**2. Secondary hyperparathyroidism**

Next to vitamin D deficiency, chronic kidney disease is known to be the second most common cause of secondary hyperparathyroidism. The prevalence of secondary hyperparathyroidism in such patients is strongly correlated with the stage of CKD. In other words, plasma PTH concentration is negatively correlated with glomerular filtration rate (GFR) in patients with CKD. Around 80% of patients with GFR of less than 20 mL/min/1.73 m2 has an increased level of PTH [1]. At the early stages of CKD, the major stimulus of the parathyroid glands is the hyperphosphatemia caused by impaired renal excretion of phosphorus in addition to impaired activation of vitamin D. Prolonged exposure to hyperphosphatemia and development of hypocalcemia in concurrence with high levels of fibroblast growth factor (FGF)-23 will lead to overproduction of PTH where hyperplasia of the parathyroid tissue ensues with persistent exposure to these metabolic abnormalities [2]. FGF-23 plays an indirect role in regulating the synthesis and secretion of PTH for being involved in regulating renal excretion of phosphate in addition to renal production of activated vitamin D. Furthermore, increasing studies suggest a direct role of FGF-23 in suppressing PTH synthesis and secretion through a direct action on the parathyroid glands. This inhibitory effect is significantly impaired in patients with CKD [3]. Persistent overstimulation of parathyroid glands is associated with hyperplasia that is categorized into 4 types which are diffuse hyperplasia, diffuse and multinodular hyperplasia, multinodular hyperplasia, and simple nodular hyperplasia [4]. Various clinical consequences are characteristic of secondary hyperparathyroidism including bone and soft tissue, skin and cardiovascular manifestations. Extraosseous calcification is the main pathophysiology of many clinical manifestations as it involves arterial walls, cutaneous tissue, viscera and even cornea and conjunctiva. This calcification is also correlated with the increased mortality rate in patients with CKD as it might involve myocardium and endocardium and the arterial walls of the aorta and coronary arteries leading to significant ventricular dysfunction, heart failure, ischemia, arrhythmia and death [5]. This might explain the increasing emphasis by many authors on serial measurement of plasma PTH in patients with CKD as a part of management.
