Plasma C-Reactive Protein in Hemodialysis Patients: A Cross-Sectional, Longitudinal Clinical Survey¹

Abstract

In hemodialysis patients, C-reactive protein (CRP), an acute-phase reactant, is a sensitive and independent marker of malnutrition, anemia, and amyloidosis. The aim of the present studies was to evaluate CRP and interleukin 6 levels in plasma samples from long-term hemodialysis patients on different extracorporeal modalities associated with or without backfiltration. Two hundred and forty-seven patients were recruited in eight hospital-based centers. All patients had been on their dialytic modality for at least 6 months. At enrollment, 46 hemodialysis patients out of 247 (18.6%) had clinical evidence of pathologies known to be associated with high CRP values. The 201 remaining patients were defined as clinically stable and were on conventional hemodialysis (34%), hemodiafiltration with infusion volumes <10 liters/session (10%), hemodiafiltration with infusion volumes <20 liters/session (32%), and double-chamber hemodiafiltration with infusion volumes <10 liters/session (22%). Analysis of CRP values in the clinically stable patients showed that an unexpectedly high proportion (47%) of the patients had CRP values higher than 5 mg/l (taken as the upper limit in normal human subjects). The values of CRP and interleukin 6 were significantly higher in hemodiafiltration with infusion volumes <10 liters/session than in hemodiafiltration with infusion volumes >20 liters/session, in hemodialysis and in double-chamber hemodiafiltration. The same pattern occurred after 6 months of follow-up in 171 out of 201 clinically stable patients. Hemodialytic conditions that expose to the risk of backfiltration such as low exchange volume hemodiafiltration may induce a chronic inflammatory state as reflected by increased plasma values of both CRP and interleukin 6, thus suggesting the need for hemodialytic strategies that reduce (hemodialysis with low-permeability membranes or hemodiafiltration with infusion volumes >20 liters) or eliminate (double-chamber hemodiafiltration) backfiltration of bacteria-derived contaminants.

An Overview of Haemodialysis and Oxidant Stress

“…Furthermore, CRP plasma values have been shown to be increased in patients on haemodialysis but not on peritoneal dialysis [97][98][99][100], suggesting the role of monocyte activation and IL-6 production in the increased CRP generation due backfiltered dialysate contaminants [97]. In a recent study, we provided evidence that CRP values are increased in an unexpectedly high percentage (47%) in otherwise clinically stable consecutive patients over the upper limit for normal human subjects (5 mg/litres) [101]. By analysing these patients according to their different haemodialytic modalities, we could observe a striking significant difference between low (!10 litres/session) vs. high (120 litres/session) volume haemodiafiltration.…”

Inflammatory Syndrome in Patients on Hemodialysis

“…This depends not only on the amount of pyrogenic substances but also on its quality, and although this transfer occurs mainly by backfiltration (76), low molecular weight substances also may enter by backdiffusion. Endotoxins can cross any type of HD membrane; however, it has been reported that this occurs more easily with highly permeable membranes, in which backfiltration is more common.…”

C-Reactive Protein as a Marker of Chronic Inflammation in Uremic Patients

“…To verify these findings in a larger population we have measured CRP and IL-6 plasma levels in 303 chronic, clinically stable dialytic patients [36]. Patients were treated for 6 months with conventional dialysis, hemodiafiltration with low exchange volume, high exchange volume and paired filtration dialysis.…”