Nowak Kristen L, Hung Adriana, Ikizler Talat Alp, Farmer-Bailey Heather, Salas-Cruz Natjalie, Sarkar Sudipa, Hoofnagle Andrew, You Zhiying, Chonchol Michel
Clin Nephrol. 2017 Sep;88(9):132-143. doi: 10.5414/CN109122.
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.
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.
Participants were 65 ± 10 years of age, 23% female, and had a mean estimated glomerular filtration rate of 38 ± 13 mL/min/1.73m. 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. .
流行病学研究表明慢性全身炎症与慢性肾脏病-矿物质和骨异常（CKD-MBD）之间存在联系。此外，肾功能下降与身体和认知功能恶化有关，这可能由全身炎症、CKD-MBD或两者共同解释。我们假设用白细胞介素-1（IL-1）受体拮抗剂抑制炎症会改善中重度CKD患者的CKD-MBD标志物以及身体/认知功能。
在一项双中心、双盲试验中，39例3-4期CKD患者完成了一项随机试验，接受IL-1受体拮抗剂rilonacept（160mg/周）或安慰剂治疗12周。在干预前后检测血清中以下CKD-MBD标志物：钙、磷、25-羟维生素D、1,25-二羟维生素D、24,25-二羟维生素D、完整甲状旁腺激素（iPTH）和成纤维细胞生长因子23（FGF23）。还对一个亚组（n=23）进行了一系列测试，以评估身体功能（耐力、运动、灵活性、平衡、力量和疲劳）和认知功能的多个领域。
参与者年龄为65±10岁，23%为女性，平均估计肾小球滤过率为38±13mL/min/1.73m²。抑制IL-1后，血清钙、磷、任何维生素D代谢物、iPTH或FGF23水平均无变化（p≥0.28）。同样，rilonacept也未改变运动、灵活性、平衡、力量、疲劳或认知功能（p≥0.13）。然而，rilonacept组（-31秒）的耐力（400米步行时间）相较于安慰剂组（-2秒；p=0.07）有改善趋势。
总之，抑制IL-1 12周并未改善CKD-MBD标志物或身体功能。
