Publications by authors named "Orly Haskin"

13 Publications

  • Page 1 of 1

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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February 2021

Peri-transplant aminophylline in pediatric kidney transplant recipients of donation after brain death: a double-blinded placebo-controlled randomized clinical trial.

Pediatr Nephrol 2020 09 16;35(9):1729-1736. Epub 2020 May 16.

Department of Pediatrics (Nephrology), Stanford University School of Medicine, Stanford, CA, USA.

Background: During kidney transplantation, the transplanted kidney undergoes ischemia reperfusion injury, with adenosine being a major mediator. This study aimed to assess whether aminophylline, an adenosine receptor antagonist, improves early graft function and reduces incidence of delayed graft function (DGF) and slow graft function (SGF).

Methods: Single center, double-blinded, placebo-controlled randomized clinical trial. Pediatric patients admitted for renal transplantation from donation after brain death donors were randomized into a treatment arm receiving aminophylline and a placebo arm receiving normal saline infusions. Primary outcome was estimated glomerular filtration rate (eGFR) at 5 days post-transplant. Secondary outcomes were rates of DGF/SGF and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels.

Results: Twenty-three patients were randomized to aminophylline and 27 to placebo. There was no difference in day 5 eGFR, rate of DGF/SGF, or urine NGAL/Creatinine level between aminophylline vs. placebo arm (eGFR 67.39 ± 38.9 ml/min/1.73m vs. 80.48 ± 52.1 ml/min/1.73mp = 0.32; DGF/SGF 5/23 (21.7%) vs. 3/27 (11.1%) p = 0.31; urine NGAL/creatinine 300.5 ng/mg IQR 105.5-1464.5 ng/mg vs. 425.4 ng/mg IQR 140.3-1126.2 ng/mg, p = 0.95; respectively). At 12 months, there was 100% patient survival and 98% graft survival. eGFR at 12 months was similar between the two arms.

Conclusions: There was no benefit in peri-transplant aminophylline administration. Our results are limited by small sample size, since sample calculations were based on primary outcome of day 5 eGFR and low rate of DGF/SGF, which may have precluded us from demonstrating efficacy. Further clinical studies are necessary to determine any benefit of aminophylline in kidney transplant recipients, particularly from high-risk donors.
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September 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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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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December 2019

Prevalence of acute kidney injury after liver transplantation in children: Comparison of the pRIFLE, AKIN, and KDIGO criteria using corrected serum creatinine.

J Crit Care 2019 04 14;50:275-279. Epub 2019 Jan 14.

Department of Pediatric Gastroenterology, Schneider Children's Medical Center of Israel, Petach Tikva, Affiliated With Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Purpose: To compare the application of three standardized definitions of acute kidney injury (AKI), using corrected serum creatinine values, in children immediately after liver transplantation.

Methods: Retrospective search of a tertiary pediatric hospital database yielded 77 patients (age < 18 years) who underwent liver transplantation in 2007-2017. Serum creatinine levels during the 24 h before and after surgery were corrected to daily fluid balance, and the prevalence of AKI was calculated using the Pediatric RIFLE (pRIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) criteria.

Results: AKI occurred in 44 children (57%) according to the pRIFLE criteria (stage I, 34%; stage II, 10%, stage III, 13%) and 33 children (43%) according to the AKIN and KDIGO criteria (stage I, 20%; stage II, 10%; stage III, 13%). There was a good correlation (kappa = 0.78) among the three criteria. AKI was associated with longer duration of mechanical ventilation (5.5 ± 6.2 vs 3.6 ± 4.0 days, p < .05) and longer ICU stay (15.2 ± 8.8 vs 12.1 ± 7.5 days, p < .05). Serum creatinine normalized in all patients (mean, 0.43 ± 0.17 mg/dl) by one year.

Conclusions: There is a good correlation among the three criteria defining AKI in pediatric liver transplant recipients. AKI is highly prevalent in this patient group and confers a worse ICU course.
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April 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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November 2018

A novel outpatient desensitization protocol for recombinant human erythropoietin allergy in a pediatric patient.

