Acute kidney injury in children hospitalised for febrile urinary tract infection.

AIM: To determine (i) prevalence and the risk factors for acute kidney injury (AKI) in children hospitalised for febrile urinary tract infection (fUTI) and (ii) role of AKI as indicator of an underlying VUR. AKI, in fact, is favoured by a reduced nephron mass, often associated to VUR. METHODS: This retrospective Italian multicentre study enrolled children aged 18 years or younger (median age = 0.5 years) discharged with a primary diagnosis of fUTI. AKI was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. RESULTS: Of 849 children hospitalised for fUTI (44.2% females, median age 0.5 years; IQR = 1.8), 124 (14.6%) developed AKI. AKI prevalence rose to 30% in the presence of underlying congenital anomalies of the kidney and urinary tract (CAKUT). The strongest AKI predictors were presence of CAKUT (OR = 7.5; 95%CI: 3.8-15.2; p = 9.4e-09) and neutrophils levels (OR = 1.13; 95%CI: 1.08-1.2; p = 6.8e-07). At multiple logistic regression analysis, AKI during fUTI episode was a significant indicator of VUR (OR = 3.4; 95%CI: 1.7-6.9; p = 0.001) despite correction for the diagnostic covariates usually used to assess the risk of VUR after the first fUTI episode. Moreover, AKI showed the best positive likelihood ratio, positive predictive value, negative predictive value and specificity for VUR. CONCLUSION: AKI occurs in 14.6% of children hospitalised for fUTI and is a significant indicator of VUR.

Uromodulin and Vesico-Ureteral Reflux: A Genetic Study.

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.

A novel NF1 mutation in a pediatric patient with renal artery aneurysm.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a neurocutaneous syndrome, due to heterozygous pathogenic variants in NF1 gene. The main clinical manifestations are multiple café au lait spots, axillary and inguinal freckling, cutaneous and plexiform neurofibromas, optic glioma, Lisch nodules and osseous lesions, such as sphenoid and tibial dysplasia. Vasculopathy is another feature of NF1; it consists of stenosis, aneurysms, and arteriovenous malformations, frequently involving renal arteries. CASE PRESENTATION: We report on a 9-year-old girl with a novel mutation in NF1 gene and renal artery aneurysm, treated by coil embolization and complicated with hypertension. CONCLUSION: Vasculopathy is a complication of NF1, affecting from 0.4 to 6.4% of patients with NF1. Among the vascular abnormalities, renal artery aneurysm is a rare manifestation, with only a few cases regarding adult patients and no pediatric reports described in current literature. The finding of a vascular abnormality in a specific site requires the evaluation of the entire vascular system because multiple vessels could be involved at the same time.

Management of the congenital solitary kidney: consensus recommendations of the Italian Society of Pediatric Nephrology.

BACKGROUND: In recent years, several studies have been published on the prognosis of children with congenital solitary kidney (CSK), with controversial results, and a worldwide consensus on management and follow-up is lacking. In this consensus statement, the Italian Society of Pediatric Nephrology summarizes the current knowledge on CSK and presents recommendations for its management, including diagnostic approach, nutritional and lifestyle habits, and follow-up. We recommend that any antenatal suspicion/diagnosis of CSK be confirmed by neonatal ultrasound (US), avoiding the routine use of further imaging if no other anomalies of kidney/urinary tract are detected. A CSK without additional abnormalities is expected to undergo compensatory enlargement, which should be assessed by US. We recommend that urinalysis, but not blood tests or genetic analysis, be routinely performed at diagnosis in infants and children showing compensatory enlargement of the CSK. Extrarenal malformations should be searched for, particularly genital tract malformations in females. An excessive protein and salt intake should be avoided, while sport participation should not be restricted. We recommend a lifelong follow-up, which should be tailored on risk stratification, as follows: low risk: CSK with compensatory enlargement, medium risk: CSK without compensatory enlargement and/or additional CAKUT, and high risk: decreased GFR and/or proteinuria, and/or hypertension. We recommend that in children at low-risk periodic US, urinalysis and BP measurement be performed; in those at medium risk, we recommend that serum creatinine also be measured; in high-risk children, the schedule has to be tailored according to kidney function and clinical data.

Childhood Idiopathic Nephrotic Syndrome: Does the Initial Steroid Treatment Modify the Outcome? A Multicentre, Prospective Cohort Study.

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).

Resident foreign patients receive adequate dialysis but fewer preemptive transplantations: data from the Italian pediatric dialysis registry.

