Vitamin D prohormone in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease

Abstract

Secondary hyperparathyroidism (sHPT) represents the adaptive and very often, finally, maladaptive response of the organism to control the disturbed homeostasis of calcium, phosphorus, and vitamin D metabolism caused by declining renal function in chronic kidney disease (CKD). sHPT leads to cardiovascular and extravascular calcifications and is directly linked to an increased risk of cardiovascular morbidity and mortality as well as excess all-cause mortality. Vitamin D plays an important role in the development of sHPT. CKD patients are characterized by a high prevalence of hypovitaminosis D. Supplementation with both vitamin D prohormones cholecalciferol and ergocalciferol enables the achievement and maintenance of a normal vitamin D status when given in adequate doses over an appropriate treatment period. In patients with earlier stages of CKD, sHPT is influenced by and can be successfully treated with vitamin D prohormone supplementation, whereas in patients with very late stages of CKD and those requiring dialysis, treatment with prohormones seems to be of limited efficacy. This review gives an overview of the pathogenesis of sHPT, summarizes vitamin D metabolism, and discusses the existing literature regarding the role of vitamin D prohormone in the treatment of sHPT in patients with CKD. Keywords: cholecalciferol, CKD, CKD-MBD, dialysis, ergocalciferol, SHPT. Pathogenesis of secondary hyperparathyroidism (sHPT) in chronic kidney disease (CKD)sHPT represents the adaptive and very often, finally, maladaptive response of the organism to control the disturbed homeostasis of calcium, phosphorus, and vitamin D metabolism caused by declining renal function in CKD. These disturbances in mineral metabolism lead to vascular 1,2 and valvular 3 calcifications and are directly linked to an increased risk of cardiovascular morbidity and mortality as well as excess all-cause mortality. 4 Apart from extra-skeletal side effects, sHPT also leads to profound alterations in bone metabolism, which become obvious in the different forms of renal osteodystrophy.5 This clinical syndrome encompassing mineral, bone, and cardiovascular abnormalities has been termed "CKD-related mineral and bone disorder" (CKD-MBD).6 sHPT generally develops in CKD stage 3 with an estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m 2 , and its prevalence increases as kidney function declines. 7,8 Initially, it is characterized by normocalcemia with intermittent transient hypocalcemia, fasting normo-or hypophosphatemia, and reduced 1,25(OH) 2 D 3 (calcitriol) concentration, together with increasing levels of fibroblast growth factor 23 (FGF23), a decrease in plasma soluble Klotho, and the development of renal osteodystrophy. [8][9][10][11] These alterations result in increased secretion

Mineral bone disorders in chronic kidney disease

“…FGF23 also inhibits the production of 1,25(OH)2D and therefore decreases intestinal Pi absorption, further decreasing serum Pi levels . The decreased 1,25(OH)2D induces hypocalcaemia and then stimulated PTH production persists, which ensues secondary hyperparathyroidism (SHPT) . As GFR continues to fall, however, these compensatory mechanisms fail, leading to hyperphosphatemia, hyperparathyroidism, and higher serum FGF‐23 concentration.…”

“…8 The decreased 1,25(OH)2D induces hypocalcaemia and then stimulated PTH production persists, which ensues secondary hyperparathyroidism (SHPT). 9 As GFR continues to fall, however, these compensatory mechanisms fail, leading to hyperphosphatemia, hyperparathyroidism, and higher serum FGF-23 concentration. The SHPT and uremic toxin accumulation accelerate bone turnover by activating osteoclastogenesis and increased the release of calcium and phosphate from bone.…”

Role of Etelcalcetide in the Management of Secondary Hyperparathyroidism in Hemodialysis Patients: A Review on Current Data and Place in Therapy

“…20 Activation of the VDR lowers PTH transcription, whereas decreased calcitriol stimulates PTH synthesis. 21 Elevated phosphorus reduces the activity of tubular 1α-hydroxylase and lowers the synthesis of calcitriol. 22 Also, it stimulates PTH production independently of changes in calcium and calcitriol concentration 23 and directly increases parathyroid-cell proliferation, 24 due to downregulation of parathyroid CaSR and VDR.…”

Pathogenetic role of vitamin D deficiency in the development of menstrual dysfunction in pubertal girls: a literature review

“…Some authors stressed upon the necessity of iodine medications intake of at least 100 mg per day for children in iodine-deficient regions, as well as vitamin and mineral supplements with micronutrients [19]. To prevent reproductive disorders, vitamin D has to be administered immediately, as soon as its deficiency is established [20].…”