Publications by authors named "Miriam Davidovits"

61 Publications

Long-term follow-up of premature infants with urinary tract infection.

Eur J Pediatr 2021 May 28. Epub 2021 May 28.

Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.

Urinary tract infection (UTI) is common in preterm infants and may have long-term sequela, such as recurrent infections and renal scarring in older children. We assessed long-term outcomes of preterm infants with UTI, born during 1996-2008 in Schneider Children's Medical Center's neonatal intensive care unit (NICU), and incidence of UTI recurrence. Of 89 preterm infants, seven were excluded due to prenatal diagnosis of congenital anomalies of the kidney and urinary tract (CAKUT), 41 interviewed by phone, 18 presented for follow-up evaluation in the nephrology clinic, and 23 lost to follow-up. No patient who completed follow-up reported additional UTI episodes or issues related to kidney and urinary tract. Clinically evaluated participants were 17.1 ± 3.6 years, born prematurely at 29.4 ± 4 weeks. All had a normal estimated glomerular filtration rate of >90 ml/min/1.73m; four (22%) had systolic blood pressure >90th percentile; none had proteinuria (mean protein/creatinine ratio 0.09 ± 0.04 mg/mg) or albuminuria (mean albumin/creatinine ratio 10.2 ± 6.3 mcg/mg). Renal ultrasonography done in the first years of life in 12 (66%) patients demonstrated normal kidney size and structure.Conclusion: In this pilot study, a single episode of UTI in premature infants without CAKUT did not constitute a risk factor for recurrence of infections or kidney injury in their first two decades of life. Thus, normal ultrasound in NICU excluding CAKUT may be sufficient for premature patients with UTI, with no need of further imaging or long-term nephrology follow-up. What is Known: • Urinary tract infection (UTI) is one of the most common bacterial infections in neonates and premature infants. Risk factors for UTI recurrence in children are congenital anomalies of the kidney and urinary tract (CAKUT) and bladder and bowel dysfunction. • The recurrence rate and long-term renal sequela of UTI in preterm infants have not been studied. Guidelines regarding management and long-term follow-up for infants less than 2 months old are lacking. What is New: • A single episode of UTI in premature infants without CAKUT probably does not constitute a risk factor for UTI recurrence, and it is unlikely to cause renal injury in the first two decades of life. • For premature infants with UTI without sonographic diagnosis of CAKUT in NICU, prophylactic antibiotic treatment, further imaging, or long-term nephrology follow-up may be unnecessary.
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http://dx.doi.org/10.1007/s00431-021-04131-xDOI Listing
May 2021

Is the prognosis of congenital single functioning kidney benign? A population-based study.

Pediatr Nephrol 2021 Feb 22. Epub 2021 Feb 22.

Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: We investigated the risk of kidney injury among adolescents with and without a congenital single functioning kidney (SFK).

Methods: This retrospective study is based on a medical evaluation database of 17-year-old Israeli conscripts, born during 1989-1999. Those with congenital SFK diagnosis, verified by a pediatric nephrologist's review of the original military medical committee classifications, were compared to the rest of the cohort. Kidney injury (KI) was defined as proteinuria, high blood pressure (BP), or estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m prior to army recruitment. Risk factors for KI were examined using logistic regression.

Results: Of 979,630 screened candidates, 353 were diagnosed with SFK. The yearly incidence of SFK gradually increased in the first years of the study, reaching a plateau in 1995 (5.5 ± 1.2/10,000 births/year). The male to female ratio was 2.7:1. Concomitant genital malformations were documented in 5.5% of those with SFK. KI was more prevalent in the SFK than the control group (42.2% vs. 23.5%, p < 0.001). All three components of KI were more common in the SFK than the control group: high BP (31.7% vs. 23.1%, p < 0.001), proteinuria (18.2% vs. 0.4%, p < 0.001), and eGFR <90 ml/min/1.73m (12.0% vs 0.1%, p < 0.001). Multivariate analysis of the SFK group revealed associations of higher mean BMI, male sex, and smaller ultrasonographic kidney length with KI.

Conclusions: This large population-based study documents a significant risk for KI among adolescents with SFK. Obesity represents a major modifiable risk factor for KI, implicating the need for closer follow-up in this group during childhood.
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http://dx.doi.org/10.1007/s00467-021-04980-6DOI Listing
February 2021

Long-term outcomes during 37 years of pediatric kidney transplantation: a cohort study comparing ethnic groups.

Pediatr Nephrol 2021 Jul 18;36(7):1881-1888. Epub 2021 Jan 18.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: This study aimed to evaluate short- and long-term outcomes of kidney transplantation over 37 years in a national referral center and compare outcomes between Israeli Jewish and Arab children.

Methods: Data on 599 pediatric transplantations performed in 545 children during 1981-2017, including demographic parameters, kidney failure disease profile, and pre-transplant dialysis duration, were retrieved from our computerized database and patient files. Patient and graft survival were estimated using the Kaplan-Meier method.

Results: Twenty-year patient survival was 91.4% for live donor (LD) and 80.2% for deceased donor (DD) kidney recipients. Respective 10-year and 20-year graft survival rates for first kidney-only transplants were 75.2% and 47.0% for LD and 60.7% and 38.4% for DD grafts. Long-term graft survival improved significantly (p < 0.001) over the study period for recipients of both LD and DD allografts and reached 7-year graft survival of 92.0% and 71.3%, respectively. The proportion of DD transplantations was higher in the Arab subpopulation: 73.8% vs. 48.4% (p < 0.001). Graft survival was not associated with age at transplantation and did not differ between the Arab (N = 202) and Jewish children (N = 343). Median (IQR) waiting time on dialysis did not differ significantly between the Arab and Jewish children: 18 (10-30) and 15 (9-30) months, respectively (p Mann-Whitney = 0.312).

Conclusions: Good and progressively improving long-term results were obtained in pediatric kidney transplantation at our national referral center, apparently due to expertise gained over time and advances in immunosuppression. Equal access to DD kidney transplant and similar graft survival were found between ethnic groups.
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http://dx.doi.org/10.1007/s00467-020-04908-6DOI Listing
July 2021

Fluid overload and renal function in children after living-donor renal transplantation: a single-center retrospective analysis.

Pediatr Res 2021 Jan 11. Epub 2021 Jan 11.

Pediatric Intensive Care Unit, Tel Aviv University, Tel Aviv, Israel.

Background: We aimed to compare renal function after kidney transplantation in children who were treated with higher vs. lower fluid volumes.

