Chronic Kidney Disease and Diabetes Mellitus Predict Resistance to Vitamin D Replacement Therapy

Background: 25-Hydroxyvitamin D [25(OH)D] is a marker of nutritional status; however, chronic kidney disease (CKD) results in alterations in vitamin D metabolism, including the loss of vitamin D-binding proteins and alterations in CYP27B1 and CYP24 enzymes that metabolize 25(OH)D. This study was designed to determine the predictors of responsiveness to correction of vitamin D deficiency with oral vitamin D-2 (ergocalciferol) in adults. Methods: A retrospective study of 183 veterans with 25(OH)D level,30 ng/mL, who were treated with 50,000 IU per week of vitamin D-2, was performed. Logistic regression models were developed to determine the factors predicting the response to treatment, defined as either the change in serum 25(OH)D level/1000 IU of vitamin D-2 or the number of vitamin D-2 doses (50,000 IU per dose) administered. Results: The mean age of the patients was 63 +/- 12 years. About 87% were men and 51% diabetic, and 29% had an estimated glomerular filtration rate of <60 mL/min/1.73 m(2). The average number of vitamin D-2 doses was 10.91 +/- 5.95; the average increase in 25(OH)D level was 18 +/- 10.80 ng/mL. 25(OH)D levels remained,30 ng/mL in 61 patients after treatment. A low estimated glomerular filtration rate and the presence of diabetes mellitus were significant independent predictors for inadequate response to vitamin D-2 treatment in logistic regression models. Patients with CKD required greater amounts of vitamin D-2 to achieve similar increases in 25(OH)D levels, versus non-CKD patients. Conclusions: The presence of CKD and diabetes mellitus is associated with resistance to correction of 25(OH)D deficiency with vitamin D-2 therapy. The underlying mechanism needs to be evaluated in prospective studies.