Acute Kidney Injury in Neonatal Intensive Care Unit: Epidemiology, Diagnosis and Risk Factors.

Acute kidney injury (AKI) is associated with long-term consequences and poor outcomes in the neonatal intensive care unit. Its precocious diagnosis represents one of the hardest challenges in clinical practice due to the lack of sensitive and specific biomarkers. Currently, neonatal AKI is defined with urinary markers and serum creatinine (sCr), with limitations in early detection and individual treatment. Biomarkers and risk factor scores were studied to predict neonatal AKI, to early identify the stage of injury and not the damage and to anticipate late increases in sCr levels, which occurred when the renal function already began to decline. Sepsis is the leading cause of AKI, and sepsis-related AKI is one of the main causes of high mortality. Moreover, preterm neonates, as well as patients with post-neonatal asphyxia or after cardiac surgery, are at a high risk for AKI. Critical patients are frequently exposed to nephrotoxic medications, representing a potentially preventable cause of AKI. This review highlights the definition of neonatal AKI, its diagnosis and new biomarkers available in clinical practice and in the near future. We analyze the risk factors involving patients with AKI, their outcomes and the risk for the transition from acute damage to chronic kidney disease.

Renal Biomarkers and Novel Therapies in Pediatric Nephrology: From Chronic Kidney Disease to Renal Transplantation.

Chronic kidney disease (CKD), a growing problem with an estimated prevalence of 74 [...].

Therapeutic Management of Children with Vesicoureteral Reflux.

Contrasting data refer to therapies for vesicoureteral reflux (VUR), such as surgical treatments and continuous antibiotic prophylaxis (CAP). This study evaluated the effectiveness of these approaches in children with VUR, analyzing the recurrence of febrile urinary tract infections (UTIs) and the resolution of VUR after the treatment. A total of 350 pediatric patients underwent contrast-enhanced voiding urosonography (ceVUS) to diagnose a VUR, whereas renal scintigraphy evaluated potential scars. After 12 months from the treatment, the VUR, the relapse of febrile UTIs, and reflux-related nephropathy were analyzed. Twenty-seven children had recurrent febrile UTIs after surgical therapy, with a greater rate of relapses observed in III and V VUR grades. Thirteen patients who underwent surgery had scars, independently of VUR grades and gender, with evidence of chronic renal failure at the end of the follow-up period. A total of 140 subjects were treated with CAP, and 30% of them continued to suffer from febrile UTIs. Ninety-five patients with VUR underwent ceVUS after 12 months, with persistent reflux in fifty-two patients. All of them had severe VUR, correlating with the age at diagnosis and gender. CAP therapy prevented scarring better than surgery, especially in children with III and V grades of VUR. A late onset of VUR or VUR involving neonatal patients is rarely a reversible process. This study identified predictors of success or failure of surgical or CAP therapies, evaluating the relapse of UTIs or persistent reflux after the treatment and giving prognostic information in children with VUR.

IL-17 serum level in patients with chronic mucocutaneous candidiasis disease.

BACKGROUND: Chronic mucocutaneous candidiasis (CMC) is defined by recurrent or persistent superficial infections involving nails, skin, and/or oral and genital mucosae. IL-17 promotes the recruitment, chemotaxis, and expansion of neutrophils and acts directly on keratinocytes and epithelial cells, driving the production of antimicrobial peptides, essential for the immune response against Candida. AIM: To evaluate the serum level of IL-17 in a family affected by CMC restricted to the nails of the hands and feet. METHODS: Serum IL-17 was assayed on 16 patients (aged 21 ± 3.1 years) suffering from persistent onychomycosis caused by Candida and 18 healthy controls (aged 19 ± 2.7 years). Comparisons between groups were performed by Student's unpaired t-test. The level of significance was set at 0.05. RESULTS: The mean serum IL-17 level in patients was 74 ± 1.42 pg/ml, whereas the control group showed a significantly lower level of 25.6 ± 6.7 pg/ml (p < 0.05). CONCLUSIONS: We showed a potential defect in the IL-17 signaling pathway in a family affected by CMC restricted to the nails of the hands and feet. Further research is needed to clarify the immunological mechanisms and the genetic etiology at the basis of the unusual clinical presentation in this family.

