Prevalence of reflux nephropathy in Iranian children with solitary kidney: results of a multi-center study.

BACKGROUND: Given the importance of the function of the remnant kidney in children with unilateral renal agenesis and the significance of timely diagnosis and treatment of reflux nephropathy to prevent further damage to the remaining kidney, we aimed to determine the prevalence of reflux nephropathy in this subgroup of pediatric patients. METHODS: In general, 274 children referred to pediatric nephrologists in different parts of Iran were evaluated, of whom 199 had solitary kidney and were included in this cross-sectional study. The reasons for referral included urinary tract infection (UTI), abnormal renal ultrasonography, being symptomatic, and incidental screening. Demographic characteristics, including age and gender were recorded. History of UTI and presence of vesicoureteral reflux (VUR) were evaluated. RESULTS: Of the 274 children evaluated in this study with the mean age (SD) of 4.71 (4.24) years, 199 (72.6%) had solitary kidney. Among these, 118 (59.3%) were male and 81 (60.7%) were female, 21.1% had a history of UTI, and VUR was present in 23.1%. The most common cause of referral was abnormal renal ultrasonography (40.2%), followed by incidental screening (21.1%), being symptomatic (14.1%), and UTI (5.5%). In 116 children (58.3%), the right kidneys and in 83 (41.7%) the left kidneys were absent. Besides, 14.6% of the participants had consanguineous parents and 3% had a family history of solitary kidney. Upon DMSA scan, the single kidney was scarred in 13.1%, of which only 7.5% were associated with VUR. In addition, proteinuria and hematuria were observed in 6.5% and 1.5% of children, respectively. CONCLUSIONS: The prevalence of reflux nephropathy was 7.5% in children with solitary kidney with a male predominance. Given the relatively high prevalence of reflux nephropathy in these children, screening for VUR in the remnant kidney appears to be essential in this population.

Association between Toxoplasma gondii Infection and Nephrotic Syndrome Risk in Children: A Case-Control Study and Systematic Review.

Some evidence suggests toxoplasmosis as an etiology of nephrotic syndrome (NS) in children; however, no observational study evaluated this relationship. In a case-control study, we enrolled 35 children with NS and 37 healthy children. All participants were examined for anti-Toxoplasma immunoglobulin G and M (IgG and IgM) antibodies using enzyme-linked immunosorbent assay. We also systematically reviewed the literature to assess this relationship. Prevalence of anti-Toxoplasma IgG was 17.4% and 13.5% in cases and controls, respectively, indicating a non-significant association (adjusted odds ratio, 1.22, 95% confidence interval, 0.35-4.41). No subjects were seropositive for IgM. In a systematic review, we found that acute toxoplasmosis can induce NS in some children and anti-Toxoplasma treatment is effective in the remission of NS in these cases. In pediatrics with NS, acute toxoplasmosis should be considered as a neglected causative factor.

Urinary tract infection in children with nephrotic syndrome: A systematic review and meta-analysis.

OBJECTIVE: Urinary tract infection (UTI) is among the most common infection diseases in children with nephrotic syndrome (NS), resulting in treatment failure and relapse. No systematic reviews have estimated the prevalence of UTI in children with NS on a global scale, therefore, did the first systematic review and meta-analysis study to estimate the prevalence of UTI in children with NS in different geographical regions and different countries. METHODS: PubMed, EMBASE, Scopus, Web of Science and Google Scholar databases were systematically searched up to 20 February 2019, for studies assessing the prevalence of UTI in children with NS. Pooled prevalence of UTI was calculated using the random effects model. Data were stratified based on WHO geographical regions and individual countries. Subgroup analysis regarding the gender and socio-demographic variables were also performed. RESULTS: Thirty studies involving 6314 children with NS were included. The pooled prevalence of UTI was 21.6% (95%CI, 17.1-26.5%), with the highest prevalence in the African region (34.8%, 95%CI: 4.7-73.9%), and lowest prevalence in the region of the Americas (7.4%, 95% CI: 1.7-16.2%). With respect to countries, the lowest and highest prevalence rates were reported from USA (3.3%) and Indonesia (45.9%). In subgroup analyses, a higher prevalence was observed in females, and in countries with lower levels of income and human development index. The most common isolated bacteria were Escherichia coli (28%), and Klebsiella spp. (22.4%). CONCLUSIONS: The high prevalence of UTI in children with NS reported in this study is a significant health threat for these patients. These results call for intervention strategies and preventive measures for children with NS to reduce the burden of UTI.

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.

COVID-19 and renal involvement in children: a retrospective study.

Background: The New coronavirus (SARS COV-2) can cause acute respiratory disease and also multiorgan dysfunction. There is insufficient data about kidney involvement in children. So, this study was done on children with COVID-19 to evaluate nephrological involvement. Methods: All children with confirmed or suspected COVID-19 who were admitted in Children Hospital .were enrolled. They were admitted in hospital from March 2020 to July 2020. Serum Blood Urea Nitrogen (BUN), creatinine, sodium, potassium, calcium and urinalysis were evaluated. Also, glomerular filtration rate (GFR) was calculated by Schertz's formula. All patients were evaluated by chest x-ray and/or computerized tomography scanning (CTS). The data were analyzed by SPSS software and P value less than 0.05 was determined as significant. Results: Forty-seven children with confirmed or suspected COVID-19 were enrolled to this study. At admission, 23.4% and 27.7% of children with COVID-19 infection had abnormal increase in serum BUN and creatinine, respectively. Also 78.8% and 25.5% of children had GFR less than 90 and 60 ml/min /1.732, respectively. Additionally, 13/47 (27.7%) of children had abnormal urine analysis (microscopic hematuria and/or proteinuria). There wasn't a significant relationship between pulmonary lesions and abnormal reduction of GFR (P<0/05). Conclusion: In the study, the risk of AKI (acute kidney injury) and decrease of GFR and also abnormal urinalysis is high in children with COVID-19. So, more attention for detection of kidney involvement is necessary and more conservative management for prevention of AKI and decrease of GFR are recommended.

COVID-19 and Digestive System in Children: A Retrospective Study.

BACKGROUND: The aim of this study was to identify gastrointestinal (GI) and liver injury presentations in children admitted with COVID-19 infection. METHODS: In this retrospective study, we studied all children with suspected symptoms of COVID-19, referred to Amirkola Children's Hospital. Clinical manifestations of the digestive and respiratory systems and liver function tests were evaluated for all cases. RESULTS: Eighteen children were studied. The most common clinical symptoms were fever, anorexia, weakness, nausea and vomiting, cough, diarrhea, and abdominal pain, respectively. Also, 5/18 (27.8%) and 7/18 (38.9%) of cases had abnormally high alanine aminotransferase (ALT), aspartate aminotransferase (AST), respectively. Additionally, in icteric cases, direct bilirubin was raised. There was no significant relationship between pulmonary lesions and abnormal excess in ALT (P = 0.59) and AST (P = 0.62). CONCLUSION: The findings showed that there were no severe clinical GI symptoms in children with COVID-19 infection. Besides, children with increased liver enzymes did not have more respiratory involvement than those without a rise in liver enzymes.

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.

Serum cyclosporine level and orange juice in pediatric renal-transplanted patients.

Organ transplant survival has been improved with CsA, but the PK of CsA may be affected by many drugs and foods. This study was performed to investigate the impact of orange juice on PK of CsA in children who had received a renal transplant. This cross-over placebo-controlled study was performed on 10 pediatric kidney-transplanted patients. All children received orange juice (Thomson novel) or water. After morning dose of CsA, patients were given 250 mL orange juice or water and investigation of the PK was performed in 12 h. Co-administration of orange juice with CsA compared with water did not significantly increase the area under the curve from 0-12 h (AUC(0-12)) of CsA (orange juice 2833 +/- 553, water 3053 +/- 1532, p > 0.05). Also, there were not significant effects on peak concentration (C(max)) or time to C(max) (t(max)). Orange juice can be used with CsA and there was no interaction between the juice and CsA in pediatric renal transplants.

Glomerular filtration rate determination by creatinine and cystatin-C in patients with acute pyelonephritis.

BACKGROUND: Measurement of glomerular filtration rate (GFR) and monitoring of it in any patient on nephrotoxic drugs is very important. Recently, cystatin C (cys-C) has been introduced as a better marker for determining and monitoring renal function than creatinine especially in a mild decrease of GFR. This study was done to assess the change of GFR measurement based on serum Cys-C and creatinine and their comparison in children with acute pyelonephritis on amikacin. METHODS: All children with acute pyelonephritis who were admitted in Nephrology ward were enrolled in this study. Serum creatinine, serum cys-C and the GFR calculation based on them were measured in patients on the day of admission (day zero) and then on days 3 and 7 after the start of treatment with amikacin and p-value less than 0.05 was considered significant. RESULTS: Among the 70 children, 61 patients were females and the others were males. Mean age was 42.66±41.53 months. Estimated GFR based on creatinine on day 0 (before amikacin administration), 3 and 7 were 72.41±20.89 ml/min/1.73 m2, 78.42±21.15 ml/min/1.73 m2 and 80.5±22.43 ml/min/1.73 m2, respectively. Moreover, GFR based on cys-C during these days were 116.23±58.9 ml/min/1.73 m2, 116.49±53.31 ml/min/1.73 m2 and 108.37±51.02 ml/min/1.73 m2, respectively (p<0.05). CONCLUSIONS: According to this study, decrease of GFR calculation based on Cys-C was seen and estimated GFR was not changed according to creatinine. So, we recommend the use of cys-C for the monitoring of renal function in any patient treated with nephrotoxic drugs such as amikacin.

Efficacy of potassium polycitrate on renal stone and microlithiasis predisposed by metabolic disorders.

BACKGROUND: According to high prevalence of renal stone in children, we evaluated the efficacy of treatment with potassium citrate and its correlation with metabolic disorders in children less than two years of age with renal stone and microlithiasis. METHODS: In this cross- sectionaly study, 100 patients (less than 2 years old) with renal stone or microlitiasis were evaluated for metabolic disorders. They were treated with potassium citrate and followed-up by ultrasonography every 3 months. Then response to treatment was evaluated according to the fresence metabolic disorders (A p-alue<0.05 was significant). RESULTS: According to this study, hyperuricosuria and hypercalciuria were the two major metabolic disorders (40-33%). Seventy three patients had complete response, and also there as not a significant difference (p<0.05) in the efficacy of treatment due to types of metabolic disorders. There was significant difference between relative response to treatment in children who had metabolic disorders and patient without any metabolic disorders. CONCLUSION: Based on our results the use of potassium citrate in all children less than 2 years with renal stone or microlithiasis especially those with metabolic disorders, are recommended.

Low-dose intradermal and subcutaneous versus intramuscular hepatitis B vaccination in primary non-responding hemodialysis patients.

OBJECTIVE: Patients with end-stage renal failure are at high risk of hepatitis B virus (HB V) infection. They have impaired immune response to HBV intramuscular (i.m.) vaccine. Non-response (anti HBs titer < 100mIU/ml) hemodialysis patients (HD) with the previous three-dose i.m. vaccination were examined with booster dose vaccine by i.m. , intradermal (i.d) and subcutaneous (s.c.) routes. MATERIAL AND METHOD: Thirty-four HD patients who had been vaccinated with three-dose vaccine (40 microgram, 2 ml, Engerix B, i. m.) and had anti-HBs titer less than 100mlU/ml were selected. They were randomly divided into three groups and received a fourth dose of vaccine by i.m. (40 microgram, 2 ml), i.d (10 microgram. 0. 5 ml) and s.c. (10 microgram, 0. 5 ml). Then, serum anti-HBs titer was determined after 45 days and 6 months. RESULTS: Forty five days after completion of the re-vaccination course, anti-HBs titer was above 100 mIU/ml in 6/11, 3/11 and 4/12 of i.m. s.c. and i. d groups, respectively (p > 0.05). After six months, 4/11, 3/11 and 2/12 of patients had anti-HBs titer above l00mlU/ml (p > 0.05). CONCLUSION: With lower dose of vaccine (10 microgram) in s.c. groups, these patients had lower change in their anti-HBs titer. Therefore, it is cost effective and practical to offer other vaccination schemes.

The effect of arbutin on lipid peroxidation and antioxidant capacity in the serum of cyclosporine-treated rats.

BACKGROUND: Cyclosporine A (CsA) is a potent immunosuppressant drug with therapeutic and toxic actions. The use of CsA is limited by its toxicity. Several researchers had proposed that oxidative stress could play an important role in CsA-induced toxicity. Arbutin has recently been shown to possess antioxidative and free radical scavenging abilities. The present study was designed to investigate the in vivo effects of arbutin on lipid peroxidation and antioxidant capacity in the serum of cyclosporine treated rats. METHODS: Adult male Wistar rats were divided into six groups (n=8/group): (I) control (no CsA and arbutin administration), (II and III) were treated subcutaneously (Sc) with arbutin (50,100 mg/kg/bw), respectively, (IV) administered CsA (25 mg/kg/bw) intraperitoneally (IP), (V and VI) received the combination of CsA (25 mg/kg/bw) i.p and arbutin (50,100 mg/kg/bw) Sc daily, respectively. At the end of the treatment (after3 weeks), serum lipid peroxidation was measured by thiobarbituric acid-reacting substances (TBARS) and serum total antioxidant capacity (ferric reducing ability of plasma [FRAP]) was assayed based on spectrophotometric method. RESULTS: TBARS had been significantly increased by CsA administration compared with control rats. Arbutin (50mg/kg/bw) completely prevented this effect, but arbutin (100 mg/kg/bw) alone or in combination with CsA significantly increased lipid peroxidation compared with controls. CONCLUSION: Our data indicate that arbutin (50mg/kg/bw) had protective effect in the CsA-induced toxicity but high concentration of arbutin (100mg/kg/bw) showed meaningful oxidative and lipoperoxidative effects.

CSWS Versus SIADH as the Probable Causes of Hyponatremia in Children With Acute CNS Disorders.