Methods: A retrospective analysis of 81 living-donor renal transplantation pediatric patients was performed between the years 2007 and 2018. We analyzed associations of the decrease in serum creatinine (delta creatinine) with fluid balance, central venous pressure (CVP), pulmonary congestion, mean arterial pressure (MAP), and MAP-CVP percentiles in the first 3 postoperative days. After correcting creatinine for fluid overload, we also assessed associations of these variables with the above parameters. Finally, we evaluated the association between delta creatinine and estimated glomerular filtration rate (eGFR) at 3 months follow-up.

Results: Both delta creatinine and delta-corrected creatinine were found to be associated with pulmonary congestion on the second and third postoperative days (p < 0.02). In addition, trends for positive correlations were found of delta creatinine with fluid balance/kg (p = 0.07), and of delta-corrected creatinine with fluid balance/kg and CVP (p = 0.06-0.07) on the second postoperative day. An association was also demonstrated between the accumulated fluid balance of the first 2 days and eGFR at 3 months after transplantation (p = 0.03).

Conclusions: An association was demonstrated between indices of fluid overload, >80 ml/kg, and greater improvement in renal function.

Impact: There is no consensus regarding the optimal fluid treatment after pediatric renal transplantation. In our cohort, indices of fluid overload were associated with better renal function immediately after the transplantation and 3 months thereafter. Fluid overload after living-donor renal transplantation in children may have short- and long-term benefits on renal function.
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http://dx.doi.org/10.1038/s41390-020-01330-4DOI Listing
January 2021

Salivary Cytokines in Children with Nephrotic Syndrome versus Healthy Children: A Comparative Study.

J Clin Med 2020 Aug 20;9(9). Epub 2020 Aug 20.

Department of Pediatric Dentistry, Hadassah School of Dental Medicine, Hebrew University, Jerusalem 91905, Israel.

Background: The aims of this study were to compare salivary cytokines and total protein between children with nephrotic syndrome (NS) and healthy children, and to examine whether saliva parameters can differentiate between steroid sensitivity and resistance and between disease remission and relapse.

Methods: Twenty-seven children with nephrotic syndrome were classified according to steroid sensitivity and resistance, and disease remission and relapse. Twenty healthy children served as controls. Whole saliva samples were collected from all the participants. Urine and blood tests done on the same day as the saliva collection were recorded. Salivary total protein was quantified using bicinchoninic acid and IFNγ, IL-4, IL-8, IL-6, and IL1β levels using ELISA.

Results: The mean ages of the nephrotic syndrome and control groups were 11.3 ± 2.4 and 9 ± 4.2, respectively. Compared to the control group, for the nephrotic syndrome group, total salivary protein was significantly lower, as were the levels of all the cytokines examined except IFNγ. Statistically significant differences were not found in any of the salivary markers examined between the children with nephrotic syndrome who were treatment sensitive ( = 19) and resistant ( = 8). Protein and IL-8 salivary levels were lower in the active ( = 7) than in the remission ( = 20) group.

Conclusions: Salivary parameters distinguished children with nephrotic syndrome in relapse from healthy children. This may be due to decreased salivary protein excretion, which reflects decreased plasma levels, consequent to proteinuria. Accordingly, salivary markers may be developed as a diagnostic or screening tool for NS activity.
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http://dx.doi.org/10.3390/jcm9092691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563862PMC
August 2020

Infections in Children With Nephrotic Syndrome: Twenty Years of Experience.

Clin Pediatr (Phila) 2020 06 1;59(7):692-698. Epub 2020 Mar 1.

Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Infections is a common complication of nephrotic syndrome (NS). Our objective was to evaluate the frequency and risk factors for serious bacterial infections (SBI) in febrile children with NS. We reviewed 239 admissions of 107 children with NS who were admitted with fever to a tertiary hospital in Israel, during 1995 to 2016. SBI was diagnosed in 35 admissions (14.6%), most commonly with pneumonia (n = 12), bacteremia/sepsis (n = 8), and urinary tract infection (n = 6). Patients with SBI were more likely to be female (60.0% vs 36.3%, = .008) and have nephrotic-range proteinuria (71.4% vs 43.6%, = .010) and edema (62.9% vs 27.0%, < .001) on admission. No differences were found between the SBI and non-SBI groups in the clinical and histopathological type of NS, immunosuppressive treatment, rate of pneumococcal vaccination, and prophylactic antibiotics. In summary, 1 of 7 children had SBI, most commonly pneumonia, bacteremia/sepsis, and urinary tract infection. Active nephrosis was associated with an increased risk for SBI.
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http://dx.doi.org/10.1177/0009922820908583DOI Listing
June 2020

Lower prednisone dosing for steroid-sensitive nephrotic syndrome relapse: a prospective randomized pilot study.

Eur J Pediatr 2020 Feb 14;179(2):279-283. Epub 2019 Nov 14.

Institute of Nephrology, Schneider Children's Medical Center of Israel, 4920235, Petach Tikva, Israel.

Relapses of steroid-sensitive nephrotic syndrome are traditionally treated with prednisone 2 mg/kg/day or 60 mg/m/day. Retrospective data support the use of lower doses. We designed a prospective randomized pilot study to investigate the efficacy of different doses in achieving remission of steroid sensitive nephrotic syndrome relapse. The cohort included 30 children with relapsed steroid sensitive nephrotic syndrome, mean age 6.3 ± 3 years and mean disease duration 2.2 ± 1.8 years. The children were randomized to receive 2, 1.5, or 1 mg/kg/day prednisone. The corresponding times to response, defined as the first of 3 consecutive days without proteinuria, were 7.2 ± 1.4, 10.2 ± 5.1, and 9 ± 3.3 days; the difference between the 1.5 and 2 mg/kg/day groups was statistically significant. One patient each in the 1 mg/kg/day and the 1.5 mg/kg/day groups failed to respond and were switched to 2 mg/kg/day, leading to a response after 3 and 10 days, respectively. Mean cumulative prednisone doses in the 3 groups were 45.5 ± 3.4, 42.7 ± 25.9, and 24.9 ± 7.4 mg/kg, respectively (P < 0.05).Conclusion: In the present study, treatment of childhood steroid sensitive nephrotic syndrome relapse with prednisone 1-1.5 mg/kg/day led to a significantly lower cumulative dose than the standard dose. Treatment with a lower dose may be equally safe and effective to the standard dose.What is Known:• Relapses of steroid-sensitive nephrotic syndrome are traditionally treated with standard-dose steroids.• Treatment with corticosteroids may have significant adverse effects mainly with long-term use.What is New:• Treatment of steroid sensitive nephrotic syndrome relapse with 1-1.5 mg/kg/day prednisone may lead to a significantly lower cumulative dose.• Treatment with a lower steroid dose may be as effective as the standard dose in achieving remission of steroid sensitive nephrotic syndrome relapse.
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http://dx.doi.org/10.1007/s00431-019-03506-5DOI Listing
February 2020

Is eculizumab indicated in patients with atypical hemolytic uremic syndrome already on prolonged dialysis? A case report and review of the literature.

