Oral Calcitriol May Reduce Mortality in Chronic Kidney Disease CME

Oral Calcitriol May Reduce Mortality in Chronic Kidney Disease CME

News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd

Release Date: May 13, 2008;

To participate in this internet activity: (1) review the target audience, learning objectives, and author disclosures; (2) study the education content; (3) take the post-test and/or complete the evaluation; (4) view/print certificate View details.

Learning Objectives

Upon completion of this activity, participants will be able to:

1. Describe the association of calcitriol use with mortality and long-term dialysis among patients with stage III or IV chronic kidney disease.
2. Describe the association of calcitriol use with hypercalcemia among patients with stage III or IV chronic kidney disease.

Authors and Disclosures

Laurie Barclay, MD
Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

Désirée Lie, MD, MSEd
Disclosure: Désirée Lie, MD, MSEd, has disclosed no relevant financial relationships.

Brande Nicole Martin
Disclosure: Brande Nicole Martin has disclosed no relevant financial information.

May 13, 2008 — In patients with chronic kidney disease (CKD) and hyperparathyroidism who have not received dialysis, intake of oral calcitriol (oral activated vitamin D) reduced mortality rates by 26%, according to the results of a study published online in the May 7 issue of Journal of the American Society of Nephrology.

"Parenteral vitamin D is associated with improved survival among long-term hemodialysis patients," write Abigail B. Shoben, from the Puget Sound Veterans' Affairs (VA) Medical Center, University of Washington in Seattle, and colleagues. "Among nondialyzed patients with chronic kidney disease (CKD), oral activated vitamin D reduces parathyroid hormone [PTH] levels, but the impact on clinical outcomes is unknown."

Using the VA Consumer Health Information and Performance Sets database, the investigators examined associations of oral calcitriol use with mortality and dialysis dependence in 1418 nondialysis patients with CKD and hyperparathyroidism. Selection criteria were stages III to IV CKD, hyperparathyroidism, and the absence of hypercalcemia before calcitriol use. Incident calcitriol users and nonusers were matched by age and estimated kidney function.

During a median follow-up of 1.9 years, 408 patients (29%) died, and 217 (16%) began long-term dialysis. Oral calcitriol use was associated with a 26% lower risk for death (95% confidence interval [CI], 5% - 42% lower; P = .016) and a 20% lower risk for death or dialysis (95% CI, 1% -35% lower; P = .038), after adjustment for demographic factors, comorbid conditions, estimated kidney function, medications, and baseline levels of PTH, calcium, and phosphorous.

The association of calcitriol with reduced mortality was not statistically different across PTH levels at baseline. Risk for hypercalcemia was greater with calcitriol use.

"Oral calcitriol use is associated with lower mortality in nondialysis patients with CKD," the study authors write.

Limitations of this study include potential for confounding by indication; relative paucity of clinical serum PTH measurements; lack of generalizability to younger, more diverse CKD populations; and lack of data on forms of vitamin D other than calcitriol.

"These data are among the first to show oral calcitriol use in relation to clinical outcomes in patients with CKD and add to a growing body of observational data linking vitamin D use with improved survival," the study authors conclude. "Randomized trials represent the next appropriate step for evaluating the health consequences of vitamin D."

The National Institutes of Health supported this study. One of the authors has disclosed various financial relationships with Abbott, Shire, and Amgen.

J Am Soc Nephrol. Published online May 7, 2008.

Clinical Context

According to Shoben and colleagues, CKD affects more than 10% of the US population with disturbances in vitamin D and mineral metabolism. In clinical trials of predialysis patients, the use of oral calcitriol lowered PTH levels with potential for improving outcomes, and in observational studies of long-term dialysis patients, intravenous vitamin D has been shown to improve survival.

This trial is an observational matched cohort study of data on patients in the VA system from 1 hospital to examine the effect of oral calcitriol on patients with stage III or IV CKD and hyperparathyroidism.
Study Highlights

* Included were 1418 nondialysis patients in the VA health information database with a first oral calcitriol prescription between 1999 and 2007, 2 outpatient estimated glomerular filtration rate (eGFR) measurements between 15 and 60 mL/minute per 1.73 m3 at least 3 months apart, and hyperparathyroidism defined as a serum PTH level higher than 70 µg/mL within 1 year before first calcitriol use.
* Incident calcitriol users were matched with control patients who had the same inclusion criteria by age, eGFR, CKD, and hyperparathyroidism.
* Computerized pharmacy records were examined to identify the date, dosage, and number of pills prescribed, and adherence was calculated as the number of days with an active calcitriol prescription, divided by number of follow-up days.
* Starting dosage was 0.25 µg/day in 55% of the patients, with the remainder taking a lower dose, most commonly 0.25 µg, 3 days a week.
* Primary outcomes were mortality and combined mortality and long-term dialysis.
* Secondary outcomes were hypercalcemia, defined as uncorrected total serum calcium of more than 10.2 mg/dL, and changes in calcium, phosphate, and PTH levels.
* There were 429 calcitriol users and 989 matched nonusers.
* Mean age was 69 years, 100% were men, 85% were white, 11% were black, two thirds had diabetes, one quarter had peripheral vascular disease, and mean body mass index was 31 kg/m2.
* Median eGFR was 29 mL/minute per 1.73 m3, and 48% had stage III and 52% stage IV CKD.
* Calcitriol users had higher serum PTH levels, slightly lower eGFR, more nephrology clinic visits, and slightly more comorbid conditions.
* Median follow-up was 1.9 years, and 3% to 4% of participants were lost to follow-up.
* Median calcitriol adherence was estimated at 85%.
* There were 109 deaths among calcitriol users and 299 among nonusers for an unadjusted mortality rate of 12.8 and 18.3 per 100 person-years, respectively.
* 75 users vs 142 nonusers initiated dialysis during follow-up for event rates of 10.4 and 10.1 for users vs nonusers, respectively.
* Cumulative incidence of mortality plus dialysis dependence remained higher in calcitriol users vs nonusers after adjusting for confounding variables such as baseline eGFR and PTH level.
* After adjustment for demographics, renal function, and other variables, calcitriol use was associated with 26% lower risk for death (P = .016) and 20% lower risk for death or long-term dialysis (P = .038).
* Each 25-pg/mL increase in PTH levels was associated with a statistically significant 3% greater mortality risk, but adjustment for PTH level did not significantly alter the strength of the association between calcitriol use and mortality (adjusted hazard ratio, 0.82).
* Associations for mortality were similar for the 2 dosages at 0.68 and 0.78 but were slightly lower among those with lower baseline PTH levels.
* Hypercalcemia was observed among 15% of calcitriol users and 11% of nonusers.
* In intent-to-treat analysis, the hazard for hypercalcemia was 4% greater for calcitriol users, but in as-treated analysis, the hazard was 52% greater for calcitriol users.
* The authors concluded that calcitriol use in patients with CKD with hyperparathyroidism was associated with reduced mortality and long-term dialysis risk, independent of other comorbidities, serum PTH, and baseline kidney function.

Pearls for Practice

* Use of calcitriol in patients with stage III or IV CKD with hyperparathyroidism is associated with reduced risk for mortality and long-term dialysis.
* Use of calcitriol in patients with stage III or IV CKD with hyperparathyroidism is associated with increased risk for hypercalcemia.

http://www.medscape.com/viewarticle/574361