Molecular Basis of Parathyroid Hyperplasia

Abstract

EARLY ALL PATIENTS with end-stagerenal disease develop secondary hyper-parathyroidism (SH), a condition characterizedby various degrees of parathyroid hyperplasia andincreased synthesis and secretion of parathyroidhormone (PTH). Hypocalcemia, hyperphos-phatemia caused by phosphate retention, and cal-citriol deficiency are the three main causes of SHin chronic kidney disease.' The elevated circulat-ing levels ofPTH cause bone loss, osteitis fibrosa,skeletal abnormalities known as renal osteodys-trophy, and systemic toxicities, including cardio-vascular, endocrine, nervous, irnrnunologic, andcutaneous dysfunctions that markedly increasemorbidity and mortality rates in patients withkidney disease.fNumerous laboratories have contributed to thecurrent understanding of the mechanisms medi-ating the control of PTH synthesis and secretionby changes in serum calcium, phosphorus, andcalcitriollevels in kidney disease. In contrast, thelack of an appropriate parathyroid cell line andthe rapid dedifferentiation of primary cultures ofhyperplastic parathyroid cells have impeded anearlier characterization of the pathogenic mech-anisms underlying the induction of parathyroidcell proliferation by kidney disease, its worseningby either high phosphorus or low dietary calcium