Pediatr Nephrol 2019 12 13;34(12):2601-2604. Epub 2019 Sep 13.

Department of Pediatric Nephrolgy, Schneider Children's Medical Center of Israel, 14 Kaplan St., Petah Tikva, Israel.

Background: Eculizumab has caused a revolution in the treatment and prognosis of atypical hemolytic uremic syndrome. Early initiation of treatment is recommended to increase chances of renal recovery.

Case-diagnosis/treatment: We describe a boy with atypical hemolytic uremic syndrome who started eculizumab therapy after being on dialysis for 4.5 months, with complete anuria. With treatment, he was weaned off dialysis.

Conclusion: We review the evidence in the literature and discuss the possible mechanism by which eculizumab induces renal recovery even in patients already on prolonged dialysis. This case report highlights the importance of a treatment trial with eculizumab, even in patients already on prolonged dialysis.
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http://dx.doi.org/10.1007/s00467-019-04341-4DOI Listing
December 2019

Response to erythropoietin in pediatric patients with chronic kidney disease: insights from an in vitro bioassay.

Pediatr Nephrol 2018 11 20;33(11):2123-2129. Epub 2018 Jul 20.

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel-Aviv University, 14 Kaplan St., Petah Tikva, Israel.

Background: Decreased production of erythropoietin (EPO) is a major cause of anemia associated with chronic kidney disease (CKD). Treatment with recombinant human EPO (rHuEPO) improves patients' quality of life and survival; however, there is a marked variability in response to rHuEPO. At present, no available laboratory test is capable of evaluating responsiveness to EPO treatment. The aim of the present study was to use an in vitro bioassay to estimate the effect of uremic environment on EPO-dependent erythroid cell proliferation.

Methods: EPO-dependent human erythroleukemia cells (UT-7) were incubated with exogenous EPO (2 u/ml) and sera obtained from 60 pediatric patients (aged 1-23 years). Three groups were studied: (1) 12 children on dialysis (4 peritoneal, 8 hemodialysis); (2) 28 patients with CKD 1-5 (not on dialysis), and (3) 20 healthy children.

Results: Sera from dialysis patients inhibited UT-7 cell growth compared to the CKD group and healthy controls at 48 h (p = 0.003 and p = 0.04, respectively) and 72 h of culture (p = 0.02 and p = 0.07, respectively). In 18 patients treated with rHuEPO, a significant inverse correlation was found between the EPO resistance index and cell proliferation at 48 h (p = 0.007, r = - 0.63) and 72 h (p = 0.03, r = - 0.52).

Conclusions: Our findings support the presence of erythropoiesis inhibitory substances in uremic sera. EPO/EPO-R-dependent mechanisms may play a role in inhibiting erythropoiesis. The in vitro bioassay described herein may serve as an indicator of rHuEPO responsiveness which may encourage further investigation of underlying mechanisms of EPO resistance.
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http://dx.doi.org/10.1007/s00467-018-4016-1DOI Listing
November 2018

Long-term Outcome of 1-step Kidney Transplantation and Bladder Augmentation Procedure in Pediatric Patients.

Transplantation 2018 06;102(6):1014-1022

Institute of Nephrology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Background: Guidelines for bladder augmentation (BA) in kidney transplantation (KT) recipients are not well-defined. In our center, simultaneous BA with KT (BA-KT) is performed. We assessed transplantation outcomes of this unique extensive procedure.

Methods: A case-control single center retrospective study. Transplantation outcomes were compared with those of KT recipients who did not need BA.

Results: Compared with 22 patients who underwent KT only, for 9 who underwent BA-KT, surgical complications and the need for revision in the early posttransplantation period were similar; early graft function was better: estimated glomerular filtration rate, 96.5 ± 17.1 versus 79.4 ± 16.6 mL/min at 0 to 6 months (P = 0.02); posttransplantation clean intermittent catheterization was more often needed: by 78% (7/9) versus 13% (3/22); and asymptomatic bacteriuria was more common: 100% versus 9% during the first 6 months (P < 0.001), 55% versus 9% (P = 0.02) and 66.6% versus 9% during the first and second years, respectively (P = 0.004). Urinary tract infection (UTI) incidence was also higher: 100% versus 23% during the first 6 months and 44% versus 9% during the second year posttransplantation. Graft function deteriorated significantly in the BA-KT group by the fifth posttransplantation year: estimated glomerular filtration rate was 47.7 ± 39.7 mL/min versus 69 ± 21.3 mL/min, with only 6 (66%) of 9 functioning grafts versus 100% in the KT only group. Causes of graft loss were noncompliance with drug therapy in 2 patients and recurrent UTIs in 2 patients.

Conclusions: Excellent short-term outcome for simultaneous BA-KT is threatened by graft loss due to a high prevalence of UTIs and patient noncompliance with the demanding complex posttransplantation therapy.
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http://dx.doi.org/10.1097/TP.0000000000002050DOI Listing
June 2018

Increasing Prevalence of Nephrolithiasis in Association with Increased Body Mass Index in Children: A Population Based Study.

J Urol 2018 04 20;199(4):1044-1049. Epub 2017 Oct 20.

Institute of Nephrology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Purpose: Epidemiological studies demonstrate an association of increased body mass index and risk of kidney stone formation in adults. We conducted a population based pediatric study to examine the epidemiology of nephrolithiasis in Israeli children during a 30-year period, and to determine body mass index distribution during the same period.

Materials And Methods: We accessed data from the compulsory medical evaluations of 17-year-old military service candidates in Israel before their enlistment during 1980 to 2013. Candidates for the army with a history of stone disease were compared to those without such a history.

Results: Of 1,908,893 candidates 1,691 reported a history of nephrolithiasis, yielding an average prevalence rate of 88.6 per 100,000. During 1980 to 1995 the average reported prevalence of nephrolithiasis was 69 cases per 100,000. From 1995 onward the reported prevalence increased by an average of 6% yearly, reaching 120 per 100,000 during 2010 to 2012. This increased prevalence was observed for males and females but was more prominent among males. Mean ± SD body mass index of stone formers was higher than that of controls (22.7 ± 3.5 vs 22.1 ± 3.9 kg/m, p <0.001). The trend of increasing body mass index among male candidates during 1995 to 2012 parallels the trend of increasing nephrolithiasis during these years. The odds ratio for nephrolithiasis in candidates with body mass index 30 or greater kg/m was 1.7 (range 1.4 to 2.1) compared to candidates with a body mass index of 18.5 to 24.9 kg/m.

Conclusions: This large, population based study documents an increasing prevalence of nephrolithiasis in children. The possible association of this finding with the increase in body mass index during the same period warrants further investigation.
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http://dx.doi.org/10.1016/j.juro.2017.10.023DOI Listing
April 2018

Headache in pediatric and adolescent patients with chronic kidney disease, with and without hemodialysis: A comparative cohort study.

Cephalalgia 2018 04 5;38(5):883-891. Epub 2017 Jul 5.

2 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background Several studies have reported dialysis-related headache in adults. We investigated headache and its characteristics in pediatric and adolescent patients with chronic kidney disease and patients treated with dialysis, and compared characteristics of patients with and without headache in the entire cohort and separately among dialysis and among chronic kidney disease patients. Methods Patients and their parents who attended a nephrology clinic and hemodialysis unit were interviewed regarding the existence of headache and its characteristics. We reviewed hospital files for medical history, blood test results, and pharmacologic treatment. Headache was defined according to International Headache Society criteria. Results The cohort comprised 60 patients: 39 with chronic kidney disease without hemodialysis and 21 treated with hemodialysis; 39 were males, mean age 11.9 ± 5.3 years. Twenty-six (43.3%) reported experiencing headaches. The hemodialysis group had a higher rate of headache than the chronic kidney disease patients, at 76.2% vs. 25.5%, p < 0.001. In the hemodialysis group, 15 out of 16 reported dialysis-related headache; 14 (87.5%) of these had migraine characteristics. For the entire cohort, headache was associated with hemodialysis, chronic kidney disease grade, lower glomerular filtration rate anemia and a higher parathyroid hormone level. In logistic regression analysis, glomerular filtration rate was significantly associated with headache, odds ratio 2.74 (95% CI 1.56-4.82, p < 0.001). Conclusions A high rate of headache, mostly migraine type, was reported by hemodialysis patients. Hemodialysis, anemia, higher parathyroid hormone levels, phosphate, and lower glomerular filtration rate are strongly associated with headache among chronic kidney disease pediatric and adolescent patients.
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http://dx.doi.org/10.1177/0333102417719235DOI Listing
April 2018

Serum Tumor Necrosis Factor-Alpha Levels in Children with Nephrotic Syndrome: A Pilot Study.

Isr Med Assoc J 2017 Jan;19(1):30-33

Department of Pediatric Nephrology Unit, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

Background: Several studies link the pathogenesis of nephrotic syndrome to tumor necrosis factor-alpha (TNFα). However, data on the serum TNFα level in children with nephrotic syndrome are sparse.

Objectives: To investigate serum TNFα levels and the effect of steroid therapy in children with nephrotic syndrome.

Methods: A prospective cohort pilot study of children with nephrotic syndrome and controls was conducted during a 1 year period. Serum TNFα levels were measured at presentation and at remission, or after a minimum of 80 days if remission was not achieved.

Results: Thirteen patients aged 2-16 years with nephrotic syndrome were compared with 12 control subjects. Seven patients had steroid-sensitive and six had steroid-resistant nephrotic syndrome. Mean baseline serum TNFα level was significantly higher in the steroid-resistant nephrotic syndrome patients than the controls (6.13 pg/ml vs. 4.36 pg/ml, P = 0.0483). Mean post-treatment TNFα level was significantly higher in the steroid-resistant than in the steroid-sensitive nephrotic syndrome patients (5.67 pg/ml vs. 2.14 pg/ml, P = 0.001). In the steroid-resistant nephrotic syndrome patients, mean serum TNFα levels were similar before and after treatment.

Conclusions: Elevated serum TNFα levels are associated with a lack of response to corticosteroids. Further studies are needed to investigate the role of TNFα in the pathogenesis of nephrotic syndrome.
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January 2017

Nephrologists need to play a key role in improving annual influenza vaccination rates in children with kidney disease.

Acta Paediatr 2017 May 23;106(5):812-818. Epub 2017 Feb 23.

Pediatric Infectious Disease Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Aim: This study investigated the under-researched area of annual influenza vaccination rates in children with chronic kidney disease and identified reasons for nonimmunisation.

Methods: A prospective cross-sectional study was conducted in the nephrology clinic and dialysis unit of a tertiary paediatric medical centre from August to October 2011 and September to October 2012. Parents were asked to complete a questionnaire on their child's immunisation against influenza.

Results: Of the 217 children studied, 45.6% were vaccinated against influenza. The major reason for nonimmunisation was because the parents had not received the necessary information from the primary physician or treating nephrologist. The nonvaccinated children were significantly more likely to be less than two years old and female and to have parents who did not believe in the benefits of vaccination (p < 0.05). Of the parents who did not vaccinate their child, 38% claimed they would have done so if the vaccine had been offered in the nephrology clinic.

Conclusion: Children with kidney disease had a higher annual influenza vaccination rate than the general population, but it was still suboptimal. Nephrologists should be alerted to the need to provide parents with information on influenza vaccinations and they should be available in nephrology clinics.
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http://dx.doi.org/10.1111/apa.13763DOI Listing
May 2017

Children after renal transplantation hospitalized for fever: Is empirical antibiotic treatment always justified?

Pediatr Transplant 2017 Mar 2;21(2). Epub 2017 Jan 2.

