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Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease.
Kidney Int. 2010 Nov; 78(10):975-80.KI

Abstract

Circulating levels of fibroblast growth factor 23 (FGF23) are elevated in patients with early chronic kidney disease (CKD) and are postulated to cause low blood levels of 1,25-dihydroxyvitamin D, as well as normal phosphate levels. In order to provide more direct evidence for the pathophysiological role of FGF23 in the settings of mineral ion homeostasis typically seen in early CKD, we studied rats with progressive CKD treated with anti-FGF23 neutralizing antibody. Without antibody treatment, rats with CKD exhibited high circulating levels of FGF23 and parathyroid hormone, low 1,25-dihydroxyvitamin D, and normal serum phosphate levels, accompanied by increased fractional excretion of phosphate. Antibody treatment, however, lessened fractional excretion of phosphate, thus increasing serum phosphate levels, and normalized serum 1,25-dihydroxyvitamin D by increased 1α-OHase and decreased 24-OHase expressions in the kidney. These antibody-induced changes were followed by increased serum calcium levels, leading to decreased serum parathyroid hormone. Hence, our study shows that FGF23 normalizes serum phosphate and decreases 1,25-dihydroxyvitamin D levels in early-stage CKD, and suggests a pathological sequence of events for the development of secondary hyperparathyroidism triggered by increased FGF23, followed by a reduction of 1,25-dihydroxyvitamin D and calcium levels, thereby increasing parathyroid hormone secretion.

Authors+Show Affiliations

Innovative Drug Research Laboratories, Kyowa Hakko Kirin, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20844473

Citation

Hasegawa, Hisashi, et al. "Direct Evidence for a Causative Role of FGF23 in the Abnormal Renal Phosphate Handling and Vitamin D Metabolism in Rats With Early-stage Chronic Kidney Disease." Kidney International, vol. 78, no. 10, 2010, pp. 975-80.
Hasegawa H, Nagano N, Urakawa I, et al. Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease. Kidney Int. 2010;78(10):975-80.
Hasegawa, H., Nagano, N., Urakawa, I., Yamazaki, Y., Iijima, K., Fujita, T., Yamashita, T., Fukumoto, S., & Shimada, T. (2010). Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease. Kidney International, 78(10), 975-80. https://doi.org/10.1038/ki.2010.313
Hasegawa H, et al. Direct Evidence for a Causative Role of FGF23 in the Abnormal Renal Phosphate Handling and Vitamin D Metabolism in Rats With Early-stage Chronic Kidney Disease. Kidney Int. 2010;78(10):975-80. PubMed PMID: 20844473.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease. AU - Hasegawa,Hisashi, AU - Nagano,Nobuo, AU - Urakawa,Itaru, AU - Yamazaki,Yuji, AU - Iijima,Kousuke, AU - Fujita,Toshiro, AU - Yamashita,Takeyoshi, AU - Fukumoto,Seiji, AU - Shimada,Takashi, Y1 - 2010/09/15/ PY - 2010/9/17/entrez PY - 2010/9/17/pubmed PY - 2011/4/9/medline SP - 975 EP - 80 JF - Kidney international JO - Kidney Int VL - 78 IS - 10 N2 - Circulating levels of fibroblast growth factor 23 (FGF23) are elevated in patients with early chronic kidney disease (CKD) and are postulated to cause low blood levels of 1,25-dihydroxyvitamin D, as well as normal phosphate levels. In order to provide more direct evidence for the pathophysiological role of FGF23 in the settings of mineral ion homeostasis typically seen in early CKD, we studied rats with progressive CKD treated with anti-FGF23 neutralizing antibody. Without antibody treatment, rats with CKD exhibited high circulating levels of FGF23 and parathyroid hormone, low 1,25-dihydroxyvitamin D, and normal serum phosphate levels, accompanied by increased fractional excretion of phosphate. Antibody treatment, however, lessened fractional excretion of phosphate, thus increasing serum phosphate levels, and normalized serum 1,25-dihydroxyvitamin D by increased 1α-OHase and decreased 24-OHase expressions in the kidney. These antibody-induced changes were followed by increased serum calcium levels, leading to decreased serum parathyroid hormone. Hence, our study shows that FGF23 normalizes serum phosphate and decreases 1,25-dihydroxyvitamin D levels in early-stage CKD, and suggests a pathological sequence of events for the development of secondary hyperparathyroidism triggered by increased FGF23, followed by a reduction of 1,25-dihydroxyvitamin D and calcium levels, thereby increasing parathyroid hormone secretion. SN - 1523-1755 UR - https://www.unboundmedicine.com/medline/citation/20844473/Direct_evidence_for_a_causative_role_of_FGF23_in_the_abnormal_renal_phosphate_handling_and_vitamin_D_metabolism_in_rats_with_early_stage_chronic_kidney_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(15)54425-6 DB - PRIME DP - Unbound Medicine ER -