Ekaterini Siomou

Duplex Collecting System Diagnosed During the First 6 Years of Life After a First Urinary Tract Infection: A Study of 63 Children

PURPOSE We determined the prevalence, anatomical variants and coexisting complications of duplex collecting systems in children with a history of UTI. Additionally, we compared the prevalence and severity of the coexisting anomalies with those found in single systems. MATERIALS AND METHODS We reviewed the records of children younger than 6 years who were evaluated following a first UTI during a 9-year period to identify those with duplex systems. Children without duplication anomalies comprised the control group. RESULTS Of 774 evaluated children 63 (8%), more commonly females than males, had duplex systems. CDS were as common as IDS. VUR was the most commonly associated anomaly, with a higher prevalence in CDS (66%) and IDS (47%) compared to single systems (26%, p <0.0001 and p = 0.007, respectively). Ectopic ureterocele, which was the second most common associated anomaly, was found in 20% of the CDS but in none of the IDS or single systems. The occurrence of renal scarring was similar among CDS, IDS (13%) and single systems (10%). Poorly functioning pole moieties occurred more often in CDS (40%) compared to IDS (4%, p = 0.003), and were observed in none of the single systems. The resolution rate of reflux tended to be higher in IDS compared to CDS. CONCLUSIONS CDS were a common finding among children with UTI who had duplication anomalies. Although CDS and IDS were accompanied by VUR more often than were single systems, CDS were associated more often with severe VUR, other serious complications and poor renal function.

Imaging strategies for vesicoureteral reflux diagnosis

The prevalence of vesicoureteral reflux (VUR), although reported to be low in the general population, is high in children with urinary tract infection (UTI), first degree relatives of patients with known VUR and children with antenatal hydronephrosis. In addition, it has been shown that VUR and UTIs are associated with renal scarring, predisposing to serious long-term complications, i.e., hypertension, chronic renal insufficiency and complications of pregnancy. Therefore, diagnostic imaging for the detection of VUR in the high-risk groups of children has been a standard practice. However, none of these associations has been validated with controlled studies, and recently the value of identifying VUR after a symptomatic UTI has been questioned. In addition, several studies have shown that renal damage may occur in the absence of VUR. On the other hand, some patients, mainly males, may have primary renal damage, associated with high-grade VUR, without UTI. Recently, increasing skepticism has been noted concerning how and for whom it is important to investigate for VUR. It has been suggested that the absence of renal lesions after the first UTI in children may rule out VUR of clinical significance and reinforces the redundancy of invasive diagnostic techniques. Therefore, the priority of imaging strategies should focus on early identification of renal lesions to prevent further deterioration.

Implications of 99mTc-DMSA Scintigraphy Performed During Urinary Tract Infection in Neonates

OBJECTIVE: To evaluate prospectively whether normal scintigraphic results during urinary tract infections (UTIs) in neonates were predictive of the absence of dilating vesicoureteral reflux (VUR) (grade ≥III) and permanent renal damage (PRD). METHODS: Term neonates with a first symptomatic, community-acquired UTI participated in the study. Urinary tract ultrasonography and technetium-99m-labeled dimercaptosuccinic acid (99mTc-DMSA) scintigraphy were performed within 72 hours after diagnosis and voiding cystourethrography within 1 to 2 months. DMSA scintigraphy, to determine the development of PRD, was repeated 6 months after UTI. RESULTS: Seventy-two neonates (144 renal units) were enrolled. Acute pyelonephritis was diagnosed through early DMSA scintigraphy in 19% of renal units, VUR in 22%, and grade ≥III VUR in 13%. The majority (71%) of renal units with grade ≥III VUR had normal early DMSA scintigraphic results. The sensitivity and specificity of abnormal early DMSA scintigraphic results to predict grade ≥III VUR were 29% (95% confidence interval: 11%–55%) and 82% (95% confidence interval: 74%–88%), respectively. PRD was found in 7% of renal units, all of which had abnormal early DMSA scintigraphic results. PRD was significantly more frequent among renal units with grade ≥III VUR than among nonrefluxing renal units (P < .05). CONCLUSIONS: Normal early DMSA scintigraphic results for neonates with symptomatic UTIs were helpful in ruling out later development of PRD but were not predictive of the absence of dilating VUR. To rule out dilating VUR, voiding cystourethrography may be required.