Fabry disease and kidney involvement: starting from childhood to understand the future.

The accumulation of globotriaosylceramide (Gb-3) in multiple organs, such as the heart, kidney, and nervous system, due to mutations in the galactosidase alpha (GLA) gene, represents the key point of Fabry disease (FD). The common symptoms appear in childhood or adolescence, including neuropathic pain, angiokeratoma, acroparesthesia, and corneal opacities. A multi-organ involvement induces a significant deterioration in the quality of life with high mortality in adulthood. The accumulation of Gb-3 involves all types of kidney cells beginning at fetal development, many years before clinical manifestations. A decline in the glomerular filtration rate is rare in children, but it can occur during adolescence. Pediatric patients rarely undergo kidney biopsy that could assess the efficacy of enzyme replacement therapy (ERT) behind its diagnostic role. To date, diagnosis is achieved by detecting reduced α-Gal-A activity in leukocytes and plasma, allowing for the early start of ERT. This review focuses on pediatric kidney involvement in FD, analyzing in depth its diagnostic processes and treatment options.

Febrile Urinary Tract Infections in Children: The Role of High Mobility Group Box-1.

BACKGROUND: Differentiating between febrile lower urinary tract infection (LUTI) and acute pyelonephritis (APN) is crucial for prompt clinical management. We investigated whether the high mobility group box-1 (HMGB1) could be a useful biomarker in differentiating between LUTI or APN. METHODS: We enrolled seventy-four pediatric patients with suspected LUTI/APN, according to the positive or negative renal scintigraphy (DMSA) scan. If the first DMSA findings were abnormal, a second DMSA was performed after six months. Voiding cystourethrography ruled out vesicoureteral reflux (VUR). RESULTS: Higher serum (s) HMGB1 levels characterized the APN group when compared to LUTI patients (13.3 (11.8-14.3) versus 5.9 (5.2-6.8) ng/mL, p: 0.02), whereas there were no differences according to urine (u) HMGB1 values. sHMGB1 correlated with C-reactive protein (CRP) levels (ß = 0.47; p: 0.02). Receiver operating characteristic curves identified the best diagnostic profile for detecting APN. sHMGB1 area under the curve was different from CRP (p: 0.01) and white blood cells (p: 0.003). After multivariate analyses, VUR (HR:4.81) and sHMGB1 (HR 1.16; p: 0.006) were independently associated with the risk of renal scarring development. CONCLUSIONS: sHMGB1 could represent a marker to differentiate APN from LUTI. Measurement of sHMGB1 could select children for early intervention or long-term follow-up.

Effectiveness of an Innovative Sensory Approach to Improve Children's Nutritional Choices.

A case-control study was conducted to investigate the effectiveness of the Edueat® Method, through experiential workshops focused on the use of all 5 senses. In two different primary schools in the same city, questionnaires were administered in two months with a follow-up one year later. Participants: 119 children (age 8.2-9.0) chosen randomly; control group 66 (55.5%). Seven lessons of 2 h each were held in the schools by experts of the Edueat® method and seven extra lessons by the teachers. The main outcome measures were the children's changes in their approach and attitude towards their eating habits. The answers were grouped with factor analysis and summarized through scores. Repeated-measures analysis of variance was conducted in order to identify the relationships between scores and treatment over time. At the end of treatment, the intervention group showed a significant appreciation towards healthy foods (+4.15 vs. -0.05, p = 0.02) and a greater capacity in identifying foods which are very good for the health (+15.6 vs. +14.4, p = 0.02). In conclusion, the Edueat® method was found to be particularly promising in transmitting knowledge of those foods which are healthy. Greater involvement of teachers and parents is crucial.

