The importance of klotho in phosphate metabolism and kidney disease

Tan, Sven‐Jean; Smith, Edwin R.; Hewitson, Tim D.; Holt, Stephen G; Toussaint, Nigel D

doi:10.1111/nep.12268

Cited by 34 publications

(36 citation statements)

References 124 publications

(290 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Study in living kidney donors with longer follow-up demonstrated that sKL increased after the initial postoperative reduction but still was lower than pre-donation [8]. Apart from Klotho’s role in ageing and phosphate homoeostasis [23], its soluble form acts as an endocrine protein that exerts pleiotropic actions, including protection of endothelial function by its antioxidant properties, inhibition of vascular calcification, suppression of fibrosis and inflammation [24, 25]. Reduced sKL may therefore contribute to many complications but how it translates to any patient-oriented measures is still a matter of debate.…”

Section: Discussionmentioning

confidence: 99%

The effect of nephrectomy on Klotho, FGF-23 and bone metabolism

et al. 2017

View full text Add to dashboard Cite

Background Increased concentration of fibroblast growth factor 23 (FGF-23) and decreased levels of soluble Klotho (sKL) are linked to negative clinical outcomes among patients with chronic kidney disease and acute kidney injury. Therefore, it is reasonable to hypothesize that GFR reduction caused by nephrectomy might alter mineral metabolism and induces adverse consequences. Whether nephrectomy due to urological indications causes derangements in FGF-23 and sKL has not been studied. The aim of the study was to evaluate the effect of acute GFR decline due to unilateral nephrectomy on bone metabolism, FGF-23 and sKL levels.MethodsThis is a prospective, single-centre observational study of patients undergoing nephrectomy due to urological indications. Levels of C-terminal FGF-23 (c-FGF-23), sKL and bone turnover markers [β-crosslaps (CTX), bone-specific alkaline phosphatase (bALP) and tartrate-resistant acid phosphatase 5b (TRAP 5b)] were measured before and after surgery (5 ± 2 days).ResultsTwenty-nine patients were studied (14 females, age 63.0 ± 11.6, eGFR 87.3 ± 19.2 ml/min/1.73 m2). After surgery, eGFR significantly declined (p < 0.0001). Nephrectomy significantly decreased sKL level [709.8 (599.9–831.2) vs. 583.0 (411.7–752.6) pg/ml, p < 0.001] and did not change c-FGF-23 concentration [70.5 (49.8–103.3) vs. 77.1 (60.5–109.1) RU/ml, p = 0.9]. Simultaneously, alterations in bone turnover markers were observed. Serum concentration of CTX increased [0.49 (0.4–0.64) vs. 0.59 (0.46–0.85) ng/ml, p = 0.001], while bALP and TRAP 5b decreased [23.6 (18.8–31.4) vs. 17.9 (15.0–22.0) U/l, p < 0.0001 and 3.3 (3.0–3.7) vs. 2.8 (2.3–3.2) U/l, p < 0.001, respectively].ConclusionsNephrectomy among patients with preserved renal function before surgery does not increase c-FGF-23 but reduces sKL. Moreover, nephrectomy results in derangements in bone turnover markers in short-term follow-up. These changes may participate in pathogenesis of bone disease after nephrectomy.

show abstract

Section: Discussionmentioning

confidence: 99%

The effect of nephrectomy on Klotho, FGF-23 and bone metabolism

et al. 2017

View full text Add to dashboard Cite

show abstract

“…This review will update current understanding of αKlotho, and its contribution to maintenance of phosphate homeostasis. The contributions of αKlotho to aging, acute kidney injury and chronic kidney disease have been recently reviewed 6-13 .…”

