Vitamin D resistance in chronic kidney disease (CKD)

BACKGROUND: Previous studies have shown that treatment with ergocalciferol in patients with CKD stage 3 + 4 is not effective with less than 33% of patients achieving a 25-OH vitamin D target of >30 ng/ml. The aim of this study was to test the response to cholecalciferol in CKD. We attempted to replete 25-OH vitamin D to a target level of 40–60 ng/ml using the response to treatment and PTH suppression as an outcome measure. METHODS: This retrospective cohort study identified patients (Stages 2–5 and Transplant) from 2001–2010 who registered at the Chronic Kidney Disease Clinic. Patients received cholecalciferol 10,000 IU capsules weekly as initial therapy. When levels above 40 ng/ml were not achieved, doses were titrated up to a maximum of 50,000 IU weekly. Active vitamin D analogs were also used in some Stage 4–5 CKD patients per practice guidelines. Patients reaching at least one level of 40 ng/mL were designated RESPONDER, and if no level above 40 ng/mL they were designated NON-RESPONDER. Patients were followed for at least 6 months and up to 5 years. RESULTS: 352 patients were included with a mean follow up of 2.4 years. Of the CKD patients, the initial 25-OH vitamin D in the NON-RESPONDER group was lower than the RESPONDER group (18 vs. 23 ng/ml) (p = 0.03). Among all patients, the initial eGFR in the RESPONDER group was significantly higher than the NON-RESPONDER group (36 vs. 30 ml/min/1.73 m(2)) (p < 0.001). Over time, the eGFR of the RESPONDER group stabilized or increased (p < 0.001). Over time, the eGFR in the NON-RESPONDER group decreased toward a trajectory of ESRD. Proteinuria did not impact the response to 25-OH vitamin D replacement therapy. There were no identifiable variables associated with the response or lack of response to cholecalciferol treatment. CONCLUSIONS: CKD patients treated with cholecalciferol experience treatment resistance in raising vitamin D levels to a pre-selected target level. The mechanism of vitamin D resistance remains unknown and is associated with progressive loss of eGFR. Proteinuria modifies but does not account for the vitamin D resistance.