Sclerostin Quo Vadis? - Is This a Useful Long-Term Mortality Parameter in Prevalent Hemodialysis Patients?

Background/Aims: Potential relationships between serum sclerostin levels and the levels of bone metabolic markers in maintenance hemodialysis (MHD) patients have yet to be evaluated. This study sought to determine whether serum sclerostin levels are associated with mortality in MHD patients. Methods: We measured serum sclerostin levels in a Japanese MHD cohort, classified the patients into tertiles according to these levels, and followed their course for a 42-month period. Results: The cohort consisted of 389 MHD patients and there were 75 deaths. Kaplan-Meier analyses showed that the tertile of serum sclerostin was not associated with mortality risk. Cox analyses showed that there were no significant associations between serum sclerostin level and mortality. Conclusion: Serum sclerostin level was not an independent predictor of mortality in MHD patients after adjustment for several confounders. However, whether clinical interventions to modulate serum sclerostin levels in MHD patients would improve their survival remains to be determined.

Section: Discussionmentioning

confidence: 99%

A Prospective Cohort Study Showing No Association Between Serum Sclerostin Level and Mortality in Maintenance Hemodialysis Patients

Sato

Hanafusa

Kawaguchi

et al. 2018

“…Secondary hyperparathyreodism is often seen in patients with end-stage kidney disease [24][25][26][27][28]. However, there are meanwhile well established therapeutic options to cope with this condition such as reducing phosphate reupsorption by phosphate binders, vitamin D treatment, treatment with calimimetitics such as cinacalcet and finally removal (partially or total) of the parathyroid gland [29].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Characteristics of Subcutaneously Applied PTH-1-37

Forssmann¹,

Tillmann²,

Hock³

et al. 2016

Background/Aims: Parathyroid hormone (PTH) derivatives exert pronounced renal and osteoanabolic properties when given intermittently. The current study was performed to assess the pharmacokinetic and pharmacodynamic properties as well as safety of subcutaneously applied PTH-1-37 after repeated dosing in healthy subjects. Methods: This randomized, double-blind, dose-escalating, placebo and active comparator controlled study was conducted in 33 healthy postmenopausal women. Subjects were allocated to one of five treatment options: 10, 20, or 40 µg PTH-1-37, 20 µg PTH-1-34 or placebo, administered as once daily subcutaneous doses for three days. Plasma drug concentrations and serum levels of endogenous PTH-1-84, and calcium as markers of biological activity were monitored during the treatment. Results: PTH was absorbed rapidly from the subcutaneous tissue with a median t_max of 30 minutes for 20 and 40 µg of PTH-1-37. t_max was 45 minutes for 20 µg PTH-1-34. Elimination half-lives were estimated as 76 ± 34 min and 70 ± 13 min for 20 µg and 40 µg PTH-1-37 (mean ± SD), and 78 ± 34 for 20 µg PTH-1-34. Both PTH fragments (PTH-1-37 and PTH-1-34) increased serum calcium. For PTH-1-37 the effect on serum calcium was dose-dependent. Suppression of endogenous PTH-1-84 was seen after the application of both PTH-1-37 and PTH-1-34. During the study period, the subjects experienced no unexpected or serious adverse events. Conclusions: PTH-1-37 is rapidly absorbed after s.c. injection, has a short plasma elimination half-life, and does not accumulate during multiple dosing. Biological activity was demonstrated by rising serum calcium and decreasing endogenous PTH-1-84 in blood plasma. The study drugs were well tolerated and safe. Our investigation presents data that PTH-1-37 is an excellent drug candidate for intervening with syndromes of dysregulation of calcium metabolism.

“…Similarly, reports from pre-dialysis CKD studies showed that higher serum ALP levels are associated with increased all-cause mortality [3][4][5]. In dialysis patients, elevated serum ALP levels are also associated with increased mortality, independent of liver and bone metabolism parameters in both, hemodialysis (HD) and peritoneal dialysis patients [6][7][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Serum Alkaline Phosphatase Levels are Not Associated with Increased Death Risk in Prevalent Hemodialysis Patients: 5-Year Experience in a Single Hemodialysis Center

Zhu

Cheng

Lee

et al. 2016

Background/Aims: Although high serum alkaline phosphatase (ALP) levels were reported as predictive factors for death risk in dialysis patients on the basis of large databank analyses, the real scenario in a single hemodialysis (HD) center is unknown. Methods: In this study, a 5-year cohort of 1126 prevalent HD patients in the largest HD center in Taiwan was studied. The associations of ALP levels expressed as baseline, time-average, and time-dependent with all-cause mortality and cardiovascular mortality were evaluated by using adjusted Cox regression models. Results: At baseline, levels of serum parathyroid hormone, calcium, and liver enzymes are increased in parallel with ALP quartiles. The hazard ratio (HR) for all-cause mortality was significantly increased in time-average and time-dependent ALP quartile in the unadjusted Cox analysis. The significance disappeared when multivariate adjusted Cox analysis was used. Similarly, HR was not significantly increased for cardiovascular mortality with ALP quartile expressed as baseline, time-average, and time-dependent in three models of Cox analyses. Conclusion: Our study demonstrated that serum ALP levels were not associated with increased death risk in prevalent HD patients over a 5-year interval.