ABSTRACT
Urinary tract infections are one of the most common types of bacterial infections in childhood. Normally, empiric antibiotic therapy is given based on local antimicrobial susceptibility. We performed a retrospective study to evaluate bacterial resistance and clinical responses to antibiotics in childhood febrile urinary tract infections (fUTIs) in the Bratislava region of Slovakia. A total of 182 children with a fUTI were enrolled in our retrospective study. 84,07% of these fUTIs were caused by pathogenic Escherichia coli (E. coli). According to microbial antibiotic susceptibility tests, the most effective antibiotic agents were third-generation cephalosporins (susceptibility was observed in 92,16% (n=141) of the cases), followed by aminopenicillins with betalactamase inhibitor (susceptibility was observed in 84,97% (n=130) of the cases) and trimethoprim-sulfamethoxazole (susceptibility was observed in 79,74% (n=122) of the cases). In contrast, E. coli was susceptible to second-generation cephalosporins in just 3,92% (n=6). Patients treated with third-generation cephalosporins achieved a clinical response to therapy almost in all of the cases (95,7% (n=66)), whereas second-generation cephalosporins were associated with a clinical response to therapy in only 55,9% (n=33) of the cases. Third-generation cephalosporins and aminopenicillins with a betalactamase inhibitor appear to be the most suitable initial antibiotic therapies in pediatric patients with fUTIs. Following current guidelines alongside the regular assessment of regional microbial antibiotic susceptibilities should provide the best treatment management for children with fUTIs.
ABSTRACT
Schimke immuno-osseous dysplasia is a rare multisystemic disorder caused by biallelic loss of function of the SMARCAL1 gene that plays a pivotal role in replication fork stabilization and thus DNA repair. Individuals affected from this disease suffer from disproportionate growth failure, steroid resistant nephrotic syndrome leading to renal failure and primary immunodeficiency mediated by T cell lymphopenia. With infectious complications being the leading cause of death in this disease, researching the nature of the immunodeficiency is crucial, particularly as the state is exacerbated by loss of antibodies due to nephrotic syndrome or immunosuppressive treatment. Building on previous findings that identified the loss of IL-7 receptor expression as a possible cause of the immunodeficiency and increased sensitivity to radiation-induced damage, we have employed spectral cytometry and multiplex RNA-sequencing to assess the phenotype and function of T cells ex-vivo and to study changes induced by in-vitro UV irradiation and reaction of cells to the presence of IL-7. Our findings highlight the mature phenotype of T cells with proinflammatory Th1 skew and signs of exhaustion and lack of response to IL-7. UV light irradiation caused a severe increase in the apoptosis of T cells, however the expression of the genes related to immune response and regulation remained surprisingly similar to healthy cells. Due to the disease's rarity, more studies will be necessary for complete understanding of this unique immunodeficiency.
Subject(s)
DNA Repair , Osteochondrodysplasias , Primary Immunodeficiency Diseases , Humans , Primary Immunodeficiency Diseases/genetics , Primary Immunodeficiency Diseases/diagnosis , Primary Immunodeficiency Diseases/immunology , Osteochondrodysplasias/genetics , Osteochondrodysplasias/immunology , DNA Repair/genetics , DNA Helicases/genetics , Nephrotic Syndrome/etiology , Nephrotic Syndrome/genetics , T-Lymphocytes/immunology , Arteriosclerosis/genetics , Arteriosclerosis/etiology , Arteriosclerosis/immunology , Male , Female , Pulmonary Embolism/genetics , Pulmonary Embolism/etiology , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/genetics , Growth Disorders/genetics , Growth Disorders/etiology , Ultraviolet Rays/adverse effects , Child , Apoptosis/genetics , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/immunologyABSTRACT