Frequency and Identification of Risk Factors of Uveitis in Juvenile Idiopathic Arthritis: A Long-term Follow-up Study in a Cohort of Italian Children.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood. The JIA-associated uveitis represents the most common extra-articular manifestation. OBJECTIVES: The main aim of this study was to evaluate frequency and risk factors of uveitis in a pediatric population affected by JIA. METHODS: One hundred eight Italian children with JIA were followed during a follow-up period of 13 years. Association between uveitis, antinuclear antibodies (ANAs), and subtype of arthritis has been estimated, and Kaplan-Meier curves were generated to assess the probability of ocular complications during the follow-up period. RESULTS: Twenty-one patients developed uveitis, after 96.5 ± 50.4 months from the enrollment. According to JIA subtypes, the oligoarthritis subtype was characterized by the highest prevalence (39%) of uveitis. The greatest risk of uveitis has been detected in oligoarthritis patients associated to ANA positivity (risk ratio, 8.6; 95% confidence interval, 2.27-32.9; χ = 20.4), whereas the worst evolution was revealed in patients with oligoarthritis and high levels of ANAs, with a progression time of 36 months (log-rank χ = 16.39; p < 0.0001; risk ratio, 18; 95% confidence interval, 7.3-44.2). CONCLUSIONS: Patients with early-onset ANA-positive oligoarticular JIA have the highest risk of developing uveitis. A routine ophthalmological follow-up is required at regular intervals, even though the joint disease is clinically quiescent.

Metformin-related lactic acidosis: is it a myth or an underestimated reality?

Metformin, belonging to a class of drugs called biguanides, is the recommended first-line treatment for overweight patients with type 2 diabetes mellitus. It has multiple mechanisms of action, such as reduction of gluconeogenesis, increases peripheral uptake of glucose, and decreases fatty acid oxidation. However, a potential serious complication, defined metformin-associated lactic acidosis (MALA), is related to increased plasma lactate levels, linked to an elevated plasma metformin concentrations and/or a coexistent condition altering lactate production or clearance. The mortality rate for MALA approaches 50% and metformin has been contraindicated in moderate and severe renal impairment, to minimize its potential toxic levels. Nevertheless, metformin prescription or administration, despite the presence of contraindications or precipitating factors for MALA, was a common topic highlighted in all reviewed papers. Routine assessment of metformin plasma concentration is not easily available in all laboratories, but plasma metformin concentrations measured in the emergency room could ensure the correct diagnosis, eliminating metformin as the cause of lactic acidosis if low plasma levels occurred. Renal replacement therapies have been successfully employed to achieve the correction of metabolic acidosis and rapidly remove metformin and lactate, but the optimal treatment modality for MALA is still controversial.

High mobility group box 1 and tumor growth factor ß: useful biomarkers in pediatric patients receiving peritoneal dialysis.

BACKGROUND: Peritonitis, the most important limitation of peritoneal dialysis (PD), could be detected by biomarkers in dialysate effluent, representing a noninvasive method to indirectly assess the peritoneum status. The aim of our study was to test high mobility group box 1 (HMGB1) in PD patients, evaluating its role as precocious marker of peritoneum damage during peritonitis. Transforming growth factor (TGF)-ß was correlated with peritoneal transport characteristics. METHODS: Six patients, treated by ambulatory PD, were enrolled. Samples were collected at the onset of peritonitis (T1) and every day until its resolution (T-end). Serum (s) and peritoneal (p) white blood cell (WBC) count was also evaluated. Peritoneal Equilibration Test evaluated the filter activity of peritoneum. RESULTS: In patients with acute peritonitis, the highest serum and peritoneal HMGB1 values (64 ± 3.6 and 70 ± 5.3 ng/mL, respectively) were assessed, with a progressive decrease of their levels at the resolution time (T-end: sHMGB1:36 ± 2.5; pHMGB1:30.5 ± 7.0 ng/mL). While no differences of sWBC and pWBC were observed between baseline and T-end values, pHMGB1 levels remained higher at T-end than those observed at T0 (pHMGB1:30.5 ± 7.0 versus 6.9 ± 3.6; p < 0.0001). TGF-ß levels were higher in patients with low peritoneal permeability than in medium or high transporter patients (81 ± 15.5 versus 24.3 ± 7.5 pg/mL; p = 0.01). An inverse correlation was found between TGF-ß levels and dialysate/plasmatic creatinine values (r = -0.83; p = 0.03). CONCLUSION: HMGB1 represents a useful biomarker for peritoneum evaluation in PD patients. A prognostic role of this alarmin, as a marker of response to therapy, could be hypothesized. TGF-ß could predict the peritoneal transport status and dialysis technique adequacy.

