Yet Another Vitamin D Analogue for the Management of Secondary Hyperparathyroidism: A Triton among the Minnows?

Given the distorted 1α-hydroxylase system in CKD patients, administration of precursors of vitamin D such as cholecalciferol (D3) or ergocalciferol (D2), also known as nutritional vitamin D agents, is often ineffective. Hence, active vitamin D analogues including synthetic calcitriol and alfacalcidol (which increase the circulating levels of 1α,25(OH) 2 D) or vitamin D mimetics including paricalcitol and maxacalcitol (which decrease the circulating level of intrinsic 1α,25(OH) 2 D) have been used to correct SHPT [4] . However, if not managed well, parathyroid glands develop progressive monoclonal and nodular hyperplasia and are rendered less responsive to medical treatment due to reduced expression of VDR and CaSR. In this case, administration of even higher doses of active vitamin D analogs or D-mimetics may be necessary to lower PTH levels. Such aggressive treatment often causes or worsens hypercalcemia and hyperphosphatemia by enhancing intestinal absorption of calcium and phosphorus. Use of calcimimetics may be more effective under such circumstances, but profound hypocalcemia and – in CKD patients with residual kidney function – worsening In patients with advanced chronic kidney disease (CKD) and particularly in those undergoing maintenance dialysis, an elevated blood level of parathyroid hormone (PTH) is common, which is referred to as secondary hyperparathyroidism (SHPT). The expression and release of fibroblast growth factor-23 (FGF23) from osteocytes is increased as a consequence of phosphorus retention in the setting of decreased glomerular filtration rate [1] . Elevated FGF23 inhibits 1α-hydroxylase expression in renal proximal tubular cells. Together with tubular damage, a marked reduction in 1α,25-dihydroxyvitamin D (1α,25(OH) 2 D), the active form of vitamin D, ensues. Given the decline in gastrointestinal (GI) absorption of calcium as a result of inadequate activation of vitamin D receptors (VDR) in the GI tract, progressive hypocalcemia ensues. Suboptimal activation of the VDR in the parathyroid glands lead to higher expression and release of PTH, which is aggravated through signal pathways via calcium-sensing receptors (CaSR) in the parathyroid gland cells and also involves Klotho receptors. These processes can lead to compensatory proliferation of the parathyroid gland cells, leading to less responsive SHPT [2, 3] . A clinically important consequence of untreated SHPT is loss of minerals from the bone, which leads to what is known as renal osteodystrophy. Published online: April 22, 2016 Nephrology American Journal of