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Infections are a major cause of morbidity and mortality after renal transplantation. However, data focusing on children are scarce. The objective of this study was to investigate the frequency and predictors of bacterial infection in pediatric renal transplant recipients in a specific setting of hospitalization due to fever. Clinical and laboratory data were retrospectively collected for all pediatric renal transplant recipients hospitalized for fever in a national renal transplantation center from 2004 to 2012. One hundred and sixty-eight hospital admissions for fever of 52 children were analyzed. A bacterial etiology was diagnosed in 85 admissions (50.6%); 49 cases (57.6%) were documented microbiologically and 36 (42.4%) clinically. Risk factors and markers of bacterial infection included older age, presence of a central venous catheter, sonographic findings, and elevated inflammatory indices. C-reactive protein level was a more sensitive marker than white blood cell count and absolute neutrophil count. In patients without identified risk factors, no bacterial infections were diagnosed. Pediatric renal transplant recipients hospitalized for fever are at high risk of bacterial infections and usually require empirical antibiotic treatment at admission. However, there is a minority of low-risk patients in whom clinicians may consider withholding antibiotic treatment with close follow-up.
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http://dx.doi.org/10.1111/petr.12862DOI Listing
March 2017

Anemia and markers of erythropoiesis in pediatric kidney transplant recipients compared to children with chronic renal failure.

Pediatr Transplant 2016 Nov 12;20(7):958-962. Epub 2016 Sep 12.

Institute of Nephrology, Schneider Children's Medical Center of Israel, Petach Tikvah, Israel.

PTA and anemia of CKD share a similar pathogenesis. However, PTA may be disproportionate to the reduction in the GFR. Data relating to the mechanism of PTA are scarce. We evaluated the erythropoiesis parameters in pediatric kidney recipients compared to children with CKD. A total of 100 patients (54 post-kidney TX, 46 with CKD) were enrolled in the single-center cohort study. GFR was found to be significantly lower in the CKD group (49.7±22.4 vs 72.9±28.5 mL/min/1.73 m², P<.001); anemia was significantly more common in the TX patients (52% vs 41.3%, P<.001). Iron transferrin saturation and serum ferritin levels were lower in the CKD patients. In both groups, hemoglobin Z scores significantly correlated with GFR (R=.31, P=.07). This correlation was more prominent in the CKD group (R=.43, P=.008) compared to the TX group (R=.31, P=.04). Anemia was significantly more common in the TX patients than in the CKD patients despite a better GFR. The higher prevalence of anemia in the TX group could not be explained by an iron deficiency or reduced EPO production. We speculate that immunosuppressive therapy together with resistance to EPO may play a role in the pathogenesis of post-transplantation anemia.
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http://dx.doi.org/10.1111/petr.12792DOI Listing
November 2016

Yield and complications of kidney biopsy over two decades in a tertiary pediatric center.

Pediatr Int 2017 Apr;59(4):452-457

Institute of Pediatric Nephrology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Background: Kidney biopsy serves as an adjunct for the diagnosis of renal disease, but it is not always productive. This study evaluated the yield and risks of kidney biopsies performed in 1995-2014 at a tertiary pediatric medical center.

Methods: The medical files of all patients who underwent closed percutaneous biopsy for various indications in native or transplanted kidneys were retrospectively reviewed for patient characteristics, technical and histopathologic findings, biopsy yield, and biopsy complications. Biopsy yield was considered positive if findings confirmed a probable diagnosis or led to a change in clinical diagnosis, disease severity/activity grade, treatment strategy, or prognosis; and negative, if findings were non-informative and in cases of technical failure.

Results: During the study period, 216 biopsies were performed on native kidneys and 84 on transplanted kidneys. In the transplanted kidney group, the most common indications for biopsy were decreased glomerular filtration rate and suspected rejection. Rates of positive biopsy yield were 86.6% in the native kidney group and 82.1% in the transplanted kidney group; the difference was not statistically significant. Significant between-group differences were found in various technical and histopathological parameters, patient age at biopsy, and sex distribution. In the native kidney group, positive biopsy yield was associated with the presence of nephrotic-range proteinuria. Post-procedural complications occurred in three patients (1.3%) with native kidneys, and in one patient (1.1%) with a transplanted kidney.

Conclusions: Kidney biopsy is an efficient and safe procedure in both native and transplanted kidneys and provides helpful diagnostic information in most cases in which it is deemed necessary.
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http://dx.doi.org/10.1111/ped.13182DOI Listing
April 2017

Impact of Pediatric Chronic Dialysis on Long-Term Patient Outcome: Single Center Study.

Int J Nephrol 2016 15;2016:2132387. Epub 2016 Aug 15.

Institute of Nephrology, Schneider Children's Medical Center of Israel, 49202 Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, 6997801 Tel Aviv, Israel.

Objective. Owing to a shortage of kidney donors in Israel, children with end-stage renal disease (ESRD) may stay on maintenance dialysis for a considerable time, placing them at a significant risk. The aim of this study was to understand the causes of mortality. Study Design. Clinical data were collected retrospectively from the files of children on chronic dialysis (>3 months) during the years 1995-2013 at a single pediatric medical center. Results. 110 patients were enrolled in the study. Mean age was 10.7 ± 5.27 yrs. (range: 1 month-24 yrs). Forty-five children (42%) had dysplastic kidneys and 19 (17.5%) had focal segmental glomerulosclerosis. Twenty-five (22.7%) received peritoneal dialysis, 59 (53.6%) hemodialysis, and 6 (23.6%) both modalities sequentially. Median dialysis duration was 1.46 years (range: 0.25-17.54 years). Mean follow-up was 13.5 ± 5.84 yrs. Seventy-nine patients (71.8%) underwent successful transplantation, 10 (11.2%) had graft failure, and 8 (7.3%) continued dialysis without transplantation. Twelve patients (10.9%) died: 8 of dialysis-associated complications and 4 of their primary illness. The 5-year survival rate was 84%: 90% for patients older than 5 years and 61% for younger patients. Conclusions. Chronic dialysis is a suitable temporary option for children awaiting renal transplantation. Although overall long-term survival rate is high, very young children are at high risk for life-threatening dialysis-associated complications.
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http://dx.doi.org/10.1155/2016/2132387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002458PMC
September 2016

Focal segmental glomerulosclerosis in pediatric kidney transplantation: 30 years' experience.

Clin Transplant 2016 10;30(10):1324-1331

Institute of Nephrology, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.