Prothrombotic State, Cardiovascular, and Metabolic Syndrome Risk Factors in Prepubertal Children Born Large for Gestational Age

OBJECTIVE To evaluate metabolic syndrome and cardiovascular disease risk factors in prepubertal children born large for gestational age (LGA) to nondiabetic, nonobese mothers. RESEARCH DESIGN AND METHODS At 6–7 years of age, the comparison of various factors was made between 31 LGA and 34 appropriate-for-gestational-age (AGA) children: fibrinogen, antithrombin III, protein C and S, fasting insulin, glucose, homeostasis assessment model of insulin resistance (HOMA-IR) index, adiponectin, leptin, visfatin, IGF-1, IGF-binding protein (IGFBP)-1, IGFBP-3, lipids, and the genetic factors V Leiden G1691A mutation, prothrombin 20210A/G polymorphism, and mutation in the enzyme 5,10-methylenetetrahydrofolate-reductase gene (MTHFR-C677T). RESULTS LGA children had higher levels of leptin (P < 0.01), fasting insulin (P < 0.01), and HOMA-IR (P < 0.01), but lower IGFBP-3 (P = 0.0001), fibrinogen (P = 0.0001), and lipoprotein(a) (P < 0.001) than AGA children. Significantly more LGA children were homozygous for the MTHFR-C677T mutation (P = 0.0016). CONCLUSIONS Being born LGA to nondiabetic, nonobese mothers is associated with diverse effects on cardiometabolic risk factors at prepuberty.

Serum osteoprotegerin, RANKL and fibroblast growth factor-23 in children with chronic kidney disease

Osteoprotegerin (OPG), receptor activator of the nuclear factor κB ligand (RANKL) and fibroblast growth factor-23 (FGF-23) play a central role in renal osteodystrophy. We evaluated OPG/RANKL and FGF-23 levels in 51 children with chronic kidney disease (CKD) [n = 26 stage 3 or 4 (CKD3–4) and n = 25 stage 5 (CKD5)] and 61 controls. Any possible association with intact parathyroid hormone (iPTH) and bone turnover markers was also investigated. The OPG levels were lower in the CKD3–4 group (p < 0.001) and higher in the CKD5 group (p < 0.01) than in the controls, while RANKL levels did not differ. The FGF-23 levels were higher in both patient groups (p < 0.0001), while the levels of phosphate and iPTH were higher only in the CKD5 group (p < 0.0001). There were independent positive correlations between OPG and RANKL (β = 0.297, p < 0.01) and FGF-23 (β = 0.352, p < 0.05) and a negative correlation with the bone resorption marker TRAP5b (β = −0.519, p < 0.001). OPG was positively correlated with iPTH (R = 0.391, p < 0.01). An independent positive correlation between FGF-23 and phosphate (β = 0.368, p < 0.05) or iPTH (β = 0.812, p < 0.0001) was noted. In conclusion, we found that higher OPG levels in patients with CKD stage 5 correlated with the levels of RANKL, FGF-23, iPTH, and TRAP5b. These findings may reflect a compensatory mechanism to the negative balance of bone turnover. High FGF-23 levels in early CKD stages may indicate the need for intervention to manage serum phosphate (Pi) levels.

Rare causes of acute hyperkalemia in the 1st week of life

We describe three neonates with hyperkalemia and renal salt wasting during the 1st week of life. Endocrinological evaluation led to the diagnosis of selective hypoaldosteronism (HA) in two neonates and secondary pseudohypoaldosteronism (PHA) in one. The infant with PHA developed a urinary tract infection, and radiological investigation demonstrated a small dysplastic left kidney with vesicoureteral reflux. The electrolyte and hormonal disturbances in this infant persisted throughout the first months of life. The two infants with selective HA improved rapidly after administration of fludrocortisone orally and the electrolytes and renin values returned to normal. Secondary PHA and selective HA should be considered in the differential diagnosis in salt-losing neonates during the first days of life. Renal ultrasonography, urine culture, and assays of aldosterone and plasma renin activity should be performed in any infant presenting with hyperkalemia and salt wasting after the exclusion of congenital adrenal hyperplasia.

Biochemical markers of bone metabolism in infants and children under intravenous corticosteroid therapy

The short-term effects of corticosteroids (CS) administered intravenously (IV) on biochemical parameters of bone metabolism were followed in infants and children. Forty-nine patients from 2 months to 10 years of age, admitted to Pediatrics Department for bronchiolitis, viral-associated wheezing and croup, were treated with IV hydrocortisone or methylprednisolone (10 or 2 mg/Kg/day, respectively) for 3 days. Blood and fasting urine were collected on admission (day 1), 2 days later (day 3) and 12 days after the end of therapy (day 15). Fifty-one children of similar age and gender without respiratory problems or bone diseases were used as controls. On day 3, suppression of the bone formation markers osteocalcin (OC) (P < 0.001) and total alkaline phosphatase (ALP) (P < 0.05) was observed, but not of the bone resorption markers of hydroxyproline, pyridinoline and calcium excretion (UHyp/UCr, UPYD/UCr and UDPD/UCr, UCa/UCr). Significant decreases were indicated in serum phosphate (Pi) and the maximum renal tubular Pi reabsorption (TmP/GFR) compared to basal (P < 0.001). No significant changes were noticed in the circulating levels of calcium (Ca), parathyroid hormone (iPTH), 25OHD, 24,25(OH)2D, 1,25(OH)2D, the insulin-like growth factor-I (IGF-I) and its binding protein-3 (IGFBP-3). Two weeks after therapy, the increase of OC to higher than basal (P < 0.01) indicated a probable activation of the osteoblasts. Serum Pi and the TmP/GFR index values that had significantly decreased by day 3 returned to pretreatment levels by day 15. When assessing the effects of the CS in relation to age, no changes were detected in the levels of OC and total ALP in the <12-month-old children, but a fall of OC was observed in the >1-year-old group (P < 0.001). In contrast to the OC, the effects on serum and renal tubular reabsorption of phosphate were similar for both groups. In conclusion, short-term IV administered CS led to significant but reversible inhibition of bone formation markers, especially detectable in the >1-year-old children, without affecting the bone resorption ones. The adverse effects on phosphate metabolism were also significant, but temporal and irrespective of age.

