How much vitamin D for children?

Recently a number of studies have reported worldwide recrudescence of biochemical and clinical rickets, despite continuous revisions of the experts about the adequate intake of vitamin D for infants and children to maintain an adequate 25-hydroxyvitamin D status and assure the achievement of peak bone mass during the growth. The aim of this review is to illustrate the current opinions and controversies about what should be considered the normal range for serum 25-hydroxyvitamin D concentrations and which doses of vitamin D supplements should be recommended in the various pediatric ages and in different contests as climatic regions, colour of skin and sunlight exposure.

Neuroblastoma presenting with acute kidney injury, hyponatremic-hypertensive-like syndrome and nephrotic proteinuria in a 10-month-old child.

Neuroblastoma is the most common extracranial solid tumor in childhood. Its presenting signs and symptoms may be highly variable, depending on the location of the primary tumor and its local or metastatic diffusion and, rarely, with paraneoplastic syndrome such as opsoclonus-myoclonus-ataxia syndrome and gastrointestinal disturbances, due to autoantibodies or to aberrant secretion of vasoactive intestinal peptide. Herein we describe a 10-month-old child with neuroblastoma presenting with a complex clinical picture characterized by acute kidney injury manifested by renal insufficiency and signs and symptoms of tubulointerstitial damage, with polyuria, polydipsia, glucosuria, aminoaciduria and hypochloremic metabolic alkalosis, and of glomerular damage with heavy proteinuria. Imaging study documented a suprarenal mass enveloping the aorta and its abdominal and renal ramifications and bilaterally renal veins. This clinical picture shows some analogies with the hyponatremic-hypertensive syndrome concerning the renovascular disease; however, in absence of systemic arterial hypertension, the heavy proteinuria and the polyuria could be explained by sectional increased intraglomerular pressure, due to local renal blood vessels constriction. Hypochloremic metabolic alkalosis probably developed because of local production of renin, responsible of renin-angiotensin-aldosterone system activation, but above all because of chloride loss through sweating. The long lasting dehydration, due to vomiting, sweating and polyuria, caused prolonged prerenal failure evolving in proximal tubular damage manifestations.

Hemolytic uremic syndrome: epidemiological and clinical features of a pediatric population in Tuscany.

We retrospectively analyzed etiological, pathological and clinical features of the patients with hemolytic uremic syndrome (HUS) observed in the Pediatric Nephrology Unit at AOU Meyer of Florence. From January 1997 to December 2008, 22 cases were identified, with an annual incidence of 0.05 cases per 100,000 inhabitants, and 0.34 cases per 100,000 children <15 years old. 60% of the patients were D+ and 40% were D-, with an age distribution from 12 days to 13 years. Twenty patients (90%) had oligoanuria, lasting 6.4 ± 4 days for D+ patients versus 11.8 ± 4 days for D- patients. The development of chronic kidney disease positively correlates with the initial blood pressure value, the length of oligoanuria, and hospitalization. Microbiological investigations showed an association of D+HUS with different strains of Shiga toxin-producing Escherichia coli in 54% of the cases. D-HUS was associated with complement factor H deficiency in one patient. In the other cases, the triggering factors were pertussis, urinary tract infections and upper airway infections. While clinical and prognostic features correspond with literature data, in Tuscany the annual incidence is lower, and the percentage of D-HUS patients is higher than that observed in other studies.

Growth hormone therapy-related hyperglycaemia in a boy with renal cystic hypodysplasia and a new mutation of the HNF1 beta gene.

We provide a molecular and pathophysiological characterization of an 11-year-old male patient, with a diagnosis of renal hypodysplasia, cysts and chronic renal failure. Although previously normoglycaemic and with a negative familial history for diabetes mellitus, he developed fasting hyperglycaemia within 12 months of the start of treatment with recombinant human growth hormone (rhGH). Direct sequencing of the HNF1 beta gene revealed a de novo heterozygous mutation in exon 2, c.535delC [Pro118LeuX7]+[=]. The appearance of fasting hyperglycaemia following rhGH treatment in children with renal cystic hypodysplasia suggests that investigation of the HNF1 beta gene is warranted, even when familial history is negative for diabetes. This is particularly important in regard to genetic counselling.

Blood pressure in children with minimal change nephrotic syndrome during oedema and after steroid therapy: the influence of familial essential hypertension.

AIMS: To verify the variations of blood pressure in children with minimal change nephrotic syndrome and to correlate the blood pressure with familial history of essential hypertension. METHODS: We measured blood pressure in 49 prepubertal nephrotic children, 17 females and 32 males, in the first week of oedema, and after 4 weeks of ISKDC (International Study of Kidney Disease in Children) standard steroid therapy. The children were divided into two groups: one with and the other without familial history of essential hypertension. RESULTS: Among all the patients, 65% showed systolic and/or diastolic blood pressure higher than the 90th percentile at the first assessment. Among the children with a familial history of essential hypertension, in the oedematous phase of the nephrotic syndrome, 88% showed blood pressure higher than the 90th percentile and no children showed blood pressure lower than the 75th percentile. After therapy, the percentage of children with blood pressure higher than the 90th percentile was 52%. In the group with a negative familial history, at the onset 53% showed blood pressure over the 90th percentile. After 4 weeks of therapy, the percentage of children with blood pressure higher than the 90th percentile was 34%. CONCLUSIONS: Our study reveals the influence of familial essential hypertension in the oedematous phase of the nephrotic syndrome in children.

