Prevalence of urinary calculi in children has been increasing in the past years. We performed an analysis of the chemical composition of stones formers of the pediatric population in our geographical ...area over the years 2005 to 2013.
Fourier transform infrared spectroscopy was employed for the determination of the calculus composition of a group of Sicilian children, and metabolic studies were performed to formulate the correct diagnosis and establish therapy.
The prevalence of stone formation was much higher for boys than for girls, with a sex ratio of 1.9:1. The single most frequent component was found to be calcium oxalate monohydrate, and calcium oxalates (pure or mixed calculi) were the overall most frequent components. Calcium phosphates ranked 2nd for frequency, most often in mixed calculi, while urates ranked 3rd. The metabolic disorder most often associated with pure calcium oxalate monohydrate calculi was hypocitraturia, while hyperoxaluria was predominantly associated with calcium oxalate dihydrate calculi.
Mixed calculi had the highest prevalence in our pediatric population. Our data showed that Fourier transform infrared spectroscopy was a useful tool for the determination of the calculi composition.
Vesicoureteral reflux in children Maringhini, Silvio; Pavone, Giovanni
Giornale italiano di nefrologia,
2011 Nov-Dec, 20111101, Letnik:
28, Številka:
6
Journal Article
Recenzirano
Vesicoureteral reflux is a common disease in children and is usually associated with urinary tract infections and renal scars. Renal damage associated with vesicoureteral reflux occurs secondary to ...renal maldevelopment during fetal life or renal infections in children and may produce hypertension, diseases in pregnancy and chronic renal failure. Bladder dysfunction may be responsible for persistent reflux and renal scars. In order to prevent renal damage, early diagnosis and prompt medical treatment or surgical correction are advised in a selected group of children. In the past all children with urinary tract infections were investigated with voiding uretrocystogram and received long-term antibiotic prophylaxis or surgery. In recent years several trials have provided information that suggest it is better to reduce the number of diagnostic and surgical procedures in children affected by vesicoureteral reflux.
Objective To analyse the timing of end stage renal disease in children with chronic kidney disease (CKD). Design A population-based cohort study. Setting A nationwide registry (ItalKid Project) ...collecting information on all patients with CKD aged <20 years. Patients 935 children with CKD secondary to renal hypodysplasia with or without urologic malformation. In a subgroup of patients (n=40) detailed pubertal staging was analysed in relation to CKD progression. Main outcome measures Kidney survival (KS) was estimated using renal replacement therapy (RRT) as the end-point. Puberty was staged by identifying the pubertal growth spurt. Results A non-linear decline in the probability of KS was observed, with a steep decrease during puberty: the probability of RRT was estimated to be 9.4% and 51.8% during the first and second decades of life, respectively. A break-point in the KS curve was identified at 11.6 and 10.9 years of age in male and female patients, respectively. Conclusions The present analysis suggests that puberty is associated with increased deterioration of renal function in CKD. The mechanism(s) underlying this unique and specific (to children) pattern of progression have not yet been identified, but it may be that sex hormones play a role in this puberty-related progression of CKD.
Early origin of adult renal disease Maringhini, Silvio; Corrado, Ciro; Maringhini, Guido ...
The journal of maternal-fetal & neonatal medicine,
10/2010, Letnik:
23, Številka:
S3
Journal Article
Recenzirano
Observational studies in humans and experimental studies in animals have clearly shown that renal failure may start early in life. 'Fetal programming' is regulated by adaptations occurring in uterus ...including maternal nutrition, placental blood supply, and epigenetic changes. Low birth weight predisposes to hypertension and renal insufficiency. Congenital abnormalities of the kidney and urinary tract, adverse postnatal events, wrong nutritional habits may produce renal damage that will become clinically relevant in adulthood. Prevention should start early in children at risk of renal disease.
Anaemia is a common and potentially treatable co-morbidity of end-stage renal disease. We aimed to determine the prevalence of the sub-target haemoglobin (Hb) level among European children on ...dialysis and to identify factors associated with a low Hb level.
