Circulating α-Klotho Levels in CKD and Relationship to Progression

Kim, Hyoung Rae; Nam, Bo Young; Kim, Dong Wook; Kang, Min Ji; Han, Jae Hyun; Lee, Mi Jung; Shin, Dong Ho; Doh, Fa Mee; Koo, Hyang Mo; Ko, Kwang Il; Kim, Chan Ho; Oh, Hyung Jung; Yoo, Tae‐Hyun; Kang, Shin Wook; Han, Dae Suk; Han, Seung Hyeok

doi:10.1053/j.ajkd.2013.01.024

Cited by 170 publications

(173 citation statements)

References 39 publications

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“…Indeed, α‐Klotho deficiency in mice leads to a limited vasodilatory response and increased permeability in the endothelial cells among other vascular complications also observed in CKD patients 22, 23, 24, 41. As reported previously in other uremic in vivo models20, 21 and CKD patients,42, 43 we confirmed that impaired kidney function induced downregulation of mRNA and α‐Klotho protein levels in kidney tissue accompanied by lower serum concentrations.…”

Section: Discussionsupporting

confidence: 88%

Vitamin D Attenuates Endothelial Dysfunction in Uremic Rats and Maintains Human Endothelial Stability

Cuenca

Ferrantelli

Meinster

et al. 2018

JAHA

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BackgroundDysfunctional endothelium may contribute to the development of cardiovascular complications in chronic kidney disease (CKD). Supplementation with active vitamin D has been proposed to have vasoprotective potential in CKD, not only by direct effects on the endothelium but also by an increment of α‐Klotho. Here, we explored the capacity of the active vitamin D analogue paricalcitol to protect against uremia‐induced endothelial damage and the extent to which this was dependent on increased α‐Klotho concentrations.Methods and ResultsIn a combined rat model of CKD with vitamin D deficiency, renal failure induced vascular permeability and endothelial‐gap formation in thoracic aorta irrespective of baseline vitamin D, and this was attenuated by paricalcitol. Downregulation of renal and serum α‐Klotho was found in the CKD model, which was not restored by paricalcitol. By measuring the real‐time changes of the human endothelial barrier function, we found that paricalcitol effectively improved the recovery of endothelial integrity following the addition of the pro‐permeability factor thrombin and the induction of a wound. Furthermore, immunofluorescence staining revealed that paricalcitol promoted vascular endothelial‐cadherin–based cell‐cell junctions and diminished F‐actin stress fiber organization, preventing the formation of endothelial intracellular gaps.ConclusionsOur results demonstrate that paricalcitol attenuates the CKD‐induced endothelial damage in the thoracic aorta and directly mediates endothelial stability in vitro by enforcing cell‐cell interactions.

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Section: Discussionsupporting

confidence: 88%

Vitamin D Attenuates Endothelial Dysfunction in Uremic Rats and Maintains Human Endothelial Stability

Cuenca

Ferrantelli

Meinster

et al. 2018

JAHA

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“…In a post hoc analysis of a prospective study, lower serum aKlotho levels were associated with more severe CKD stage, and baseline aKlotho independently predicted the renal outcome after adjustment for several variables, including eGFR and FGF23. 13 In contrast, in a larger study comprising 444 well characterized patients with CKD stages 2-4, we failed to observe a strong relationship between eGFR and soluble aKlotho. 14,15 Of note, although we confirmed a weak association between age and soluble aKlotho, we did not find any correlation of soluble aKlotho with parameters of calciumphosphate metabolism, progression, 16 or cardiovascular end points.…”

contrasting

confidence: 73%

Klotho Deficiency and the Cardiomyopathy of Advanced CKD

Floege

Fliser

2015

Journal of the American Society of Nephrology

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“…Lower levels of serum Klotho significantly correlate with lower eGFR levels in patients with CKD (75). Importantly, Kim et al (76) found that low levels of serum Klotho are linked to the progression of CKD independently of FGF23, proteinuria, or PTH, suggesting that a-Klotho may serve as a useful clinical biomarker for progression of CKD. In addition, Barker et al (77), using a novel synthetic antibody, recently found that soluble Klotho was decreased early in CKD, preceding hyperphosphatemia and increases in FGF23 and PTH.…”

Section: Phosphate and Ckdmentioning

confidence: 99%

Phosphate Toxicity in CKD: The Killer among Us

Ritter¹,

Slatopolsky²

2016

CJASN

121

113

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Maintenance of a normal serum phosphate level depends on absorption in the gut, reabsorption and excretion by the kidney, and the flux between the extracellular and skeletal pools. Phosphate homeostasis is a coordinated, complex system of crosstalk between the bone, intestine, kidney, and parathyroid gland. Dysfunction of this system has serious clinical consequences in healthy individuals and those with conditions, such as CKD, in which hyperphosphatemia is associated with increased risks of cardiovascular morbidity and mortality. The last halfcentury of renal research has helped define the contribution of the parathyroid hormone, calcitriol, fibroblast growth factor 23, and Klotho in the regulation of phosphate. However, despite new discoveries and insights gained during this time, what remains unchanged is the recognition that phosphate retention is the initiating factor for the development of many of the complications observed in CKD, namely secondary hyperparathyroidism and bone and cardiovascular diseases. Controlling phosphate load remains the primary goal in the treatment of CKD. This review discusses the clinical effects of dysregulated phosphate metabolism, particularly in CKD, and its association with cardiovascular disease. The importance of early control of phosphate load in the treatment of CKD is emphasized, and the latest research in the treatment of phosphate retention is discussed.

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Circulating α-Klotho Levels in CKD and Relationship to Progression

Cited by 170 publications

References 39 publications

Vitamin D Attenuates Endothelial Dysfunction in Uremic Rats and Maintains Human Endothelial Stability

Vitamin D Attenuates Endothelial Dysfunction in Uremic Rats and Maintains Human Endothelial Stability

Klotho Deficiency and the Cardiomyopathy of Advanced CKD

Phosphate Toxicity in CKD: The Killer among Us

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