Factors associated with serum soluble inhibitors of <scp>W</scp>nt‐β‐catenin signaling (sclerostin and dickkopf‐1) in patients undergoing peritoneal dialysis

Yamada, S.; Tsuruya, Kazuhiko; Tokumoto, Masanori; Yoshida, Haruhiko; Ooboshi, Hiroaki; Kitazono, Takanari

doi:10.1111/nep.12509

Cited by 11 publications

(9 citation statements)

References 34 publications

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“…Sclerostin levels also increase with age in nondialyzed CKD and HD patients [18, 33]. In 2015, Yamada et al reported that serum sclerostin was positively associated with age in PD patients [34]. However, in the present study, patients with above-median sclerostin levels were characterized by older age, with only marginally statistical significance, probably because of our limited sample size.…”

Section: Discussioncontrasting

confidence: 62%

Serum sclerostin levels are positively related to bone mineral density in peritoneal dialysis patients: a cross-sectional study

et al. 2019

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Background Sclerostin, an antagonist of the Wingless-type mouse mammary tumor virus integration site (Wnt) pathway that regulates bone metabolism, is a potential contributor of chronic kidney disease (CKD)–mineral and bone disorder (MBD), which has various forms of presentation, from osteoporosis to vascular calcification. The positive association of sclerostin with bone mineral density (BMD) has been demonstrated in CKD and hemodialysis (HD) patients but not in peritoneal dialysis (PD) patients. This study assessed the association between sclerostin and BMD in PD patients. Methods Eighty-nine PD patients were enrolled; their sera were collected for measurement of sclerostin and other CKD–MBD-related markers. BMD was also assessed simultaneously. We examined the relationship between sclerostin and each parameter through Spearman correlation analysis and by comparing group data between patients with above- and below-median sclerostin levels. Univariate and multiple logistic regression models were employed to define the most predictive of sclerostin levels in the above-median category. Results Bivariate analysis revealed that sclerostin was correlated with spine BMD ( r = 0.271, P = 0.011), spine BMD T-score ( r = 0.274, P = 0.010), spine BMD Z-score ( r = 0.237, P = 0.027), and intact parathyroid hormone (PTH; r = − 0.357, P < 0.001) after adjustments for age and sex. High BMD, old age, male sex, increased weight and height, diabetes, and high osteocalcin and uric acid levels were observed in patients with high serum sclerostin levels and an inverse relation was noticed between PTH and sclerostin. Univariate logistic regression analysis demonstrated that BMD is positively correlated with above-median sclerostin levels (odds ratio [OR] = 65.61, P = 0.002); the correlation was retained even after multivariate adjustment (OR = 121.5, P = 0.007). Conclusions For the first time, this study demonstrated a positive association between serum sclerostin levels and BMD in the PD population.

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Section: Discussioncontrasting

confidence: 62%

Serum sclerostin levels are positively related to bone mineral density in peritoneal dialysis patients: a cross-sectional study

et al. 2019

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“…Sclerostin level had been found to be negatively correlated with iPTH level in CKD-5D patients, 12 in maintenance hemodialysis patients, 37 , 38 and in patients who underwent peritoneal dialysis. 39 However, several studies failed to observe such correlation in predialysis CKD patients. 14 , 36 , 40 In fact, we also failed to find a significant correlation between sclerostin and iPTH levels in our RT recipients.…”

Section: Discussionmentioning

confidence: 99%

Serum Sclerostin as an Independent Marker of Peripheral Arterial Stiffness in Renal Transplantation Recipients

