The vicious circle of chronic kidney disease and hypertriglyceridemia: What is first, the hen or the egg?

Chronic kidney disease (CKD) is documented to cause alterations in lipid metabolism, and this was considered a potent driver of increased cardiovascular risk. Among the diverse alteration of lipid traits in CKD, research endeavours have predominantly concentrated on low-density lipoproteins (LDL) in view of the potent pro-atherogenic role of these lipoprotein particles and the demonstration of protective cardiovascular effect of reducing LDL. However, few studies have focused on the metabolism of triglyceride-rich lipoproteins and even fewer on their role in causing kidney damage.

Response to therapy of creatine transporter deficiency caused by a hypomorphic variant in SLC6A8.

Cerebral creatine deficiency syndromes (CCDS) are rare inherited metabolic disorders caused by defective biosynthesis or transport of creatine. These conditions are characterized by reduced accumulation of creatine in the brain, mild to severe intellectual disability, global developmental delay, and speech-language disorders. The amount of brain creatine reduction needed to cause symptoms is not known.

Newborn Screening: Current Practice and Our Journey over the Last 60 Years.

Background: Inborn errors of metabolism comprise a set of more than 2000 known disorders which can result in significant morbidity and may be rapidly fatal. Diagnosing these disorders at birth and treating immediately, however, may often result in a normal to near-normal life for the affected infant. Thus, newborn screening (NBS) has saved or improved the lives of countless individuals since its inception in the 1960s.

Diagnosing X-Linked Adrenoleukodystrophy after Implementation of Newborn Screening: A Reference Laboratory Perspective.

Adrenoleukodystrophy (ALD) is caused by pathogenic variants in the gene, encoding for the adrenoleukodystrophy protein (ALDP), leading to defective peroxisomal β-oxidation of very long-chain and branched-chain fatty acids (VLCFA). ALD manifests in both sexes with a spectrum of phenotypes, but approximately 35% of affected males develop childhood cerebral adrenoleukodystrophy (CCALD), which is lethal without hematopoietic stem cell transplant performed before symptoms start. Hence, ALD was added to the Recommended Uniform Screening Panel after the successful implementation in New York State (2013-2016).

Biochemical signatures of disease severity in multiple sulfatase deficiency.

Sulfatases catalyze essential cellular reactions, including degradation of glycosaminoglycans (GAGs). All sulfatases are post-translationally activated by the formylglycine generating enzyme (FGE) which is deficient in multiple sulfatase deficiency (MSD), a neurodegenerative lysosomal storage disease. Historically, patients were presumed to be deficient of all sulfatase activities; however, a more nuanced relationship is emerging.

Specifications of the ACMG/AMP guidelines for ACADVL variant interpretation.

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD) is a relatively common inborn error of metabolism, but due to difficulty in accurately predicting affected status through newborn screening, molecular confirmation of the causative variants by sequencing of the ACADVL gene is necessary. Although the ACMG/AMP guidelines have helped standardize variant classification, ACADVL variant classification remains disparate due to a phenotype that can be nonspecific, the possibility of variants that produce late-onset disease, and relatively high carrier frequency, amongst other challenges. Therefore, an ACADVL-specific variant curation expert panel (VCEP) was created to facilitate the specification of the ACMG/AMP guidelines for VLCADD.

Evaluation of partial pressure CO change in the dialyzer blood inlet during hemodialysis as a measure of vascular access recirculation.

Introduction: Vascular access recirculation during hemodialysis is associated with reduced effectiveness and worse survival outcomes. To evaluate recirculation, an increase in pCO in the blood of the arterial line during hemodialysis (threshold of 4.5 mmHg) was proposed.

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study.

Background: Severe secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery.

Methods: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months.

Acylglycine Analysis by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS).

Quantitative analysis of urine acylglycines has shown to be a highly sensitive and specific method with proven clinical utility for the diagnosis of several inherited metabolic disorders including: medium chain acyl-CoA dehydrogenase deficiency, multiple acyl-CoA dehydrogenase deficiency, short chain acyl-CoA dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase deficiency, 2-methylbutyryl-CoA dehydrogenase deficiency, isovaleric acidemia, propionic academia, and isobutyryl-CoA dehydrogenase deficiency. Here, a method that is currently performed using ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) is described. © 2023 Wiley Periodicals LLC.

Association between Cognitive Impairment and Malnutrition in Hemodialysis Patients: Two Sides of the Same Coin.

Cognitive impairment and malnutrition are prevalent in patients on hemodialysis (HD), and they negatively affect the outcomes of HD patients. Evidence suggests that cognitive impairment and malnutrition may be associated, but clinical studies to assess this association in HD patients are lacking. The aim of this study was to evaluate the association between cognitive impairment evaluated by the Montreal Cognitive Assessment (MoCA) score and nutritional status evaluated by the malnutrition inflammation score (MIS) in HD patients.

Quantification of Very-Long-Chain and Branched-Chain Fatty Acids in Plasma by Liquid Chromatography-Tandem Mass Spectrometry.

