Publications by authors named "FREUNDLICH M"

Introduction: Hyperparathyroidism (HPT) can contribute to metabolic bone disease following kidney transplantation. We evaluated post-transplant trends in intact parathyroid hormone (iPTH) and determined predictors of HPT in pediatric kidney transplant (KTx) recipients.

Methods: In this single-center study, retrospective data were collected on 88 children from 2013 to 2019.

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The nexus of chronic kidney disease (CKD) and cardiovascular disease (CVD) amplifies the morbidity and mortality of CKD, emphasizing the need for defining and establishing therapeutic initiatives to modify and abrogate the progression of CKD and concomitant CV risks. In addition to the traditional CV risk factors, disturbances of mineral metabolism are specific risk factors that contribute to the excessive CV mortality in patients with CKD. These risk factors include dysregulations of circulating factors that modulate phosphate metabolism, including fibroblast growth factor 23 (FGF23) and soluble Klotho.

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Hypertension (HTN) and chronic kidney disease (CKD) are increasingly recognized in pediatric patients and represent risk factors for cardiovascular morbidity and mortality later in life. In CKD, enhanced tubular sodium reabsorption is a leading cause of HTN due to augmented extracellular fluid volume expansion. The renin-angiotensin-aldosterone system (RAAS) upregulates various tubular sodium cotransporters that are also targets of the hormone fibroblast growth factor 23 (FGF23) and its co-receptor Klotho.

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The renin-angiotensin-aldosterone system (RAAS) is the main plasma volume regulator, which maintains cardiovascular and hydrosaline homeostasis. In the classical pathway, the angiotensin converting enzyme (ACE) generates Angiotensin II (AngII), which is powerfully inflammatory and vasoconstrictive. This classical pathway is also regulated by ACE2, which converts AngI to Ang 1-9, and degrades AngII to Ang 1-7, whose vasodilatory and anti-inflammatory functions balance out the effects of AngII.

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Article Synopsis
  • Preterm babies with breathing problems like BPD and high blood pressure in the lungs (PH) face serious health issues as they grow up.
  • Klotho is a special protein that helps slow down aging and protect the lungs, and lower levels of this protein in preterm babies could make their breathing problems worse.
  • In tests with baby rats, giving extra Klotho helped protect their lungs from damage caused by too much oxygen, showing that keeping Klotho levels high might help preterm babies breathe better in the long run.
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Background: Experimental studies have shown fibroblast growth factor 23 FGF23)-mediated upregulation of the distal tubule sodium/chloride (NaCl) co-transporter leading to increased Na reabsorption, volume expansion and hypertension. However, data on the associations of FGF23 with renal Na regulation and blood pressure (BP) are lacking in young CKD patients.

Methods: FGF23 and other determinants of mineral metabolism, plasma renin activity (PRA), fractional excretion of Na (FENa) and BP, were analyzed at a single center in 60 patients aged 5-22 years with CKD Stages 1 ( = 33) and Stages 2-3 ( = 27) defined by cystatin C- and creatinine-based estimating equations (estimated glomerular filtration rate, eGFR).

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Purpose: To advance fundamental biological and translational research with the bacterium Neisseria gonorrhoeae through the prediction of novel small molecule growth inhibitors via naïve Bayesian modeling methodology.

Methods: Inspection and curation of data from the publicly available ChEMBL web site for small molecule growth inhibition data of the bacterium Neisseria gonorrhoeae resulted in a training set for the construction of machine learning models. A naïve Bayesian model for bacterial growth inhibition was utilized in a workflow to predict novel antibacterial agents against this bacterium of global health relevance from a commercial library of >10 drug-like small molecules.

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Recessive mutations in diacylglycerol kinase epsilon (DGKE) display genetic pleiotropy, with pathological features reported as either thrombotic microangiopathy or membranoproliferative glomerulonephritis (MPGN), and clinical features of atypical hemolytic uremic syndrome (aHUS), nephrotic syndrome or both. Pathophysiological mechanisms and optimal management strategies have not yet been defined. In prospective and retrospective studies of aHUS referred to the United Kingdom National aHUS service and prospective studies of MPGN referred to the National Registry of Rare Kidney Diseases for MPGN we defined the incidence of DGKE aHUS as 0.

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Background: Hyperoxia (HO) causes kidney injury in preterm infants; however, whether these effects are modifiable is unknown. We hypothesized that administration of exogenous soluble Klotho, a kidney-derived antioxidant, would attenuate HO-induced kidney injury during postnatal nephrogenesis in rats.

Methods: Sprague Dawley neonatal rats assigned to normoxia (21% O) or HO (85% O) groups from postnatal day (P) 1 to 21 were randomly assigned to receive alternate day intraperitoneal injections of recombinant Klotho or placebo for 3 weeks.

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Background: The incidence of nephrolithiasis in children and adolescents is increasing and appears to double every 10 years. The most important role of the pediatric nephrologist is to diagnose and modify various metabolic and non-metabolic risk factors, as well as prevent long-term complications especially in the case of recurrent nephrolithiasis.

Objective: The purpose of this review is to summarize the existing literature on the etiology and management of pediatric nephrolithiasis.

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Background: In uremic animals, vitamin D receptor (VDR) agonists like paricalcitol (Pc) attenuate cardiac hypertrophy, but this effect has not been replicated consistently in humans with chronic kidney disease. Elevated fibroblast growth factor 23 (FGF23) levels cause cardiac hypertrophy with activation of the myocardial calcineurin/nuclear factor of activated T cell (NFAT) axis and may antagonize the cardioprotective effects of VDR agonist therapy. We hypothesized that the effectiveness of Pc may depend on the prevailing circulating levels of FGF23 and could be potentiated by the combined administration of a pan-FGF23 receptor (FGFR) blocker agent (PD173074).