Inner ear abnormalities in four patients with dRTA and SNHL: clinical and genetic heterogeneity.

A significant number of patients affected by autosomal recessive primary distal renal tubular acidosis (dRTA) manifest sensorineural hearing loss (SNHL). Mutations in ATP6V1B1 are associated with early onset SNHL, whereas ATP6V0A4 mutations have been described in dRTA and late-onset SNHL. Enlarged vestibular aqueduct (EVA) was described in patients with recessive dRTA and SNHL, and recently, this abnormality has been associated with mutations in the ATP6V1B1 gene. In our study, we evaluated the presence of inner-ear abnormalities in four patients affected by dRTA and SNHL, characterized by molecular analysis. Two patients affected by severe dRTA with early onset SNHL showed the same mutation in the ATP6V1B1 gene and bilateral EVA with a different degree of severity. The other two presented similar clinical manifestations of dRTA and different mutations in the ATP6V0A4 gene: one patient, showing EVA, developed an early SNHL, whereas in the other one, the SNHL appeared in the second decade of life and the vestibular aqueduct was normal. Our study confirms the association of EVA and mutations in the ATP6V1B1 gene and demonstrates that mutations in the ATP6V0A4 gene can also be associated with EVA probably only when the SNHL has an early onset. The pathophysiology of SNHL and EVA are still to be defined.

Medullary sponge kidney associated with primary distal renal tubular acidosis and mutations of the H+-ATPase genes.

BACKGROUND: Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse ectasia or dilation of precalyceal collecting tubules. Although its pathogenesis is unknown, the association with various congenital diseases suggests that it could be a developmental disorder. In addition to the typical clinical features of nephrocalcinosis and urolithiasis, patients with MSK show tubular function defects of acidification and concentration. These are considered to be secondary to morphological changes of collecting tubules. Primary distal renal tubular acidosis (dRTA) is a rare genetic disease caused by mutations in different genes involved in the secretion of H(+) ions in the intercalated cells of the collecting duct required for final excretion of fixed acids. Both autosomal dominant and autosomal recessive forms have been described, the latter is also associated with sensorineural hearing loss. METHODS AND RESULTS: We report two patients presenting with dRTA, late sensorineural hearing loss and MSK, in whom molecular investigations demonstrated the presence of mutations of the H(+) proton pump ATP6V1B1 and ATP6V0A4 genes. CONCLUSIONS: These observations, including a previous description of a similar case in the literature, indicate that MSK could be a consequence of the proton pump defect, thus can potentially provide new insights into the pathogenesis of MSK.

Lesch-Nyhan syndrome presenting with acute renal failure in a 3-day-old newborn.

Acute renal failure developed during the first 3 days after birth in a newborn subsequently diagnosed with hypoxanthine-guanine-phosphoribosyl-transferase (HPRT) deficiency. Fluid infusion and allopurinol therapy normalised renal function and serum uric acid levels. Only a few cases of acute renal failure due to acute hyperuricemic nephropathy related to HPRT deficiency have previously been reported in infants, and there are no reported cases in newborns as young as 3 days old.

Peritoneal dialysis in neonates with inborn errors of metabolism: is it really out of date?

Peritoneal and extracorporeal dialysis are used to treat newborns affected by inborn errors of metabolism to minimize the effects of the acute accumulation of neurotoxic metabolites that can produce irreversible and severe neurological damage and even death. In recent papers, extracorporeal dialysis has been described as more effective than peritoneal dialysis in improving the prognosis in newborns with inborn errors of metabolism and hyperammonemia. However, it appears that the outcome is primarily related to the duration of neonatal hyperammonemic coma. Here we report seven newborns with hyperammonemia caused by inborn errors of metabolism (five with organic acidemias, two with urea-cycle disorders). They received dietetic and pharmacological treatment as well as peritoneal dialysis. Four of the five patients with organic acidemia survived with and without mild neurological impairment (follow-up 3.5-10 years). One died from bacterial sepsis after peritoneal dialysis was discontinued and the peritoneal catheter was removed. One of the two patients affected by urea-cycle disorders, a boy, died during the neonatal period, and the other, a girl, died at the age of 13 months due to severe neurological damage. Our results demonstrate that peritoneal dialysis may still be an effective treatment for neonatal hyperammonemia caused by inborn errors of metabolism. Furthermore, peritoneal dialysis can be administered quickly and easily in all settings, clearly an advantage when fast intervention is so crucial.

No clear evidence of ACEi efficacy on the progression of chronic kidney disease in children with hypodysplastic nephropathy--report from the ItalKid Project database.