Introduction: Hepatocyte nuclear factor 1-beta (HNF1B) gene variants or the chromosome 17q12 deletion (17q12del) represent the most common monogenic cause of developmental kidney disease. Although neurodevelopmental disorders have been associated with the 17q12del, specific genotype-phenotype associations with respect to kidney function evolution have not yet been fully defined. Here, we aimed to determine whether 17q12del or specific HNF1B variants were associated with kidney survival in a large patient population with HNF1B disease. Methods: This was a retrospective observational study involving 521 patients with HNF1B disease from 14 countries using the European Reference Network for rare kidney diseases with detailed information on the HNF1B genotype (HNF1B variants or the 17q12del). Median follow-up time was 11 years with 6 visits per patient. The primary end point was progression to chronic kidney disease (CKD) stage 3 (estimated glomerular filtration rate [eGFR] < 60 ml/min per 1.73 m2). Secondary end points were the development of hypomagnesemia or extrarenal disorders, including hyperuricemia and hyperglycemia. Results: Progression toward CKD stage 3 was significantly delayed in patients with the 17q12del compared to patients with HNF1B variants (hazard ratio [HR]: 0.29, 95% confidence interval [CI]: 0.19-0.44, P < 0.001). Progression toward CKD stage 3 was also significantly delayed when HNF1B variants involved the HNF1B Pit-1, Oct-1, and Unc-86 homeodomain (POUh) DNA-binding and transactivation domains rather than the POU-specific domain (POUs) DNA-binding domain (HR: 0.15 [95% CI: 0.06-0.37), P < 0.001 and HR: 0.25 (95% CI: 0.11-0.57), P = 0.001, respectively). Finally, the 17q12del was positively associated with hypomagnesemia and negatively associated with hyperuricemia, but not with hyperglycemia. Conclusion: Patients with the 17q12del display a significantly better kidney survival than patients with other HNF1B variants; and for the latter, variants in the POUs DNA-binding domain lead to the poorest kidney survival. These are clinically relevant HNF1B kidney genotype-phenotype correlations that inform genetic counseling.
ABSTRACT
There is no specific treatment for proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a disease that is very rare in the pediatric population. We report the case of a 15-year-old boy who presented with mildly reduced kidney function and nephrotic syndrome. Kidney biopsy revealed PGNMID with monoclonal deposits of IgG3 with kappa light chain restriction. Flow cytometry showed a significant CD38 plasma cell population in the peripheral blood in the absence of other signs of hematological malignancy. The patient was treated with a 6-month course of daratumumab, a monoclonal antibody targeting CD38. There was a significant reduction in proteinuria and normalization of kidney function. Based on positive experience with adults, daratumumab should also be studied in children with PGNMID.
ABSTRACT
BACKGROUND: Several previous studies have reported a more severe course of nephrotic syndrome in children with low birth weight. PATIENTS: Cohort of 223 children with idiopathic nephrotic syndrome. METHODS: We aimed to investigate the association between course of nephrotic syndrome and low birth weight. Data from seven paediatric nephrology centres were used. RESULTS: Children with low birth weight had 3.84 times higher odds for a more severe course of steroid-sensitive nephrotic syndrome (95% CI 1.20-17.22, P=0.041), and those with low birth weight and remission after 7 days had much higher odds for a more severe course of disease (OR 8.7). Low birth weight children had a longer time to remission (median 12 vs. 10 days, P=0.03). They had a higher need for steroid-sparing agents (OR for the same sex=3.26 [95% CI 1.17-11.62, P=0.039]), and the odds were even higher in females with low birth weight (OR 6.81). There was no evidence of an association either between low birth weight and focal segmental glomerulosclerosis or between low birth weight and steroid-resistant nephrotic syndrome. DISCUSSION: We conducted the first multicentric study confirming the worse outcomes of children with NS and LBW and we found additional risk factors. CONCLUSIONS: Low birth weight is associated with a more severe course of steroid-sensitive nephrotic syndrome, while being female and achieving remission after 7 days are additional risk factors.
