Unraveling chronic kidney disease in children: a surprising manifestation of celiac disease.

Celiac disease, firstly described in children, is a type of T-cell enteropathy that occurs in individuals genetically predisposed to gluten exposure. The estimated global prevalence of celiac disease is continuously increasing. Although, traditionally, celiac disease was diagnosed in children with failure to thrive and digestive issues, it is now recognized that may present with a wide range of symptoms beyond gastrointestinal ones. Celiac disease continues to pose significant challenges due to the continuous advancement of knowledge in understanding its pathophysiology, diagnosing the condition, managing its effects, and exploring potential therapeutic approaches. The prevalence of celiac disease is increased among individuals with chronic kidney disease, also. The most frequent associations are with diabetic nephropathy, IgA nephropathy and urolithiasis. A gut-kidney axis has been recognized to play a significant role in chronic kidney diseases. This literature review aims to review the chronic renal pathology associated with celiac disease, with emphasis on childhood.

Cystic fibrosis management in pediatric population-from clinical features to personalized therapy.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). In 1949, it's been identified as a monogenic disease and was thought to primarily affect individuals of Northern European descent. It was the most prevalent autosomal recessive disease that shortens life. With the availability of multiple testing methodologies nowadays, there is a chance to create novel and enhanced treatment options. Even in the absence of a high sweat chloride test (SCT) result, the discovery of two causal mutations is diagnostic for cystic fibrosis (CF). For a CF diagnosis, however, at least two positive E sweat chloride tests are still required. In order to achieve early and active intervention to manage cystic fibrosis (CF) and its comorbidities, treatment regimens for pediatric patients should be evaluated, improved, and closely monitored. New developments in the treatment of cystic fibrosis (CF) have led to the development of medications derived from molecules that target the pathogenetic pathway of the illness. These options are very efficient and allow pediatric patients to receive individualized care. However, in order to better direct patient care and enhance patient outcomes, it is crucial to research uncommon CF mutations, which can provide crucial information about the prognosis of the disease and the relationships between genotype and phenotype. To ensure the success of creating novel, safer, and more efficient treatment approaches, a deeper understanding of the pathogeny of the illness is required. In the age of customized medicine, genetic research will be essential to improving patient care and quality of life for those with uncommon mutations.

Celiac disease - a pluripathological model in pediatric practice.

Being defined as an autoimmune, chronic pathology, frequently encountered in any age group, but especially in pediatrics, celiac disease (also called gluten enteropathy), is gaining more and more ground in terms of diagnosis, but also interest in research. The data from the literature of the last decades attest the chameleonic way of its presentation, there may be both classic onset symptoms and atypical symptoms. Given the impact played by celiac disease, especially in the optimal growth and development of children, the current narrative review aims to highlight the atypical presentation methods, intended to guide the clinician towards the inclusion of the pathology in the differential diagnosis scheme. To these we add the summary presentation of the general data and therapeutic lines regarding the underlying condition and the existing comorbidities. In order to place the related information up to date, we performed a literature review of the recent articles published in international databases. We bring forward the current theories and approaches regarding both classic celiac disease and its atypical manifestations. Among these we note mainly constitutional, skin or mucous, bone, neuro-psychic, renal, reproductive injuries, but also disorders of biological constants and association with multiple autoimmunities. Knowing and correlating them with celiac disease is the key to optimal management of patients, thus reducing the subsequent burden of the disease.

Current Approaches in the Multimodal Management of Asthma in Adolescents-From Pharmacology to Personalized Therapy.

