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Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.
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Estudo de Associação Genômica Ampla , Síndrome Nefrótica , Humanos , Criança , Síndrome Nefrótica/genética , Predisposição Genética para Doença , Haplótipos , Fatores de Risco , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Lithium intoxication is still an undefined and underestimated disease, especially those cases requiring extracorporeal treatment. Lithium is a monovalent cation with small molecular mass of 7 Da that has been regularly and successfully used since 1950 in the treatment of mania and bipolar disorders. However, its careless assumption can lead to a wide spectrum of cardiovascular, central nervous system and kidney diseases in case of acute, acute on chronic and chronic intoxications. In fact, lithium serum range is strict between 0.6 and 1.3 mmol/L, with a mild lithium toxicity observed at the steady-state of 1.5-2.5 mEq/L, moderate toxicity when lithium reaches 2.5-3.5 mEq/L, and severe intoxication with observed serum levels > 3.5 mEq/L. Its favorable biochemical profile allows the complete filtration and partial reabsorption in the kidney due to the similarity to sodium and also the complete removal by renal replacement therapy, that should be considered in specific poisoning conditions. In this narrative and updated review we discussed a clinical case of lithium intoxication, the different pattern of diseases attributable to excessive lithium load and the current indications for extracorporeal treatment.
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Transtorno Bipolar , Nefropatias , Humanos , Lítio/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Nefropatias/tratamento farmacológico , Terapia de Substituição Renal , CoraçãoRESUMO
Vesicoureteral reflux (VUR) is associated with urinary tract infections (UTI) and renal scars. The kidney damage is correlated with the grade of reflux and the number of UTI, but other factors may also play a role. Uromodulin (UMOD) is a protein produced by kidney tubular cells, forming a matrix in the lumen. We evaluated whether the common variant rs4293393 in the UMOD gene was associated with febrile UTI (FUTI) and/or scars in a group of children with VUR. A total of 31 patients with primary VUR were enrolled. Renal scars were detected in 16 children; no scar was detected in 15 children. Genotype rs4293393 TC (TC) was present in 8 patients, 7 (88%) had scars; genotype rs4293393 TT (TT) was found in 23 patients, and 9 (39%) had scars. Among children with scars, those with TC compared with those with TT were younger (mean age 77 vs. 101 months), their reflux grade was comparable (3.7 vs. 3.9), and the number of FUTI was lower (2.9 vs. 3.7 per patient). Children with VUR carrying UMOD genotype rs4293393 TC seem more prone to developing renal scars, independent of FUTI.
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Background: A great majority of children with idiopathic nephrotic syndrome will relapse after successful treatment of the initial episode. The possibility that different steroid dosing regimens at onset, adjusted for risk factors, can reduce the rate of relapse represents an interesting option to investigate. Objectives: To evaluate the effect of the initial steroid regimen, adjusted for time to remission (TTR), on the frequency of relapses and steroid dependence, and to verify the influence of prognostic factors on disease course. Methods: A multicentre, prospective, cohort study. Children with nephrotic syndrome, with TTR ≤ 10 days (Group A), were given a 20-week prednisone regimen (2,828 mg/m2) and those with a TTR >10 days, a 22-week regimen (3,668 mg/m2) (Group B). Previously published retrospective data from the same centers were also evaluated. Main outcomes were: relapse rate, number of frequent relapsers + steroid dependent children and total prednisone dose after induction. Results: 143 children were enrolled. Rate of relapsed subjects (77 vs. 79%) and frequent relapsers + steroid dependent subjects (40 vs. 53%) did not differ between Groups A and B, or between the retrospective and prospective cohorts. The cumulative prednisone dose taken after the induction treatment was similar in both groups and in the retrospective and prospective cohorts. TTR was not associated with relapse risk. Age at onset and total serum protein were significantly lower in relapsing patients. At ROC analysis, the best cut-off was 5.3 years for age at onset and 4.2 g/dL for total serum protein. According to these cut-offs, older children with higher total serum protein had a higher relapse free survival rate (58%) than younger children with lower total serum protein (17%). Conclusions: TTR was not found to be a prognostic factor of relapse; because of this, different steroid regimens, adjusted for TTR, did not modify the relapse rate in any relevant measure. Conversely, younger age and low total serum protein were independent predictors of relapse risk, however this outcome was not modified by higher prednisone regimens. Clinical Trial Registration:https://www.ClinicalTrials.gov/, identifier: NCT01386957 (www.nefrokid.it).
