Inflammation is a complex biologic response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation provides a protective reaction of the organism to the injurious stimuli. The acute-phase response is a major pathophysiologic phenomenon that accompanies inflammation. Acute-phase proteins are defined as those proteins whose plasma concentrations increase (positive acute-phase proteins), such as C reactive protein (CRP), or decrease (negative acute-phase proteins), such as albumin, during inflammatory states. Measurement of the levels of these proteins is frequently utilized to define the presence and/or degree of inflammation in a given patient. CRP is the most widely used marker of inflammation because of its reliability, low cost, and availability.1 Despite its name, the “acute”-phase response can persist over months to years and become chronic. In such states of chronic inflammation, positive acute-phase proteins including CRP may be slightly but persistently increased.

Acute and chronic inflammatory processes are common in individuals with chronic kidney disease (CKD) and especially end-stage kidney disease (ESKD). Many factors contribute to inflammation in those patients, including the uremic milieu, elevated levels of circulating proinflammatory cytokines, oxidative stress, carbonyl stress, protein-energy wasting (PEW), enhanced incidence of infections (especially dialysis access related).2, 3, 4, 5, 6, 7, 8 Some factors can further enhance the inflammatory process in patients undergoing hemodialysis (HD): exposure to dialysis tubing and dialysis membranes,9,10 poor quality of dialysis water and back-filtration or back-diffusion of contaminants, presence of foreign bodies,11, 12, 13 clotted arteriovenous graft. Factors that can contribute to inflammation in peritoneal dialysis (PD) patients are: overt or latent peritonitis or peritoneal dialysis catheter-related infections, constant exposure to peritoneal dialysis solution, loss of residual kidney function and fluid overload.7,14, 15, 16, 17

In many CKD patients, especially in maintenance dialysis patients, serum CRP levels are persistently between 5 and 50 mg/l, although they may fluctuate widely.18 Chronically increased CRP was shown to be associated with an increased risk of atherosclerotic cardiovascular disease (CVD).18 Increased serum CRP levels in ESKD patients are as strong a predictor of cardiovascular mortality as serum albumin concentration.2,3,19 Among patients with CKD, the presence of a chronic inflammatory state may also be closely related to accelerated atherogenesis, protein-energy wasting (PEW), and anemia.20, 21, 22 In addition to atherosclerosis, inflammation may cause other adverse outcomes in kidney disease such as refractory anemia, laboratory signs of iron overload, or a poor quality of life.23,24 Apart from predicting CVD and mortality in dialysis patients, inflammation has other effects on this patient population. It is known that hypoalbuminemia, which can be attributed to malnutrition, predicts death in dialysis patients. Emerging evidence suggests that inflammation as represented by increased CRP and cytokines levels, can predict albumin concentration in dialysis patients, thus making the acute phase reaction largely responsible for the effect of hypoalbuminemia on mortality in hemodialysis.2 It seems that the inflammatory process may contribute to PEW and death associated with hypoalbuminemia in dialysis patients.

Elevated plasma concentration of CRP is a risk factor for CVD in the general population and in hemodialysis patients, and it seems that this is also true for PD.25,26 One study showed that every 1 mg/l increase in high- sensitivity CRP was independently predictive of higher all-cause mortality and cardiovascular mortality in peritoneal dialysis patients.27 It was demonstrated that HS-CRP predicted 2-year mortality and technique survival in PD patients independent of age, diabetes, hypoalbuminemia, and the occurrence of cardiovascular events.28 Another study suggests that serum CRP at enrollment is an independent predictor of 2-year patient survival in continuous ambulatory peritoneal dialysis (CAPD) patients.7 In addition, CRP was found to be a significant risk factor for the loss of residual renal function.17

While the long-term consequences of chronic CRP elevation in dialysis patients were clearly demonstrated, no information reported regarding the prognostic significance of acute increase in CRP among asymptomatic dialysis patients. The purpose of this study was to characterize such increases and determine whether acute CRP elevation found in regular patient follow-up visits could be associated with future short-term adverse events such an infection and needs further investigation.