Asthma and adolescence are two sensitive points and are difficult to manage when they coexist. The first is a chronic respiratory condition, with frequent onset in early childhood (between 3 and 5 years), which can improve or worsen with age. Adolescence is the period between childhood and adulthood (12-19 years), marked by various internal and external conflicts and a limited capacity to understand and accept any aspect that is delimited by the pattern of the social circle (of the entourage) frequented by the individual. Therefore, the clinician is faced with multiple attempts regarding the management of asthma encountered during the adolescent period, starting from the individualization of the therapy to the control of compliance (which depends equally on the adverse reactions, quality of life offered and support of the close circle) and the social integration of the subject, communication probably having a more important role in the monitoring and evolution of the condition than the preference for a certain therapeutic scheme. Current statistics draw attention to the increase in morbidity and mortality among children with bronchial asthma, an aspect demonstrated by the numerous hospitalizations recorded, due either to an escalation in the severity of this pathology or to faulty management. The purpose of this article is to review the delicate aspects in terms of controlling symptoms and maintaining a high quality of life among teenagers.

Exploring a Complex Interplay: Kidney-Gut Axis in Pediatric Chronic Kidney Disease.

The human intestinal microbiota is a highly intricate structure with a crucial role in promoting health and preventing disease. It consists of diverse microbial communities that inhabit the gut and contribute to essential functions such as food digestion, nutrient synthesis, and immune system development. The composition and function of the gut microbiota are influenced by a variety of factors, including diet, host genetics, and environmental features. In pediatric patients, the gut microbiota is particularly dynamic and vulnerable to disruption from endogenous and exogenous factors. Recent research has focused on understanding the interaction between the gut and kidneys. In individuals with chronic kidney disease, there is often a significant disturbance in the gut microbiota. This imbalance can be attributed to factors like increased levels of harmful toxins from the gut entering the bloodstream, inflammation, and oxidative stress. This review looks at what is known about the link between a child's gut-kidney axis, how dysbiosis, or an imbalance in the microbiome, affects chronic kidney disease, and what treatments, both pharmaceutical and non-pharmaceutical, are available for this condition.

The Disease with a Thousand Faces and the Human Microbiome-A Physiopathogenic Intercorrelation in Pediatric Practice.

Numerous interrelationships are known in the literature that have the final effect of unmasking or influencing various pathologies. Among these, the present article aims to discuss the connection between systemic lupus erythematosus (SLE) and the human microbiome. The main purpose of this work is to popularize information about the impact of dysbiosis on the pathogenesis and evolutionary course of pediatric patients with SLE. Added to this is the interest in knowledge and awareness of adjunctive therapeutic means that has the ultimate goal of increasing the quality of life. The means by which this can be achieved can be briefly divided into prophylactic or curative, depending on the phase of the condition in which the patient is. We thus reiterate the importance of the clinician acquiring an overview of SLE and the human microbiome, doubled by in-depth knowledge of the physio-pathogenic interactions between the two (in part achieved through the much-studied gut-target organ axes-brain, heart, lung, skin), with the target objective being that of obtaining individualized, multimodal and efficient management for each individual patient.

Pediatric COVID-19 and Diabetes: An Investigation into the Intersection of Two Pandemics.

Coronavirus disease 2019 (COVID-19) is a complex infectious disease caused by the SARS-CoV-2 virus, and it currently represents a worldwide public health emergency. The pediatric population is less prone to develop severe COVID-19 infection, but children presenting underlying medical conditions, such as diabetes mellitus, are thought to be at increased risk of developing more severe forms of COVID-19. Diabetic children face new challenges when infected with SARS-CoV-2. On one hand, the glycemic values become substantially more difficult to manage as COVID-19 is a predisposing factor for hyperglycemia. On the other hand, alongside other risk factors, high glycemic values are incriminated in modulating immune and inflammatory responses, leading to potentially severe COVID-19 cases in the pediatric population. Also, there are hypotheses of SARS-CoV-2 being diabetogenic itself, but this information is still to be confirmed. Furthermore, it is reported that there was a noticeable increase in the number of cases of new-onset type 2 diabetes among the pediatric population, and the complications in these patients with COVID-19 include the risk of developing autoimmune diseases under the influence of stress. Additionally, children with diabetes mellitus are confronted with lifestyle changes dictated by the pandemic, which can potentially lead to the onset or exacerbation of a potential underlying anxiety disorder or depression. Since the literature contains a series of unknowns related to the impact of COVID-19 in both types of diabetes in children, the purpose of our work is to bring together the data obtained so far and to identify potential knowledge gaps and areas for future investigation regarding COVID-19 and the onset of diabetes type 1 or type 2 among the pediatric population.