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Corticosteroid-related toxicity in children with steroid-sensitive nephrotic syndrome is primarily related to the cumulative dose of prednisone. To optimize treatment of relapses, we conducted the PROPINE study, a multicentric, open-label, randomized, superiority trial. Seventy-eight relapsing children aged 3-17 years who had not received steroid-sparing medications during the previous 12 months were randomized to receive, from day five after remission, either 18 doses of 40 mg/m2 of prednisone on alternate days (short arm), or the same cumulative dose tapered over double the time (long arm). Patients were monitored with an ad-hoc smartphone application, allowing daily reporting. The primary outcome was the six-month relapse rate at which time, 23/40 and 16/38 patients had relapsed in the long and short arms, respectively (no significant difference). Additionally, 40/78 patients were also enrolled in a secondary crossover study and were allocated to the opposite arm. Altogether, at six months, the relapse rate was 32/40 and 28/40 in the long and short arms, respectively (no significant difference). A post-hoc analysis excluding 30 patients treated with low-dose prednisone maintenance therapy failed to show significant differences between the two arms. No differences in adverse events, blood pressure and weight gain were observed. Thus, our data do not support the prescription of prolonged tapering schedules for relapses of steroid-sensitive nephrotic syndrome in children.
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Síndrome Nefrótica , Anti-Inflamatórios/uso terapêutico , Criança , Estudos Cross-Over , Epinefrina/análogos & derivados , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Prednisona/efeitos adversos , RecidivaRESUMO
AIM: Our aim was to update the recommendations for the diagnosis, treatment and follow-up of the first febrile urinary tract infection in young children, which were endorsed in 2012 by the Italian Society of Pediatric Nephrology. METHODS: The Italian recommendations were revised on the basis of a review of the literature published from 2012 to October 2018. We also carried out an ad hoc evaluation of the risk factors to identify children with high-grade vesicoureteral reflux or renal scarring, which were published in the previous recommendations. When evidence was not available, the working group held extensive discussions, during various meetings and through email exchanges. RESULTS: Four major modifications have been introduced. The method for collecting urine for culture and its interpretation has been re-evaluated. We have reformulated the algorithm that guides clinical decisions to proceed with voiding cystourethrography. The suggested antibiotics have been revised, and we have recommended further restrictions of the use of antibiotic prophylaxis. CONCLUSION: These updated recommendations have now been endorsed by the Italian Society of Pediatric Nephrology and the Italian Society for Pediatric Infectivology. They can also be used to compare other recommendations that are available, as a worldwide consensus in this area is still lacking.
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Infecções Urinárias , Refluxo Vesicoureteral , Criança , Pré-Escolar , Febre/diagnóstico , Febre/etiologia , Febre/terapia , Seguimentos , Humanos , Lactente , Itália , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico , Refluxo Vesicoureteral/diagnóstico , Refluxo Vesicoureteral/terapiaRESUMO
Renal Diseases represent almost 6% of all Rare Diseases but are often misdiagnosed. In a survey made in Sicily in 2016, based on cases reported from all public hospitals according to a list of rare kidney diseases, we were able to collect 337 cases (199 males and 138 females). The highest prevalence was detected in children: 13.9 cases in 100.000 children; the mean age was 10, and the median 5 years, at the time of the diagnosis. Comparing our data with those available in the Sicilian Register of Rare Diseases we found that only 141 cases (54%) were present in the register. Promoting regional registries of rare kidney diseases in Italy may be useful for epidemiologic studies.
