Michelle Hall

Febrile Urinary Tract Infections in 0- to 3-Month-Old Infants: A Prospective Follow-Up Study

OBJECTIVE To track the clinical evolution of febrile urinary tract infection (UTI) diagnosed in 0- to 3-month-old infants and characterize uropathogen frequencies, antimicrobial resistance rates, renal abnormalities, and differences in the sexes in this age group. STUDY DESIGN We observed prospectively 46 infants identified in a cohort of 209 children with first UTI diagnosed between July 2006 and July 2008 at the age of 0 to 3 months. Renal ultrasound scanning and voiding cystourethrography examinations were performed in all infants. RESULTS Infants < 3 months old represented 21% of all children with first UTI. Of these children, 26% were female and 74% were male. Escherichia coli was isolated in 88% of cases and had a high rate of resistance to ampicillin (71%) and to trimethoprim/sulfamethoxazole (47%); 21% of children had vesicoureteral reflux, which was of low-grade in 67% of cases, with spontaneous resolution before 2 years in all cases. In infants with normal ultrasound scanning results, a low-grade vesicoureteral reflux was subsequently found in 10% of cases. CONCLUSION Infants aged 0 to 3 months represent 21% of children treated for febrile UTI. Boys represent 74% of these cases. E coli is responsible for 88% of UTIs, with a high rate of resistance to antibiotics. When ultrasound scanning examination results are normal, the risk of missing a significant renal abnormality is expected to be extremely low.

Mutational analysis of the PLCE1 gene in steroid resistant nephrotic syndrome

Background Mutations in the PLCE1 gene encoding phospholipase C epsilon 1 (PLCɛ1) have been recently described in patients with early onset nephrotic syndrome (NS) and diffuse mesangial sclerosis (DMS). In addition, two cases of PLCE1 mutations associated with focal segmental glomerulosclerosis (FSGS) and later NS onset have been reported. Method In order to better assess the spectrum of phenotypes associated with PLCE1 mutations, mutational analysis was performed in a worldwide cohort of 139 patients (95 familial cases belonging to 68 families and 44 sporadic cases) with steroid resistant NS presenting at a median age of 23.0 months (range 0–373). Results Homozygous or compound heterozygous mutations were identified in 33% (8/24) of DMS cases. PLCE1 mutations were found in 8% (6/78) of FSGS cases without NPHS2 mutations. Nine were novel mutations. No clear genotype–phenotype correlation was observed, with either truncating or missense mutations detected in both DMS and FSGS, and leading to a similar renal evolution. Surprisingly, three unaffected and unrelated individuals were also found to carry the homozygous mutations identified in their respective families. Conclusion PLCE1 is a major gene of DMS and is mutated in a non-negligible proportion of FSGS cases without NPHS2 mutations. Although additional variants in 19 candidate genes (16 other PLC genes, BRAF,IQGAP1 and NPHS1) were not identified, it is speculated that other modifier genes or environmental factors may play a role in the renal phenotype variability observed in individuals bearing PLCE1 mutations. This observation needs to be considered in the genetic counselling offered to patients.

Characteristics of first urinary tract infection with fever in children: A prospective clinical and imaging study

Background: Our objective is to provide the clinical characteristics, uropathogen frequencies, and antimicrobial resistance rates of first urinary tract infection (UTI) diagnosed in febrile Belgian children. The ability of noninvasive ultrasound to detect renal abnormalities and vesicoureteral reflux (VUR) in these patients was also assessed. Methods: We prospectively followed (median, 20 months) 209 children treated for first febrile UTI. Renal ultrasound (US) and voiding cystourethrography examinations were performed in all patients. Results: Among these children, 63% were females and 37% were males, and 75% of them had their first UTI before the age of 2 years. The most common causative agent was Escherichia coli (91% of cases) with high rate resistance to ampicillin (58%) and trimethoprim/sulfamethoxazole (38%). Of these children, 25% had evidence of VUR (15 boys and 38 girls). VUR was of low grade in 85% of cases. The overall performance of renal US as a diagnostic test to detect significant uropathies excluding low-grade VUR was excellent; the sensitivity attained 97% and the specificity 94%. Conclusion: Girls represent 63% of cases with first UTI. For 91% of UTIs, Escherichia coli is held responsible with a high rate of resistance to ampicillin and trimethoprim/sulfamethoxazole. US is an excellent screening tool that allows avoidance of unjustified voiding cystourethrography studies.