From the European Society for Paediatric Nephrology (ESPN)/European Renal Association-European Dialysis Transplant Association (ERA-EDTA) registry, data were available on 2351 children between 1 month and 18 years of age, totalling 5546 measurements from 19 countries.
The mean Hb level was 10.8 g/dL (5th-95th percentiles, 7.4-13.9). Among those above 2 years of age, the mean Hb level was 10.9 g/dL (11.4% below 8.5 g/dL), while it was 10.3 g/dL among those below 2 years (11.2% below 8.0 g/dL). A total of 91.2% of the patients were on an erythropoiesis-stimulating agent (ESA). Hb levels increased with age and were higher in peritoneal dialysis compared with haemodialysis patients. Patients with congenital anomalies of the kidney and urinary tract showed the highest Hb levels, and those with cystic kidney diseases or metabolic disorders the lowest ones. Ferritin levels between 25 and 50 ng/mL were associated with the highest Hb levels. We found a weak inverse association between parathyroid hormone (PTH) and Hb. Whereas standardized blood pressure (BP) was not elevated in patients with above-target Hb, elevated systolic BP z-score was noted in those with sub-target Hb levels.
Sub-target Hb levels remain common in children on dialysis, in spite of virtually all children being treated with ESA; although we cannot exclude under-dosing. Optimal ferritin levels seemed to be slightly lower in children (25-50 ng/mL) than those in adults. Other risk factors for sub-target Hb are dialysis modality and a high PTH level.
The European Society of Hypertension has recently published its recommendations on prevention, diagnosis and treatment of high blood pressure in children and adolescents. Taking this contribution as ...a starting point the Study Group of Hypertension of the Italian Society of Pediatrics together with the Italian Society of Hypertension has conducted a reappraisal of the most recent literature on this subject. The present review does not claim to be an exhaustive description of hypertension in the pediatric population but intends to provide Pediatricians with practical and updated indications in order to guide them in this often unappreciated problem. This document pays particular attention to the primary hypertension which represents a growing problem in children and adolescents. Subjects at elevated risk of hypertension are those overweight, with low birth weight and presenting a family history of hypertension. However, also children who do not present these risk factors may have elevated blood pressure levels. In pediatric age diagnosis of hypertension or high normal blood pressure is made with repeated office blood pressure measurements that show values exceeding the reference values. Blood pressure should be monitored at least once a year with adequate methods and instrumentation and the observed values have to be interpreted according to the most updated nomograms that are adjusted for children's gender, age and height. Currently other available methods such as ambulatory blood pressure monitoring and home blood pressure measurement are not yet adequately validated for use as diagnostic instruments. To diagnose primary hypertension it is necessary to exclude secondary forms. The probability of facing a secondary form of hypertension is inversely proportional to the child's age and directly proportional to blood pressure levels. Medical history, clinical data and blood tests may guide the differential diagnosis of primary versus secondary forms. The prevention of high blood pressure is based on correct lifestyle and nutrition, starting from childhood age. The treatment of primary hypertension in children is almost exclusively dietary/behavioral and includes: a) reduction of overweight whenever present b) reduction of dietary sodium intake c) increase in physical activity. Pharmacological therapy will be needed rarely and only in specific cases.
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Introduction: Atypical hemolytic uremic syndrome (aHUS) is a progressive, life-threatening disease of uncontrolled and chronic complement activation, leading to systemic thrombotic microangiopathy ...(TMA) and severe end-organ damage. Prior to an effective pharmacologic treatment, and despite intensive management with plasma exchange/plasma infusion, up to 25% of children died during the initial presentation, and up to 48% reached end-stage renal disease or died 5 years after disease onset. In a prospective study of children and adolescents with aHUS, eculizumab (ECU), a terminal complement inhibitor, was shown to inhibit TMA and improve hematologic outcomes and renal function by 26 weeks. Here, we report 1-year data from this prospective trial.