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Nefropatias/epidemiologia , Doenças Raras/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Nefropatias/genética , Masculino , Pessoa de Meia-Idade , Prevalência , Doenças Raras/genética , Sistema de Registros/estatística & dados numéricos , Distribuição por Sexo , Sicília/epidemiologia , Adulto JovemRESUMO
A 9-year-old boy with petechiae on the legs and abdominal pain was unsuccessfully treated with steroids. He was admitted to our hospital for the onset of fever, ecchymosis, and arthralgia. Skin lesions suggested vasculitis, but they were not typical of Henoch-Schönlein purpura. He showed ecchymosis of the scrotal bursa, diffusion of petechiae to the trunk and arms, vomiting, severe abdominal pain, oliguria with hyponatremia, hypoalbuminemia, low C3 levels, high levels of creatinine, blood urea nitrogen, and tubular enzymes, proteinuria, and glycosuria. The urinary sediment showed macrohaematuria, and hyaline and cellular casts. Ultrasound showed polyserositis. He was treated with intravenous furosemide, albumin, and methylprednisolone. He underwent colonoscopy and gastroscopy because of development of acute pancreatitis and severe anaemia. Typical lesions of Henoch-Schönlein purpura were observed in the small intestine and colon mucosa. He received three high doses of methylprednisolone, followed by intravenous cyclophosphamide. A dramatic and persistent response was observed after these doses. A single high dose of cyclophosphamide is appropriate in Henoch-Schönlein purpura with acute renal failure and severe pancreatitis that are non-responsive to high-dose steroids.
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Injúria Renal Aguda/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Vasculite por IgA/tratamento farmacológico , Imunossupressores/uso terapêutico , Pancreatite/tratamento farmacológico , Injúria Renal Aguda/complicações , Injúria Renal Aguda/patologia , Anti-Inflamatórios/uso terapêutico , Criança , Quimioterapia Combinada , Humanos , Vasculite por IgA/complicações , Vasculite por IgA/patologia , Masculino , Metilprednisolona/uso terapêutico , Pancreatite/complicações , Pancreatite/patologia , PrognósticoRESUMO
INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Oxalato de Cálcio/urina , Hiperoxalúria/urina , Espectroscopia de Infravermelho com Transformada de Fourier , Urinálise/métodos , Cálculos Urinários/urina , Adolescente , Biomarcadores/urina , Fosfatos de Cálcio/urina , Criança , Pré-Escolar , Feminino , Humanos , Hiperoxalúria/diagnóstico , Hiperoxalúria/epidemiologia , Lactente , Recém-Nascido , Masculino , Valor Preditivo dos Testes , Prevalência , Sicília/epidemiologia , Ácido Úrico/urina , Cálculos Urinários/diagnóstico , Cálculos Urinários/epidemiologiaRESUMO
This consensus document is aimed at providing an updated, multidisciplinary overview on the diagnosis and treatment of pediatric nephrotic syndrome (NS) at first presentation. It is the first consensus document of its kind to be produced by all the pediatric nephrology centres in Italy, in line with what is already present in other countries such as France, Germany and the USA. It is based on the current knowledge surrounding the symptomatic and steroid treatment of NS, with a view to providing the basis for a separate consensus document on the treatment of relapses. NS is one of the most common pediatric glomerular diseases, with an incidence of around 2-7 cases per 100000 children per year. Corticosteroids are the mainstay of treatment, but the optimal therapeutic regimen for managing childhood idiopathic NS is still under debate. In Italy, shared treatment guidelines were lacking and, consequently, the choice of steroid regimen was based on the clinical expertise of each individual unit. On the basis of the 2015 Cochrane systematic review, KDIGO Guidelines and more recent data from the literature, this working group, with the contribution of all the pediatric nephrology centres in Italy and on the behalf of the Italian Society of Pediatric Nephrology, has produced a shared steroid protocol that will be useful for National Health System hospitals and pediatricians. Investigations at initial presentation and the principal causes of NS to be screened are suggested. In the early phase of the disease, symptomatic treatment is also important as many severe complications can occur which are either directly related to the pathophysiology of the underlying NS or to the steroid treatment itself. To date, very few studies have been published on the prophylaxis and treatment of these early complications, while recommendations are either lacking or conflicting. This consensus provides indications for the prevention, early recognition and treatment of these complications (management of edema and hypovolemia, therapy and prophylaxis of infections and thromboembolic events). Finally, recommendations about the clinical definition of steroid resistance and its initial diagnostic management, as well as indications for renal biopsy are provided.