OBJECTIVE: There is a major problem about the incidence, diagnosis, and differentiation of cerebral salt wasting syndrome (CSWS) and syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in patients with acute central nervous system (CNS) disorders. According to rare reports of these cases, this study was performed in children with acute CNS disorders for diagnosis of CSWS versus SIADH. MATERIALS & METHODS: This prospective study was done on children with acute CNS disorders. The definition of CSWS was hyponatremia (serum sodium ≤130 mEq/L), urine volume output ≥3 ml/kg/hr, urine specific gravity ≥1020 and urinary sodium concentration ≥100 mEq/L. Also, patients with hyponatremia (serum sodium ≤130 mEq/L), urine output < 3 ml/kg/hr, urine specific gravity ≥1020, and urinary sodium concentration >20 mEq/L were considered to have SIADH. RESULTS: Out of 102 patients with acute CNS disorders, 62 (60.8%) children were male with mean age of 60.47±42.39 months. Among nine children with hyponatremia (serum sodium ≥130 mEq/L), 4 children had CSWS and 3 patients had SIADH. In 2 cases, the cause of hyponatremia was not determined. The mean day of hyponatremia after admission was 5.11±3.31 days. It was 5.25±2.75 and 5.66±7.23 days in children with CSWS and SIADH, respectively. Also, the urine sodium (mEq/L) was 190.5±73.3 and 58.7±43.8 in patients with CSWS and SIADH, respectively. CONCLUSION: According to the results of this study, the incidence of CSWS was more than SIADH in children with acute CNS disorders. So, more attention is needed to differentiate CSWS versus SIADH in order to their different management.

Prediction of vesicoureteral reflux in children with first urinary tract infection by dimercaptosuccinic Acid and ultrasonography.

OBJECTIVE: Urinary tract infection (UTI) is one of the most common causes of febrile pediatric diseases. Also, vesicoureteral reflux (VUR) is a significant risk factor for UTI. Voiding cystourethrography (VCUG) is the method of choice for evaluation of VUR. This study was done to predict VUR by DMSA scan (technetium 99 m-labeled dimercaptosuccinic acid) and ultrasonography (US). METHODS: In a prospective study, all children with first time acute pyelonephritis were selected and evaluated by DMSA scan and US. Then VCUG was done with negative urine culture. All children with final diagnosis of obstructive congenital anomaly were excluded. The sensitivity, specifity, positive predictive values, negative predictive values, Confidence Interval of DMSA scan and US were calculated for prediction or exclusion of VUR. FINDINGS: Among 100 children with UTI diagnosis, VUR was detected in 39 children and 63 (31.5%) kidneys. DMSA scan was abnormal in 103 (51.5%) units, 45 units had VUR (PPV=44%), 79 units with normal DMSA scan had no VUR (NPV=81%). Of kidney units that were abnormal by DMSA or US, 51 units had VUR. PPV and NPV were 44% and 56%, respectively. CONCLUSION: DMSA scan alone or with US cannot predict VUR (especially low grade VUR). But according to NPV, it seems that absence of VUR can be predicted. So, more studies are needed to determine the usefulness of DMSA scan and US instead of VCUG for detection of VUR.

Effect of tangerine juice on cyclosporine levels in renal transplant children.

The aim of our study was to investigate the effect of tangerine juice on the pharmacokinetics of cyclosporine A (CsA), in children who had received a renal transplant. This placebo-controlled study was done on ten kidney transplant recipients with stable cyclosporine trough levels who received either tangerine (Unshio Satsuma) juice or water. Patients were given their morning doses of CsA and then 250 ml water or the juice, and 12 h, investigations of the pharmacokinetics (PK) were performed. The main outcome measures were peak concentration and time to peak and area under the concentration-time curve. Administration of CsA with tangerine juice compared with water did not increase significantly the area under the whole-blood concentration versus time curve from 0-12 h (AUC(0-12)) of CsA, (tangerine juice 2,797 +/- 1,361 (P = 0.5); water 3,053 +/- 1,532). Co-administration of tangerine juice with CsA compared with water had no significant effects on the AUC(0-12), peak concentration (C(max)) or time to C(max) (t(max)) of the CsA in pediatric renal transplantation.

Urinary calcium to creatinin ratio in children.

Due to difficulty of 24hr urine collection in children for detection of hypercalciura, random urine calcium to creatinin ratio (U Ca/Cr) has been used for screening hypercalciuria. The purpose of this study was to determine normal U Ca/Cr ratio in primary school age children in North of Iran. This study was performed on 590 healthy school-age children, aged between 7-11 years. Early morning random urine samples from all children were analyzed for calcium and creatinine. Mean value and 95th percentile for U Ca/Cr ratio were 0.155 +/- 0.095 and 0.36, respectively. A negative correlation observed between age and U Ca/Cr ratio was R=-0.101, P=0.014. With regard to variations in U Ca/Cr ratio among different studies, it is recommended to determine this ratio in every geographic area.