Peroxisomal disorders are a heterogeneous group of genetic disorders caused by impaired peroxisomal biogenesis or by defects in single peroxisomal proteins. The most common peroxisomal disorders are Zellweger spectrum disorders (ZSDs), due to pathogenic variants in one of the 13 PEX genes, and X-linked adrenoleukodystrophy/adrenomyeloneuropathy (X-ALD/AMN), due to pathogenic variants in ATP-binding cassette transporter type D1 (ABCD1) gene. Peroxisomes perform multiple essential cellular functions, including β-oxidation of very-long-chain fatty acids (VLCFAs), pristanic acid and some bile acid intermediates, and α-oxidation of phytanic acid.

Quantitation of Butyrylcarnitine, Isobutyrylcarnitine, and Glutarylcarnitine in Urine Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS).

Acylcarnitines are formed when an acyl group is transferred from coenzyme A to a molecule of L-carnitine. In organic acidemias, and in fatty acid oxidation disorders, specific acylcarnitine species accumulate in a pattern that is characteristic for each disease. For this reason, acylcarnitine analysis is widely used for screening and diagnosis of inherited disorders of metabolism.

Diastolic Pressure and ACR Are Modifiable Risk Factors of Arterial Stiffness in T2DM Without Cardiovascular Disease.

Aim: To evaluate early, before the onset of cardiovascular events and of chronic renal insufficiency, the association between chronic kidney disease (CKD)-mineral bone disorder (MBD) biomarkers and vascular stiffness [Cardio Ankle Vascular Index (CAVI)] in the course of type 2 diabetes (T2DM).

Method: We evaluated 174 T2DM patients [median age 56 years; male/female (M/F) 100/74] with diabetes duration < 10 years and without decreased estimated glomerular filtration rate (eGFR; ≥60 mL/min/1.73 m2) or macrovascular complications.

Towards a Newborn Screening Common Data Model: The Utah Newborn Screening Data Model.

As newborn screening programs transition from paper-based data exchange toward automated, electronic methods, significant data exchange challenges must be overcome. This article outlines a data model that maps newborn screening data elements associated with patient demographic information, birthing facilities, laboratories, result reporting, and follow-up care to the LOINC, SNOMED CT, ICD-10-CM, and HL7 healthcare standards. The described framework lays the foundation for the implementation of standardized electronic data exchange across newborn screening programs, leading to greater data interoperability.

Quantitative analysis of urine acylglycines by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS): Reference intervals and disease specific patterns in individuals with organic acidemias and fatty acid oxidation disorders.

Background: Acylglycine species accumulate in specific disorders of branched-chain amino acid metabolism and fatty acid β-oxidation. These species are excreted in urine and their analysis can facilitate diagnosis. Previous studies evaluated reference ranges and increases in metabolic patients, but these involved small numbers of individuals.

Creatine metabolism in patients with urea cycle disorders.

The urea cycle generates arginine that is one of the major precursors for creatine biosynthesis. Here we evaluate levels of creatine and guanidinoacetate (the precursor in the synthesis of creatine) in plasma samples (n = 207) of patients (n = 73) with different types of urea cycle disorders (ornithine transcarbamylase deficiency (n = 22; n = 7), citrullinemia type 1 (n = 60; n = 22), argininosuccinic aciduria (n = 81; n = 31), arginase deficiency (n = 44; n = 13)). The concentration of plasma guanidinoacetate positively correlated ( < 0.

Prospective identification by neonatal screening of patients with guanidinoacetate methyltransferase deficiency.

Introduction: Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited metabolic disorder that impairs the synthesis of creatine (CRE). Lack of CRE in the brain can cause intellectual disability, autistic-like behavior, seizures, and movement disorders. Identification at birth and immediate therapy can prevent intellectual disability and seizures.

Focus on the Possible Role of Dietary Sodium, Potassium, Phosphate, Magnesium, and Calcium on CKD Progression.

The impressive estimated number of chronic kidney disease (CKD) patients in the world justifies any possible effort at implementing preventive measures of disease progression. Renal insufficiency is associated with significant changes in the electrolyte handling and body balance of sodium, potassium, phosphate, magnesium, and calcium, all of which are biologically vital molecules. Dietary habits could contribute significantly to the optimal management of possible derangements.

Oxygen extraction ratio to identify patients at increased risk of intradialytic hypotension.

Intradialytic hypotension (IDH) is a hemodynamic phenomenon recently associated with decreased blood oxygen saturation (SO). The ratio between peripheral oxygen saturation (SpO) and central venous SO (ScvO) or Oxygen Extraction Ratio (OER), which represents a roughly estimate of the amount of oxygen claimed by peripheral tissues, might be used to estimate haemodialysis (HD) related hypoxic stress. Aim of this pilot study was to evaluate the relationship between OER increments during dialysis sessions (ΔOER) and episodes of IDH.

Inflammation, Oxidative Stress, and Bone in Chronic Kidney Disease in the Osteoimmunology Era.

Bone is not only a mineralized and apparently non-vital structure that provides support for locomotion and protection to inner organs. An increasing number of studies are unveiling new biologic functions and connections to other systems, giving the rise to new fields of research, such as osteoimmunology. The bone marrow niche, a new entity in bone physiology, seems to represent the site where a complex crosstalk between bone and immune/inflammatory responses takes place.