Delayed graft function and chronic allograft nephropathy: diagnostic and prognostic role of neutrophil gelatinase-associated lipocalin.

CONTEXT: Available markers are not reliable parameters to early detect kidney injury in transplanted patients. OBJECTIVE: Examine neutrophil gelatinase associated lipocalin (NGAL) in early detection of delayed graft function (DGF) and as a long-term predictor of graft outcome. PATIENTS AND METHODS: NGAL was evaluated in 124 transplanted patients. RESULTS: Urinary NGAL levels were associated to a 10% (HR: 1.10; 95% CI: 1.04-1.25; p < 0.001) and 15% (HR: 1.15; 95% CI: 1.09-1.26; p < 0.001) increased risk of DGF and allograft nephropathy progression, respectively. CONCLUSION: NGAL reflects the entity of renal impairment in transplanted patients, representing a biomarker and an independent risk factor for DGF and chronic allograft nephropathy progression.

Sputum high mobility group box-1 in asthmatic children: a noninvasive sensitive biomarker reflecting disease status.

BACKGROUND: The monitoring of asthma is based mainly on clinical history, physical examination, and lung function test evaluation. To improve knowledge of the disease, new biomarkers of airway inflammation, including high mobility group box-1 (HMGB1), are being developed. OBJECTIVE: To evaluate sputum HMGB1 levels in children with stable, off-therapy, allergic asthma and to evaluate the relation between HMGB1 levels and lung function parameters. METHODS: Fifty children with asthma (28 boys and 22 girls, median age 11.56 ± 1.41 years) and 44 healthy children (22 boys and 22 girls, median age 11.07 ± 2.12 years) were enrolled. Sputum HMGB1 was assessed in the cohort study. Lung function (predicted percentage of forced expiratory volume in 1 second [FEV1%] and forced expiratory flow between 25% and 75% [FEF25%-75%]), serum total IgE levels, and asthma severity by validated Global Initiative for Asthma criteria were recorded. RESULTS: Sputum HMGB1 levels were higher in children with asthma than in healthy controls (100.68 ± 10.03 vs 9.60 ± 3.76 ng/mL, P < .0001). Sputum HMGB1 levels also were positively related to total IgE levels in children with asthma (r = 0.6567, P < .0001). An inverse and strict correlation between sputum HMGB1 levels and pulmonary function indices also were observed in children with mild (FEV1%, r = -0.86544, P < .0001; FEF25%-75%, r = -0.53948, P < .05), moderate (FEV1%, r = -0.99548, P < .0001; FEF25%-75%, r = -0.48668, P < .05), and severe (FEV1%, r = -0.90191, P < .0001; FEF25%-75%, r = -0.66777, P < .05) asthma. CONCLUSION: The present study provides evidence that sputum HMGB1 is a sensitive biomarker of allergic asthma in children because it was increased and correlated directly with asthma severity and inversely with lung function indices.

Thalassaemia major and infectious risk: High Mobility Group Box-1 represents a novel diagnostic and prognostic biomarker.

