**2. Inflammation (C-reactive protein) in patients with chronic kidney disease: prevalence and prognostic factor**

CRP is considered the prototypical acute-phase reactant in man. Plasma CRP is produced by hepatocytes although other sites of local CRP synthesis have been suggested.

The plasma half-life of CRP is about 19 hours and is constant under all conditions of health and disease, so that the sole determinant of circulating CRP concentration is the synthesis rate, which thus directly reflects the intensity of the pathological process stimulating CRP production. In most disease, the circulating value of CRP reflects ongoing inflammation and/or tissue damage much more accurately than other laboratory parameters of the acutephase response. The CRP concentration is thus a very useful nonspecific biochemical marker of inflammation, measurement of which contributes importantly to screening for organic disease, monitoring of the response to treatment of inflammation and infection and detection of intercurrent infection (Pepys et al., 2003).

Biomarkers in Chronic Kidney Disease -

al., 2007; Schouten et al. 2000).

hospitalization rate (table 1).

\*Median (interquartile range).

Group I

*n* = 23

(CRP>6 mg/dL)

CRP (mg/L)\* 21.6 (12.9 - 32.6) 2 (2 - 4.6) 0.00001 Albumin (g/dL) 3.5 ± 0.4 3.8 ± 0.4 0.017 Hemoglobin (g/dL) 11.6 ± 1.1 12.2 ± 0.8 0.045 Epo (IU/kg/week) 67 ± 32 43 ± 20 0.025 Hemoglobin/Epo 0.19 ± 0.08 0.32 ± 0.13 0.004 Hospitalization (n) 0.52 ± 0.8 0.03 ± 0.19 0.004 Table 1. Comparison of the evolution of analytical and clinical data between patients with high (Group I) or low (Group II) CRP levels at baseline. Mean ± standard deviation.

In summary, at this point we know that inflammation is high prevalent among patients with CKD, that the prevalence is higher among patients with associated CVD, that inflammation tends to increase with the decline of renal function but that only about one third of patients with advance renal function shows persistently high levels of inflammatory

Group II

*n* = 43

(CRP<6 mg/dL)

*P* value

**5. Possible causes of inflammation** 

The Linkage Between Inflammation, Ventricular Dysfunction and Overhydration 267

However, a similar prevalence of inflammation has been described in patients with advanced renal failure not yet on dialysis (Ortega et al., 2002; Panichi et al., 2002; Stenvinkel et al., 1999). An inverse correlation between CRP levels and clearance of creatinine has been observed (Panichi et al., 2002); thus, CRP levels increase as renal function declines. This finding suggests the possibility of a decreased renal clearance of CRP as a cause of an activated acute-phase response in patients with chronic kidney disease. Another possibility could be that uremia by itself could be the cause of inflammation among these patients. However, in another study performed in pre-dialysis patients with a more homogeneous clearance of creatinine (Ortega et al., 2002), a non-normal distribution of CRP levels were detected. That means that only a group of patients with advanced renal failure shows high levels of CRP, whereas other patients with the same degree of renal insufficiency have even normal CRP values. Hence, it seems that uremia by itself is not the unique cause of inflammation. Probably, inflammation could be related to some factors, frequently associated with renal failure, which can worsen with the worsening of renal function. In this study (Ortega et al., 2002), CRP levels were higher in those patients with a previous history of CVD. Comparing with patients with normal CRP levels at baseline, patients with higher levels maintained significant higher levels on follow-up. This group of inflamed patients showed during the study period persistently lower serum albumin, lower blood hemoglobin, needed higher doses of erythropoietin stimulating agents and showed higher

The causes of inflammation in patients with CKD patients remained unclear over time. Several studies have attempted to address the question as to whether some factors related to the dialysis technique by itself could induce the inflammatory response. Activation of monocytes with the subsequent enhanced release of inflammatory cytokines can be caused by membrane-induced complement activation, by direct cell-membrane interaction and by dialysis fluids containing endotoxins (Carracedo et al., 2006; Honkanen et al., 1991; Kerr et

Elevated CRP levels have been described in a significant proportion of end-stage-renaldisease patients on hemodialysis or peritoneal dialysis (Arici et al., 2001). About one-third of patients with chronic renal failure have serum CRP concentration > 10 mg/l (Owen et al., 1998). In healthy men, high CRP level has been identified as a risk factor for cardiovascular disease (Ridker et al., 2001). As occurs in the general population, prospective studies point to a correlation between CRP plasma levels and overall and cardio-vascular mortality also in end-stage-renal disease patients (Arici et al., 2001; Ikizler et al., 1999; Noh et al., 1998; Owen et al., 1998; Panichi et al., 2008; Wang et al., 2009; Yeun et al. 2000; Zimmermann et al., 1999).