From 1982 to 2011, 53 kidney transplantations (KT) for pediatric focal segmental glomerulosclerosis (FSGS) were recorded in the National Israeli Kidney Transplant Registry (NIKTR): 22-primary (1◦) FSGS, 25-proved/suspected genetic-secondary (2◦) FSGS, six lost/incomplete files/other. Half (56%) of 23 patients with 2◦ FSGS were Israeli-Arabs vs 29% of 1◦ FSGS KT recipients. 1◦ FSGS recurrence occurred in 64% (14/22) of 22 KT in 17 patients aged (median) 14 years vs 1/25 of 2◦ FSGS (P<.001). Early graft days/nonfunction occurred in 9/14 (64%), 2/8 (25%) and 2/25 (4%) of recurrent 1◦ FSGS (rFSGS), nonr1◦ FSGS and 2◦ FSGS, respectively. Twelve biopsies performed in nine of these grafts at (median) 8 days (range 5-60 days) post-KT showed: ATN-5, suspected rejection-4, rFSGS-2, normal kidney-1; rFSGS was diagnosed eventually in 8/9. Dialysis need during the first month post-KT was significantly associated with FSGS recurrence: 6/14 (43%) for rFSGS vs 2/8 (25%) for non-rFSGS. Plasmapheresis (PP) achieved complete and partial rFSGS remission in 5/9 and 2/9 grafts, respectively. Three grafts were excised during the first 60 days post-KT for: nonfunction (1) and bleeding (2). Remaining grafts' GFR was: 78, 42, and 91 mL/min (median) at 5.3, 4.75, and 8 years follow-up for non-rFSGS, rFSGS, and 2◦ FSGS grafts, respectively.

Conclusions: Early PP implementation should be considered after KT for 1◦ FSGS patients with early graft dysfunction despite delayed proteinuria and nonspecific biopsy.
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http://dx.doi.org/10.1111/ctr.12825DOI Listing
October 2016

Post-Infectious Glomerulonephritis in Pediatric Patients over Two Decades: Severity-Associated Features.

Isr Med Assoc J 2016 Jun;18(6):336-40

Background: The incidence of post-infectious glomerulonephritis (PIGN) has decreased over the last decades. As a result, recent epidemiological data from industrialized countries are scarce.

Objectives: To evaluate patterns of PIGN in children and detect possible predictors of disease severity.

Methods: We collected clinical and laboratory data of patients with PIGN admitted to Schneider Children's Medical Center during 1994-2011. Diagnostic criteria included presence of hematuria with/without other features of nephritic syndrome along with hypocomplementemia and/or microbiological/serological evidence of streptococcal infection. Patients with other diseases (systemic lupus erythematosus, vasculitis, etc.) were excluded from the study.

Results: A total of 125 patients with a mean age of 5.8 ± 3.3 years (range 1.5-17.6), of whom 16% were < 3 years, matched the study criteria. Presenting features included hypertension in 103 (82.4%) patients, azotemia in 87 (70.2%), fever in 49 (40/6), and elevated C-reactive protein in 75 (81.5%). Isolated macrohematuria was found in 21 (16%). Full-blown nephritic syndrome was diagnosed in 51 patients (41.1%) and 28 (22.9%) had nephritic syndrome with nephrotic-range proteinuria. Depressed C3 complement levels were associated with the presence of nephritic syndrome (OR 0.73, 95% CI 0.60-0.88, P = 0.001) as well as older age (OR 1.24, Cl 1.08-1.43, P = 0.001). At last follow-up (mean 42 months) all examined patients (100 of 125) had normal renal function, 6 had hypertension, and 1 had proteinuria.

Conclusions: PIGN remains an important cause of glomerular disease in children and may affect very young patients. Nephrotic-range proteinuria with hypoalbuminemia seems to be more frequent than previously reported. Hypocomplementemia is associated with a more severe disease course, namely, azotemia and nephritic syndrome.
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June 2016

Loss of function of NaPiIIa causes nephrocalcinosis and possibly kidney insufficiency.

Pediatr Nephrol 2016 12 4;31(12):2289-2297. Epub 2016 Jul 4.

Institute of Physiology, University of Zurich, Zurich, Switzerland.

Background: Inherited metabolic disorders associated with nephrocalcinosis are rare conditions. The aim of this study was to identify the genetic cause of an Israeli-Arab boy from a consanguineous family with severe nephrocalcinosis and kidney insufficiency.

Methods: Clinical and biochemical data of the proband and family members were obtained from both previous and recent medical charts. Genomic DNA was isolated from peripheral blood cells. The coding sequence and splice sites of candidate genes (CYP24A1, CYP27B1, FGF23, KLOTHO, SLC34A3 and SLC34A1) were sequenced directly. Functional studies were performed in Xenopus laevis oocytes and in transfected opossum kidney (OK) cells.

Results: Our patient was identified as having nephrocalcinosis in utero, and at the age of 16.5 years, he had kidney insufficiency but no bone disease. Genetic analysis revealed a novel homozygous missense mutation, Arg215Gln, in SLC34A1, which encodes the renal sodium phosphate cotransporter NaPiIIa. Functional studies of the Arg215Gln mutant revealed reduced transport activity in Xenopus laevis oocytes and increased intracellular cytoplasmic accumulation in OK cells.

Conclusions: Our findings show that dysfunction of the human NaPiIIa causes severe renal calcification that may eventually lead to reduced kidney function, rather than complications of phosphate loss.
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http://dx.doi.org/10.1007/s00467-016-3443-0DOI Listing
December 2016

Is serum CRP level a reliable inflammatory marker in pediatric nephrotic syndrome?

Pediatr Nephrol 2016 08 8;31(8):1287-93. Epub 2016 Mar 8.

Institute of Pediatric Nephrology, Schneider Children's Medical Center of Israel, Petach Tikva, 49202, Israel.

Background: This study tested the hypothesis that during massive proteinuria, C-reactive protein (CRP) may be lost into the urine along with other proteins, making serum CRP (sCRP) level an unreliable marker of infection severity in nephrotic syndrome (NS).

Methods: Children with active NS (n = 23) were compared with two matched control groups: patients with febrile non-renal infectious disease (n = 30) and healthy subjects (n = 16). Laboratory measurements included sCRP, urine protein, creatinine, IgG, and protein electrophoresis. Urinary CRP (uCRP) was measured by ELISA.

Results: Sixty-nine patients were enrolled: 23 patients with NS, 30 patients with non-renal febrile infectious diseases, and 16 healthy children. Median uCRP concentrations were 0 mcg/gCr (0-189.7) in NS, 11 mcg/gCr (0-286) in the febrile group, and 0 mcg/gCr (0-1.8) in the healthy group. The uCRP/creatinine ratio was similar in the NS and healthy groups (p > 0.1) and significantly higher in the febrile group than the other two groups (p < 0.0001). There was no association of uCRP concentration with severity of proteinuria or IgG excretion.