The Footprint of Microbiome in Pediatric Asthma-A Complex Puzzle for a Balanced Development.

Considered to be of greater complexity than the human genome itself, the microbiome, the structure of the body made up of trillions of bacteria, viruses, and fungi, has proven to play a crucial role in the context of the development of pathological processes in the body, starting from various infections, autoimmune diseases, atopies, and culminating in its involvement in the development of some forms of cancer, a diagnosis that is considered the most disabling for the patient from a psychological point of view. Therefore, being a cornerstone in the understanding and optimal treatment of a multitude of ailments, the body's microbiome has become an intensively studied subject in the scientific literature of the last decade. This review aims to bring the microbiome-asthma correlation up to date by classifying asthmatic patterns, emphasizing the development patterns of the microbiome starting from the perinatal period and the impact of pulmonary dysbiosis on asthmatic symptoms in children. Likewise, the effects of intestinal dysbiosis reflected at the level of homeostasis of the internal environment through the intestine-lung/vital organs axis, the circumstances in which it occurs, but also the main methods of studying bacterial variability used for diagnostic purposes and in research should not be omitted. In conclusion, we draw current and future therapeutic lines worthy of consideration both in obtaining and maintaining remission, as well as in delaying the development of primary acute episodes and preventing future relapses.

Is There a Potential Link between Gastroesophageal Reflux Disease and Recurrent Respiratory Tract Infections in Children?

BACKGROUND: The implications of gastroesophageal reflux disease in respiratory tract infections have been investigated over time. The aim of our study was to evaluate the relationship between these two pathologic entities and the outcome after proper antireflux treatment. METHODS: A group of 53 children with recurrent respiratory tract infections admitted in the gastroenterology clinic of a children's hospital in North-East Romania was investigated for gastroesophageal reflux disease through 24 h pH-metry. Those with a Boix-Ochoa score higher than 11.99 received proton pump inhibitor treatment and were reevaluated after 2 months. RESULTS: A total of 41 children were found with a positive Boix-Ochoa score. After 2 months of antireflux therapy, eight patients still had a positive Boix-Ochoa score. CONCLUSIONS: Recurrent respiratory tract infections with symptoms resistant to treatment should be considered a reason to investigate for gastroesophageal reflux, because the symptoms may be due to micro- or macro-aspiration of the gastric refluxate or to an esophageal-bronchial reflex mediated through the vagal nerve.

Predictor Factors for Chronicity in Immune Thrombocytopenic Purpura in Children.

(1) Background: Immune thrombocytopenia (ITP) is an acute autoimmune blood disorder that is the main cause of thrombocytopenia in children. It is characterized by a decrease in platelets below 100 × 109/L, and limited evolution with severe complications such as intracranial hemorrhage. The chronic form is defined by the persistence of thrombocytopenia more than 12 months after diagnosis. (2) Methods: We performed a retrospective study over a period of 10 years (1 January 2011-31 December 2020) at the Emergency Clinical Hospital for Children "Sf. Maria", Iasi. The aim of the study was to describe the clinical characteristics and to determine the prognostic factors in immune thrombocytopenia in children. (3) Results: In this study we included 271 children with ITP, comprising 123 females (45.4%) and 148 males (54.6%). The remission rate was higher in males, being 68.9% compared to 56.1% in females. Children with ITP under 9 years of age had a higher remission rate. Children with a platelet count > 10 × 109/L at diagnosis had a higher likelihood-of-remission rate compared to patients who presented initial platelet count below this value. (4) Conclusions: The risk factors highly suggestive for chronicity are: age at diagnosis, female sex, and the number of platelets at the onset of the disease.

Advances in Understanding the Human Gut Microbiota and Its Implication in Pediatric Celiac Disease-A Narrative Review.

