Plasma Pentraxin 3 in Patients with Chronic Kidney Disease: Associations with Renal Function, Protein-Energy Wasting, Cardiovascular Disease, and Mortality Mengli Tong,* † Juan Jesu ´ s Carrero,* ‡ A. Rashid Qureshi,* ‡ Bjo ¨ rn Anderstam, ‡ Olof Heimbu ¨ rger, ‡ Peter Ba ´ra ´ny, ‡ Jonas Axelsson,* ‡ Anders Alvestrand, ‡ Peter Stenvinkel, ‡ Bengt Lindholm,* ‡ and Mohamed E. Suliman* ‡ Divisions of *Baxter Novum and ‡ Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; and † Division of Renal Medicine, HangZhou Hospital of Traditional Chinese Medicine, HangZhou, China Background and Objectives: Plasma protein pentraxin 3 concentrations are elevated in a wide range of diseased states. However, no study has evaluated protein pentraxin 3 in patients with chronic kidney disease. Design, Setting, Participants, & Measurements: Plasma protein pentraxin 3 concentrations were analyzed in relation to GFR, inflammation, cardiovascular disease, and protein-energy wasting in 71 patients with stages 3 to 4 chronic kidney disease, 276 patients with stage 5 chronic kidney disease, and 61 control subjects. Survival (5 yr) in patients with stage 5 chronic kidney disease was analyzed in relation to protein pentraxin 3 levels. Results: Both patient groups with chronic kidney disease had higher protein pentraxin 3 concentrations than control subjects, with the highest concentration in patients with stage 5 chronic kidney disease. In all patients with chronic kidney disease, protein pentraxin 3 correlated negatively with GFR and positively with inflammatory markers. Patients with protein-energy wasting, inflammation, and cardiovascular disease had higher concentrations of protein pentraxin 3 than their counterparts. Patients with high protein pentraxin 3 levels had higher all-cause and cardiovascular mortality. After adjustment for age, gender, C-reactive protein, and cardiovascular disease, all-cause mortality was still significantly higher in patients with high protein pentraxin 3. Finally, protein pentraxin 3 showed a predictive value of mortality similar to that of IL-6 and better than C-reactive protein. Conclusion: Plasma protein pentraxin 3 increases as GFR declines and is associated with the presence of cardiovascular disease and protein-energy wasting. Furthermore, in patients with chronic kidney disease, elevated protein pentraxin 3 predicted all-cause mortality. Clin J Am Soc Nephrol 2: 889-897, 2007. doi: 10.2215/CJN.00870207 A constellation of protein-energy wasting (PEW), chronic low-grade inflammation, and cardiovascular disease (CVD) are present in a large proportion of patients with advanced chronic kidney disease (CKD) (1), and each of these risk factors independently predicts outcome in these patients (2– 4). The causes of inflammation in patients with CKD are probably multifactorial (5,6). To date, C-reactive protein (CRP) is the most common biomarker to assess the inflammatory status. However, it is not know yet whether CRP is only a marker of inflammation (7) or a direct mediator of vascular disease (8). Pentraxins are a superfamily of evolutionarily conserved pro- teins characterized by a cyclic multimeric structure (9). On the basis of the primary structure of the subunit, the pentraxins are divided into two groups: Short pentraxins (e.g., CRP, serum amyloid P) and long pentraxins. The prototype protein of the long pentraxin group is pentraxin 3 (PTX3). Whereas CRP and serum amyloid P are produced primarily in the liver in re- sponse to IL-6 (10), PTX3 is produced by a variety of tissues and cells and in particular by innate immunity cells in response to proinflammatory signals and endothelial cells (11–13). Because of this extrahepatic synthesis and in contrast to CRP, PTX3 levels are believed to be a true independent indicator of disease activity produced at sites of inflammation (14). Previous studies in nonrenal patients aimed at assessing the usefulness of PTX3 in diverse human pathologic conditions with an inflammatory component, such as angina pectoris, myocardial infarction, rheumatoid arthritis, and psoriasis (15– 20). In these studies, it was hypothesized that PTX3, unlike CRP, may represent a rapid marker for primary local activation of innate immunity and inflammation and an indicator of dis- ease activity. Indeed, in some clinical studies, correlation be- tween levels of PTX3 and CRP was weak and even nonsignif- Received February 21, 2007. Accepted June 25, 2007. Published online ahead of print. Publication date available at www.cjasn.org. Address correspondence to: Dr. Mohamed E. Suliman, Divisions of Renal Med- icine and Baxter Novum, K56, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. Phone: +46-8-58583982; Fax: +46-8-58583925; E-mail: mohamed.suliman@ki.se Copyright © 2007 by the American Society of Nephrology ISSN: 1555-9041/205–0889