Short-term Interleukin Inhibition Ineffective in CKD-MBD

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Serum phosphorus and intact parathyroid hormone levels were not reduced with 12 weeks of rilonacept therapy.
Serum phosphorus and intact parathyroid hormone levels were not reduced with 12 weeks of rilonacept therapy.

Despite an association between systemic inflammation and chronic kidney disease-mineral and bone disorder (CKD-MBD), 12-weeks treatment with direct interleukin-1 (IL-1) inhibition did not improve markers of CKD-MBD or physical function.

As part of a double-blind trial, Kristen L. Nowak, PhD, MPH, of the University of Colorado Denver Anschutz Medical Campus in Aurora, Colorado, and colleagues randomly assigned 39 stage 3-4 CKD patients (mean age 65 years) to the IL-1 decoy receptor rilonacept (160 mg/week after loading dose) or placebo. Over 12 weeks, treated patients experienced no improvements in serum calcium, phosphorus, any vitamin D metabolite, intact parathyroid hormone, or fibroblast growth factor 23, according to findings published online ahead of print in Clinical Nephrology.

More than half of patients subsequently underwent physical and cognitive function testing. Rilonacept recipients performed no better in tests of locomotion, dexterity, balance, strength, fatigue, or cognitive function. Endurance measured by the 400-meter walk test improved by 31 seconds in those receiving the drug versus 2 seconds in the placebo arm, but the difference was not statistically significant.

“Our study is the first randomized controlled trial to evaluate changes in markers of CKD-MBD in response to direct inhibition of interleukin-1,” Dr Nowak, assistant professor in the division of Renal Diseases and Hypertension, told Renal & Urology News. “The results indicate that in contrast with epidemiological evidence to date, which has suggested regulation of mineral metabolism by inflammation, direct inhibition of inflammation via the IL-1 trap rilonacept did not change any markers of mineral metabolism.”

Administering rilonacept earlier in CKD or for a longer period may have yielded different results, according to the investigators.

 

Reference

Nowak KL, Hung A, Alp Ikizler T, et al. Interleukin-1 inhibition, chronic kidney disease-mineral and bone disorder, and physical function. Clin Nephrol. DOI: 10.5414/CN109122. [Epub ahead of print]

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