ABSTRACT
As the molecular mechanism of nephrotic syndrome remains largely undiscovered, patients continue to be exposed to the pros and cons of uniform glucocorticoid treatment. We explored whether the exposure of in vitro-cultivated podocytes to sera from children with steroid-sensitive or steroid-resistant nephrotic syndrome induces differences in gene expression profiles, which could help to elucidate the pathogenesis of the steroid response. Human immortalized podocytes were cultivated with patient sera for 3 days. After cell lysis, RNA extraction, 3'-mRNA libraries were prepared and sequenced. There were 34 significantly upregulated and 14 downregulated genes (fold difference <0.5 and >2.0, respectively, and false discovery rate-corrected p < 0.05) and 22 significantly upregulated and 6 downregulated pathways (false discovery rate-corrected p < 0.01) in the steroid-sensitive (n = 9) versus steroid-resistant group (n = 4). The observed pathways included upregulated redox reactions, DNA repair, mitosis, protein translation and downregulated cholesterol biosynthesis. Sera from children with nephrotic syndrome induce disease subtype-specific transcriptome changes in human podocytes in vitro. However, further exploration of a larger cohort is needed to verify whether clinically distinct types of nephrotic syndrome or disease activity may be differentiated by specific transcriptomic profiles and whether this information may help to elucidate the pathogenesis of the steroid response.
Subject(s)
Nephrotic Syndrome , Podocytes , Child , Humans , Nephrotic Syndrome/genetics , Podocytes/metabolism , Transcriptome , Glucocorticoids/pharmacology , Steroids/metabolismABSTRACT
Volume depletion is a common condition and a frequent cause of hospitalization in children. Proper assessment of the patient includes a detailed history and a thorough physical examination. Biochemical tests may be useful in selected cases. Understanding the pathophysiology of fluid balance is necessary for appropriate management. A clinical dehydration scale assessing more physical findings may help to determine dehydration severity. Most dehydrated children can be treated orally; however, intravenous therapy may be indicated in patients with severe volume depletion, in those who have failed oral therapy, or in children with altered consciousness or significant metabolic abnormalities. Proper management consists of restoring circulatory volume and electrolyte balance. In this paper, we review clinical aspects, diagnosis, and management of children with volume depletion.
Subject(s)
Dehydration , Fluid Therapy , Child , Humans , Dehydration/diagnosis , Dehydration/etiology , Dehydration/therapy , Fluid Therapy/adverse effects , Water-Electrolyte Balance , Physical ExaminationABSTRACT
OBJECTIVES: Nutrition plays a vital role in the outcome of critical illness in children, particularly those with acute kidney injury. Currently, there are no established guidelines for children with acute kidney injury treated with continuous kidney replacement therapy. Our objective was to create clinical practice points for nutritional assessment and management in critically ill children with acute kidney injury receiving continuous kidney replacement therapy. METHODS: An electronic search using PubMed and an inclusive academic library search (including MEDLINE, Cochrane, and Embase databases) was conducted to find relevant English-language articles on nutrition therapy for children (<18 y of age) receiving continuous kidney replacement therapy. RESULTS: The existing literature was reviewed by our work group, comprising pediatric nephrologists and experts in nutrition. The modified Delphi method was then used to develop a total of 45 clinical practice points. The best methods for nutritional assessment are discussed. Indirect calorimetry is the most reliable method of predicting resting energy expenditure in children on continuous kidney replacement therapy. Schofield equations can be used when indirect calorimetry is not available. The non-intentional calories contributed by continuous kidney replacement therapy should also be accounted for during caloric dosing. Protein supplementation should be increased to account for the proteins, peptides, and amino acids lost with continuous kidney replacement therapy. CONCLUSIONS: Clinical practice points are provided on nutrition assessment, determining energy needs, and nutrient intake in children with acute kidney injury and on continuous kidney replacement therapy based on the existing literature and expert opinions of a multidisciplinary panel.