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Corticosteroides/administração & dosagem , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Guias de Prática Clínica como Assunto , Criança , Pré-Escolar , Consenso , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Itália , Masculino , Síndrome Nefrótica/mortalidade , Prognóstico , Recidiva , Retratamento , Sociedades Médicas , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Diabetes and obesity are already recognized as potential risk factors for nephrolithiasis, especially for uric acid stones. Insulin resistance and hyperinsulinemia actively contribute to impaired ability to excrete an acid load and altered ammonium production, leading to a lower urinary pH compared to non-diabetic controls. All these electrolytic disorders play an important role in stone formation and aggregation, especially in uric acid stones. There are still missing points in scientific evidence if the increased risk in stone formation is already existing even in the prediabetic statuses (isolated impaired glucose tolerance, isolated impaired fasting glucose, and associated impaired glucose tolerance/impaired fasting glucose) as well as it is worth to consider the same level of risk. Urolithiasis is the most frequent urological cause of hospitalization in diabetic patients and its cost is usually higher compared to non-diabetic patients, but less is known in others altered glycaemic diseases. The aim of this review article is to focus on the association between stone formation and altered glycaemic statuses, beyond the already known link between nephrolithiasis and diabetes mellitus.
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Diabetes Mellitus/urina , Cálculos Renais/etiologia , Síndrome Metabólica/urina , Obesidade/urina , Diabetes Mellitus/epidemiologia , Humanos , Concentração de Íons de Hidrogênio , Cálculos Renais/química , Cálculos Renais/epidemiologia , Cálculos Renais/urina , Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Ácido Úrico/química , Ácido Úrico/urinaRESUMO
BACKGROUND/AIMS: Loss-of-function mutations in the CYP24A1 gene, which encodes the vitamin D-24 hydroxylase, have been recognized as a cause of elevated 1,25-dihydroxyvitamin D concentrations, hypercalcemia, hypercalciuria, nephrocalcinosis and nephrolithiasis in infants and adults. As only a case report describing 2 adult patients has been reported in Italian population, we report here the mutation analysis of CYP24A1 gene in an Italian cohort of 12 pediatric and adult patients with idiopathic infantile hypercalcemia (IIH). METHODS: We performed mutational screening of CYP24A1 gene in a cohort of 12 Italian patients: 8 children with nephrocalcinosis, hypercalcemia and PTH levels <10 pg/ml and 4 adult patients with nephrolithiasis, mild hypercalcemia and PTH levels <10 pg/ml from 11 unrelated Italian families. Clinical and biochemical data were collected. Genomic DNA was extracted from peripheral blood leucocytes using standard methods, and whole coding sequence of CYP24A1 gene was analysed in all patients and family members by polymerase chain reaction and direct sequencing. The potential pathogenicity of the newly identified missense mutations was evaluated by 3 different in silico approaches (Sorting Intolerant from Tolerant, Polyphen and Mutation Taster) and by comparative analysis in 14 different species using ClustalW software. RESULTS: CYP24A1 bi-allelic mutations were found in 8 individuals from 7 Italian families (7/11; 64%). Overall, 6 different CYP24A1 mutations, including one small deletion (p.Glu143del), 4 missense mutations (p.Leu148Pro; p.Arg396Trp; p.Pro503Leu; p.Glu383Gln) and one nonsense mutation (p.Tyr220*) were identified. Two out of 6 mutations (p.Tyr220* and p.Pro503Leu) were not previously described. Moreover, a new CYP24A1 variant was identified by genetic screening of asymptomatic controls. CONCLUSION: To the best of our knowledge, this is the first report of a CYP24A1 molecular analysis performed in an Italian cohort of adult and pediatric Italian patients. This study (1) confirms that CYP24A1 plays a causal role in some but not all cases of IIH (64%); (2) expands the spectrum of known CYP24A1 pathogenic mutations; (3) describes 2 hotspots detected in 50% of all Italian cases; and (4) emphasizes the importance of recognition and genetic diagnosis of CYP24A1 defects in infantile as well as adult hypercalcemia.