Allergy Asthma Clin Immunol 2018 12;14. Epub 2018 Mar 12.

1Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Stanford University School of Medicine, 269 Campus Drive, CCSR 3215, MC 5366, Stanford, CA 94305 USA.

Background: Recombinant human erythropoietin, such as epoetin alfa and darbepoetin alfa, is an important therapy for anemia due to chronic renal failure. Allergy to recombinant human erythropoietin and the need for desensitization are rare.

Case Presentation: We report here a novel epoetin alfa outpatient desensitization protocol in a girl who developed delayed cutaneous hypersensitivity to subcutaneous epoetin alfa and intravenous darbepoetin alfa. An initial attempt at traditional epoetin alfa desensitization failed, so we created a slower 17-day outpatient desensitization that succeeded and allowed treatment continuation.

Conclusions: This case highlights the notion that delayed-type hypersensitivity to recombinant human erythropoietin can occur as evident by reproducible reactions after repeated exposures and slow outpatient desensitization can be considered when a trial of more rapid induction of tolerance is unsuccessful.
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March 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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April 2018

The Effect of Intradialytic Intralipid Therapy in Pediatric Hemodialysis Patients.

J Ren Nutr 2017 03 5;27(2):132-137. Epub 2016 Dec 5.

Pediatric Nephrology Department, Stanford University School of Medicine, Stanford, California.

Objective: Growth of children on maintenance hemodialysis is poor. Oral nutritional supplements are the preferred way to augment nutrition; however, many children have difficulties adhering to prescribed oral supplements. In our unit, we have been utilizing intralipid (IL) therapy as nutritional supplement during hemodialysis sessions. The aim of this study was to assess the safety, efficacy, and benefits of intradialytic IL therapy.

Design: A retrospective chart review.

Subjects: Fifteen pediatric hemodialysis patients receiving intradialytic IL therapy for at least 3 months from July 2011 through July 2014.

Main Outcome Measure: For each patient, anthropometric measurements and laboratory nutritional parameters were compared prior to and at the end of IL therapy. Anthropometric measurements evaluated were dry weight, height, body mass index (BMI), and BMI corrected for height age. Laboratory nutritional parameters evaluated were albumin, normalized protein catabolic rate, predialysis blood urea nitrogen, transferrin, cholesterol, and triglyceride levels. Adverse events during therapy were also noted.

Results: Significant improvement was noted in albumin levels, predialysis blood urea nitrogen, and normalized protein catabolic rate during therapy (P = .02; P = .03; P = .03, respectively). Six patients (37.5%) improved their weight standard deviation score, and eight patients (50%) improved their BMI standard deviation score though not statistically significant (P = .59; P = .9, respectively). No significant side effects were noted.

Conclusions: Administration of IL alone during hemodialysis is well tolerated with beneficial effects on nutritional parameters. The provision of IL alone is relatively cheap and does not require additional resources. In conjunction with other measures of nutritional support, it can help improve nutritional status of pediatric hemodialysis patients.
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March 2017

44-h ambulatory blood pressure monitoring: revealing the true burden of hypertension in pediatric hemodialysis patients.

Pediatr Nephrol 2015 Apr 26;30(4):653-60. Epub 2014 Sep 26.

Division of Nephrology, Department of Pediatrics, Stanford University, 300 Pasteur Drive, Room G306, Stanford, CA, 94305-5208, USA.

Background: The blood pressure (BP) burden is high in pediatric hemodialysis (HD) patients and adversely affects prognosis. The aim of this study was to examine whether 44-h ambulatory BP monitoring (ABPM) provides additional relevant BP data compared with 24-h ABPM.

Methods: ABPM was initiated at the end of the mid-week dialysis run in 13 stable pediatric HD patients and continued until the next run for 44 h. Day 1 was defined as the initial 24-h ABPM and Day 2 as the time period after that until the next dialysis run. All patients had an echocardiogram to calculate the left ventricular mass index (LVMI).

