Patients with chronic kidney disease (CKD) frequently suffer from vascular calcification that can cause chronic heart failure. Similar to patients with CKD, mice that lack the FGF23 receptor klotho (kl/kl) exhibit hyperphosphatemia, hyperaldosteronism, and extensive vascular and soft tissue calcification. Vascular calcification involves de-differentiation and reprogramming of vascular smooth muscle cells into an osteo- and chrondrogenic phenotype that promotes vascular calcification. Voekl et al. found that treatment with the mineralocorticoid receptor antagonist spironolactone reduced vascular calcification and increased the lifespan of kl/kl mice. Spironolactone also reduced the expression of osteoinductive factors in calcified tissues, suggesting that spironolactone could help treat vascular calcification in CKD patients. The accompanying image shows expression of the osteogenic protein osterix (green) in the renal tissue of wild type mice, kl/kl mice, and kl/kl mice treated with spironolactone.
Klotho is a potent regulator of 1,25-hydroxyvitamin D3 [1,25(OH)2D3] formation and calcium-phosphate metabolism. Klotho-hypomorphic mice (
Jakob Voelkl, Ioana Alesutan, Christina B. Leibrock, Leticia Quintanilla-Martinez, Volker Kuhn, Martina Feger, Sobuj Mia, Mohamed S.E. Ahmed, Kevin P. Rosenblatt, Makoto Kuro-o, Florian Lang