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Hipercalcemia/genética , Mutação , Vitamina D3 24-Hidroxilase/genética , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Linhagem , Adulto JovemRESUMO
Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Ativação do Complemento/efeitos dos fármacos , Inativadores do Complemento/uso terapêutico , Adolescente , Fatores Etários , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Síndrome Hemolítico-Urêmica Atípica/imunologia , Austrália , Criança , Pré-Escolar , Inativadores do Complemento/efeitos adversos , Inativadores do Complemento/farmacocinética , Europa (Continente) , Feminino , Humanos , Lactente , Masculino , América do Norte , Troca Plasmática , Estudos Prospectivos , Diálise Renal , Fatores de Tempo , Resultado do TratamentoRESUMO
Tumor lysis syndrome is a serious and dangerous complication usually associated with antiblastic treatment in some malignancies characterized by high cell turn-over. Mild or severe electrolyte abnormalities including high serum levels of uric acid, potassium, phosphorus, creatinine, bun and reduction of calcium can be responsible for multi-organ failure, involving mostly kidneys, heart and central nervous system. Renal damage can be followed by acute renal failure, weight gain, progressive liver impairment, overproduction of cytokines, and subsequent maintenance of multi-organ damage. Life-threatening acute respiratory failure associated with tumor lysis syndrome is rare. We describe a child with T-cell acute lymphoblastic leukemia, who developed an unusually dramatic tumor lysis syndrome, after administration of the first low doses of steroid, that was rapidly associated with severe acute respiratory distress syndrome. Subsequent clinical course and treatment modalities that resulted in the gradual and full recovery of the child are also described.
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Cardiovascular disease (CVD) is the most important risk factor for morbidity and mortality in patients with chronic kidney disease (CKD). Aim of this study was to evaluate cardiac and vascular geometry in children with CKD stages 2, 3 and 4.Twenty-seven patients (18 males and 9 females) mean age 10.9 +/- 5.4 years with CKD and 30 children (control group) were enrolled with comparable age and sex. Weight, height, systolic and diastolic blood pressure were evaluated. We also analyzed biochemical assessments and proteinuria. We performed echocardiography with Philips iE33 and pulse wave velocity (PWV) with Vicorder PWS system. We documented significantly higher level of left ventricular mass index (LVMI) (30.3 +/- 7.6 g/m2.7) and PWV (4.7 +/- 1.6 m/sec) in CKD patients. Left ventricular hypertrophy (LVH) was present in 12 % and concentric remodelling in 36% of our patients. PWV values were significantly correlated with interventricular septal thickness (p<0.01) and with LVMI (p<0.05). In this study we documented the alterations of cardiac and vascular geometry since the early stages of CKD. PWV and echocardiographic measurements must be considered to assess cardiovascular risk in children with CKD stages 2-4.