Methods: This was an open-label, single-arm, Phase 2 trial of ECU in pediatric patients (pts) with aHUS. Inclusion criteria included platelet count less than the lower limit of normal (LLN) at screening and at baseline (BL), lactate dehydrogenase (LDH) ≥1.5 times the upper limit of normal (ULN) at the start of the current manifestation, and elevated serum creatinine (SCr) at screening. An identified complement abnormality was not required. Pts with STEC-HUS (Shiga toxin + E. coli) or severe ADAMTS13 deficiency (<5%) were excluded. The primary endpoint was the proportion of pts who achieved complete TMA response, defined as hematologic normalization (platelet count ≥150x109/L; LDH ≤ULN), and improvement of renal function (≥25% decrease in SCr from BL, confirmed by ≥2 consecutive measurements obtained ≥4 weeks apart). Dosing was based on weight cohorts, and the regimen was designed with investigators and regulatory agencies to ensure that ≥95% of pts had complete and sustained terminal complement inhibition (defined as >80% inhibition in a hemolytic assay), including in times of increased complement activity (eg, infection or surgery).
Results: 22 pts (aged 1 month to 17 years) were enrolled and 19 completed 26 weeks of treatment. The median time from the current manifestation to enrollment was 0.20 months (range, 0.03–4.26). At the 1-year update, the mean (SD) treatment duration was 12.5 (6.38) months, with a median (range) of 12.6 (0.0–24.5) months. At week 26, 14 pts (64%) achieved the primary endpoint of complete TMA response (Table), and that number increased to 15 (68%) at 1 year. Platelet levels (Fig 1) and estimated glomerular filtration rate (eGFR) (Fig 2) increased significantly from BL through the 26-week study period, and those gains were maintained or further improved at 1 year. Nine of 11 pts (82%) on dialysis at BL discontinued dialysis, and all remained dialysis-free at 1 year. 11 pts not on dialysis at BL also remained dialysis-free at 1 year. Quality of life significantly improved. ECU was well tolerated and there were no meningococcal infections or deaths.
Conclusions: Longer-term analysis at 1 year further demonstrates the safety and efficacy of ongoing ECU therapy in pediatric aHUS pts. It is interesting to note that renal function, as represented by eGFR, further increased between weeks 26 and 1 year: this highlights the need to pursue ECU treatment over the long term. These findings show that treatment with ECU results in life-altering outcomes, in stark contrast to the natural history of the disease.
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Greenbaum:Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Ardissino:Alexion Pharmaceuticals: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Al-Akash:Alexion Pharmaceuticals: Honoraria, Speakers Bureau. Lieberman:Alexion Pharmaceuticals: Honoraria, Speakers Bureau; Questcor: Honoraria, Speakers Bureau. Rees:Alexion Pharmaceuticals: Honoraria. van de Kar:Alexion Pharmaceuticals: Member of International Advisory Board of aHUS Other. Vande Walle:Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Ogawa:Alexion Pharmaceuticals: Employment. Bedrosian:Alexion Pharmceuticals: Employment. Licht:Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Achillon Pharmaceuticals: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau.
Background
The condition called renal dysplasia is considered to be a frequent cause of chronic kidney disease in children. Formally, it is defined by histological parameters. In current nephrology ...practice, however, the appearance of the kidneys on ultrasound scanning is often used as a basis for the diagnosis.
Methods
The European Society for Pediatric Nephrology Working Group on Congenital Anomalies of the Kidney and Urinary Tract hypothesized that the current diagnostic approach with regard to renal dysplasia was not homogeneous. Accordingly, we here report the results of a survey targeting pediatric nephrologists with 12 questions regarding their perceptions of the ultrasonographic characteristics of renal dysplasia and further tests that they might undertake.
Results
Of almost 1200 physicians who successfully received the invitation, 248 from 54 countries completed the survey. There was a notable lack of homogeneity regarding the ultrasonographic diagnosis of renal dysplasia and also of follow-up tests, including genetic testing and further radiology.
