Renal Klotho expression in patients with acute kidney injury is associated with the severity of the injury

Seo, Min Young; Yang, Jihyun; Lee, Jun Yong; Kim, Kitae; Kim, Sun Chul; Chang, Hyojeong; Won, Nam Hee; Kim, Myung Gyu; Jo, Sang Kyung; Cho, Won-Yong; Kim, Hyoung Kyu

doi:10.3904/kjim.2015.30.4.489

Cited by 33 publications

(20 citation statements)

References 15 publications

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“…In many experimental animal models of disease, s-Klotho expression is severely decreased and the deficiency of s-Klotho further worsens kidney function. In human studies, Seo et al reported that the expression of renal Klotho decreased significantly according to the severity of AKI, meanwhile, a low s-Klotho level predicted a poorer outcome 13. Shimamura et al observed that s-Klotho levels were reduced in the early stages of CKD, and it continued to fall as CKD progressed 15.…”

Section: Discussionmentioning

confidence: 99%

Plasma S-Klotho is Related to Kidney Function and Predicts Adverse Renal Outcomes in Patients with Advanced Chronic Kidney Disease

Liu

et al. 2018

Journal of Investigative Medicine

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To investigate whether the soluble Klotho (s-Klotho) level in patients with chronic kidney disease (CKD) is related to kidney function and whether a low s-Klotho level can predict adverse renal outcomes or CKD progression in patients with advanced CKD. 112 patients with CKD stages 3-5 and 30 healthy volunteers were enrolled. Blood samples were collected to measure serum creatinine, calcium, phosphorus, intact parathyroid hormone, and hemoglobin. s-Klotho and fibroblast growth factor 23 (FGF23) were determined by ELISA. We first conducted a cross-sectional study to investigate correlations between s-Klotho and estimated glomerular filtration rate (eGFR) and other parameters. Patients were then followed prospectively for 20.1±10.1 months according to s-Klotho median level until serum creatinine doubled, or initiation of renal replacement therapy, or death. s-Klotho levels inpatients with CKD were significantly lower than that in the control group. For patients with CKD, there were no differences in age distribution among subgroups. However, s-Klotho level differed significantly across CKD stages, and it was lower in the advanced CKD group compared with the moderate CKD group. Correlation analysis revealed that s-Klotho was positively associated with eGFR, but inversely associated with FGF23. During the follow-up of 20.1±10.1 months, patients with higher s-Klotho levels showed a reduced risk of kidney adverse outcomes, including serum creatinine doubling and initiation of renal replacement therapy. Cox regression analysis revealed that low s-Klotho was an independent risk factor for CKD progression. s-Klotho level was closely correlated with kidney function, further, low s-Klotho level could predict adverse kidney disease outcomes in patients with progressive CKD.

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Section: Discussionmentioning

confidence: 99%

Plasma S-Klotho is Related to Kidney Function and Predicts Adverse Renal Outcomes in Patients with Advanced Chronic Kidney Disease

Liu

et al. 2018

Journal of Investigative Medicine

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“…In humans, soluble Klotho levels were decreased in patients with AKI (67). In another study, the expression of renal Klotho decreased in patients with AKI according to the severity of the disease, regardless of the etiology, and low Klotho expression associated with a poor short-term outcome (68). Therefore, decreased Klotho may be a key pathologic feature in AKI development and progression to CKD.…”

Section: Phosphate and Ckdmentioning

confidence: 95%

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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“…Kidney Klotho downregulation has been reported in experimental and human AKI and CKD (44,52,104,124). In human CKD, reduced urinary Klotho was the earliest calcium and phosphate metabolism-related abnormality (39).…”

Section: Decreased Renal Klotho In Kidney Injury: Role Of Inflammationmentioning

confidence: 98%

Downregulation of kidney protective factors by inflammation: role of transcription factors and epigenetic mechanisms

Ruiz‐Andrés

Sanchez-Niño

Moreno

et al. 2016

American Journal of Physiology-Renal Physiology

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Chronic kidney disease (CKD) is associated to an increased risk of death, CKD progression, and acute kidney injury (AKI) even from early stages, when glomerular filtration rate (GFR) is preserved. The link between early CKD and these risks is unclear, since there is no accumulation of uremic toxins. However, pathological albuminuria and kidney inflammation are frequent features of early CKD, and the production of kidney protective factors may be decreased. Indeed, Klotho expression is already decreased in CKD category G1 (normal GFR). Klotho has anti-aging and nephroprotective properties, and decreased Klotho levels may contribute to increase the risk of death, CKD progression, and AKI. In this review, we discuss the downregulation by mediators of inflammation of molecules with systemic and/or renal local protective functions, exemplified by Klotho and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a transcription factor that promotes mitochondrial biogenesis. Cytokines such as TWEAK, TNF-α, or transforming growth factor -β1 produced locally during kidney injury or released from inflammatory sites at other organs may decrease kidney expression of Klotho and PGC-1α or lead to suboptimal recruitment of these nephroprotective proteins. Transcription factors (e.g., Smad3 and NF-κB) and epigenetic mechanisms (e.g., histone acetylation or methylation) contribute to downregulate the expression of Klotho and/or PGC-1α, while histone crotonylation promotes PGC-1α expression. NF-κBiz facilitates the repressive effect of NF-κB on Klotho expression. A detailed understanding of these mediators may contribute to the development of novel therapeutic approaches to prevent CKD progression and its negative impact on mortality and AKI.

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Renal Klotho expression in patients with acute kidney injury is associated with the severity of the injury

Cited by 33 publications

References 15 publications

Plasma S-Klotho is Related to Kidney Function and Predicts Adverse Renal Outcomes in Patients with Advanced Chronic Kidney Disease

Plasma S-Klotho is Related to Kidney Function and Predicts Adverse Renal Outcomes in Patients with Advanced Chronic Kidney Disease

Phosphate Toxicity in CKD: The Killer among Us

Downregulation of kidney protective factors by inflammation: role of transcription factors and epigenetic mechanisms

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