High mobility group box -1 (HMGB1) represents a common causal agent for various types of diseases, including infective pathologies. This study aimed to investigate the role of HMGB1 in ß-thalassemia major (TM) by evaluating its diagnostic and prognostic role. Fifty-one TM patients and 30 healthy subjects (HS) were enrolled. Receiver operating characteristics (ROC) analysis was employed to calculate the area under the curve (AUC) for HMGB1 to determine the best cut-off values capable of identifying infectious episodes. Adjusted risk estimates for infective events were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. Serum HMGB1 levels were higher in TM patients than in HS (14·6 ± 8·7 vs. 2·08 ± 0·9 ng/ml, P < 0·0001). Patients who underwent splenectomy were characterized by lower levels of HMGB1, when compared with patients with an intact spleen (10·2 ± 8 vs. 19·1 ± 7 ng/ml, P = 0·004). ROC analyses revealed an AUC for serum HMGB1 of 0·801, with a sensitivity and specificity of 92·3% and 68·2% to detect an infectious episode. Low HMGB1 levels predicted high risk of infective events (HR: 0·81; P = 0·006). HMGB1 represents a prognostic marker for TM patients and a predictive factor for infectious events.

Endocrinopathies, metabolic disorders, and iron overload in major and intermedia thalassemia: serum ferritin as diagnostic and predictive marker associated with liver and cardiac T2* MRI assessment.

INTRODUCTION: Endocrinopathies and metabolic disorders-characterized ß thalassemic (ßT) patients and the prevention and treatment of these comorbidities are important targets to be achieved. The aim of the study was to analyze the diagnostic and prognostic role of ferritin for endocrinopathies and metabolic disorders in ßT patients. The ability of iron chelators to treat iron overload and to prevent or reverse metabolic disorders and endocrinopathies was also evaluated. PATIENTS AND METHODS: Seventy-two ßT patients were treated with different chelation strategies during the study. Receiver operating characteristics analysis was employed to calculate the area under the curve for serum ferritin to find the best cutoff values capable of identifying endocrine dysfunction in thalassemic patients. Kaplan-Meier curves were generated to assess the incidence of endocrinopathy. Adjusted risk estimates for endocrinopathy were calculated using univariate followed by multivariate Cox proportional hazard regression analysis. RESULTS: High ferritin levels were observed in patients with hypothyroidism [1500 (872.5-2336.5) µg/L], hypogonadism [878 (334-2010) µg/L], and in patients with hypoparathyroidism or osteoporosis [834 (367-1857) µg/L]. A strict correlation between ferritin and T2* magnetic resonance imaging of heart (r = -0.64; P:0.0006) and liver (r = -0.40; P:0.03) values was observed. Patients with ferritin values above 1800 µg/L experienced a significantly faster evolution to hypothyroidism [log-rank (χ(2) ):7.7; P = 0.005], hypogonadism [log-rank (χ(2) ):10.7; P = 0.001], and multiple endocrinopathies [log-rank (χ(2) ):5.72; P = 0.02]. Ferritin predicted high risk of endocrine dysfunction independently of confounding factors (HR:1.23; P < 0.0001). The intensification of chelation therapy led to an amelioration of hypothyroidism. CONCLUSIONS: Ferritin represents a prognostic marker for ßT patients and a predictive factor for progression to endocrine dysfunctions. Intensive chelation therapy allows the reversibility of hypothyroidism.

Apelin beyond kidney failure and hyponatremia: a useful biomarker for cancer disease progression evaluation.

Apelin regulates angiogenesis, stimulating endothelial cell proliferation and migration. It is upregulated during tumor angiogenesis, and its overexpression was reported to increase tumor growth. Furthermore, apelin controls vasopressin release and body fluid homeostasis. The aim of this study was to examine the correlations between apelin expression and clinical outcomes in oncologic patients, such as cancer disease progression and patient's survival. Apelin levels were evaluated in a cohort of 95 patients affected by different varieties of cancer. Partial remission and stable disease were assigned to the 'no progression' group, comparing it with the progressor group. Patients were followed up for 2 years. Receiver operating characteristics analysis was employed for identifying the progression of the oncologic disease and Kaplan-Meier curves assessed the survival. Adjusted risk estimates for progression endpoint were calculated using Cox proportional hazard regression analysis. Oncologic patients had higher apelin levels compared with healthy subjects, and apelin was closely related to the stages of the disease. In the hyponatremia group, apelin values were significantly higher than patients with eunatremia. After the follow-up of 24 months, 41 patients (43%) reached the endpoint. Progressor subjects presented significantly increased apelin values at baseline compared with non-progressor. Univariate followed by multivariate Cox proportional hazard regression analysis showed that apelin predicted cancer progression independently of other potential confounders. In patients with cancer, apelin closely reflects the stage of the disease and represents a strong and independent risk marker for cancer progression.

