Comparative Effects of Doxercalciferol and Calcitriol on Secondary Hyperparathyroidism in ESRD

Secondary hyperparathyroidism (SHPT), characterized by markedly elevated parathyroid hormone (PTH) levels, arises from the metabolic abnormalities associated with end-stage renal disease (ESRD). It affects the majority of patients undergoing dialysis and contributes to a wide range of complications, including cognitive impairment, bone disease, and cardiovascular morbidity. SHPT develops early during chronic kidney disease (CKD), often beginning in stage G2, when impaired phosphate excretion stimulates increased secretion of PTH. As kidney function declines further, hyperphosphatemia and hypocalcemia become more pronounced, leading to progressive parathyroid gland hyperplasia and excessive hormone production.

Clinically, SHPT is a major component of chronic kidney disease-mineral and bone disorder (CKD-MBD), which is characterized by bone pain, skeletal deformities, spontaneous fractures, soft tissue calcification, and muscle weakness. Persistent elevations in PTH also contribute to vascular calcification, left ventricular hypertrophy, and other cardiovascular complications that significantly increase morbidity and mortality among dialysis patients. Consequently, uncontrolled SHPT adversely affects both quality of life and long-term survival.

Parathyroid hormone plays a central role in calcium and phosphate homeostasis. It maintains serum calcium levels by stimulating bone resorption and enhancing calcium mobilization from the skeleton. Although PTH increases phosphate release from bone, it also promotes phosphate excretion through the kidneys by reducing tubular phosphate reabsorption. In patients with CKD, these regulatory mechanisms become impaired, resulting in chronic elevations of PTH and progressive disturbances in mineral metabolism. Sustained hyperparathyroidism can lead to high-turnover bone disease, renal osteodystrophy, vascular calcification, and increased cardiovascular risk.

Intravenous doxercalciferol and oral calcitriol are commonly used vitamin D receptor activators for the management of SHPT in hemodialysis patients. Calcitriol, the active form of vitamin D, directly binds to vitamin D receptors and effectively suppresses PTH secretion. However, its use is frequently associated with increases in serum calcium and phosphate levels, potentially increasing the risk of vascular calcification. Doxercalciferol, a synthetic vitamin D analog, requires hepatic activation and has been shown to provide effective PTH suppression while producing fewer calcemic effects. These pharmacological differences may influence treatment outcomes and safety profiles in dialysis populations.

Recent evidence suggests that both agents are effective in reducing PTH levels, although intravenous doxercalciferol may offer improved biochemical control and a lower incidence of hypercalcemia. As secondary hyperparathyroidism remains highly prevalent among hemodialysis patients, identifying the most effective and safest therapeutic option is of considerable clinical importance.

In Bangladesh and other low- and middle-income countries, the growing burden of CKD and dependence on maintenance hemodialysis present substantial healthcare challenges. Medication cost, availability, and patient adherence play important roles in treatment selection. Oral calcitriol is widely available and relatively inexpensive, whereas intravenous doxercalciferol may be less accessible in resource-constrained settings. Furthermore, adherence to oral therapy may be affected by pill burden and other practical barriers. Therefore, evidence comparing the efficacy and safety of these treatment options is essential for guiding cost-effective and evidence-based clinical practice.

Despite the widespread use of both agents, high-quality comparative studies in hemodialysis patients from resource-limited settings remain limited. Most available evidence originates from high-income countries, and its applicability to South Asian populations is uncertain. A direct comparison of intravenous doxercalciferol and oral calcitriol with respect to PTH control, biochemical outcomes, safety, and treatment practicality is therefore warranted. This study aims to address this knowledge gap and provide evidence to support optimal management of secondary hyperparathyroidism among hemodialysis patients in resource-constrained environments.