The relation of vitamin D status with metabolic syndrome in childhood and adolescence: an update.

Abstract Among children and adolescents, metabolic syndrome (MetS) is more common than previously believed. Hence, any information on the relation between vitamin D insufficiency/deficiency and insulin resistance (IR) in this population with risk of developing MetS is of great importance. This review analyzes and evaluates the existing evidence from cross-sectional, observational, and retrospective studies concerning the effect of vitamin D insufficiency/deficiency on MetS as a whole or on its various components. Most data show that insufficient vitamin D status is associated with increased prevalence of MetS or its individual components, mainly blood pressure and IR, often independent of overall obesity or abdominal adiposity. The implications of these findings could be associated with increased risk for developing cardiovascular disease and type 2 diabetes mellitus in later life. The very few randomized control trials examining any possible beneficial effects of vitamin D supplementation are also included.

FGF-23 in children with CKD: a new player in the development of CKD–mineral and bone disorder

Disturbances in mineral and bone metabolism in children with chronic kidney disease (CKD) lead to specific abnormalities of skeletal homeostasis called CKD-mineral and bone disorder (CKD-MBD). These disturbances should be diagnosed and managed appropriately to prevent bone deformities and disturbed growth. Changes in the vitamin D and parathyroid hormone (PTH), and the subsequent alterations in calcium (Ca) and phosphate (P) homeostasis are considered responsible for the development of CKD-MBD. Recently, a phosphaturic hormone, the fibroblast growth factor-23 (FGF-23), has been reported as a key regulator of P and vitamin D metabolism. A number of recent studies in paediatric populations have documented that the FGF-23 levels are increased early in CKD, before any abnormalities in serum Ca, P or PTH are apparent. The elevated FGF-23 levels result in a negative P balance to maintain P homeostasis, inducing phosphaturia, independently of PTH, and suppressing vitamin D synthesis. Therefore, the bone-kidney-parathyroid endocrine axis mediated by FGF-23 should be a novel therapeutic target in clinical practice, even in early stages of CKD in children.

Visfatin Levels in Prepubertal Children Born Small or Large for Gestational Age

Children born small (SGA) or large (LGA) for gestational age are prone to develop insulin resistance (IR) during childhood. Visfatin, a hormone with insulin-mimetic actions, has been associated with IR. This study was designed to examine whether serum level of visfatin is correlated with metabolic indices of IR, in prepuberty in association with the intrauterine growth pattern. The following parameters were evaluated at a mean age of 6.5±1.2 years in 155 prepubertal children born appropriate for the gestational age (AGA) (n=63), or SGA (n=42), or LGA (n=50): serum levels of visfatin, adiponectin, leptin, fasting glucose (G(F)) and insulin (I(F)), the homeostasis model assessment IR index (HOMA-IR), plasma lipids, anthropometric indices at birth and the time of evaluation, and obesity indices [waist circumference (WC), body mass index (BMI) and skinfold thickness]. The mean serum level of visfatin was lower in the SGA than in the AGA and the LGA children (9±5.2 vs. 11.8±5.1 and 12.7±5.6 ng/ml, respectively, p<0.01). Girls had lower visfatin levels than boys (10.4±4.3 ng/ml vs. 12.5±6.7 ng/ml, p<0.05). Visfatin was not correlated with IR indices. In multiple regression analysis visfatin level was positively correlated with birth weight z-score (t=2.56, beta=0.24, p<0.01) and crown to heel z-score (t=2.46, beta=0.22, p=0.014), independent of age, gender, maternal weight before pregnancy, maternal weight gain during pregnancy, BMI z-score, WC z-score, serum leptin and adiponectin, and HOMA-IR. In conclusion serum visfatin level was lower in prepubertal SGA children but not correlated with IR indices. Low birth weight was an independent predictor of visfatin level.