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Background: Studies in the use of the calcimimetic, cinacalcet, in pediatric chronic kidney disease (CKD) are few and limited to older children with secondary hyperparathyroidism (sHPT), a major morbid complication contributing to poor growth, bone deformities, and cardiovascular disease. Our objectives were to determine a safe and effective dosing regimen of cinacalcet in the treatment of infants and young children with sHPT that was refractory to standard care and to examine their growth during treatment.

Methods: Ten young pediatric patients with advanced CKD were studied retrospectively during 11 courses of treatment with cinacalcet.

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The complex pathophysiology of progressive chronic kidney disease (CKD) and the development of mineral and bone disorder, abbreviated as CKD-MBD, is of vital importance to a pediatric patient. Paricalcitol, the 19 nor-1,25(OH)D analogue was shown to be effective and safe in the treatment of secondary hyperparathyroidism (SHPT) in adults almost two decades ago. It also significantly improved survival in dialysis patients compared to the standard calcitriol.

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Background: The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on fluid and drug therapy in adults with acute respiratory distress syndrome (ARDS) was to provide clinically relevant, evidence-based treatment recommendations according to standards for trustworthy guidelines.

Methods: The guideline was developed according to standards for trustworthy guidelines, including a systematic review of the literature and use of the GRADE methodology for assessment of the quality of evidence and for moving from evidence to recommendations.

Results: A total of seven ARDS interventions were assessed.

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Background: As 1,25(OH)2D3 vitamin D3 induces fibroblast growth factor-23 (FGF-23) production and suppresses the renin-angiotensin-aldosterone system (RAAS), its absence in vitamin-D-dependent rickets type I (VDDR-I) may have adverse health consequences.

Case Description: An infant presented at age 8 months with hypocalcemia and rickets and very low 1,25(OH)2D3 levels. Genetic analysis confirmed VDRR-I, and calcitriol therapy was initiated.

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Mechanical ventilation is an important part of intensive care. It requires intense observation and has several severe complications. Weaning from mechanical ventilation should be started as soon as possible and immediately after the cause of the pulmonary dysfunction has been treated.

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Heme, the prosthetic group of hemoglobin, may be released from its host due to an intrinsic instability of hemoglobin and accumulate in the erythrocytes. Free heme is in the form of hematin (Fe(3+) protoporphyrin IX OH) and follows several pathways of biochemical toxicity to tissues, cells, and organelles since it catalyzes the production of reactive oxygen species. To determine concentration of soluble free heme in human erythrocytes, we develop a new method.

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Background: Fibroblast Growth Factor-23 (FGF23) and cofactor Klotho are key regulators of mineral metabolism in chronic kidney disease (CKD), but little is known about the mechanisms that regulate their production. This study evaluates longitudinal changes of FGF23 and Klotho levels and their regulatory factors in children on chronic peritoneal dialysis (PD).

Methods: FGF23, Klotho, 25(OH) vitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone (PTH) plasma concentrations were measured during 1 year of follow-up in PD children.

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Background: Pediatric patients with chronic kidney disease (CKD) are at increased risk of early cardiovascular disease and premature death. Abnormalities in microvascular structure and function may presage end-organ damage including vascular calcification and myocardial ischemia associated with disordered mineral metabolism. Early detection of microvascular rarefaction (reduced density of capillaries) may identify at-risk patients and prompt timely therapeutic interventions.

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Background: The objective of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) task force on mechanical ventilation in adults with the acute respiratory distress syndrome (ARDS) is to formulate treatment recommendations based on available evidence from systematic reviews and randomised trials.

Methods: This guideline was developed according to standards for trustworthy guidelines through a systematic review of the literature and the use of the Grading of Recommendations Assessment, Development and Evaluation system for assessment of the quality of evidence and for moving from evidence to recommendations in a systematic and transparent process.

Results: We found evidence of moderately high quality to support a strong recommendation for pressure limitation and small tidal volumes in patients with ARDS.

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Mechanical ventilation is an important part of intensive care. It requires intense observation and has several severe complications. Weaning from mechanical ventilation should be started as soon as possible and immediately after the cause of the pulmonary dysfunction has been treated.

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Background: The mechanisms responsible for the hyperphosphatemia in patients with sickle cell disease (SCD) and preserved glomerular filtration rate (GFR) are not fully understood. The role of fibroblast growth factor 23 (FGF23), a phosphaturic hormone has not been investigated in SCD. Hence, we evaluated parameters of renal tubular phosphorus handling and their relation to prevailing FGF23 levels in a cohort of young SCD patients.

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Background: Children undergoing chronic hemodialysis are at risk of cardiovascular disease and often develop left ventricular hypertrophy (LVH). Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is known to better predict cardiovascular morbidity than casual blood pressure (BP) measurement. Given the BP variability attributed to interdialytic fluid overload, 44-h ABPM should better delineate cardiovascular morbidity in pediatric hemodialysis patients.

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Pediatric cardiomyopathies, which are rare but serious disorders of the muscles of the heart, affect at least one in every 100,000 children in the USA. Approximately 40% of children with symptomatic cardiomyopathy undergo heart transplantation or die from cardiac complications within 2 years. However, a significant number of children suffering from cardiomyopathy are surviving into adulthood, making it an important chronic illness for both pediatric and adult clinicians to understand.

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