et al. 2016

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Wnt/β-catenin signaling pathway is thought to be implicated in the development of arterial stiffness and vascular calcification. As a Wnt signaling pathway inhibitor, it is interesting to investigate whether sclerostin or dickkopf-1 (DKK1) level is correlated with arterial stiffness in renal transplant (RT) recipients. Fasting blood samples were obtained for biochemical data, sclerostin, DKK1, and osteoprotegerin (OPG) determinations. In this study, we applied automatic pulse wave analyzer (VaSera VS-1000) to measure brachial-ankle pulse wave velocity and either sides of brachial-ankle pulse wave velocity value, which greater than 14.0 m/s was determined as high arterial stiffness. Among 68 RT recipients, 30 patients (44.1%) were in the high arterial stiffness group. Compared with patients in the low arterial stiffness group, patients in the high arterial stiffness group had higher prevalence of hypertension (P = 0.002), diabetes (P < 0.001), metabolic syndrome (P = 0.025), longer posttransplant duration (P = 0.005), higher systolic blood pressure (P < 0.001) and diastolic blood pressure (P = 0.018), and higher fasting glucose (P = 0.004), total cholesterol (P = 0.042), blood urea nitrogen (P = 0.020), phosphorus (P = 0.042), and sclerostin levels (P = 0.001). According to our multivariable forward stepwise linear regression analysis, age (β = 0.272, P = 0.014), phosphorus (β = 0.308, P = 0.007), and logarithmically-transformed OPG (log-OPG; β = 0.222, P = 0.046) were positively associated with sclerostin levels, and multivariate logistic regression analysis, sclerostin (odds ratio 1.052, 95% confidence interval 1.007–1.099, P = 0.024), and posttransplant duration (odds ratio 1.024, 95% confidence interval 1.004–1.045, P = 0.019) were the independent predictors of peripheral arterial stiffness in RT recipients. In this study, serum sclerostin level, but not DKK1, was proved to be involved in the pathogenetic process of peripheral arterial stiffness in RT recipients.

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“…Yamada et al . noted that the serum sclerostin level was significantly associated with the iPTH level in PD patients [34]. Our study noted that the serum sclerostin level was not associated with the serum log-iPTH level ( r = 0.017, P = 0.883) and the serum iPTH level was not associated with aortic AIx values in PD patients.…”

Section: Discussionmentioning

confidence: 41%

The serum sclerostin level is positively associated with the aortic augmentation index in patients on peritoneal dialysis

et al. 2019

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Objective: Sclerostin is a canonical Wingless (Wnt)/β-catenin signaling pathway inhibitor and had been associated with high arterial stiffness in patients with chronic kidney disease. The aortic augmentation index (AIx), a noninvasive method of assessing central hemodynamics/wave reflections, has been widely used as a clinical index of arterial stiffness. The aim of this study was to evaluate the relationship between fasting serum sclerostin levels and AIx values in peritoneal dialysis (PD) patients. Materials and Methods: Fasting blood samples were obtained from 75 PD patients. The aortic AIx value was measured using a validated tonometry system (SphygmoCor, AtCor Medical, Sydney, New South Wales, Australia). Serum sclerostin and dickkopf-1 (DKK1) levels were quantified using commercial enzyme-linked immunosorbent assay kits. Results: Women PD patients had higher aortic AIx values than men ( P = 0.039), while lower aortic AIx values were found in PD patients who used statins ( P = 0.004). Univariate linear analysis of the aortic AIx values in PD patients showed that systolic blood pressure ( P = 0.001), diastolic blood pressure ( P = 0.018), and serum sclerostin levels ( P = 0.001) were positively correlated, while height ( P = 0.018), body weight ( P = 0.001), body mass index ( P = 0.043), and weekly total creatinine clearance ( P = 0.015) were negatively correlated with aortic AIx values in PD patients. Multivariate linear regression analysis of the factors significantly associated with the aortic AIx values showed that serum sclerostin levels (adjusted R 2 = 0.057, P = 0.011) and systolic blood pressure (adjusted R 2 = 0.125, P = 0.004) were positively associated, while body weight (adjusted R 2 = 0.113, P = 0.002) was inversely associated with aortic AIx values in PD patients. Conclusion: In this study, the serum sclerostin level, but not DKK1, was positively associated with aortic AIx values in PD patients.

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Factors associated with serum soluble inhibitors of Wnt‐β‐catenin signaling (sclerostin and dickkopf‐1) in patients undergoing peritoneal dialysis

Abstract: Serum sclerostin was associated with serum intact parathyroid hormone, while Dkk-1 was associated with serum fibroblast growth factor 23 in patients undergoing PD. The utility of determining soluble Wnt-β-catenin inhibitors levels in patients undergoing PD requires further investigation.

Cited by 11 publications

References 34 publications

Serum sclerostin levels are positively related to bone mineral density in peritoneal dialysis patients: a cross-sectional study

Serum sclerostin levels are positively related to bone mineral density in peritoneal dialysis patients: a cross-sectional study

Serum Sclerostin as an Independent Marker of Peripheral Arterial Stiffness in Renal Transplantation Recipients

The serum sclerostin level is positively associated with the aortic augmentation index in patients on peritoneal dialysis

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