Celiac disease (CD) is a multifactorial disorder, defined by a complex interplay of genetic and environmental factors. Both genetic predisposition and dietary exposure to gluten are essential factors in triggering CD. However, there is proof that their presence is necessary, but not sufficient, for disease development. Through gut microbiota modulation, several additional environmental factors have shown their potential role as co-factors in CD pathogenesis. The aim of this review is to illustrate the possible mechanisms that stand behind the gut microbiota's involvement in CD pathogenesis. Furthermore, we discuss microbiota manipulation's potential role as both a preventative and therapeutic option. The available literature provides evidence that even before CD onset, factors including cesarean birth and formula feeding, as well as intestinal infection exposure, amplify the risk of CD in genetically predisposed individuals, due to their influence on the intestinal microbiome composition. Active CD was associated with elevated levels of several Gram-negative bacterial genera, including Bacteroides, Escherichia, and Prevotella, while beneficial bacteria such as lactobacilli and bifidobacteria were less abundant. Viral and fungal dysbiosis has also been described in CD, evidencing specific taxa alteration. A gluten-free diet (GFD) may improve the clinical symptoms and duodenal histopathology, but the persistence of intestinal dysbiosis in CD children under a GFD urges the need for additional therapy. Probiotics, prebiotics, and fecal microbial transplant have demonstrated their efficacy in restoring gut microbiota eubiosis in adult CD patients; however, their efficacy and safety as adjunctive therapies to a GFD in pediatric patients needs further investigation.

Connection between Celiac Disease and Systemic Lupus Erythematosus in Children-A Development Model of Autoimmune Diseases Starting from What We Inherit to What We Eat.

Celiac disease (CD) and systemic lupus erythematosus (SLE) are two diseases intensively studied in all age groups, with an increasing incidence at the global level, possibly due to the increased awareness of the diseases and their accurate diagnosis and as a consequence of the new research and innovation technologies that have appeared in medicine. The first is a controllable condition found in approximately 1% of the entire population in the form of a reaction to environmental stimuli affecting individuals with genetic susceptibility, causing gluten intolerance, gastrointestinal and extradigestive symptoms, starting from subclinical stages and culminating in severe malabsorption. On the other hand, lupus is an autoimmune disease with chameleon-like symptoms and found mainly in the female sex, which leaves its clinical mark on most organs, from the skin, eyes, and kidneys to the cardiovascular, pulmonary, neurological, osteoarticular, and hematological systems. Current studies focus on the correlation between celiac disease and other autoimmune pathologies such as autoimmune thyroiditis (Hashimoto and Graves-Basedow), type I diabetes, and systemic lupus erythematosus. The current review aims to present a summary of the data from the specialized literature regarding the intercurrents between celiac disease and lupus by analyzing the most recent studies published on PubMed.

The Implication of the Gut Microbiome in Heart Failure.

Heart failure is a worldwide health problem with important consequences for the overall wellbeing of affected individuals as well as for the healthcare system. Over recent decades, numerous pieces of evidence have demonstrated that the associated gut microbiota represent an important component of human physiology and metabolic homeostasis, and can affect one's state of health or disease directly, or through their derived metabolites. The recent advances in human microbiome studies shed light on the relationship between the gut microbiota and the cardiovascular system, revealing its contribution to the development of heart failure-associated dysbiosis. HF has been linked to gut dysbiosis, low bacterial diversity, intestinal overgrowth of potentially pathogenic bacteria and a decrease in short chain fatty acids-producing bacteria. An increased intestinal permeability allowing microbial translocation and the passage of bacterial-derived metabolites into the bloodstream is associated with HF progression. A more insightful understanding of the interactions between the human gut microbiome, HF and the associated risk factors is mandatory for optimizing therapeutic strategies based on microbiota modulation and offering individualized treatment. The purpose of this review is to summarize the available data regarding the influence of gut bacterial communities and their derived metabolites on HF, in order to obtain a better understanding of this multi-layered complex relationship.