Section: Introductionmentioning

confidence: 99%

Alpha Klotho and phosphate homeostasis

Bian

Xing

2014

J Endocrinol Invest

View full text Add to dashboard Cite

The Klotho family consists of three single-pass transmembrane proteins—αKlotho, βKlotho and γKlotho. Each of them combines with fibroblast growth factor (FGF) receptors (FGFRs) to form receptor complexes for various FGF’s. αKlotho is a co-receptor for physiological FGF23 signaling and appears essential for FGF23-mediated regulation of mineral metabolism. αKlotho protein also plays a FGF23-independent role in phosphate homeostasis. Animal experimental studies and clinical observations have demonstrated that αKlotho deficiency leads to severe hyperphosphatemia; moderate elevation of αKlotho reduces serum phosphate and extremely high αKlotho induces hypophosphatemia and high-FGF23. αKlotho maintains circulating phosphate in a narrow range by modulating intestinal phosphate absorption, urinary phosphate excretion by the kidney, and phosphate distribution into bone rather than soft tissue in concerted interaction with other calciophosphotropic hormones such as PTH, FGF23, and 1,25-(OH)2 vitamin D. The role of αKlotho in maintenance of phosphate homeostasis is mediated by direct suppression of Na-dependent phosphate cotransporters in target organs. Therefore, αKlotho manipulation may be a novel strategy for genetic and acquired phosphate disorders and for medical conditions with αKlotho deficiency such as chronic kidney disease in future.

show abstract

“…7) Emerging evidence has revealed that the "aging suppressor" gene klotho deficiency is an early event in AKI, and a pathogenic factor that exacerbates acute kidney damage and contributes to long-term outcomes. 8) The klotho gene encodes for a single-pass transmembrane protein expressed primarily in renal tubules, which can be released into circulation as soluble klotho (sklotho). 9) A previous study has revealed that sklotho rapidly decreased as early as at 3 hours in plasma and urine after injury, and the changes of sklotho occurred earlier than changes of serum creatinine (sCr) (24 hours) and even changes of NGAL (5 hours), suggesting that sklotho could be a novel biomarker for early AKI diagnosis.…”

mentioning

confidence: 99%

A Nomogram to Predict Contrast Induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention

Zhuang

et al. 2017

Int. Heart J.

View full text Add to dashboard Cite

SummaryContrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute kidney injury (AKI). Emerging evidence has revealed that soluble klotho (sklotho) could be a novel biomarker for early AKI diagnosis. The aims of this study were to assess the predictive role of sklotho for CIN and to develop a prediction nomogram in patients undergoing percutaneous coronary intervention (PCI). This study is registered on Clinicaltrials.gov (NCT 02650336).Patients aged 18 years or older undergoing planned PCI were prospectively recruited between May 2014 and July 2015. CIN was defined as an increase in serum creatinine of 0.5 mg/dL within 48-72 hours after the procedure. Plasma sklotho was measured by enzyme linked immunosorbent assay (ELISA). Stratified analysis, interaction test, covariate screening, and curve fitting were performed to explore the association between sklotho and CIN. A nomogram was then developed and validated using the bootstrapped technique.A total of 192 patients aged 54.75 ± 12.19 years were selected, 32 (16.7%) of whom were diagnosed with CIN. A logistic regression model indicated significant associations between CIN and sklotho, age > 75 years, diabetes, and the Mehran risk score. Saturation effects analysis detected a two-stage change between sklotho and CIN, with the inflection point was 477.4 pg/mL. The area under the ROC curve was 0.758 and the sensitivity and specificity of this point were 90.6% and 53.9%, respectively. A nomogram was developed for the prediction of CIN and showed a bootstrapped-corrected area under the curve value of 0.913. In addition, sklotho significantly increased the predictive value of the nomogram.A strong association between sklotho and CIN was identified in patients undergoing elective PCI. A lower level of sklotho would be well correlated with CIN. The nomogram with sklotho is a useful tool to predict CIN in patients who will undergo PCI. (Int Heart J 2017; 58: 191-196)

show abstract

The importance of klotho in phosphate metabolism and kidney disease

Cited by 34 publications

References 124 publications

The effect of nephrectomy on Klotho, FGF-23 and bone metabolism

The effect of nephrectomy on Klotho, FGF-23 and bone metabolism

Alpha Klotho and phosphate homeostasis

A Nomogram to Predict Contrast Induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention

Contact Info

Product

Resources

About