Subject(s)
Acute Kidney Injury , Continuous Renal Replacement Therapy , Critical Illness , Nutrition Assessment , Humans , Acute Kidney Injury/therapy , Critical Illness/therapy , Child , Continuous Renal Replacement Therapy/methods , Nutritional Status , Child, Preschool , Adolescent , Renal Replacement Therapy/methods , Calorimetry, Indirect/methods , Delphi TechniqueABSTRACT
BACKGROUND: Nutrition plays a vital role in the outcome of critically ill children, particularly those with AKI. Currently, there are no established guidelines for children with AKI treated with continuous RRT (CRRT). A thorough understanding of the metabolic changes and nutritional challenges in AKI and CRRT is required. Our objective was to create clinical practice points for nutritional assessment and management in critically ill children with AKI receiving CRRT. METHODS: PubMed, MEDLINE, Cochrane, and Embase databases were searched for articles related to the topic. Expertise of the authors and a consensus of the workgroup were additional sources of data in the article. Available articles on nutrition therapy in pediatric patients receiving CRRT through January 2023. RESULTS: On the basis of the literature review, the current evidence base was examined by a panel of experts in pediatric nephrology and nutrition. The panel used the literature review as well as their expertise to formulate clinical practice points. The modified Delphi method was used to identify and refine clinical practice points. CONCLUSIONS: Forty-four clinical practice points are provided on nutrition assessment, determining energy needs, and nutrient intake in children with AKI and on CRRT on the basis of the existing literature and expert opinions of a multidisciplinary panel.
Subject(s)
Acute Kidney Injury , Continuous Renal Replacement Therapy , Humans , Child , Consensus , Critical Illness/therapy , Acute Kidney Injury/therapy , Nutritional StatusABSTRACT
RATIONALE: The manuscript aimed to show that an unmeasurable capillary C-reactive protein (CRP) should be a red flag that can indicate a possible severe hematological pathology. PATIENTS CONCERNS AND DIAGNOSES: The authors present 3 case reports of children with fever examined at the pediatric emergency department. Fever is among the most frequently exhibited symptoms of acute pediatric infectious diseases. However, sometimes fever can be the manifestation of other serious noninfectious diseases. CRP is a marker widely used in clinical pediatric practice to help us evaluate inflammation and possible bacterial infection. All mentioned patients had unmeasurable CRP from capillary blood, even though venous CRP ranged from 14 to 21 mg/L. All of the patients were consequently diagnosed with severe hemato-oncological disease. Possible explanations are that a change in blood viscosity or an elevation of circulating immune complexes in the blood of patients with leukemia leads to malfunctioning immunoturbidimetry measurement. LESSON: Although these findings are very interesting and could lead to faster recognition of acute leukemia in pediatric clinical practice, further prospective study is needed for their confirmation.
Subject(s)
Bacterial Infections , Leukemia , Child , Humans , C-Reactive Protein/analysis , Bacterial Infections/diagnosis , Fever/etiology , Leukemia/complications , Prospective StudiesABSTRACT
Priapism is a urologic emergency requiring prompt management. There are three types of priapism: stuttering (intermittent), non-ischemic (high-flow/arterial), and ischemic (low-flow/veno-occlusive). Here, we present the first case of an infant with recurrent non-ischemic priapism as the first sign of severe hypertension. An 11-month-old infant was admitted to the hospital for high-flow priapism. On admission, he was found to have severe hypertension that required a combination of five antihypertensive drugs; abdominal ultrasound showed polycystic kidneys, splenomegaly, and a parenchymal liver lesion. The priapism resolved spontaneously and did not recur again after the initiation of antihypertensive treatment. Genetic analysis confirmed autosomal recessive polycystic kidney disease (ARPKD). We found no other explanation for the priapism, such as genital trauma, hematologic disease, or anything else. Decreased nitric oxide (NO) bioavailability seen in patients with hypertension seems to be the principal mechanism of hypertension causing priapism. This hypothesis is supported by animal models of genetically modified mice lacking nitric oxide synthase. The same mechanism is thought to be the genesis of priapism and other complications, such as pulmonary hypertension, in patients with sickle cell disease. We present a case of severe hypertension-associated priapism in a child with unrecognized ARPKD. The endothelial dysfunction with decreased NO bioavailability seen in patients with hypertension may be the principal pathogenic mechanism.