BACKGROUND: Chronic kidney diseases (CKD) tend to progress to end-stage renal failure (ESRF). As it has been demonstrated that angiotensin-converting enzyme inhibitors (ACEi) have a renoprotective effect in adults with proteinuric disease and may be effective in reducing hyperfiltration and proteinuria, they are also frequently used as anti-progression agents in paediatric patients with CKD despite the lack of data confirming their role in the nephropathies peculiar to children. The aim of this study was to investigate whether patients with hypodysplastic CKD (the most common cause of ESRF in children) treated with ACEi show a significantly slower decline in creatinine clearance (Ccr). METHODS: The analysis was based on the information available in the database of the ItalKid Project, a nationwide, population-based registry of chronic renal insufficiency (CRI) in children in Italy. Of the 822 patients with CRI due to hypodysplasia, we selected those who had been continuously treated with ACEi; the control patients were identified from the same diagnostic group and matched for gender, age and baseline Ccr. RESULTS: Progression was analysed as the slope of Ccr in a total of 164 patients: 41 cases and 123 matched controls. There were no significant between-group differences in blood pressure, duration of follow-up or pre-study slope of Ccr (-0.31+/-2.26 vs -0.33+/-3.58 ml/min/1.73 m2/year; P=NS). After an average of 4.9+/-2.3 years, the mean slope of Ccr was 40% lower in the ACEi-treated cases in comparison to controls (-1.08+/-2.08 vs -1.80+/-4.42 ml/min/1.73 m2/year), however, this difference was not statistically significant (P=0.31). CONCLUSIONS: We conclude that ACEi treatment does not significantly modify the naturally progressive course of hypodysplastic nephropathy in children and further studies are necessary before such treatment is routinely proposed for anti-progression purposes in children with CKD.

Prescription of drugs blocking the renin-angiotensin system in Italian children.

Little is known about the prescription pattern of antihypertensive drugs for children with impaired kidney function. We have therefore documented the use of antihypertensive drugs in this patient group by evaluating the Italian pediatric population-based registry of patients with chronic kidney disease on conservative treatment (ItalKid) from 1995 to 2003. In 1995, prescriptions written for antihypertensive drugs for use by children were approximately equally divided among drugs blocking the renin-angiotensin system and calcium channel blockers (38 vs. 43% of all prescriptions), followed by beta-blockers and diuretics (15 and 4%, respectively). During subsequent years the proportion of prescriptions for drugs blocking the renin-angiotensin system increased (2003: 61%; p<0.001) and that of calcium channel blockers decreased (2003: 18%, p<0.001). In 1995, blockers of the renin-angiotensin system were prescribed, either as monotherapy or in combination, in 53% of the patients, but the relative frequency of the patients prescribed these drugs increased up to 83% in 2003 (p<0.0005). In conclusion, physicians caring for Italian children with impaired kidney function are increasingly prescribing drugs blocking the renin-angiotensin system.

Patients with biallelic mutations in the chloride channel gene CLCNKB: long-term management and outcome.

BACKGROUND: Little information on the management and long-term follow-up of patients with biallelic mutations in the chloride channel gene CLCNKB is available. METHODS: Long-term follow-up was evaluated from 5.0 to 24 years (median, 14 years) after diagnosis in 13 patients with homozygous (n = 10) or compound heterozygous (n = 3) mutations. RESULTS: Medical treatment at last follow-up control included supplementation with potassium in 12 patients and sodium in 2 patients and medical treatment with indomethacin in 9 patients. At the end of follow-up, body height was 2.0 standard deviation score or less in 6 patients; 2 of these patients had growth hormone deficiency. Body weight (

Hyponatraemic-hypertensive syndrome in a 15-month-old child with renal artery stenosis.

In this report we present the case of a 15-month-old girl with hyponatraemic-hypertensive syndrome (HHS) caused by stenosis of the left renal artery. On sonographic examination the contralateral non-stenotic kidney appeared enlarged and with cortical hyperechogenicity mimicking a parenchymal lesion. After successful percutaneous transluminal angioplasty, when the girl became normotensive, her serum electrolyte and acid-base balance became normal within a few days. The contralateral non-stenotic kidney hyperechogenicity also disappeared, but only after a period of 6 months, suggesting parenchymal damage due to tubulointerstitial injury, even though reversible. Our case confirms that renovascular hypertension may rarely also be present with HHS in children and that metabolic and morphological alterations are reversible after the resolution of arterial stenosis.

Hypokalemic rhabdomyolysis in a child with Bartter's syndrome.

Hypokalemia represents a rare cause of rhabdomyolysis. Some reports have described a few adult patients affected by Bartter's syndrome and Gitelman's syndrome with rhabdomyolysis due to severe hypokalemia. We report the first pediatric patient with Bartter's syndrome in whom rhabdomyolysis developed when her plasma potassium level was less than 2 mEq/l. Prompt intravenous fluid and potassium prevented tubular damage and acute renal failure. We recommend determining serum creatine phosphokinase in all patients affected by Bartter's syndrome and profound hypokalemia.