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Review
. 2021 Nov 10;11(11):770.
doi: 10.3390/metabo11110770.

Cardiovascular Safety of Anti-Sclerostin Therapy in Chronic Kidney Disease

Daniel Cejka  1
Affiliations
Review

Cardiovascular Safety of Anti-Sclerostin Therapy in Chronic Kidney Disease

Daniel Cejka. Metabolites. .

Abstract

The significance of sclerostin for bone and cardiovascular health in patients with chronic kidney disease (CKD) is complex and incompletely understood. Experimental evidence suggests that anti-sclerostin therapy shows diminished efficacy on bone in the setting of CKD. Limited clinical evidence suggests that the osteoanabolic and anti-resorptive activity is attenuated, but hypocalcemia is more prevalent in patients with advanced CKD (eGFR < 30 mL/min) treated with anti-sclerostin (romosozumab) therapy as compared to patients without kidney disease. Furthermore, sclerostin is prominently expressed in uremic arteries. Whether the inhibition of sclerostin has adverse effects on cardiovascular health in CKD is currently unknown. This review summarizes the current understanding of the physiology and pathophysiology of sclerostin in CKD, with a focus on the cardiovascular safety of anti-sclerostin therapy in patients with or without CKD.

Keywords: cardiovascular safety; chronic kidney disease (CKD); chronic kidney disease–mineral and bone disorder (CKD–MBD); romosozumab; sclerostin.

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Conflict of interest statement

Regarding anti-sclerostin therapy, the author wishes to disclose potential conflicts of interest: consultancy for UCB, educational grants from UCB and a research grant from Amgen.

Figures

Figure 1
Figure 1
Time to first cardiovascular event in ARCH (romosozumab vs. alendronate), according to study arm. Note the absence of cardiovascular events in the first three months in the alendronate arm (source: FDA website [83], free for reproduction).
Figure 2
Figure 2
Peak percentual change in bone turnover markers from baseline after a single injection of romosozumab 210 mg, according to renal function. Adapted from [88]. Healthy—healthy controls; CKD 4—chronic kidney disease stage 4; CKD 5D—chronic kidney disease stage 5D (dialysis); P1NP—procollagen type 1 N-terminal propeptide; BSAP—bone-specific alkaline phosphatase; CTX—carboxy-terminal collagen crosslinks; TRAP5b—tartrate-resistant acid phosphatase 5b.
Figure 3
Figure 3
Mean values of (A) albumin-corrected calcium (Ca alb.corr.) and (B) intact parathyroid hormone (iPTH, log-scale) after a single injection of romosozumab 210 mg according to renal function. Adapted from [87]. Healthy—healthy controls; CKD 4—chronic kidney disease stage 4; CKD 5D—chronic kidney disease stage 5D (dialysis).
See this image and copyright information in PMC

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