The Role of Urinary NGAL in the Management of Primary Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is the most frequent congenital urinary tract malformation and an important risk factor for urinary tract infections (UTIs). Up to 50% of children with VUR may develop reflux nephropathy (RN), and the diagnosis and monitoring of renal scars are invasive and costly procedures, so it is paramount to find a non-invasive and accurate method to predict the risk of renal damage. Neutrophil gelatinase-associated lipocalin (NGAL) has already proven to be a good predictive biomarker in acute kidney injuries, but there are few studies that have investigated the role of NGAL in primary VUR in children. Our aim is to review the predictive value of urine NGAL (uNGAL) as a non-invasive biomarker of RN in children with primary VUR, as well as its ability to predict the evolution of chronic kidney disease (CKD). Based on our analysis of the available original studies, uNGAL can be an accurate and reliable biomarker of RN and its progression to CKD. Some studies suggested a good correlation between VUR severity and uNGAL levels, but other studies found no significant correlation. The relationship between VUR severity and uNGAL levels is likely complex and influenced by factors such as UTIs, the timing of the urine sample collection, and the age and overall health of the patient.

The Overlap of Kidney Failure in Extrapulmonary Sarcoidosis in Children-Case Report and Review of Literature.

Sarcoidosis is a non-necrotizing granulomatous inflammatory multisystemic disorder of unknown etiology. In children, as in adults, it can involve a few or all organ systems to a varying extent and degree, entailing multisystemic manifestations. Kidney involvement in pediatric-onset adult-type sarcoidosis is rare, with a wide range of renal manifestations, most of them related to calcium metabolism. Children with renal sarcoidosis tend to be more symptomatic than adults, although male patients have a higher prevalence. We present the case of a 10-year-old boy who presented with advanced renal failure with nephrocalcinosis and important hepatosplenomegaly. The diagnosis was established by histopathological examination, with consequent cortisone therapy and hemodialysis. This review emphasizes that sarcoidosis should be considered in the differential diagnosis of pediatric patients with acute kidney insufficiency or chronic kidney disease of an unknown etiology. As far as we know, this is the first study regarding extrapulmonary sarcoidosis in children from Romania.

Hantavirus Infection in Children-A Pilot Study of Single Regional Center.

BACKGROUND: Hantaviruses are infectious etiological agents of a group of rodent-borne hemorrhagic fevers, with two types of clinical manifestations in humans: hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). According to available statistics, the disease occurs mainly in adults, but the lower incidence in the pediatric population might also be related to a lack of diagnosis possibilities or even unsatisfactory knowledge about the disease. MATERIALS AND METHODS: The purpose of this study was to evaluate the cases of hemorrhagic fever with renal syndrome diagnosed and treated in the Department of Nephrology at St. Mary's Emergency Hospital for Children in Iasi, Romania, representative of the North-East of Romania. We also reviewed the specialized literature on the topic. RESULTS: Between January 2017 and January 2022, eight cases of HFRS, all men, and seven from rural areas, aged 11-18 years old, were referred to our clinic because of an acute kidney injury (AKI). Seven cases were identified as Dobrava serotype while one case was determined by Haantan serotype. CONCLUSIONS: HFRS should always be considered as a differential diagnosis when faced with a patient with AKI and thrombocytopenia. Dobrava serotype is the most common hantavirus subtype in the Balkans. For the specific prevention of human infections, mainly in high-risk groups, vaccines are needed. As far as we know, this is the first study on HFRS in Romanian children.

Pitfalls of Thrombotic Microangiopathies in Children: Two Case Reports and Literature Review.