BACKGROUND: Sociocultural issues play a key role in children needing kidney replacement therapy (KRT). METHODS: Data of incident patients < 18 years treated with chronic dialysis or preemptive kidney transplantation (pTx) between 2007 and 2016 were retrospectively collected from the Italian Pediatric Dialysis Registry; KRT modality and outcome were compared between patients with at least one non-Italian parent ("resident foreign patients," RFPs) and those from native parents ("domestic patients," DPs) and between the quinquennium 2007-2011 (period 1) and 2012-2016 (period 2). RESULTS: We included 448 children (26.8% RFPs). The percentage of RFPs increased from 23 to 30.3% (p = 0.08) from periods 1 to 2. They were younger (6.7 vs. 9.4 years, p = 0.025) and less often treated with pTx (3.3 vs. 13.4%, p = 0.009) than DPs. The percentage of pTx increased from period 1 to 2 in RFPs only (8.4-18.6%, p = 0.006). Independent predictors of a lower probability of pTx were lower age, belonging to RFPs group, starting KRT in period 1 and focal segmental glomerulosclerosis or glomerulopathy as primary kidney disease. Peritoneal dialysis was the preferred dialysis modality in both groups. Age, primary kidney disease, and center size were independently associated with dialysis modality choice. Patient survival, waiting time to Tx, and dialysis modality survival were not different between the two groups. CONCLUSIONS: The proportion of patients receiving KRT born from immigrant families increased in recent years in Italy. They were younger and less often treated with pTx than domestic patients. In case of dialysis, the outcome was not different between the two groups. Graphical abstract.

Haemodiafiltration use in children: data from the Italian Pediatric Dialysis Registry.

BACKGROUND: High volume haemodiafiltration (HDF) is associated with better survival than conventional haemodialysis (HD) in adults, but data concerning its use in children are lacking. The aim of this study was to assess the prevalence of paediatric HDF use and its associated factors in recent years in Italy. METHODS: We retrospectively reviewed the files of patients from the Italian Pediatric Dialysis Registry's database who were registered between January 1, 2004 and December 31, 2016 and treated with extracorporeal dialysis for at least 6 months, looking in particular at modality and its associated factors. RESULTS: One hundred forty-one out of 198 patients were treated exclusively with bicarbonate HD (71.2%), 57 with HDF (28.8%). Patients treated with HDF were younger (median 9.7 vs 13.2 years, p = 0.0008), were less often incident patients (52.6% vs 75.9%, p = 0.0031), had longer duration of the HD cycle (26.9 vs 20.8 months, p = 0.0036) and had a longer time to renal transplantation (32 vs 25 months, p = 0.0029) than those treated with bicarbonate HD only. The percentage of patients treated with HDF increased with dialysis vintage (16.9% at 6 months, 38.1% after more than 2 years of dialysis). The use of HDF was stable over time and was more common in the largest centres. CONCLUSIONS: Over the observation period, HDF use in Italy has been limited to roughly a quarter of patients on extracorporeal dialysis, in particular to those with high dialysis vintage, younger age or a long expected waiting time to renal transplantation.

Correlation between hypertrophy and risk of hypertension in congenital solitary functioning kidney.

PURPOSE: Solitary functioning kidney (SFK) may be associated to hypertrophy, hypertension and chronic kidney disease. We evaluated blood pressure (BP) of children with congenital SFK comparing agenesis to multicystic dysplastic kidney (MCDK) and correlated BP profiles with renal dimensions of affected and contralateral kidney. METHODS: We compared 40 patients with MCDK, grouped for either treatment options (A: conservative vs B: nephrectomy) or involution time (A1: before 4 years-of-age vs A2: persistence-of-MCDK), to 10 unilateral agenesis (C). Patients were evaluated with ultrasound, scintigraphy, office-ambulatory BP monitoring. RESULTS: Compensatory hypertrophy was demonstrated in most of the subjects, without differences between subgroups, with an increase over time (p < 0.001). A1-C showed an overall percentage of hypertrophy significantly higher than A2-B (83%-88% vs 70%-73%, respectively; p = 0.03); moreover, cumulative risk to develop hypertension in A1-C is significantly higher compared to A2-B in office and ambulatory BP monitoring (p = 0.03). Insufficient dipping in systolic and/or diastolic BP was found in 82% children, without differences between subtypes. CONCLUSIONS: Patients with a small/absent dysplastic kidney have an increased risk to develop hypertrophy and hypertension compared to patients with a large residual, regardless of nephrectomy. ABPM revealed absent dipping in most patients with SFK, warning further investigations in apparently not symptomatic patients.

A propensity-matched comparison of hard outcomes in children on chronic dialysis.

Data concerning outcomes of children on hemodialysis (HD) and peritoneal dialysis (PD) are scarce and frequently derived from single-center experiences. We sought to compare survival and transplantation rates in a large cohort of PD and HD patients. We extracted all patients initiating dialysis under 16 years of age between 2004 and 2013 from the Italian Registry of Pediatric Chronic Dialysis. Patients on PD were propensity-matched to those on HD based on gender, age, primary cause of ESRD, and the number of co-morbidities. Stratified Cox proportional hazard models were used to compare outcomes by dialysis modality. Three hundred ten patients were matched from 452 incident patients. In the unmatched cohort, PD patients were younger, more likely to be diagnosed with CAKUT, and had a higher urine output than HD patients. In the propensity-matched cohort, covariates were balanced between the two groups. At 2 years, the cumulative hazard ratio for death was similar (CHR 0.95, 95% CI 0.17-5.20) for HD relative to PD patients; and at 5 years, the CHR was lower for HD patients (0.22 95% CI 0.16-0.29). The cumulative incidence of transplantation at 3 years after dialysis initiation was 60.9% in HD patients and 59.7% in PD patients, with a CHR of 1.03 (95% CI 0.73-1.45). CONCLUSIONS: Pediatric PD and HD patients have distinct characteristics. After controlling for treatment-selection biases, children selected to start on PD or HD exhibit a similar mortality risk during the first 2 years on treatment, after which this risk increases in PD children. What is Known: • Few studies have compared hard outcomes in children on maintenance dialysis. • Children started on different dialysis modalities have distinct characteristics that impact on survival. What is New: • After controlling for treatment-selection biases, children selected to start dialysis on PD or HD exhibit a similar mortality risk during the first 2 years on treatment, after which this risk appears to be increased in PD children. • An "integrative care" approach should be used in children on PD, switching them to HD when PD-related morbidity tends to increase.

