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C reactive protein in patients with chronic renal diseases
V Panichi1, M Migliori, S De Pietro
1Department of Internal Medicine of Pisa, University of Pisa, Italy. v.panichi@int.med.unipi.it
Insights
Chronic inflammation markers, C-reactive protein (CRP) and interleukin-6 (IL-6), increase as kidney function declines in pre-dialysis patients. This suggests inflammation contributes to cardiovascular risks even before dialysis.
Area of Science:
- Nephrology
- Cardiology
- Inflammation Research
Background:
- Elevated baseline C-reactive protein (CRP) predicts myocardial infarction and cardiac death in healthy individuals, implicating chronic inflammation in atherothrombosis.
- Interleukin-6 (IL-6) is a key cytokine driving the acute phase response and CRP production.
- Cardiovascular disease is the leading cause of mortality in chronic renal failure patients, yet CRP and IL-6 levels in pre-dialysis stages are poorly understood.
Purpose of the Study:
- To investigate plasma levels of C-reactive protein (CRP) and interleukin-6 (IL-6) in patients with pre-dialysis chronic renal failure.
- To determine the relationship between CRP and IL-6 levels and the degree of renal function impairment.
- To explore the association of CRP and IL-6 with other markers of inflammation and cardiovascular risk.
Main Methods:
- Plasma CRP measured by laser nephelometry; IL-6 by immunoassay.
- Standard laboratory techniques used for fibrinogen, albumin, cholesterol, triglycerides, hematocrit, white blood cell count, ESR, and urinary protein.
- Study included 102 pre-dialysis patients with a mean creatinine clearance (C(Cr)) of 52 mL/min.
Main Results:
- CRP levels were significantly correlated with declining renal function (CRP vs. C(Cr), r=-0.40, p <0.001).
- IL-6 levels also correlated with renal function (IL-6 vs. C(Cr), r=-0.45, p <0.001).
- Patients with C(Cr) < 20 mL/min had significantly higher CRP levels (7.4 mg/L) compared to those with C(Cr) > 20 mL/min (2.76 mg/L).
Conclusions:
- Both CRP and IL-6 levels are elevated in pre-dialysis renal failure patients and increase as renal function decreases.
- These findings indicate activation of inflammatory mechanisms contributing to cardiovascular morbidity and mortality in early-stage renal failure.
- The study highlights the importance of monitoring inflammation markers in pre-dialysis patients to assess cardiovascular risk.
Abstract:
Base-line serum levels of plasma C-reactive protein (CRP) are predictive of future myocardial infarction and sudden cardiac death in apparently healthy subjects, suggesting the hypothesis that chronic inflammation might be important in the pathogenesis of atherothrombosis. CRP production is mediated by several inflammatory mediators: interleukin 6 (IL-6) is currently felt to be the major cytokine influencing the acute phase response. CRP and other acute phase proteins are elevated in dialysis patients and cardiovascular diseases represent the single largest cause of mortality in chronic renal failure patients. Little information is available, however regarding CRP and IL-6 plasma levels in pre-dialysis renal failure. Plasma CRP was determined by a modification of the laser nephelometry technique; IL-6 by immunoassay (RD System); and fibrinogen, serum albumin, cholesterol, triglycerides, hematocrit, white blood cell count, erythrocytic sedimentation rate (ESR) and urinary protein levels by standard laboratory techniques. Results were obtained in 102 chronic pre-dialysis patients whose mean age was 53+/-5.8 years with a mean creatinine clearance (C(Cr)) of 52+/-37 mL/min). CRP was greater than 5 mg/L in 25% of the global population. CRP and IL-6 were 4.0+/-4.6 mg/L and 5.8+/-5.6 pg/mL, respectively and were not significantly correlated (r=0.11, p=n.s.). CRP and IL-6 were however related with renal function (CRP versus C(Cr) r=-0.40 p <0.001; IL- 6 versus C(Cr) r=-0.45; p <0.001). When patients were divided in two groups according to renal function, CRP resulted 7.4+/-6.3 mg/L in the group of patients with a C(Cr) lower than 20 mL/min (n=32) and 2.76+/-4.35 in the group of patients with a C(Cr) higher than 20 mL/min (n = 70) (p <0.0001). CRP and IL-6 were positively related with ESR (r=0.32 and 0.46 respectively). Serum albumin levels were not significantly different in the two groups of patients (3.2+/-0.4 versus 3.0+/-0.5 g/dL). CRP and serum albumin were not significantly related (r=0.17). CRP and IL-6 correlated positively with ESR (r=0.32 and 0.46 respectively). In pre-dialysis patients we have demonstrated an increase in both CRP and IL-6 that occurs as renal function decreases. These data provided evidence of the activation - even in the predialysis phase of renal failure - of mechanisms known to contribute to the enhanced cardiovascular morbidity and mortality of the uremic syndrome.