Sjöberg B, Qureshi A R, Heimbürger O, Stenvinkel P, Lind L, Larsson A, Bárány P, Ärnlöv J
Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Division of Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
J Intern Med. 2016 Feb;279(2):173-9. doi: 10.1111/joim.12411. Epub 2015 Sep 9.
Higher levels of the novel inflammatory marker pentraxin 3 (PTX3) predict cardiovascular mortality in patients with chronic kidney disease (CKD). Yet, whether PTX3 predicts worsening of kidney function has been less well studied. We therefore investigated the associations between PTX3 levels, kidney disease measures and CKD incidence.
Cross-sectional associations between serum PTX3 levels, urinary albumin/creatinine ratio (ACR) and cystatin C-estimated glomerular filtration rate (GFR) were assessed in two independent community-based cohorts of elderly subjects: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, n = 768, 51% women, mean age 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 651, mean age 77 years). The longitudinal association between PTX3 level at baseline and incident CKD (GFR <60 mL(-1) min(-1) 1.73 m(-2) was also analysed (number of events/number at risk: PIVUS 229/746, ULSAM 206/315).
PTX3 levels were inversely associated with GFR [PIVUS: B-coefficient per 1 SD increase -0.16, 95% confidence interval (CI) -0.23 to -0.10, P < 0.001; ULSAM: B-coefficient per 1 SD increase -0.09, 95% CI -0.16 to -0.01, P < 0.05], but not ACR, after adjusting for age, gender, C-reactive protein and prevalent cardiovascular disease in cross-sectional analyses. In longitudinal analyses, PTX3 levels predicted incident CKD after 5 years in both cohorts [PIVUS: multivariable odds ratio (OR) 1.21, 95% CI 1.01-1.45, P < 0.05; ULSAM: multivariable OR 1.37, 95% CI 1.07-1.77, P < 0.05].
Higher PTX3 levels are associated with lower GFR and independently predict incident CKD in elderly men and women. Our data confirm and extend previous evidence suggesting that inflammatory processes are activated in the early stages of CKD and drive impairment of kidney function. Circulating PTX3 appears to be a promising biomarker of kidney disease.
新型炎症标志物五聚体3(PTX3)水平升高可预测慢性肾脏病(CKD)患者的心血管死亡率。然而,PTX3是否能预测肾功能恶化的研究较少。因此,我们研究了PTX3水平、肾病指标与CKD发病率之间的关联。
在两个基于社区的老年受试者独立队列中评估血清PTX3水平、尿白蛋白/肌酐比值(ACR)和胱抑素C估算的肾小球滤过率(GFR)之间的横断面关联:乌普萨拉老年人血管前瞻性研究(PIVUS,n = 768,51%为女性,平均年龄75岁)和乌普萨拉成年男性纵向研究(ULSAM,n = 651,平均年龄77岁)。还分析了基线时PTX3水平与新发CKD(GFR<60 mL(-1) min(-1) 1.73 m(-2))之间的纵向关联(事件数/风险数:PIVUS为229/746,ULSAM为206/315)。
在横断面分析中,调整年龄、性别、C反应蛋白和心血管疾病患病率后,PTX3水平与GFR呈负相关[PIVUS:每增加1个标准差的B系数为-0.16,95%置信区间(CI)为-0.23至-0.10,P<0.001;ULSAM:每增加1个标准差的B系数为-0.09,95%CI为-0.16至-0.01,P<0.05],但与ACR无关。在纵向分析中,两个队列中PTX3水平均能预测5年后的新发CKD[PIVUS:多变量比值比(OR)为1.21,95%CI为1.01-1.45,P<0.05;ULSAM:多变量OR为1.37,95%CI为1.07-1.77,P<0.05]。
较高的PTX3水平与较低的GFR相关,并能独立预测老年男性和女性的新发CKD。我们的数据证实并扩展了先前的证据,表明炎症过程在CKD早期被激活并导致肾功能损害。循环中的PTX3似乎是一种有前景的肾病生物标志物。