ABSTRACT
Aim: The aim of this review is to provide clinicians with characteristics of children with nephrotic syndrome and cerebral sinovenous thrombosis (CSVT). Methods: We have reviewed 37 articles of pediatric cases and provided 1 new case. PRISMA guidelines were followed. Results: Sixty-two patients were included in the review. CSVT was more common in males, usually occurred within 6 months of nephrotic syndrome onset and was found more often in outpatients. The superior sagittal sinus was the most common sinus affected. Non-contrast computed tomography was the most frequent radiologic study performed, with 30% of results negative for CSVT. Headache and vomiting were the most common symptoms while neurologic symptoms were less frequent. Anticoagulation treatment was strongly inconsistent throughout the literature. Thrombosis outcomes were favorable. The most common possible risk factors were corticosteroid treatment, proteinuria and hypoalbuminemia. Four children had a genetic predisposition diagnosed after thrombosis. No markers for anticoagulation prophylaxis seemed to be relevant for the majority of thrombosis occurring in outpatients. Conclusion: Prophylactic anticoagulation does not seem reasonable to prevent CSVT. Knowledge of nonspecific symptoms and of nephrotic syndrome being a state of hypercoagulation and early use of appropriate radiologic study seem to be of major importance.
ABSTRACT
Paroxysmal cold hemoglobinuria (PCH) is a rare condition in childhood characterized by complement-mediated premature destruction of red blood cells. PCH is associated with intravascular hemolysis causing hemoglobinuria, which may result in acute kidney injury of various severity. We aimed to retrospectively analyze clinical and laboratory features of children with PCH-associated acute kidney injury received at tertiary Pediatric Hematology and Nephrology Center, University Motol Hospital, Prague, Czech Republic during the period 2016 to 2022. We present here 3 children with PCH-associated acute kidney failure requiring renal replacement therapy. We highlight the association of PCH with kidney disease. Renal parameters and urine examination should be regularly tested in all children with PCH.
Subject(s)
Acute Kidney Injury , Hemoglobinuria, Paroxysmal , Humans , Child , Hemoglobinuria, Paroxysmal/complications , Hemoglobinuria, Paroxysmal/diagnosis , Retrospective Studies , Erythrocytes , Acute Kidney Injury/complications , Hemolysis , Cold TemperatureABSTRACT
It is known that prematurity and low birth weight are associated with chronic kidney disease and hypertension. A positive correlation between kidney volume and birth weight was also described. In our ongoing observational study in 5-year-old children, we perceived highly abnormal kidney ultrasound and functions of a male patient born weighing 370 grams. It was his first nephrology examination since discharge from the hospital. We believe that thorough follow up and timely diagnosis of developing renal insufficiency may help us to initiate proper treatment in high-risk children (Tab. 1, Fig. 1, Ref. 7). Text in PDF www.elis.sk Keywords: prematurity; extremely low birth weight; chronic kidney disease; renal ultrasound; renal function.
Subject(s)
Infant, Extremely Premature , Kidney , Premature Birth , Renal Insufficiency, Chronic , Ultrasonography , Humans , Child, Preschool , Kidney/abnormalities , Kidney/diagnostic imaging , Male , Renal Insufficiency, Chronic/diagnostic imaging , Renal Insufficiency, Chronic/prevention & controlABSTRACT
BACKGROUND: Streptococcus pneumoniae-associated hemolytic uremic syndrome (P-HUS) is a rare and severe disease. Only a few reports have been published about eculizumab use in P-HUS. METHODS: We analyzed demographic, clinical, and laboratory data of patients with P-HUS from our center. RESULTS: The cohort consisted of 4 females and 3 males. All patients had pneumonia. Four were given eculizumab (days 1-3). The eculizumab group required a shorter duration of dialysis and mechanical ventilation (medians 20 vs. 28.5 and 30 vs 38.5 days, respectively) compared with the non-eculizumab group, but this was still much longer than normally reported; the thrombocytopenia resolution was similar in both groups (medians 10 vs. 8 days). Chronic kidney disease (CKD) was correlated with the duration of dialysis and mechanical ventilation duration at 1 year (r = 0.797, P = 0.032 and r = 0.765, P = 0.045) and last follow-up (r = 0.807, P = 0.028 and r = 0.814, P = 0.026, respectively); our scoring system showed even stronger correlations (r = 0.872, P = 0.011 and r = 0.901, P = 0.0057, respectively). The eculizumab group showed slightly better 1-year and last follow-up CKD stage (2.75 vs. 3, P = 0.879 and 2.5 vs. 3.67, P = 0.517). CONCLUSIONS: Despite the fact that the eculizumab group showed better outcomes, eculizumab does not seem to improve the course of P-HUS compared with previous reports. Kidney outcomes are strongly correlated with the duration of dialysis and mechanical ventilation duration. A higher resolution version of the Graphical abstract is available as Supplementary information.
