Miriam Davidovits

Prevalence of Vesicoureteral Reflux in Neonatal Urinary Tract Infection

Vesicoureteral reflux (VUR) after a first episode of urinary tract infection (UTI) is apparently diagnosed much more frequently (25%-40%) in children than in neonates. The aims of the study were to determine the actual rate of VUR in neonates with UTI and to define the clinical clues to its diagnosis. The study sample included term infants with a diagnosis of UTI during their first month of life who were seen in this hospital between January 1997 and May 1999. All infants underwent complete diagnostic work-up (renal ultrasound and voiding cystourethrography [VCUG]). The medical files were reviewed for patient sex, age at UTI diagnosis, laboratory findings (including causative pathogen), and ultrasonographic findings. These parameters were correlated with the finding of VUR on VCUG. Sixty-four neonates (55 males, 9 females) with UTI were included in this study. UTI was 6 times more common in males than females, although the incidence of VUR was equal between the sexes (about 20%). The presence of VUR was associated with a significantly younger age at presentation of UTI (11.4±4 vs 16.9±6.6 days, p<0.01). VUR was diagnosed at a fourfold higher rate in neonates with Klebsiella-induced UTI compared to those with E. Coli-UTI. In 80% of those with significantly abnormal ultrasonographic findings VUR was found on VCUG. Jaundice was noted at UTI diagnosis 3 times more often in infants with VUR, and elevated creatinine level, 2.5 times more often.

New-onset post-transplantation food allergy in children--is it attributable only to the immunosuppressive protocol?

Abstract:  New‐onset post‐transplantation food allergy has been described mainly after liver transplantation, and its pathogenesis was attributed to the immunomodulatory effects of tacrolimus therapy. The aim of the present study was to evaluate the association of food allergy with solid organ transplantation in our center. The medical records of children who underwent kidney transplantation and children who underwent liver or liver and kidney transplantation from 1986 to 2005 were reviewed. A total of 189 children (124 after kidney transplantation, 65 after liver or liver and kidney transplantation) received tacrolimus as part of the immunosuppressive regimen. New‐onset post‐transplantation food allergy was documented in four of them: two with liver transplants and two with combined kidney and liver transplants. The absence of new‐onset food allergy in the children with isolated kidney transplants is compatible with other reports in the literature. This study supports the concept that the functioning liver itself, and not only tacrolimus immunosuppression, is a main contributor to food allergy in this patient population.

Calcium-deficiency rickets in a four-year-old boywith milk allergy

A 4-year-old boy was found to have rickets associated with normal serum levels of 25-hydroxyvitamin D and high serum levels of 1,25-dihydroxyvitamin D. These findings were thought to be the result of dietary calcium deficiency caused by the prolonged elimination from his diet of cow milk and milk products because of allergy. Adequate intake of calcium resulted in rapid improvement.

Renal Hypodysplasia Associates with a Wnt4 Variant that Causes Aberrant Canonical Wnt Signaling

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.

The correlation between dental calculus and disturbed mineral metabolism in paediatric patients with chronic kidney disease

BACKGROUND Vascular calcifications have been documented in children with end-stage renal disease. However, only a few reports have described abundant dental calculus formation in children suffering from chronic kidney disease (CKD). Moreover, dental calculus scores (DCS) and their correlation with renal disease severity have not been studied. METHODS DCS in 74 young CKD patients were evaluated: 25 pre-dialytic (PrD), 18 on dialysis (D) and 31 with transplants (T) compared to 32 healthy participants (C). Saliva and serum analysis included creatinine (Cr), urea (U), calcium (Ca), phosphorous (P), magnesium (Mg) as well as intraoral pH levels. RESULTS All patient groups presented high DCS. DCS and pH levels were higher in the D group with a positive correlation between pH and lower incisor DCS (r = 0.56, P = 0.017). The highest salivary Ca was found in the PrD group. Salivary P in the PrD group was found to be higher than in the T and C groups. The lowest salivary Mg was found in the D group while the highest salivary Ca x P product was found in the PrD group. In all patient groups, salivary U was higher than in the C group with a 2.5-fold increase in the D group. Salivary Cr resembled the U salivary concentrations. CONCLUSIONS Alterations in salivary Ca, P, Mg, U, Cr and intraoral pH levels were observed in the patient groups. DCS correlated with renal disease severity and therefore may be a reflection of other tissue calcification pathologies found in these patients.

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

BackgroundHypercalcemia 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.MethodsWe 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.ResultsTypical 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.ConclusionsThis 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.

Maxillomandibular brown tumor – a rare complication of chronic renal failure

Abstract We report a 17-year-old hemodialysis patient with a rapidly growing maxillary mass diagnosed as a brown tumor. Although successful control of the parathyroid hormone (PTH) levels was achieved by treatment with vitamin D pulse therapy, the lesion progressed, invaded the maxillary sinus, and caused severe eating and speech disabilities. No recurrence was observed following surgical excision. The differential diagnosis and considerations regarding the causes of the disease in a child, therapy options, and review of the literature are presented.

The efficacy and safety of valganciclovir vs. oral ganciclovir in the prevention of symptomatic CMV infection in children after solid organ transplantation

Lapidus‐Krol E, Shapiro R, Amir J, Davidovits M, Steinberg R, Mor E, Avitzur Y. The efficacy and safety of valganciclovir vs. oral ganciclovir in the prevention of symptomatic CMV infection in children after solid organ transplantation.
Pediatr Transplantation 2010: 14:753–760.

Post-transplantation lymphoproliferative disorder in pediatric kidney-transplant recipients - A national study

Cleper R, Ben Shalom E, Landau D, Weissman I, Krause I, Konen O, Rahamimov R, Mor E, Bar‐Nathan N, Frishberg Y, Davidovits M. Post‐transplantation lymphoproliferative disorder in pediatric kidney‐transplant recipients – A national study.

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

Cardiovascular‐related mortality is 100‐fold higher in pediatric renal transplant recipients than in the age‐matched general population. Seventy‐seven post‐renal transplant childrens 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.