Klotho in Aging and the Failing Kidney

Klotho is one of the few longevity-associated genes with robustly demonstrated effects in both directions: reduce its expression and life span is reduced, increase its expression and life span is increased. Klotho levels decline with age, and this decline is strongly associated with loss of cognitive function, but, interestingly, this may be a very indirect effect that exists due to klotho's influence over kidney function in aging. More klotho implies a slower decline in kidney function, and loss of kidney function is also shown to be a contributing factor in cognitive decline. Thus there is some interest in the research community in developing therapies based on delivery of klotho to patients; Unity Biotechnology added klotho to its otherwise senolytics-focused pipeline last year, for example. Klotho has been recognized as a gene involved in the aging process in mammals for over 30 years, where it regulates phosphate homeostasis and the activity of members of the fibroblast growth factor (FGF) family. The α-Klotho protein is the receptor for Fibroblast Growth Factor-23 (FGF23), regulating phosphate homeostasis and vitamin D metabolism. Phosphate toxicity is a hallmark of mammalian aging and correlates with diminution of Klotho levels with increasing age. As such, modulation of Klotho activity is an attractive target for therapeutic intervention in aging; in particular for chronic kidney disease (CKD), where Klotho has been implicated directly in the pathophysi...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs

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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Purpose of review Vitamin D deficiency is common in patients with kidney disease and many patients receive vitamin D supplementation. Several large, well-designed clinical trials have been published in the last few years evaluating the effects of vitamin D supplementation on important outcomes for patients with kidney disease including effects on cardiovascular disease, secondary hyperparathyroidism, and kidney disease progression. Recent findings Several negative trials have been published showing no effect of cholecalciferol supplementation on cardiovascular events, kidney disease progression, and albuminuria. Long-...
Source: Current Opinion in Nephrology and Hypertension - Category: Urology & Nephrology Tags: CLINICAL NEPHROLOGY: Edited by David S. Goldfarb Source Type: research
In conclusion, our study shows that free vitamin D serum concentrations are independently associated with major cardiovascular events in chronic kidney disease patients on dialysis.Kidney Blood Press Res
Source: Kidney and Blood Pressure Research - Category: Urology & Nephrology Source Type: research
This study examined whether an association between the two entities exists. METHOD: We analysed 2953 known hypertensive subjects surveyed by NHANES (National Health and Nutrition Examination Survey) among the United States population between 2003 and 2006. Subjects were categorized as having either resistant hypertension or hypertension based on the number of anti-hypertensives in use and their overall blood pressure control. Subjects were also categorized as vitamin D deficient if they had 25(OH)D (25-hydroxycholecalciferol) levels less than 20ng/ml. RESULTS: Out of the 2953 subjects, 362 (12%) were found to hav...
Source: Clinical and Experimental Hypertension - Category: Cardiology Authors: Tags: Clin Exp Hypertens Source Type: research
Abstract Background: Vitamin D deficiency is associated with renal progression in chronic kidney disease. Moreover, improvement of clinical outcomes after vitamin D supplementation has been reported in the diabetic and chronic kidney disease population. Objective: We investigated the association between renal hyperfiltration (RHF) and vitamin D status in a relatively healthy population. Design: Data were retrieved from the Korean NHANES, a nationwide population-based cross-sectional study from 2008 to 2015. Overall, 33,210 subjects with normal renal function were included in the final analysis. Severe vi...
Source: Am J Clin Nutr - Category: Nutrition Authors: Tags: Am J Clin Nutr Source Type: research
CONCLUSIONS: In this study, it was proven that vitamin D deficiency in children was related to nondiabetic and nondialysis CKD. PMID: 30367018 [PubMed - in process]
Source: Iranian Journal of Kidney Diseases - Category: Urology & Nephrology Tags: Iran J Kidney Dis Source Type: research
ConclusionsCAKUT was the commonest cause of CKD. Late detection and high prevalence of comorbidities even in early stages of CKD were observed.
Source: Indian Journal of Pediatrics - Category: Pediatrics Source Type: research
This study aimed to evaluate the vitamin D status and its association with body adiposity, CVD risk factors, estimated glomerular filtration rate (eGFR) and proteinuria in RTR, living in Rio de Janeiro, Brazil (a low-latitude city (22°54'10"S)), taking into account body adiposity evaluated by dual-energy X-ray absorptiometry (DXA). This cross-sectional study included 195 RTR (114 men) aged 47·6 (sd 11·2) years. Nutritional evaluation included anthropometry and DXA. Risk factors for CVD were hypertension, diabetes mellitus, dyslipidaemia and the metabolic syndrome. eGFR was evaluated using the Chronic...
Source: The British Journal of Nutrition - Category: Nutrition Authors: Tags: Br J Nutr Source Type: research
Conclusions We suggest that the effectiveness of β-blocker treatment for PVCs in CKD patients was observed in all 25(OH)D levels. However, the responsiveness was higher in patients with a normal range of 25(OH)D in comparison to patients with deficiency or insufficiency in 25(OH)D levels. Whether vitamin D supplementation increases the efficacy of beta-blocker mediated suppression of PVCs requires further evaluation.
Source: IJC Metabolic and Endocrine - Category: Endocrinology Source Type: research
Publication date: Available online 23 November 2016 Source:The Lancet Author(s): Angela C Webster, Evi V Nagler, Rachael L Morton, Philip Masson The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m2, or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in man...
Source: The Lancet - Category: Journals (General) Source Type: research
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