Conclusions: NS in children is not characterized by significant loss of CRP into the urine. Therefore, sCRP may serve as a reliable marker of inflammation in this setting. The significant urinary excretion of CRP in children with transient non-renal infectious disease might be attributable to CRP synthesis in renal epithelial cells.
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http://dx.doi.org/10.1007/s00467-016-3328-2DOI Listing
August 2016

Novel factor H mutation associated with familial membranoproliferative glomerulonephritis type I.

Pediatr Nephrol 2015 Dec 20;30(12):2129-34. Epub 2015 Aug 20.

Institute of Nephrology, Schneider Children's Medical Center of Israel, Petach, Tikva, Israel, 49202.

Background: Idiopathic membranoproliferative glomerulonephritis (MPGN) is a rare disease, accounting for 3-5% of all cases of primary nephritic syndrome. We report an uncommon case of familial MPGN type I associated with a new mutation in the complement factor H gene (CFH).

Methods: Clinical data were collected on three siblings with known factor H deficiency who presented with MPGN. All underwent immunological and genetic assays. Their parents and ten healthy adults served as controls for the DNA analysis.

Results: All three children presented with recurrent episodes of hematuria and proteinuria, the youngest starting at age 5 months. One child currently has nephrotic syndrome and end-stage renal disease. All of the children were found to be homozygous for a C.262C > A (p.Pro88Thr) mutation in exon 3 of CFH that is associated with a quantitative/functional deficiency of factor H. The parents of the three siblings were found to be heterozygous for the mutation. None of the controls carried this mutation.

Conclusions: Different mutations in CFH may be responsible for different glomerular diseases, including MPGN type I. A modifier gene or an environmental trigger may contribute to this phenotype-genotype discrepancy. Understanding the role of the alternative complement pathway in this disease would allow us to offer these patients more targeted therapy, including a clinical trial of eculizumab.
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http://dx.doi.org/10.1007/s00467-015-3166-7DOI Listing
December 2015

Prenatal sonographic predictors of postnatal pyeloplasty in fetuses with isolated hydronephrosis.

Prenat Diagn 2015 Feb 2;35(2):142-7. Epub 2014 Nov 2.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objective: To define prenatal sonographic predictors of ureteropelvic junction obstruction requiring postnatal pyeloplasty, in fetuses with isolated hydronephrosis.

Methods: Retrospective data on prenatal sonographic parameters were compared between patients who had been diagnosed prenatally with hydronephrosis and either underwent postnatal pyeloplasty for ureteropelvic junction obstruction (n = 39) or were treated conservatively (n = 30).

Results: Significant differences between the surgically and conservatively treated patients were found for mean anterior-posterior renal diameter (22.8 ± 8.6 vs 14.2 ± 5.9 mm, respectively, p < 0.0001) and parenchymal thickness (5.9 ± 2.8 vs 8.1 ± 2.6 mm, p = 0.009). Anterior-posterior diameter >14 mm was the best single predictor of the need for surgery (area under the ROC curve, 0.817), with sensitivity 77%, specificity 69%, positive predictive value (PPV) 77% and negative predictive value (NPV) 69% (β = 1.17, 95%CI = 1.07-1.28, p < 0.001). Mean ratio of anterior-posterior diameter to parenchymal thickness was significantly higher in the postnatal pyeloplasty group (5.4 ± 4.5 vs 2.1 ± 1.4, p = 0.0001). A ratio >2.1 had a sensitivity of 87% and specificity of 65% for the need for surgery (area under the curve 0.822, PPV 79%, NPV 77%; β = 1.92, 95%CI = 1.16-3.17, p < 0.001).

Conclusion: In cases of prenatal isolated hydronephrosis, the pelvic anterior-posterior diameter and parenchymal thickness may predict the need for postnatal pyeloplasty. A ratio of >2.1 of pelvic anterior-posterior diameter to parenchymal thickness suggests ureteropelvic junction obstruction and supports the use of more intensive prenatal and postnatal surveillance.
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http://dx.doi.org/10.1002/pd.4505DOI Listing
February 2015

Maternal and infantile hypercalcemia caused by vitamin-D-hydroxylase mutations and vitamin D intake.

Pediatr Nephrol 2015 Jan 7;30(1):145-52. Epub 2014 Sep 7.

Department of Nephrology and Hypertension, The Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, 52621, Israel,

Background: Hypercalcemia is caused by many different conditions and may lead to severe complications. Loss-of-function mutations of CYP24A1, encoding vitamin D-24-hydroxylase, have recently been identified in idiopathic infantile hypercalcemia and in adult kidney stone disease. The aim of this study was to investigate the genetics and clinical features of both infantile and maternal hypercalcemia.

Methods: We studied members of four unrelated Israeli families with hypercalcemia, namely, one woman during pregnancy and after delivery and three infants. Clinical and biochemical data were obtained from probands' medical charts. Genomic DNA was isolated from peripheral blood and CYP24A1 was sequenced.

Results: Typical symptoms of hypercalcemia associated with the intake of recommended doses of vitamin D developed in the infants and pregnant woman. Four different loss-of-function CYP24A1 mutations were identified, two of which are reported here for the first time (p.Trp134Gly and p.Glu315*). The infants from families 1 and 2, respectively, were found to be compound heterozygotes, and the infant from family 3 and the pregnant woman were found to be homozygous.

Conclusions: This is the first report of maternal hypercalcemia caused by a CYP24A1 mutation, showing that not only infants are at risk for this complication. Our findings emphasize the importance of recognition, genetic diagnosis and proper treatment of this recently identified hypercalcemic disorder in this era of widespread vitamin D supplements.
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http://dx.doi.org/10.1007/s00467-014-2889-1DOI Listing
January 2015

Atypical HUS due to factor H antibodies in an adult patient successfully treated with eculizumab.

Ren Fail 2014 Aug 15;36(7):1119-21. Epub 2014 May 15.

Department of Nephrology and Hypertension, Rabin Medical Center , Petah-Tikva , Israel .

Background: Anti-complement factor H (CFH) antibodies is an extremely rare cause of atypical hemolytic uremic syndrome (aHUS) in adults, with less than 10 cases reported thus far. Although infectious diarrhea is a common inciting trigger for aHUS episode, there are no reports of an association with inflammatory bowel disease. Eculizumab is an emerging treatment for aHUS. Eculizumab has not been reported thus far to be given for aHUS due to anti-CFH antibodies. We report here for the first time on an adult patient with ulcerative colitis (UC) who developed aHUS due to anti-CFH antibodies, presented with decreased serum levels of both C3 and C4. She had an excellent response to treatment with eculizumab.