Results: A higher percentage of patients were diagnosed with hypertension from the 44-h ABPM than from the 24-h ABPM. All BP indexes and loads (except nighttime diastolic load) were significantly higher on Day 2 than on Day 1. Patients with BP loads of ≥ 25 % on 44-h ABPM had significantly higher LVMI than those patients with normal BP loads. No such association was found with 24-h ABPM and LVMI. Higher interdialytic weight gain was associated with higher Day-2 nighttime systolic BP load.

Conclusions: The 44-h ABPM provides more information than the 24-h ABPM in terms of diagnosing and assessing the true burden of hypertension in pediatric HD patients. Elevated BP loads from 44-h ABPM correlate with a higher LVMI on the echocardiogram.
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April 2015

Haemophilus influenzae Type b Meningitis in the Short Period after Vaccination: A Reminder of the Phenomenon of Apparent Vaccine Failure.

Case Rep Infect Dis 2012 16;2012:950107. Epub 2012 Aug 16.

Department of Pediatrics C, Schneider Children's Medical Center, 14 Kaplan Street, 49202 Petach Tikva, Israel.

We present two cases of bacterial meningitis caused by Haemophilus influenzae type b (Hib) which developed a few days after conjugate Hib vaccination. This phenomenon of postimmunization provocative time period is reviewed and discussed. These cases serve as a reminder to clinicians of the risk, albeit rare, of invasive Hib disease in the short period after successful immunization.
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September 2012

Severe abdominal pain as a presenting symptom of probable catastrophic antiphospholipid syndrome.

Pediatrics 2012 Jul 18;130(1):e230-5. Epub 2012 Jun 18.

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

Catastrophic antiphospholipid syndrome (APS) in pediatric medicine is rare. We report 3 adolescents who presented with acute onset of severe abdominal pain as the first manifestation of probable catastrophic APS. The 3 patients, 2 male patients and 1 female patient were 14 to 18 years old. One had been diagnosed with systemic lupus erythematosus in the past, but the other 2 had no previous relevant medical history. All presented with excruciating abdominal pain without additional symptoms. Physical examination was noncontributory. Laboratory results were remarkable for high inflammatory markers. Abdominal ultrasonography was normal, and abdominal computed tomography scan showed nonspecific findings of liver infiltration. Only computed tomography angiography revealed evidence of extensive multiorgan thrombosis. All patients had elevated titers of antiphospholipid antibodies. The patients were treated with full heparinization, high-dose steroids, and intravenous immunoglobulin with a resolution of symptoms. One patient was resistant to the treatment and was treated with rituximab. In conclusion, severe acute abdominal pain can be the first manifestation of a thromboembolic event owing to catastrophic APS even in previously healthy adolescents. Diagnosis requires a high index of suspicion with prompt evaluation and treatment to prevent severe morbidity and mortality.
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July 2012

[Acne--merely a cosmetic problem? Acne associated musculoskeletal syndromes].

Harefuah 2008 Jan;147(1):12-5, 96

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

Acne can be associated with severe musculoskeletal and constitutional symptoms. This is a case history of a 15 year-old boy with severe acne, treated with isotretinoin, who was admitted because of high fever and weight loss of 3 weeks duration. His complaints were of severe chest and back pain, and inability to walk. His laboratory results revealed elevated erythrocyte sedimentation rate and C-reactive protein. On a pelvic radiograph bilateral sacroiliitis was noticed. Radionuclide bone scan revealed increased uptake in the right sacroiliac joint, in small vertebral bodies and sternum. A diagnosis of acne-associated musculoskeletal syndrome was made and the patient was treated with high dose steroids. His symptoms resolved and his acne improved. This case report sheds light on the relationship between acne and associated musculoskeletal syndromes. Physicians should be aware of this association in order to provide prompt and efficient treatment.
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January 2008