Chronic kidney disease and diabetes mellitus predict resistance to vitamin D replacement therapy

Abstract

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 D2 (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 D2, 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 D2 or the number of vitamin D2 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. The average number of vitamin D2 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 D2 treatment in logistic regression models. Patients with CKD required greater amounts of vitamin D2 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 D2 therapy. The underlying mechanism needs to be evaluated in prospective studies.

FIGURE 1.

Flow diagram for derivation of study cohort. 25(OH)D, 25-hydroxyvitaminD; eGFR, estimated glomerular filtration rate.

FIGURE 2.

Relationship between serum 25(OH)D and serum creatinine level showing pre- (●) and post (Δ) treatment 25(OH) D level. 25(OH)D, 25-hydroxyvitaminD.

FIGURE 3.

Relationship between actual change in serum 25 (OH)D level and estimated glomerular filtration rate. 25(OH)D, 25-hydroxyvitaminD.

FIGURE 4.

Conditional effect plot showing the relationship between the estimated probability of inadequate response to ergocalciferol treatment (ergocalciferol dose >10) and estimated glomerular filtration rate in diabetic and non-diabetic patients.