Novelty in hypertension in children and adolescents: focus on hypertension during the first year of life, use and interpretation of ambulatory blood pressure monitoring, role of physical activity in prevention and treatment, simple carbohydrates and uric acid as risk factors.

The present article intends to provide an update of the article "Focus on prevention, diagnosis and treatment of hypertension in children and adolescents" published in 2013 (Spagnolo et al., Ital J Pediatr 39:20, 2013) in this journal. This revision is justified by the fact that during the last years there have been several new scientific contributions to the problem of hypertension in pediatric age and during adolescence. Nevertheless, for what regards some aspects of the previous article, the newly acquired information did not require substantial changes to what was already published, both from a cultural and from a clinical point of view. We felt, however, the necessity to rewrite and/or to extend other parts in the light of the most recent scientific publications. More specifically, we updated and extended the chapters on the diagnosis and management of hypertension in newborns and unweaned babies, on the use and interpretation of ambulatory blood pressure monitoring, and on the usefulness of and indications for physical activity. Furthermore, we added an entirely new section on the role that simple carbohydrates (fructose in particular) and uric acid may play in the pathogenesis of hypertension in pediatric age.

Anterior ischemic optical neuropathy in children on chronic peritoneal dialysis: report of 7 cases.

BACKGROUND: Anterior ischemic optic neuropathy (AION) is characterized by infarction of the optic nerve head due to hypoperfusion of the posterior ciliary arteries and causes sudden blindness in adults on chronic dialysis, but has rarely been described in children. Unlike adults, children do not have comorbidities related to aging. METHODS: We retrospectively analyzed data of 7 children on nocturnal continuous cycling peritoneal dialysis (CCPD) who developed AION identified within the Italian Registry of Pediatric Chronic Dialysis. We also summarized data from 10 cases reported in the literature. RESULTS: Our 7 patients suffered from acute onset bilateral blindness. Their mean age was 3.2 years and chronic hypotension had been observed prior the AION in 3 of the 7 children. Low systolic blood pressure (SBP) was associated with higher risk of developing AION according to statistical analysis. None recovered completely. In total, 11 out of 16 experienced a partial recovery and no clear evidence emerged favoring specific treatments. CONCLUSIONS: Hypotensive children treated with CCPD are at increased risk of developing AION, which often results in irreversible blindness.

[Nephrocalcinosis in children].

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.

[Atypical Hemolytic Uremic Syndrome: experience of a pediatric center].

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.

[Cardiovascular Disease In Children With Ckd]. / Alterazioni cardiovascolari nei bambini affetti da malattia renale cronica.

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.

Adiponectin, resistin and leptin in paediatric chronic renal failure: correlation with auxological and endocrine profiles.

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.

Early origin of adult renal disease.

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.

Prevalence of biliary lithiasis in a Sicilian population of chronic renal failure patients.

BACKGROUND: The aim of this study was to evaluate the prevalence of biliary lithiasis (BL) and associated risk factors in a population of undialysed patients with chronic renal failure (CRF), and to compare these with findings we had obtained previously in chronic haemodialysis (HD) patients and in subjects from the general population located in the same geographic region. METHODS: A total of 118 CRF patients on conservative treatment were included in the study. In all subjects, we measured several clinical and humoral parameters potentially correlated with BL. Liver and biliary tract ultrasonography was performed with a 3.5 MHz linear probe after at least 12 h of fasting. RESULTS: The prevalence of BL in CRF patients was 22%, which was higher than in the general population (chi(2) = 9.4, P < 0.002) but lower than in HD patients (chi(2) = 25.9, P < 0.0001). Age was similar in the three groups. Body mass index (BMI) was significantly higher in the CRF group than in both HD patients (P < 0.0001) and the general population (P < 0.0001). When the CRF group was divided into subjects with or without BL, the only difference was lower serum calcium levels in the subgroup with BL (P < 0.04). CONCLUSIONS: The prevalence of BL in a Sicilian population of CRF patients was higher than in the general population, but lower than in patients with CRF on chronic HD. Apart from BMI, none of the risk factors traditionally associated with BL in the general population were related to BL in the CRF patients. These data suggest that other factors inherent to kidney pathology contribute to the high prevalence of BL in CRF patients.