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Doenças Cardiovasculares/etiologia , Insuficiência Renal Crônica/complicações , Doenças Cardiovasculares/epidemiologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Nephrocalcinosis (NC) is a renal disease characterized by deposition of calcium salts into the renal medulla. There are several causes, organic, iatrogenic, hereditary and sometimes related to extrarenal diseases. We studied 34 children affected by NC, 21 M and 13 F (average age at diagnosis 7.8 months), with the aim of analyzing the associated diseases, clinical manifestations, metabolic abnormalities, growth and renal function at onset and after follow-up. At onset 70% of patients were asymptomatic and diagnosis was occasional. Renal function was normal in 33 patients. The most frequent clinical symptoms were failure to thrive (9%), abdominal pain (6%), proteinuria/hematuria (7%). The associated diseases were: tubulopathies (8 pcs - tubular acidosis, Dent, Bartter and Lowe Syndromes), medullary sponge kidney, policalicosis (3 pcs ), Short bowel Syndrome (3 pcs), hyperparathyroidism, hypothyroidism (2 pcs), thalassemia (1pc), tyrosinemia (1 pc.). We recognized two forms of hypervitaminosis D. In a pc NC would be correlated with prematurity, another one with lipid necrosis. Among the metabolic abnormalities, observed in 25% of pcs, hyperoxaluria is the most frequent (47%), hypercalciuria (20%), hypercalcemia (15%). In some cases we found endocrine non pathogenic alterations: hypovitaminosis D (2 pcs) and hypoparathyroidism (6 pcs). During follow-up the growth was normal in 87% of cases and glomerular function was stable in 90% of pcs; IRC developed in 3 cases. From our analysis, it appears that the treatment of the underlying condition of NC is associated with catch-up growth and stabilization of renal function in most patients, but not with the reduction of the degree of the NC.
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In the last two years we admitted in our Hospital 38 children with acute renal failure (ARF). Six of them were affected by hemolytic uremic syndrome (HUS) atypical. The aHUS is diagnosed in the presence of thrombotic microangiopathy (MAT), renal insufficiency (GFR 5%). The clinical presentation of our children has been varied and so also its evolution. Patients observed were all male, aged 2 to 12 years, and no one had a family history of kidney disease. In four patients we documented alterations of complement factors (MCP deficiency and factor H and presence of anti factor H). Repeated blood transfusions were required in 4 patients and in 3 patients the platelet count was slightly reduced. In 5 patients we did plasmapheresis and in 3 patients dialysis (hemodialysis and peritoneal dialysis). In three patients in whom the diagnosis was not clear, renal biopsy was performed to confirm the diagnosis. Eculizumab was administered in 3 patients resistant to plasma exchange. We obtain a rapid response on MAT with normalization of platelet count. The effect on renal function was variable (complete remission in a patient, partial improvement in another, and unresponsiveness in the last). The last had on Kidney biopsy signs of severe impairment and we documented the presence of antibodies to eculizumab. HUS is a rare condition, but probably much more common than reported. In children with ARF and microangiopathic anemia is necessary evaluated complement factors as early to obtain an improved clinical response to treatment with eculizumab.
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BACKGROUND: The optimal therapeutic regimen for managing childhood idiopathic nephrotic syndrome (INS) is still under debate. We have evaluated the choice of steroid regimen and of symptomatic treatment adopted by pediatricians and pediatric nephrologists in a large number of centers as the first step towards establishing a shared protocol METHODS: This was a multicenter, retrospective study. A total of 231 children (132 admitted to pediatric units) aged 6 months to <15 years who presented with onset of nephrotic syndrome to 54 pediatric units and six pediatric nephrology units in Italy between 2007 and 2009 were eligible for entry into the study. RESULTS: Median steroid dosing was 55 (range 27-75) mg/m(2)/day. The overall median cumulative dose regimen for the first episode was 3,440 (1,904-6,035) mg/m(2), and the median duration of the therapeutic regimen was 21 (9-48) weeks. The total duration and cumulative steroid dose were significantly higher in patients treated by pediatricians than in those treated by pediatric nephrologists (p = 0.001 and p = 0.008). Among the patient cohort, 55, 64 and 22 % received albumin infusions, diuretics and acetyl salicylic acid treatment, respectively, but the laboratory and clinical data did not differ between children treated or not treated with symptomatic drugs. Albumin and diuretic use did not vary between patients in pediatric units and those in pediatric nephrology units. CONCLUSIONS: This study shows major differences in steroid and symptomatic treatment of nephrotic syndrome by pediatricians and pediatric nephrologists. As these differences can influence the efficacy of the treatments and the appearance of side-effects, shared guidelines and their implementation through widespread educational activities are necessary.
