The use of LP533401 as a therapeutic option for renal osteodystrophy affects, renal calcium handling, vitamin D metabolism, and bone health in uremic rats

Expert Opinion on Therapeutic Targets
Dariusz PawlakKrystyna Pawlak

Abstract

Klotho is a key regulator of phosphate and Ca2+-transport in the kidney. Recently, we showed that treatment with LP533401 improved bone health in rats with chronic kidney disease (CKD) via the normalization of serum phosphate resulting from the reduced renal expression of phosphate cotransporters, including Klotho. We evaluated the effect of LP533401 therapy on Klotho-expression-dependent Ca2+-transporters, renal calcium handling, and the potential consequences for the bone of uremic rats. Treatment with LP533401 and its vehicle resulted in the inhibition of transient receptor potential vanilloid receptor subtypes 5 and 6 (TRPV5, TRPV6) and calbindin (CaBP-28k, CaBP-9k) expression. The compensatory acceleration in renal expression of Na+/Ca2+-exchanger, 25-hydroxyvitamin d-1α-hydroxylase (CYP27B1), the intensification of vitamin D metabolism, and disruption of sophisticated balance between 1,25-dihydroxyvitamin D-serotonin was observed, especially in rats treated with LP533401. The imbalance between 1,25-dihydroxyvitamin D-serotonin levels led to intensified bone remodeling and improvement in bone geometry, mineral status, and strength in animals treated with LP533401. The modulation of circulating serotonin and its relation to...Continue Reading

References

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