Evolution of fetal ultrasonography.

The authors wish to highlight the evolution that has occurred in fetal ultrasound in recent years. A first significant evolution lies in the increasing contribution of first trimester ultrasound for the detection of fetal anomalies. Malformations of several organs and systems have been diagnosed during the first trimester. Furthermore the systematic measurement of the fetal neck translucency has led to increasing rate of detection of aneuploidies and heart malformations. For several years now, three-dimensional (3D) and 4D ultrasound (US) have been used as a complementary tool to 2D US for the evaluation of fetal morphology. This brings an improved morphologic assessment of the fetus. Applications of the techniques are increasing, especially for the fetal face, heart and extremities. The third field where fetal US is continuously providing important information is the knowledge of the natural history of diseases. This has brought significant improvement in the postnatal management of several diseases, especially urinary tract dilatation and broncho-pulmonary malformation.

A hypothesis for the higher incidence of vesico-ureteral reflux and primary megaureters in male babies

The authors propose a new explanation for the male preponderance in cases with prenatally diagnosed vesico-ureteral reflux and primary megaureters. The theory is based on conclusions drawn from the characteristics of 4 patients (3 perinatal cases and 1 occurring in a 14-year-old boy) presenting with unusual anomalies of the lower urinary tract. In this hypothesis, the male preponderance could be related to an abnormal dilatation of the posterior urethra occurring during the embryological development of the male urethra. The dilatation leads to a flap valve mechanism and to a functional obstruction of the bladder outlet and finally to secondary dilatation of the upper urinary tract. This obstruction may be transitory; reflux and megaureters found in utero or after birth could be considered as sequellae of this phenomenon.

Early prognostic factors of infants with chronic renal failure caused by renal dysplasia

Abstract Renal dysplasia (RD) is a common cause of chronic renal failure (CRF) in children. The evolution towards end-stage renal failure is unpredictable due to the paucity of early prognostic factors. In order to identify early prognostic clinical criteria, we have retrospectively analyzed renal function and growth in 11 infants with RD and CRF from birth up to 4 years of age. Children with obstructive RD were not included. Glomerular filtration rate (GFR) was estimated from Schwartz formula. In infants with a GFR below 15 ml/min per 1.73 m2 at 6 months of age (group A, n=5), kidney function did not further improve; 4 reached end-stage renal failure between 8 months and 6 years of age. In contrast, infants with a GFR above 15 ml/min per 1.73 m2 at 6 months of age (group B, n=6) experienced a significant improvement in renal function during follow-up, and none required renal replacement therapy. During the first 3 months of life all infants with RD and CRF developed severe growth retardation. Between 6 months and 4 years of age, children from group B grew significantly better than those from group A. In conclusion, our experience suggests that GFR, estimated from Schwartz formula at 6 months of age, is a useful prognostic factor in infants with RD and CRF. Infants with a GFR below 15 ml/min per 1.73 m2 are at risk of severe growth delay and the need for early renal replacement therapy, whereas those with a GFR above 15 ml/min per 1.73 m2 have a relatively favorable long-term prognosis.

Perinatal assessment of hereditary cystic renal diseases: the contribution of sonography

The aims of this review article were to clarify the steps that may lead to a proper diagnosis of fetal and neonatal renal cystic diseases. All the hereditary cystic diseases are reviewed and a classification is proposed. The various sonographic patterns that can be used to ascertain the diagnosis are also reviewed. Finally, tables with differential diagnoses are presented to help the reader in the work-up of such pathologies.