Thrombotic microangiopathy can present itself in the form of several clinical entities, representing a real challenge for diagnosis and treatment in pediatric practice. Our article aims to explore the evolution of two rare cases of pediatric thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS) with extremely similar clinical pictures, which, coincidentally, presented at approximately the same time in our hospital. These cases and our literature review demonstrate the multiple facets of thrombotic microangiopathy, which can produce various determinations and salient manifestations even among the pediatric population. TTP and aHUS may represent genuine diagnostic pitfalls through the overlap of their clinical and biological findings, although they develop through fundamentally different mechanisms that require different therapeutic approaches. As a novelty, we underline that COVID-19 infection cannot be excluded as potential trigger for TTP and aHUS in our patients and we predict that other reports of such an association will follow, raising a complex question of COVID-19's implication in the occurrence and evolution of thrombotic microangiopathies. On this matter, we conducted literature research that resulted in 15 cases of COVID-19 pediatric infections associated with either TTP or aHUS. Taking into consideration the morbidity associated with TTP and aHUS, an elaborate differential diagnosis and prompt intervention are of the essence.

Helicobacter pylori Infection in Children: A Possible Reason for Headache?

(1) Background: The correlation between infection with Helicobacter pylori (H. pylori) and headache has been argued and explored for a long time, but a clear association between the simultaneous presence of the two in children has not been established yet. In this study, we aimed to explore this relationship in children from the Northeast region of Romania. (2) Methods: A retrospective study exploring the correlation between children having H. pylori infection and headache or migraine was conducted on a batch of 1757 children, hospitalized over 3 years in a pediatric gastroenterology department in Northeast Romania. (3) Results: A total of 130 children of both sexes had headache. From 130 children, 54 children (41.5%) also presented H. pylori infection. A significant association between headache and H. pylori infection (χ2; p < 0.01) was noticed. (4) Conclusions: More studies are needed on this relationship, and we emphasize the importance of further analyses, as they present great clinical importance for both prompt diagnosis and treatment.

Pediatric Acute Lymphoblastic Leukemia Emerging Therapies-From Pathway to Target.

Over the past 40 years, the 5-years-overall survival rate of pediatric cancer reached 75-80%, and for acute lymphoblastic leukemia (ALL), exceeded 90%. Leukemia continues to be a major cause of mortality and morbidity for specific patient populations, including infants, adolescents, and patients with high-risk genetic abnormalities. The future of leukemia treatment needs to count better on molecular therapies as well as immune and cellular therapy. Advances in the scientific interface have led naturally to advances in the treatment of childhood cancer. These discoveries have involved the recognition of the importance of chromosomal abnormalities, the amplification of the oncogenes, the aberration of tumor suppressor genes, as well as the dysregulation of cellular signaling and cell cycle control. Lately, novel therapies that have already proven efficient on relapsed/refractory ALL in adults are being evaluated in clinical trials for young patients. Tirosine kinase inhibitors are, by now, part of the standardized treatment of Ph+ALL pediatric patients, and Blinatumomab, with promising results in clinical trials, received both FDA and EMA approval for use in children. Moreover, other targeted therapies such as aurora-kinase inhibitors, MEK-inhibitors, and proteasome-inhibitors are involved in clinical trials that include pediatric patients. This is an overview of the novel leukemia therapies that have been developed starting from the molecular discoveries and those that have been applied in pediatric populations.

Palm-Plant Pain, Sign of a Severe Systemic Disease? Case Report and Review of Literature.

Fabry disease is an X-linked lysosomal storage disease, second in prevalence after Gaucher disease. The onset of symptoms occurs in childhood or adolescence with palmo-plantar burning pains, hypo hidrosis, angiokeratomas, and corneal deposits. In the absence of diagnosis and treatment, the disease will progress to the late phase, characterized by progressive cardiac, cerebral and renal damage, and possible death. We present the case of an 11-year-old male boy who was transferred to the Pediatric Nephrology Department for palmo-plantar burning pain and end stage renal disease. Following the evaluations for the etiology of end stage renal disease we excluded the vasculitis, the neurologic diseases, extrapulmonary tuberculosis. Because of suggestive aspect at CT scan and lack of etiologic diagnosis of renal insufficiency we performed lymph node and kidney biopsy, with a surprising result for storage disease. The specific investigation confirmed the diagnosis.