Ellen Neven defended her PhD thesis in december 2009, entitled: Vascular media calcification in experimental chronic renal failure. Cell biological aspects and phosphate binder treatment.
The main cause of death in patients with chronic kidney disease are cardiovascular complications. Hereby a prominent feature is vascular calcification or the deposition of calcium in the blood vessel wall.
Besides the formation of significant calcifications in atherosclerotic plaques in the intima, in patients with renal failure extensive diffuse calcifications of the tunica media are seen as well. Both types of calcification are causes of increased cardiovascular mortality in this population, while the traditional set of risk factors for vascular calcification do not tell the whole story.
Often, inhibitors of the calcification process, like matrix Gla protein, fetuin-A, pyrophosphate and osteoprotegerin are disturbed. Additional risk factors are high serum phosphate levels due to strongly reduced renal excretion and a high serum calcium-phosphate product .
Serum phosphate, associated with secondary hyperparathyroidism, is treated by phosphate binders, either calcium containing compounds or the new calcium free phosphate binders sevelamer and lanthanum carbonate. Typically, this treatment is combined by 1,25(OH)2 vitamin D3 or calcimimetics, inhibiting the excessive PTH secretion.
Calcium containing phosphate binders give rise to episodes of hypercalcemia, raising the risk of vascular calcification, especially when combined with 1,25(OH)2 vitamin D3.
In this thesis, the effect of the calcium free phosphate binder lanthanum carbonate on the development of vascular calcifications in a uremic rat model of chronic renal failure was studied.