What’s the latest evidence affecting clinical management of mineral and bone disorder in chronic kidney disease? Updated recommendations by the Kidney Disease: Improving Global Outcomes (KDIGO) Global Network are now available.
The 2017 KDIGO Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) guideline update has implications for diagnosis, evaluation, prevention, and treatment of secondary CKD-MBD in children and adults. The full guideline has been published as a supplement to Kidney International; an Executive Summary appears in the July issue of Kidney International.
Updating the previous guideline published in 2009, the revision reflects new research related to management of CKD-MBD. In a key change, it recommends against routine use of calcitriol or vitamin D analogs for treatment of abnormal parathyroid hormone (PTH) levels.
That change reflects a continued lack of data on the optimal PTH level for patients with CKD G3a to G5. Meanwhile, the 2017 Update Working Group believes that modest rises in PTH may be an “appropriate adaptive response” to decreased kidney function.
“Randomized controlled trials have not really shown a benefit and perhaps harm because of hypercalcemia,” said Michael J. Germain, MD, Professor of Medicine, Tufts University School of Medicine and Nephrologist/Partner, Western New England Renal & Transplant Associates, PC, Springfield, Mass. Calcitriol and vitamin D analogs “do a good job in terms of suppressing PTH, but they haven’t shown a benefit in terms of other outcomes, [including] cardiovascular outcomes.”
The update suggests that calcitriol and vitamin D analogs “not be routinely used” in adults with CKD G3a-G5 not on dialysis. Although there was no “uniform consensus” regarding this recommendation, it reflects a lack of data showing benefits of these older drugs on patient-level outcomes.
The revised guideline mentions a potential new alternative for secondary hyperparathyroidism. Extended-release (ER) calcifediol (Rayaldee) was recently approved for use in adults with stage 3 or 4 CKD and serum total 25-hydroxyvitamin D less than 30 ng/mL. Approval was based on trials showing that ER calcifediol reduced intact PTH while increasing 25D. Effects on calcium and phosphorus were similar to placebo.
“This is a medication that can be used in predialysis patients,” said Dr. Germain. “It has the advantage, as opposed to the activated vitamin Ds, of doing a good job in replacing nutritional 25D in the body and normalizing the blood level. By its mechanism of action, it does prevent catabolic pathways from breaking down vitamin D.” The data on ER calcifediol were published after the KDIGO evidence review, and do not include patient-level outcomes.
Extended-release calcifediol is not indicated for dialysis patients. OPKO, manufacturer of Rayaldee, states that it “plans to start a Phase 2 trial in dialysis in partnership with Vifor by the end of the year.”
Dr. Germain notes that calcimimetics are “a reasonably good treatment” for the more severe hyperparathyroidism seen in dialysis patients. He points out that the intravenous calcimimetic etelcalcetide (Parsabiv) was approved for use in dialysis patients earlier this year.
An updated recommendation states that it’s “reasonable” to reserve calcitriol and vitamin D analogs for patients with CKD G4-G5 with severe progressive hyperparathyroidism. In children, these drugs “may be considered” to maintain serum calcium in the normal range for age.
KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2017; 7:1–59.
Ketteler M, et al.: Executive summary of the 2017 KDIGO Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters. Kidney Int. 2017; 92:26–36.
Sprague SM, et al.: Use of extended-release calcifediol to treat secondary hyperparathyroidism in stages 3 and 4 chronic kidney disease. Am J Nephrol. 2016; 44:316–325.