Adrenal disorders and the paediatric brain: pathophysiological considerations and clinical implications.

Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency) has been reported with neurological and magnetic resonance imaging (MRI) abnormalities (e.g., delayed myelination and brain atrophy) due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH), a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF) pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS) through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric) CNS seems to be particularly vulnerable to alterations induced by adrenal disorders and/or supraphysiological doses of corticosteroids. Physicians should be aware of potential neurological manifestations in children with adrenal dysfunction to achieve better prevention and timely diagnosis and treatment of these disorders. Further studies are needed to explore the potential neurological, cognitive, and psychiatric long-term consequences of high doses of prolonged corticosteroid administration in childhood.

High-mobility group box 1 (HMGB1) in childhood: from bench to bedside.

UNLABELLED: High-mobility group box protein 1 (HMGB1) is a nonhistone nuclear protein that has a dual function. Inside the cell, HMGB1 binds DNA, regulating transcription and determining chromosomal architecture. Outside the cell, HMGB1 activates the innate system and mediates a wide range of physiological and pathological responses. HMGB1 exerts these actions through differential engagement of multiple surface receptors, including Toll-like receptor (TLR)2, TLR4, and receptor for advanced glycation end products (RAGE). HMGB1 is implicated as a late mediator of sepsis and is also involved in inflammatory and autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Interestingly, HMGB1 was associated with tumor progression, becoming a potential therapeutic target, due to its involvement in the resistance to chemotherapy. Its implication on the pathogenesis of systemic vasculitis and inflammatory bowel diseases has also been evaluated. Moreover, it regulates neuroinflammation after traumatic brain injuries or cerebral infectious diseases. The aim of this review is to analyze these different roles of HMGB1, both in physiological and pathological conditions, discussing clinical and scientific implications in the field of pediatrics. CONCLUSION: HMGB1 plays a key role in several pediatric diseases, opening new scenarios for diagnostic biomarkers and therapeutic strategies development.

Nonalcoholic Fatty liver disease/non-alcoholic steatohepatitis in childhood: endocrine-metabolic "mal-programming".

CONTEXT: Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased. EVIDENCE ACQUISITION: A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver". RESULTS: NAFLD/NASH is probably promoted by "multiple parallel hits": environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown. CONCLUSIONS: Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH.

Vitamin D intoxication in two brothers: be careful with dietary supplements.

Vitamin D (VitD) intoxication, a well-known cause of hypercalcaemia in children, has renal, cardiac and neurological consequences. Iatrogenic or accidental administrations are the most common causes. We present two cases of hypervitaminosis D due to over-the-counter VitD supplement self-medication. A 12-year-old boy was hospitalised for abdominal pain, constipation and vomiting. Routine biochemistry indicated severe hypercalcaemia and renal failure. Plasma 25-OH VitD level was very high and parathyroid hormone was suppressed. Renal ultrasound showed nephrolithiasis. Hydration, diuretics and prednisone induced a progressive reduction of calcium levels. His brother, who was receiving the same treatment, was hospitalised although asymptomatic. Normal serum calcium and renal function were revealed, while 25-OH VitD was high and parathyroid hormone was suppressed. Renal ultrasound was within the normal range. Examination of the VitD content of the over-the-counter supplement revealed a higher amount than declared. VitD administration implies several risks and must be prescribed only when needed and under strict medical control.