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Síndrome Nefrótica/tratamento farmacológico , Pediatria/normas , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
INTRODUCTION: Chronic renal failure (CRF) compromises nutrition, growth, puberty, glycometabolic homeostasis, and adipokine secretion (i.e. adiponectin, resistin, and leptin). Adipokines play a role in the clinical outcome, but data in paediatric patients is scant. AIM: To evaluate the link between kidney function, adiponectin, resistin, leptin, hormonal status, nutritional state and late outcome of CRF children. MATERIALS AND METHODS: We studied leptin, adiponectin and resistin levels in 31 CRF patients (19 males, 12 females, aged 12.1 ± 4.47 years) managed conservatively, and 30 healthy age- and gender-matched controls. Clinical, auxological, biochemical, hormonal data, glucose and insulin levels were correlated with adipokine levels. RESULTS: Six percent of patients had glycaemia T0' > 126 mg/dl, 23 % glycaemia T60' > 126, and 23 % glycaemia T120' ≥ 140. Glycated haemoglobin (HbA1c) measured during follow-up was in the normal range in all patients (4-5.6 %). Insulinaemia was significantly higher in CRF patients than controls. Homeostatic model of assessment-insulin resistance (HOMA-IR) levels were more elevated in patients (32 % had HOMA-IR > 2.5) than controls. Leptin levels were significantly higher in CRF patients than controls and differed significantly between males and females. Leptin correlated significantly with creatinine, body mass index (BMI), BA, pubertal stage, insulin-like growth factor 1, and HOMA-IR in females. Adiponectin levels were significantly higher in patients than controls, higher in patients with BMI < 85th centile and significantly inversely correlated to BMI, BA, haemoglobin, ferritin, proteins, albumin, and creatininuria. Resistin levels showed a direct correlation with C-reactive protein and an inverse correlation with haemoglobin. CONCLUSION: Normal resistin levels are an expression of both adequate nutritional state and controlled inflammatory state. Adiponectin could protect against chronic inflammation, atherosclerosis, and cardiovascular diseases. Preventing obesity and ensuring a correct nutritional state are primary goals for physicians following children with CRF. Adipokines could be a useful marker in the follow-up.
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Adiponectina/sangue , Falência Renal Crônica/sangue , Leptina/sangue , Estado Nutricional , Resistina/sangue , Adolescente , Fenômenos Fisiológicos da Nutrição do Adolescente , Fatores Etários , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Estudos de Casos e Controles , Criança , Progressão da Doença , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/fisiopatologia , Masculino , Obesidade/sangue , Obesidade/etiologia , Obesidade/fisiopatologia , Prognóstico , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Paediatric literature about encapsulating peritoneal sclerosis (EPS) is limited and comes primarily from anecdotic experiences. In this study, we described the incidence and characteristics of EPS in a large paediatric chronic peritoneal dialysis (CPD) patient population. METHODS: We reviewed files of patients starting CPD at <16 years of age, recorded from January 1986 to December 2011 by the Italian Registry of Pediatric Chronic Dialysis (n = 712). Moreover, in December 2011, a survey was performed involving all the Italian Pediatric Nephrology Units to report such EPS cases that occurred after CPD withdrawal. RESULTS: Fourteen EPS cases were reported, resulting in a prevalence of 1.9%. The median age of EPS cases was 4.8 years (range 0.6-14.4) at the start of CPD and 14.3 years (6.5-26.8) at EPS diagnosis. Eleven EPS cases received CPD for longer than 5 years. At diagnosis, nine patients were still on CPD, two were on haemodialysis and three were transplanted. In eight patients, the primary renal disease was represented by glomerulopathy, mainly focal segmental glomerulosclerosis (n = 5). In the last 6 months prior to CPD discontinuation, 10 patients were treated with solutions containing more than 2.27% glucose. Peritonitis incidence was 1:26.8 CPD-months, similar to that calculated in children >12 months of age from the same registry (1:28.3 CPD-months). The mortality rate was 43%. A more aggressive course and an association with calcineurin inhibitors were observed in transplanted patients. CONCLUSIONS: Surveillance for EPS should be maintained in high-risk children who received long-term PD even after years from CPD withdrawal.