Secondary hyperparathyroidism: present and future therapeutic implications

Abstract

Secondary Hyperparathyroidism: Present and Future Therapeutic Implications was the first programme in a series of clinically oriented Masterclasses in Nephrology which took place in Vienna, Austria in November 2001. Designed to heighten awareness and understanding within specific areas of nephrology, this masterclass examined issues surrounding the pathogenesis, epidemiology, health consequences and medical management of secondary hyperparathyroidism (HPT) in patients with chronic renal failure (CRF). The pathogenesis of secondary HPT in CRF is associated with disturbances of calcium and phosphate metabolism. The three major factors involved in triggering an increase in parathyroid hormone (PTH) secretion appear to be low plasma calcitriol, hypocalcaemia and hyperphosphataemia. A low calcitriol level prevents the inhibition of preproPTH gene transcription. Hypocalcaemia and hyperphosphataemia result in the stabilization of PTH mRNA, leading to an increase in PTH synthesis. Epidemiological studies investigating the incidence of parathyroidectomy (PTx) among uraemic patients have provided conflicting results. The Lombardy epidemiological study [1] found that the prevalence and incidence of PTx in Lombardy was lower than that previously reported for Europe and Italy, probably because of improvements in the monitoring and management of dialysis patients. However, in more recent years as the Lombardy study has continued, no additional decrease in the incidence of PTx has been observed. One major health consequence of secondary HPT is renal osteodystrophy (ROD). ROD includes bone remodelling disorders, where bone quality is altered, and bone loss disorders, where bone mass is reduced; both abnormalities being potentially associated. Adynamic bone disease is now the most common bone remodelling disorder found in patients with end-stage renal disease [2], while osteoporosis is a significant risk factor for both pre-dialysis and dialysis patients. The dose requirements of recombinant human erythropoietin (rHuEpo) in patients with CRF vary considerably, and many patients do not achieve recommended target haemoglobin levels of )11 gudl. Some evidence suggests that HPT may have an inhibitory effect on erythropoiesis. However, other factors, such as inflammation and iron deficiency, might play a more predominant role in rHuEpo hyporesponsiveness. Control of hyperphosphataemia and maintenance of normocalcaemia form the basis of medical management of secondary HPT. Novel approaches include the use of non-calcium-based phosphate binders, different dialysis modalities, new vitamin D metabolites, second-generation calcimimetics and advances in surgical techniques.