Pathogenesis of renal secondary hyperparathyroidism

The majority of patients with chronic renal disease will develop renal secondary hyperparathyroidism (sHPT). Pronounced sHPT is associated, besides osseous symptoms, with extraosseous complications, namely increased cardiovascular morbidity and mortality. Pathogenesis of renal sHPT is complex. Reduced renal synthesis of the active vitamin D hormone calcitriol results in increased PTH-synthesis and parathyroid proliferation (i.e. an increase in the pool of PTH-secreting cells). Hyperphosphatemia stimulates PTH-synthesis and parathyroid proliferation through direct effects on the parathyroids and through indirect effects. Hypocalcemia and reduced activation of the parathyroid calcium-sensing receptor (CaR) cause decreased calcium-sensitivity of parathyroid glands, enhanced PTH-synthesis and parathyroid proliferation. Nodular parathyroid hyperplasia which occurs more frequently with increasing duration of uremia favors development of autonomous HPT. Nodular hyperplasia is associated with reduced vitamin D receptor and CaR expression and with chromosomal alterations which favor monoclonal growth. Additional factors which are involved in pathogenesis of sHPT comprise skeletal PTH-resistance, deficiency of native vitamin D, metabolic acidosis and possibly increased circulating FGF-23.