Renal Clearance of Mineral Metabolism Biomarkers.
Journal: 2016/June - Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Abstract:
CKD leads to disturbances in multiple interrelated hormones that regulate bone and mineral metabolism. The renal handling of mineral metabolism hormones in humans is incompletely understood. We determined the single-pass renal clearance of parathyroid hormone, fibroblast growth factor 23, vitamin D metabolites, and phosphate from paired blood samples collected from the abdominal aorta and renal vein in 17 participants undergoing simultaneous right and left heart catheterization and estimated associations of eGFR with the renal elimination of metabolites. The mean age ±SD of the study population was 71.4±10.0 years and 11 participants (65%) were male. We found a relatively large mean±SD single-pass renal extraction of parathyroid hormone (44.2%±10.3%) that exceeded the extraction of creatinine (22.1%±7.9%). The proportionate renal extraction of parathyroid hormone correlated with eGFR. The renal extraction of fibroblast growth factor 23 was, on average, lower than that of parathyroid hormone with greater variability across individuals (17.1%±19.5%). There were no differences in the mean concentrations of vitamin D metabolites across the renal vein and artery. In summary, we demonstrate substantial single-pass renal extraction of parathyroid hormone at a rate that exceeds glomerular filtration. Impaired renal clearance of parathyroid hormone may contribute to secondary hyperparathyroidism in CKD.
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J Am Soc Nephrol 27(2): 392-397
PMID: 26047790

Renal Clearance of Mineral Metabolism Biomarkers

University of Washington, Kidney Research Institute, Seattle, Washington;
Nephrology Division and
Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts; and
Cardiology Division, Massachusetts General Hospital and
Harvard Clinical Research Institute, Boston, Massachusetts
Corresponding author.
Correspondence: Dr. A.J. van Ballegooijen, Kidney Research Institute, Box 35906, Seattle, Washington. Email: ude.wu@2bvh
Received 2014 Dec 22; Accepted 2015 Mar 30.
Copyright © 2016 by the American Society of Nephrology

Abstract

CKD leads to disturbances in multiple interrelated hormones that regulate bone and mineral metabolism. The renal handling of mineral metabolism hormones in humans is incompletely understood. We determined the single-pass renal clearance of parathyroid hormone, fibroblast growth factor 23, vitamin D metabolites, and phosphate from paired blood samples collected from the abdominal aorta and renal vein in 17 participants undergoing simultaneous right and left heart catheterization and estimated associations of eGFR with the renal elimination of metabolites. The mean age ±SD of the study population was 71.4±10.0 years and 11 participants (65%) were male. We found a relatively large mean±SD single-pass renal extraction of parathyroid hormone (44.2%±10.3%) that exceeded the extraction of creatinine (22.1%±7.9%). The proportionate renal extraction of parathyroid hormone correlated with eGFR. The renal extraction of fibroblast growth factor 23 was, on average, lower than that of parathyroid hormone with greater variability across individuals (17.1%±19.5%). There were no differences in the mean concentrations of vitamin D metabolites across the renal vein and artery. In summary, we demonstrate substantial single-pass renal extraction of parathyroid hormone at a rate that exceeds glomerular filtration. Impaired renal clearance of parathyroid hormone may contribute to secondary hyperparathyroidism in CKD.

Keywords: renal clearance, extraction, mineral metabolism biomarkers
Abstract

CKD leads to disturbances in multiple interrelated hormones that regulate bone and mineral metabolism.1 Serum concentrations of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) rise early during the course of CKD in parallel with a decline in 1,25-dihydroxyvitamin D (1,25[OH]2D) and 24,25-dihydroxyvitamin D (24,25[OH]2D).2,3 Known causes of these hormonal changes include alterations in circulating calcium and phosphate concentrations and inadequate production of 1,25(OH)2D and klotho by the failing kidneys.

The renal handling of mineral metabolism hormones in humans is incompletely understood. Older studies using early PTH antibodies suggested renal clearance of PTH via peritubular uptake and, to a lesser extent, glomerular filtration. Some experimental studies also indicate that impaired degradation of PTH contributes to the high circulating levels of PTH in CKD.4–6 FGF23 is produced in bone and cleaved in the circulation; however, little is known about the renal clearance of FGF23. It is possible that reduced renal clearance of mineral metabolism hormones contributes to their accumulation in CKD.

To understand how the human kidney modulates circulating biomarkers of mineral metabolism, we determined the single-pass renal clearance of PTH, FGF23, vitamin D metabolites, and phosphate from paired blood samples collected from the abdominal aorta and renal vein among patients undergoing left and right heart catheterization.

Values are mean±SD or frequency and percentage.

ACE, angiotensin converting enzyme inhibitors; ARB, angiotensin receptor blockers; eGFR, estimated glomerular filtration rate based on CKD-EPI 2009 (creatinine).

Acknowledgments

This research was supported by the Niels Stensen Fellowship 2014, the Extramural Grant Program by Satellite Healthcare, and NIH grants K08-{"type":"entrez-nucleotide","attrs":{"text":"DK090142","term_id":"187636266","term_text":"DK090142"}}DK090142 and R01-DK099199.

Acknowledgments

Footnotes

Published online ahead of print. Publication date available at www.jasn.org.

Footnotes

References

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