Treatment Failure of Active Vitamin D Therapy in Chronic Kidney Disease: Predictive Factors

BACKGROUND: In patients with chronic kidney disease (CKD), impaired renal function leads to decreased vitamin D levels, which causes an increase in parathyroid hormone (PTH) production and contributes to the development of secondary hyperparathyroidism (SHPT). This may result in adverse clinical effects such as bone disorders, vascular calcification, cardiovascular disease, and increased mortality. Current treatment practices and associated outcomes with active vitamin D treatment in patients with CKD were reviewed with the objective to assess parameters (such as PTH and serum calcium levels) that may be used to define the failure of vitamin D treatment. SUMMARY: Reports based on observational data have noted improved outcomes with active vitamin D treatment (calcitriol, paricalcitol, alfacalcidol, or doxercalciferol) in patients with CKD. Criteria for the identification of active vitamin D treatment failure are unclear from current guidelines, although up to 50% of patients may experience treatment failure eventually because of development of hypercalcemia or resistant SHPT, characterized by an elevated intact PTH (iPTH) level despite treatment. We propose a definition of vitamin D treatment failure as iPTH >600 pg/ml after 6 months of intravenous active vitamin D treatment and corrected total calcium serum levels >10.2 mg/dl, and review factors that may predict the response to vitamin D treatment. Key Message: Active vitamin D treatment failure is an important challenge in clinical practice. The aim of the proposed definition is to suggest a possible framework for hypothesis generation and to encourage further research into this common problem.