Subject(s)
Atypical Hemolytic Uremic Syndrome , Hemolytic-Uremic Syndrome , Renal Insufficiency, Chronic , Male , Female , Humans , Streptococcus pneumoniae , Renal Dialysis , Kidney , Hemolytic-Uremic Syndrome/complications , Hemolytic-Uremic Syndrome/drug therapy , Renal Insufficiency, Chronic/complications , Atypical Hemolytic Uremic Syndrome/complications , Atypical Hemolytic Uremic Syndrome/drug therapyABSTRACT
Salt-losing tubulopathies are well-recognised diseases predisposing to metabolic disturbances in affected patients. One of the most severe complications can be life-threatening arrhythmias causing sudden cardiac arrest. We present here the first case of a pediatric patient with Gitelman syndrome associated sudden cardiac arrest without precipitating event. A 10-year-old boy collapsed due to ventricular fibrillation in the Prague tram. Lay cardiopulmonary resuscitation was initiated and external defibrillation restored sinus rhythm within minutes. Initial laboratory examination revealed severe hypokalemia requiring large amounts of electrolyte supplementation. Genetic testing focused to tubulopathies was performed and the diagnosis of Gitelman syndrome was made following the identification of two pathogenic variants in SLC12A3 gene (c.2633 + 1G>A and c.2221G>A). Implantable cardioverter-defibrillator was implanted to prevent sudden cardiac death. The patient was in a good clinical condition with satisfactory electrolyte serum levels at the last follow-up. Causes of electrolyte abnormalities in children should be identified early to prevent the development of rare but potentially fatal complications.
ABSTRACT
BACKGROUND: Immunoglobulin A vasculitis is the most common vasculitis in children. It is usually a self-limiting condition, and the long-term prognosis depends on the severity of renal involvement. Although cyclosporin A is not generally recommended for the management of moderate immunoglobulin A vasculitis nephritis, a few previous reports showed its efficacy. Our aim was to determine whether the treatment with cyclosporin A in combination with corticosteroids is safe and effective for moderate pediatric immunoglobulin A vasculitis nephritis. METHODS: Nine children underwent treatment. Mean follow-up was 3.1±1.6 (1.4-5.8) years. RESULTS: All children (seven females and two males) reached complete remission (65.8±27.6 [24-99]) days. No patient had relapse, one patient had slightly impaired kidney function (glomerular filtration rate 84.4 mL/min/1.73 m2), and two patients had microscopic hematuria without proteinuria at last follow-up. One patient with delayed treatment had microscopic hematuria at last follow-up and developed early albuminuria after cessation of immunosuppression. We observed no serious complications or side effects of the treatment. CONCLUSIONS: Cyclosporin A in combination with corticosteroids seems to be a safe and effective treatment for moderate immunoglobulin A vasculitis nephritis. More studies with cyclosporin A should be conducted to better determine the best therapeutic approach.
ABSTRACT
The number of pediatric solid organ transplantations is growing. This therapy leads often to better quality of life but also brings some specific complications. Our review summarizes practical recommendations for long-time care of the children after kidney and liver transplantation. The knowledge of the issues related to transplantation is essential for the first contact physicians, whose cooperation with transplant centre contributes highly to adequate management of these children.