title: Vitamin D resistance in chronic kidney disease (CKD).
abstract: 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 m2) (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.
authors.forename: Amay
authors.initials: A
authors.lastname: Parikh
authors.forename: Herbert S
authors.initials: HS
authors.lastname: Chase
authors.forename: Linda
authors.initials: L
authors.lastname: Vernocchi
authors.affiliation: Nephrology, Columbia University, New York, NY, USA. ls38@columbia.edu.
authors.forename: Leonard
authors.initials: L
authors.lastname: Stern
mesh_terms: D000368:Aged; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood* / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome; D014807:Vitamin D / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D014808:Vitamin D Deficiency / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D014815:Vitamins; D014807:Vitamin D