Conclusions
Based on the responses to this large survey, a picture emerges of nephrologists’ current clinical practice with regard to renal dysplasia. The Working Group considers that these results serve as an important sounding board which can provide the basis for more definitive recommendations regarding the challenges to clinical diagnosis and diagnostic follow-up of this important condition.
aHUS is a rare, genetic, life-threatening disease of uncontrolled and chronic complement activation, leading to systemic TMA and severe end-organ damage. Despite plasma exchange/plasma infusion ...(PE/PI), up to 65% of all pts sustain permanent renal damage, progress to end-stage renal disease, or die within a year of diagnosis. Ecu, a terminal complement inhibitor, is approved for the treatment of aHUS, and was shown to be safe and effective in pediatric pts in a retrospective study. Previous studies have shown that early intervention with Ecu leads to significant, time-dependent improvements in hematologic and renal outcomes. Here, we report safety and efficacy results from the first prospective trial of pediatric pts with aHUS at 26 weeks (wks).
This was an open-label, single-arm, Phase 2 trial of Ecu in pediatric pts with aHUS. Admission criteria included platelet count < the lower limit of normal (LLN) at screening and at baseline (BL), LDH ≥1.5 times the upper limit of normal (ULN) at the start of the current aHUS manifestation, and elevated serum creatinine (Cr) at screening. An identified complement gene mutation was not required. Pts with STEC-HUS (shiga toxin + E. coli) or severe ADAMTS13 deficiency (<5%) were excluded. The primary endpoint was complete TMA response at 26 wks (normalization of platelets and LDH, and ≥25% improvement in Cr from BL on 2 consecutive measurements ≥4 wks apart). Dosing was based on weight cohorts.
22 pts (1 month to 17 yrs) were enrolled and 19 completed 26 wks. 16 pts (73%) were newly diagnosed, with a median of 6 days from diagnosis to the first dose of ECU. 12 pts (55%) had no PE/PI during the current manifestation. At wk 26, 14 pts (64%) achieved the primary endpoint of complete TMA response (Table). Platelets (Fig 1) and eGFR (Fig 2) increased significantly from BL through the 26-wk study period. 9 of 11 pts (82%) on dialysis at BL discontinued dialysis. 100% of the 11 pts not on dialysis at BL remained off dialysis through wk 26. Mean increase in eGFR through wk 26 was 64 mL/min/1.73m2. All 10 pts on PE/PI at BL discontinued PE/PI. QoL significantly improved. Ecu was safe and well tolerated. 1 pt withdrew due to an SAE (agitation). No pts had meningococcal infection or died.
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In this, the first prospective trial of pediatric pts with aHUS, early intervention with Ecu improved hematologic and renal parameters. 82% of pts discontinued dialysis, and no pt initiated dialysis during the 26-wk study. Use of Ecu has been recommended as first-line therapy in children with aHUS. This trial confirms that Ecu inhibits complement-mediated TMA, and is safe and effective as first-line therapy at the approved dose regimen in pediatric pts with aHUS. Treatment in this clinical trial is ongoing.
Greenbaum:Alexion Pharmaceuticals: Consultancy, Honoraria, Research Funding. Ardissino:Alexion Pharmaceuticals: Formal Advisory Activities Other, Honoraria. Henning:Alexion Pharmaceuticals: Grant Support Other, Research Funding. Pape:Novartis Pharmaceuticals, Alexion Pharmaceuticals: Grant Support Other, Honoraria, Research Funding, Speakers Bureau. Kar:Alexion Pharmaceuticals: Member of the Int. Advisory Board aHUS Other. Vande Walle:Alexion Pharmaceuticals: Ferring Safety Board, Astellas Safety and Investigator Board for Solifenacin, Mitsubishi Safety Board, Alexion Registry Review Board Other, Research Funding, Speakers Bureau. Ogawa:Alexion Pharmaceuticals: Employment. Bedrosian:Alexion Pharmaceuticals: Employment.
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