Lanthanum carbonate--new data on parathyroid hormone control without liver damage

Recent investigations have provided conclusive evidence that abnormalities in mineral and bone metabolism are associated with increased cardiovascular (CV) morbidity and mortality in chronic kidney disease (CKD) patients [1,2]. In fact, elevated serum phosphate (P) levels play an important role in the pathogenesis of secondary hyperparathyroidism (SHPT) [3]. Recent studies have shown the molecular mechanisms by which P may regulate parathyroid (PT) function. Within 2 weeks after 5/6 nephrectomy (Nx) in rats, uraemia-induced mitotic activity is further enhanced by high dietary P, but prevented by P-restriction [4,5]. In contrast to the mitogenic effects of hyperphosphataemia, low dietary P appears to counteract the proliferative signals induced by uraemia, thus preventing PT cell replication and consequently, the increase in PT gland size [6,7]. Moreover, the regulation of PTH mRNA by P has been found to occur post-transcriptionally through binding of PT cytosolic proteins to the 30-untranslated region (UTR) and in particular to the terminal 60 nucleotides of PTH-mRNA [8]. Hyperphosphataemia not only induces SHPT, but also plays a major role in the pathogenesis of vascular calcification (VC) in the uraemic population [9]. In fact, recent in vitro studies have shown how vascular smooth muscle cells calcify when incubated in a medium containing elevated concentrations of inorganic P [10]. Together with classical passive precipitation of calcium phosphate in soft tissues, inorganic P may cause extra-skeletal calcification directly through a real ‘ossification’ of the tunica media in the vasculature of uraemic patients [11]. Therefore, P-control represents the major challenge for any clinical nephrologist. The classic treatment of hyperphosphataemia in CKD patients consists of either calcium(Ca) or aluminium (Al)-based P-binders. Unfortunately, this ‘first generation’ class of therapy is not free of complications. New free-Ca and -Al P-binders, such as sevelamer hydrochloride and lanthanum carbonate, may be used to treat hyperphosphataemia and prevent both SHPT and VC in CKD.