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Renal elimination of sclerostin increases with declining kidney function
Daniel Cejka1, Rodrig Marculescu, Nicolas Kozakowski
1Department of Medicine III (D.C., M.P., T.R., M.H.), Division of Nephrology and Dialysis, Department of Laboratory Medicine (R.M.), Clinical Institute of Pathology (N.K.), and Department of Medicine III (A.G.), Division of Endocrinology and Metabolism, Medical University Vienna (D.C., R.M., N.K., M.P., T.R., A.G., M.H.), 1090 Vienna, Austria.
The Journal of Clinical Endocrinology and Metabolism
|November 5, 2013
Summary
Kidney disease (CKD) increases sclerostin levels, but the kidneys actually excrete more sclerostin as kidney function declines. This finding is crucial for understanding CKD-related bone disease treatments.
Area of Science:
- Nephrology
- Endocrinology
- Bone Metabolism
Background:
- Sclerostin serum levels are elevated in patients with chronic kidney disease (CKD).
- Osteoporosis and CKD frequently coexist.
- Anti-sclerostin antibodies are under development for osteoporosis treatment.
Purpose of the Study:
- To investigate the renal handling and excretion of sclerostin in patients with varying stages of CKD.
Main Methods:
- Cross-sectional study involving 120 CKD patients (stages 1-5).
- Measured serum and urine sclerostin, estimated glomerular filtration rate (eGFR), and other biomarkers.
- Utilized ELISA for sclerostin quantification and immunohistochemistry on kidney biopsies.
Main Results:
- Urinary sclerostin excretion and fractional excretion significantly increased with declining eGFR.
- Fractional excretion of sclerostin correlated positively with fractional excretion of α1-microglobulin.
- Sclerostin was localized to proximal tubular cells in kidney biopsies.
Conclusions:
- Elevated serum sclerostin in CKD is not due to reduced renal elimination; rather, renal excretion increases as kidney function decreases.
- The implications for anti-sclerostin antibody therapy in CKD patients require further investigation.
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