Case Presentation: A 27-year-old Caucasian woman, who suffered from steroid-dependent UC, was admitted with microangiopathic hemolytic anemia and acute kidney injury with nephrotic syndrome. ADAMTS 13 was normal and comprehensive workout for secondary causes of HUS was negative. Both serum complement level of C3 and C4 were low. Kidney biopsy was compatible with the diagnosis of HUS with negative immunofluorescence. Because of only partial response to plasma exchange and high dose steroids, eculizumab was commenced. After two weeks signs of microangiopathy subsided, and kidney function began to recover. Few months after the diagnosis, a complement components investigation revealed antibodies against CFH at high titer of 2000 arbitrary units. Today her creatinine is stable with no proteinuria and no signs of HUS.
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http://dx.doi.org/10.3109/0886022X.2014.917574DOI Listing
August 2014

Cardiovascular risk factors in children after kidney transplantation--from short-term to long-term follow-up.

Pediatr Transplant 2014 Feb 18;18(1):23-8. Epub 2013 Oct 18.

Pediatric Nephrology, Schneider Children Medical Center, Petach Tikva, Israel.

Cardiovascular-related mortality is 100-fold higher in pediatric renal transplant recipients than in the age-matched general population. Seventy-seven post-renal transplant children's charts were reviewed for cardiovascular risk factors at two and six months after transplantation (short term) and at two yr after transplantation and the last follow-up visit (mean 7.14 ± 3.5 yr) (long term). Significant reduction was seen in cardiovascular risk factors prevalence from two months after transplantation to last follow-up respectively: Hypertension from 52.1% to 14%, hypercholesterolemia from 48.7% to 33%, hypertriglyceridemia from 50% to 12.5%, anemia from 29.6% to 18.3%, hyperparathyroidism from 32% to 18.3% and hyperglycemia from 11.7% to 10%, and left ventricular hypertrophy from 25.8% at short term to 15%. There was an increase in the prevalence of obesity from 1.5% to 3.9% and of CKD 3-5 from 4.75% to 24%. The need for antihypertensive treatment decreased from 54% to 42%, and the percentage of patients controlled by one medication rose from 26% to 34%, whereas the percentage controlled by 2, 3, and 4 medications decreased from 21.9%, 5.5%, and 1.4% to 6%, 2%, and 0. Children after renal transplantation appear to have high rates of cardiovascular risk factors, mainly on short-term follow-up.
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http://dx.doi.org/10.1111/petr.12174DOI Listing
February 2014

Long-term follow-up evaluation of renal function in patients treated with peritoneal dialysis after cardiac surgery for correction of congenital anomalies.

J Thorac Cardiovasc Surg 2014 Jan 30;147(1):451-5. Epub 2013 Apr 30.

Pediatric Cardiac Intensive Care Unit, Schneider Children's Medical Center of Israel, Petach Tikva, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Available data on the long-term renal outcome of patients who required renal replacement therapy after cardiac surgery for correction of congenital cardiac anomalies are scarce. The aim of the present study was to investigate the long-term renal prognosis of children treated with peritoneal dialysis after surgical correction of congenital heart anomalies.

Methods: The present single-center cohort study was based on clinical data from patients who underwent surgery for the correction of congenital heart disease between 1996 and 2004 at the Schneider's Children's Medical Center of Israel, and developed acute kidney injury (AKI) requiring peritoneal dialysis. Perioperative risk factors were analyzed. Survivors were followed up for 3.5 to 10.5 years after their surgery. Renal function was assessed in survivors by physical examination, including blood pressure, growth evaluation, urinalysis, glomerular filtration rate estimated from plasma creatinine using the Schwartz formula, and ultrasonographic examination of the kidneys.

Results: There were 2994 children who underwent surgery during the study period. Eighty-four children (2.84%) developed postoperative AKI that was managed with peritoneal dialysis. Seventy-six children were included in our study, 8 were excluded because of a lack of complete data. Of the 76 children included, 35 died during the immediate postoperative period, 15 died during the interim of nonrenal causes, and 26 were alive at the time of follow-up evaluation. Twenty-five patients with a complete evaluation had blood pressure measurements in the normal range. Plasma creatinine levels were normal for age. Only 1 child, who had a pre-existing congenital renal anomaly, had an abnormal glomerular filtration rate. None of the children had proteinuria. Three children were treated with angiotensin-converting enzyme inhibitors and 2 were treated with furosemide for congestive heart failure. We found no risk factors associated with immediate postoperative death.

Conclusions: Despite the development of AKI requiring dialysis after surgical correction of congenital cardiac anomalies, the long-term renal prognosis in survivors is good.
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http://dx.doi.org/10.1016/j.jtcvs.2013.03.032DOI Listing
January 2014

Renal hypodysplasia associates with a WNT4 variant that causes aberrant canonical WNT signaling.

J Am Soc Nephrol 2013 Mar 21;24(4):550-8. Epub 2013 Mar 21.

Department of Pediatrics, Talpiot Medical Leadership Program, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Abnormal differentiation of the renal stem/progenitor pool into kidney tissue can lead to renal hypodysplasia (RHD), but the underlying causes of RHD are not well understood. In this multicenter study, we identified 20 Israeli pedigrees with isolated familial, nonsyndromic RHD and screened for mutations in candidate genes involved in kidney development, including PAX2, HNF1B, EYA1, SIX1, SIX2, SALL1, GDNF, WNT4, and WT1. In addition to previously reported RHD-causing genes, we found that two affected brothers were heterozygous for a missense variant in the WNT4 gene. Functional analysis of this variant revealed both antagonistic and agonistic canonical WNT stimuli, dependent on cell type. In HEK293 cells, WNT4 inhibited WNT3A induced canonical activation, and the WNT4 variant significantly enhanced this inhibition of the canonical WNT pathway. In contrast, in primary cultures of human fetal kidney cells, which maintain WNT activation and more closely represent WNT signaling in renal progenitors during nephrogenesis, this mutation caused significant loss of function, resulting in diminished canonical WNT/β-catenin signaling. In conclusion, heterozygous WNT4 variants are likely to play a causative role in renal hypodysplasia.
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http://dx.doi.org/10.1681/ASN.2012010097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609130PMC
March 2013

Severe Bordetella pertussis infection associated with hemolytic uremic syndrome.

Isr Med Assoc J 2012 Jul;14(7):456-8

Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petah Tikva, affiliated with Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.

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July 2012