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Interleukin-1 inhibition, chronic kidney disease-mineral and bone disorder, and physical function?.


ABSTRACT:

Objective

Epidemiologic studies have suggested a link between chronic systemic inflammation and chronic kidney disease-mineral and bone disorder (CKD-MBD). Additionally, declining renal function is associated with worsening physical and cognitive function, which may potentially be explained by systemic inflammation, CKD-MBD, or both. We hypothesized that inhibiting inflammation with an interleukin-1 (IL-1) trap would improve markers of CKD-MBD as well as physical/cognitive function in patients with moderate-to-severe CKD.

Methods

In a two-site, double-blind trial, 39 patients with stage 3 - 4 CKD completed a randomized trial receiving either the IL-1 trap rilonacept (160 mg/week) or placebo for 12 weeks. The following CKD-MBD markers were assessed in serum before and after the intervention: calcium, phosphorus, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, intact parathyroid hormone (iPTH), and fibroblast growth factor 23 (FGF23). A battery of tests was also administered in a subgroup (n = 23) to assess multiple domains of physical function (endurance, locomotion, dexterity, balance, strength, and fatigue) and cognitive function.

Results

Participants were 65 ± 10 years of age, 23% female, and had a mean estimated glomerular filtration rate of 38 ± 13 mL/min/1.73m2. There were no changes in serum calcium, phosphorus, any vitamin D metabolite, iPTH, or FGF23 levels (p ? 0.28) with IL-1 inhibition. Similarly, rilonacept did not alter locomotion, dexterity, balance, strength, fatigue, or cognitive function (p ? 0.13). However, endurance (400-m walk time) tended to improve in the rilonacept (-31 s) vs. placebo group (-2 s; p = 0.07).

Conclusions

In conclusion, 12 weeks of IL-1 inhibition did not improve markers of CKD-MBD or physical function.?.

SUBMITTER: Nowak KL 

PROVIDER: S-EPMC6595399 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Interleukin-1 inhibition, chronic kidney disease-mineral and bone disorder, and physical function
.

Nowak Kristen L KL   Hung Adriana A   Ikizler Talat Alp TA   Farmer-Bailey Heather H   Salas-Cruz Natjalie N   Sarkar Sudipa S   Hoofnagle Andrew A   You Zhiying Z   Chonchol Michel M  

Clinical nephrology 20170901 9


<h4>Objective</h4>Epidemiologic studies have suggested a link between chronic systemic inflammation and chronic kidney disease-mineral and bone disorder (CKD-MBD). Additionally, declining renal function is associated with worsening physical and cognitive function, which may potentially be explained by systemic inflammation, CKD-MBD, or both. We hypothesized that inhibiting inflammation with an interleukin-1 (IL-1) trap would improve markers of CKD-MBD as well as physical/cognitive function in pa  ...[more]

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