R R EVIEW EVIEW 3 www.sin-italy.org/jnonline – www.jnephrol.com Management of secondary hyperparathyroidism in uremic patients: the role of the new vitamin D analogs JNEPHROL 2007; 20: 3-9 Diego Brancaccio 1 , Mario Cozzolino 1 , Andrea Galassi 1 , Giusy Chiarelli 1 , Alessandra Butti 1 , Antonio Bellasi 1 , Lisa Rocca-Rey 1 , Angela Volpi 1 , Adriana Anelli 1 , Ulisse Zoni 1 , Maria Fusaro 1 , Claudia Brambilla 1 , Elena Missaglia 1 , Cesar Crovetto 1 , Micol Russo 2 , Carlo Longhini 2 , Rossana Provenzano 3 , Francesca Incalcaterra 3 , Giovanni Cerasola 4 , Maurizio Li Vecchi 3 , Maurizio Gallieni 1 1 Chair of Nephrology, University of Milan, Ospedale San Paolo, Milan - Italy 2 Chair of Cardiology, University of Ferrara, Ospedale Giudecca di Ferrara, Ferrara - Italy 3 Chair of Nephrology, University of Palermo, Ospedale Policlinico, Palermo - Italy 4 Department of Internal Medicine, Cardiovascular and Renal Diseases, University of Palermo, Ospedale Policlinico, Palermo - Italy ABSTRACT: Secondary hyperparathyroidism - a common comorbid condition in patients with chronic renal insuffi- ciency - is considered a consequence of critical determinants such as hypocalcemia, phosphate retention and reduced levels of calcitriol production. In this complex mechanism, the skeletal apparatus and the nonskeletal targets such as vascular and heart valves are often involved, thus explaining the increased risk of cardiovascular morbidity and mor- tality of uremic patients. In this review we will focus on the major role played by Calcitriol deficiency as a trigger of secondary hyperparathy- roidism and the crucial need for obiquitous vitamin D receptor activation in order to have an optimal PTH control and to obtain a modulation between inhibitors and inducers of soft tissue calcification. This review will also elucidate the possible role of paricalcitol - a new vitamin D analog - in conditioning morbidity and mortality of patients on renal re- placement therapy (RRT). Key words: Chronic renal failure, Secondary hyperparathyroidism, Calcitriol, Paricalcitol, Vitamin D analogs large cohort of hemodialysis patients that PTH levels >495 pg/mL are associated with a significantly in- creased relative risk of sudden death from cardiovas- cular disease (relative risk [RR] = 1.06; p<0.05), compared with a reference group with lower PTH lev- els (197-495 pg/mL). The possible role of PTH in con- ditioning the cardiovascular outcomes of patients on regular dialysis has also been evaluated in a more re- cent European study performed prospectively for 6 years. It has been shown that serum PTH levels higher than 471 pg/mL were associated with a greater risk of cardiovascular death than lower levels of the hormone (RR=3.9) (5). However PTH can not be considered the only meta- bolic actor involved in the cardiovascular death of ure- mic patients. It has been shown that patients with a serum phosphorus level greater than 6.5 mg/dL have a 41% greater risk of death compared with patients with serum levels of 2.4-6.5 mg/dL (4). Similar data INTRODUCTION Secondary hyperparathyroidism (SH) is a common co- morbid condition in patients with chronic renal insuf- ficiency, characterized by increased serum parathyroid hormone (PTH) levels, parathyroid hyperplasia and di- valent ion imbalance (1, 2). SH is considered a conse- quence of critical determinants such as hypocalcemia, phosphate retention and reduced levels of calcitriol production. In this complex mechanism, other factors are also involved in conditioning PTH synthesis and se- cretion, such as aluminum burden, diabetic status, es- trogens and catecholamines (3). In this condition, PTH is responsible for a variety of long-term clinical consequences involving primarily the skeletal appara- tus. In addition, nonskeletal targets such as vascular and heart valves are often involved, thus explaining the increased risk of cardiovascular morbidity and mortal- ity of uremic patients. Ganesh et al (4) showed in a