Combined liver-kidney transplantation in primary hyperoxaluria type 1 : bone histopathology and oxalate body content

In three patients with end-stage renal failure due to primary hyperoxaluria type 1, successful combined liver-kidney transplantation enabled us to assess the insoluble oxalate pool, which was compared with the histopathological changes observed in iliac crest biopsy specimens. Good correlation was observed between the histopathological grade of bone oxalosis and the estimated oxalate content of the body. In the end-stage of oxalate bone disease, hyperparathyroidism does not play a significant role in bone resorption, which appears to be the consequence of the granulomatous reaction induced by oxalate deposition. Combined liver-kidney transplantation should be performed long before this stage. Early hepatorenal grafting in uremia secondary to primary hyperoxaluria type 1 would avoid the deleterious clinical consequences of systemic oxalosis and shorten the duration of postransplant hyperoxaluria, which may compromise the course of kidney graft.

Predicting the clinical outcome of antenatally detected unilateral pelviureteric junction stenosis.

OBJECTIVE To determine, in children with antenatally detected pelviureteric junction (PUJ) stenosis, what factors may be predictive for deterioration of differential renal function (DRF) in case of conservative treatment or improvement of DRF in case of pyeloplasty. METHODS This study analyzed and compared the initial level of hydronephrosis, DRF, quality of renal drainage, and cortical transit with the late DRF outcome. We reviewed the medical charts of 161 consecutive children with antenatally diagnosed PUJ stenosis during a 10-year period (between 1997 and 2007). From this cohort, we retained 81 children with unilateral PUJ and strictly normal contralateral kidney, with a median follow-up of 67 months. Repeated ultrasounds, voiding cystourethrography, and radionuclide renograms were performed in all children. RESULTS Fifty patients never underwent a surgical intervention (62%), whereas surgical repair (Anderson-Hynes dismembered pyeloplasty) was performed in 31 (38%). During conservative follow-up, DRF deterioration was observed in 11% of patients. After pyeloplasty, DRF improvement was observed in 25% of patients. Abnormal cortical transit was the only predictive factor of DRF deterioration in case of conservative approach, whereas the initial degree of hydronephrosis, or renal drainage, and the initial DRF level were not predictive. In children who were operated on, only impaired cortical transit was predictive of DRF improvement postoperatively. CONCLUSION Conservative management of children with unilateral PUJ stenosis is a safe procedure. Impaired cortical transit although imperfect, seems the best criterion for identifying children for whom pyeloplasty is warranted.

Can severely impaired cortical transit predict which children with pelvi-ureteric junction stenosis detected antenatally might benefit from pyeloplasty?

IntroductionUntil recently, renogram, performed in children with pelvi-ureteric junction stenosis detected antenatally, has not been able to predict the probability of function improvement after surgery or the risk of function deterioration in case of conservative attitude. Recently, Schlotmann et al. have suggested that cortical transit might have this predictive role. The aim of this study, focused on those kidneys with severely impaired cortical transit, was to verify this statement. MethodsAll renograms performed in children during a 3-year period (n=729) were retrospectively reviewed and 19 pediatric patients were selected based on an antenatally detected unilateral pelvi-ureteric junction syndrome, the existence of at least two renograms during the follow-up and a severe cortical transit impairment, visually defined. Twenty-six pairs of data could be analyzed and allowed comparing preoperative and postoperative differential renal function (DRF), and the DRF changes during the conservative management. ResultsAmong the 16 patients who underwent pyeloplasty, 10 showed a significant DRF improvement. Among the 10 patients with conservative follow-up, four showed a significant DRF deterioration. ConclusionSeverely impaired cortical transit seems to be a valuable marker of those patients who could benefit from a pyeloplasty, either because of the high probability of postoperative DRF improvement, or because of DRF deterioration in case of an conservative approach. However, a normal cortical transit, as defined in this study, does not exclude the risk of DRF deterioration. Alternatively, the design of this study does not allow excluding the fact that DRF might improve after pyeloplasty despite a normal cortical transit.