Introduction: Aortic pulse wave velocity (Ao-PWV) predicts cardiovascular and kidney disease in type 2 diabetes (T2D). Klotho is a circulating antiaging hormone (sKlotho) with putative cardiorenal protective effects. The relationship between sKlotho and Ao-PWV in diabetic kidney disease (DKD) is unknown.
Methods: In a cross-sectional cohort study, the correlation of sKlotho measured by a validated immunoassay, and Ao-PWV measured by applanation tonometry, was investigated in 172 participants with T2D and early stage DKD (all had estimated glomerular filtration rate [eGFR] >45 ml/min) on stable renin angiotensin system (RAS) inhibition. In cultured human aortic smooth muscle cells (HASMCs) stimulated with angiotensin II (AngII), the effects of recombinant human sKlotho pretreatment were assessed on intracellular calcium ([Ca]) responses and expression of proteins associated with proosteogenic HASMC phenotypes.
Results: Mean (range) age of the cohort was 61.3 years (40-82) and 65% were male. Mean (±SD) Ao-PWV was 11.4 (±2.3) m/s, eGFR 78.8 (±23.5) and median (interquartile range) sKlotho of 358.5 (194.2-706.3) pg/ml. In multivariable linear regression analyses, we observed a statistically significant inverse relationship between sKlotho and Ao-PWV, which was independent of clinical risk factors for cardiorenal disease. Pretreatment of cultured HASMC with sKlotho significantly attenuated AngII-stimulated [Ca] transients and reduced osteogenic collagen (Col1a2) expression.
Conclusions: In individuals with T2D and early DKD, lower levels of sKlotho are associated with increased Ao-PWV. Taken together with the direct effect of sKlotho on mediators of aortic wall stiffness , these findings may explain the enhanced risk of cardiorenal disease in DKD.
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http://dx.doi.org/10.1016/j.ekir.2023.04.021 | DOI Listing |
Background: The new anti-Aβ antibody drugs aducanumab and lecanemab (approved in the US, not yet in Europe) must be followed up closely and regularly long-term. Previous knowledge on progression of AD in routine clinical settings longterm is crucial when introducing new dementia medications. The Swedish national quality database on dementia/cognitive disorders, SveDem, where data on different dementia disorders at the time of the dementia diagnosis since 2007 and on mild cognitive impairment (MCI) since 2021 with annual follow-ups of MMSE scores can provide this unique information.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Waterloo, Waterloo, ON, Canada.
Background: The Medication Review in Cognitive Impairment and Dementia (MedRevCiD) checklist is a new tool designed to assist health care professionals in optimizing medication use in individuals with Mild Cognitive Impairment (MCI) or dementia. It consists of 6 domains, each of which addresses a specific medication use issue such as medication management and adherence. The primary objective of this study was to compare the mean number of drug-related problems (DRPs) identified with MedRevCiD Checklist to the Medication Appropriateness Index (MAI) in older adults attending a primary care-based memory clinic.
View Article and Find Full Text PDFCurr Cardiol Rev
January 2025
Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India.
Cardiovascular-kidney-metabolic (CKM) syndrome is the association between obesity, diabetes, CKD (chronic kidney disease), and cardiovascular disease. GDF-15 mainly acts through the GFRAL (Glial cell line-derived neurotrophic factor Family Receptor Alpha-Like) receptor. GDF-15 and GDFRAL complex act mainly through RET co-receptors, further activating Ras and phosphatidylinositol-3-kinase (PI3K)/Akt pathways through downstream signaling.
View Article and Find Full Text PDFClin Chem Lab Med
January 2025
Laboratory of Clinical Pathology, Azienda Sanitaria Universitaria Integrata, Udine, Italy.
Objectives: External quality assessment (EQA) programs play a pivotal role in harmonizing laboratory practices, offering users a benchmark system to evaluate their own performance and identify areas requiring improvement. The objective of this study was to go through and analyze the UK NEQAS "Immunology, Immunochemistry and Allergy" EQA reports between 2012 and 2021 to assess the overall level of harmonization in autoimmune diagnostics and identify areas requiring improvement for future actions.
Methods: The EQA programs reviewed included anti-nuclear (ANA), anti-dsDNA, anti-centromere, anti-extractable nuclear antigen (ENA), anti-phospholipids, anti-neutrophil cytoplasm (ANCA), anti-proteinase 3 (PR3), anti-myeloperoxidase (MPO), anti-glomerular basement membrane (GBM), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), mitochondrial (AMA), liver-kidney-microsomal (LKM), smooth muscle (ASMA), APCA, and celiac disease antibodies.
FASEB J
January 2025
Department of Hematology, Nephrology, and Rheumatology, Graduate School of Medicine, Akita University, Akita, Japan.
Various tubular diseases in patients with multiple myeloma (MM) are caused by monoclonal immunoglobulin light chains (LCs). However, the physicochemical characteristics of the disease-causing LCs contributing to the onset of MM-associated tubular diseases remain unclear. We herein report a rare case of MM-associated combined tubulopathies: non-crystalline light chain proximal tubulopathy (LCPT) and crystalline light chain cast nephropathy (LCCN).
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