciuria. It is therefore recommended that the presence of severe renal dysfunction in thalassemic patients should be investigated using sensitive and specific tests, mainly NAG, to prevent progress towards the complications.

Bardet-biedl syndrome in a child with chronic kidney disease.

A 4-year old boy was referred for evaluation of renal failure, posterior urethral valve (PUV) and urinary tract infection. His parents added complaints of polyuria, polydipsia, enuresis, shortness of stature, and inappropriate obesity. Serum blood urea nitrogen and creatinine levels were 45 and 3.5 mg/dL, respectively. Urine culture was positive for Pseudomonas aeruginosa, and abdominal ultrasound revealed bilateral small kidneys. The patient's history included mild to moderate mental retardation and postaxial polydactyly of both lower limbs amputated two years ago. The combination of mental retardation, obesity, postaxial polydactyly, and bilateral renal hypoplasia were compatible with the diagnosis Bardet-Biedl syndrome (BBS). The combination of PUV and BBS is a rare condition that caused this early onset of renal failure and inappropriate obesity guided us to the diagnosis.

Causes and outcome of prenatally diagnosed hydronephrosis.

Hydronephrosis is the most common abnormal finding in the urinary tract on prenatal screening with ultrasonography (U/S). Hydronephrosis may be obstructive or non-obstructive; obstructive lesions are more harmful to the developing kidneys. The aim of the study was to evaluate the causes of renal pelvic dilatation and the outcome of postnatal treatment in infants with hydronephrosis diagnosed prenatally with U/S. We prospectively studied 67 (60 males) newborns with hydronephrosis diagnosed prenatally and confirmed postnatally with U/S from Sept. 2005 to Oct. 2007. The patients were allocated to three groups based on the mea-surement of the anteroposterior renal pelvic diameter (APRPD) in transverse plane: mild (6-9.9 mm), moderate (10-14.9 mm) and severe (> or =15 mm) hydronephrosis. Voiding cystourethrography (VCUG) was obtained in all of the patients to rule out vesicoureteral reflux (VUR). In cases with negative VUR, Diethylenetriamine-pentaacetic acid (DTPA) scan with diuretic renography was performed to detect ureteropelvic joint obstruction (UPJO). Twenty two cases (32.8%) had mild, 20 (29.9%) had moderate, and 25 (37.3%) had severe hydronephrosis. The causes of hydroneph-rosis were VUR (40.2%), UPJO (32.8%), posterior urethral valves (PUVs) (13.4 %), and transient hydronephrosis (13.4 %). The lesion was obstructive in 37 (55.2%) infants. Totally, 33 (49.2%) patients with hydronephrosis (9 mild, 9 moderate, and 15 severe) subsequently developed com-plications such as UTI and renal insufficiency, or required surgery. Associated abnormalities were observed in 15 (22.4%) patients. We conclude that every newborn with any degree of hydro-nephrosis should be assessed postnatally for specific diagnosis and treatment.

A clinicopathological study of lupus nephritis in children.

To assess clinical characteristics, pathological findings, and therapeutic response in children with lupus nephritis (LN), we retrospectively studied 25 children under 16 years of age with LN at the Abozar children's hospital from 1995 to 2006. The study included 13(65%) girls and 7(35%) boys. The mean age at the time of diagnosis of SLE was 10.2 (+/- 4.8) years. Eighteen patients (90%) were more than 8 years old. Sixty percent of the patients presented as nephritic-nephrotic syndrome. All the patients underwent percutaneous renal biopsy and were followed up for at least 36 months. The clinical and serologic parameters at the time of renal biopsy were recorded. Twenty patients were treated with the following regimens: one (class I) with low dose prednisone, 7 (class II, III) with high-dose of prednisone, 12 (class IV) with high-dose prednisone plus 13 intermittent intravenous cyclophosphamide (CTX) pulses (monthly for 6 months and then every 3 months), followed by mycophenolate mofetil (MMF) as maintenance therapy. Remission was achieved in 17 (85%) cases; one required hemodialysis and 2 died due to renal failure and central nervous system involvement. Among 12 cases with class IV, 11 responded to prednisone and intravenous CTX pulses. We conclude that i.v. pulses of CTX induced clinical remission of renal disease in the majority of children with severe LN. MMF maintenance therapy was effective after induction of remission in refractory cases. However, this study was performed in a small number of subjects, further studies to confirm the long-term efficacy and safety of CTX pulse therapy on larger numbers of patients are warranted.

The first Molecular genetics analysis of individuals suffering from nephropatic cystinosis in the Southwestern Iran

Objective: Nephropatic Cystinosis (NC) is a rare metabolic disorder due to mutation in the CTNS gene in which more than 90 different mutations have already been reported so far. This study was performed to investigate mutations of the CTNS gene and its promoter in a number of Iranian patients with NC. Methods: Polymerase chain reaction and direct sequencing were performed for molecular characterization of the CTNS gene in 25 patients from 24 unrelated Iranian families with NC. Results: None of the patients showed the 57kb deletion in heterozygous or homozygous manner. One was homozygous for a novel mutation, which was termed as "c.153-155insCT", while one of the cases was homozygous and another was compound heterozygous for the second novel mutation c.923G>A. Moreover three known mutations c.18-21delGACT, c.1017G>A, and c.681G>A in 11 of the patients were detected. No apparent mutation was observed in the rest of patients (44%, n=11). Conclusion: The present data exhibit a fundament for molecular carrier detection and prenatal diagnosis of a relatively large percentage of Iranian patients suffering from NC, at least in the Southwestern Iran, where Arab ethnicity is one of the common ethnicities of the region (AU)

Objetivos: La cistinosis nefropática (CN) es una rara enfermedad metabólica que se debe a la mutación del gen CNTS, para que el que ya se han registrado más de 90 mutaciones diferentes. El estudio se realizó para investigar las mutaciones del gen CTNS y su promotor en un determinado número de pacientes iraníes con CN. Métodos: Para la determinación molecular del gen CTNS en 25 pacientes con CN procedentes de 24 familias iraníes no emparentadas, se han llevado a cabo análisis con reacción en cadena de la polimerasa y con secuenciación directa. Resultados: Ninguno de los pacientes mostró deleción de 57-kb ni heterocigócita ni homocigótica. Uno resultó homocigoto para una mutación no descrita que se denominó «c.153-155insCT», mientras que otro de los casos resultó homocigoto y otro heterocigoto compuesto para una segunda mutación no descrita, c.923G>A. Además, se detectaron otras tres mutaciones conocidas c.18-21delGACT, c.1017G>A y c.681G>A en 11 pacientes. En el resto de los pacientes (44 %, n = 11) no se observaron mutaciones aparentes. Conclusión: Los datos de este estudio muestran un fundamento para la detección de transportadores moleculares y el diagnóstico prenatal de un porcentaje relativamente elevado de pacientes iraníes que sufren CN, al menos en el sudoeste de Irán, donde la etnia árabe es una de las comunes en la región (AU)