Inflammation and outcome in end-stage renal failure: does female gender constitute a survival advantage?
BACKGROUND
Elevated C-reactive protein (CRP) is a strong predictor of cardiovascular events and all-cause mortality in end-stage renal disease (ESRD) patients. However, although sex hormones may influence serum levels of inflammatory proteins, gender has not been taken into consideration in previous studies of inflammation and outcome in ESRD patients.


METHODS
We included 663 (374 males) ESRD patients (59 +/- 1 year) from three European renal centers (Sweden, Germany and Italy) in which CRP levels and outcome data (follow-up 33 +/- 1 months) were available. The relation between outcome and serum levels of the soluble intercellular adhesion molecule (sICAM-1) was evaluated in 312 of the patients.


RESULTS
The present study shows that elevated CRP is a strong predictor of outcome, but whereas no difference in all-cause mortality was observed between non-inflamed (CRP <or=3.4 mg/L) males and females, inflamed males had a significantly (log rank 6.1; P = 0.01) higher mortality rate than inflamed females. A strong positive correlation between CRP and sICAM-1 was found in the combined patient material (rho = 0.37; P < 0.0001) as well as in the male (rho = 0.25; P < 0.01) and female (rho = 0.52; P < 0.0001) subgroups. The Cox proportional hazard model showed that whereas both elevated sICAM-1 and log CRP predicted outcome in males, neither predicted outcome significantly in females.


CONCLUSIONS
As inflamed female patients have a better outcome that inflamed males the present observation suggests that sex hormones may have important cardioprotective effects that limit the effect of inflammation on vascular injury in female ESRD patients.
Stenvinkel
Peter
P
Division of Renal Medicine, Department of Clinical Science, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. peter.stenvinkel@klinvet.ki.se
Wanner
Christoph
C
Metzger
Thomas
T
Heimbürger
Olof
O
Mallamaci
Francesca
F
Tripepi
Giovanni
G
Malatino
Lorenzo
L
Zoccali
Carmine
C
D017677:Age Distribution; D015415:Biomarkers; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D005060:Europe; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D017678:Sex Distribution; D012995:Solubility; D016019:Survival Analysis; D014657:Vasculitis / Q000276:immunology* / Q000401:mortality*
D015415:Biomarkers; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein