Comorbidity and Acute Clinical Events as Determinants of C-Reactive Protein Variation in Hemodialysis Patients: Implications for Patient Survival

Background

Patients with chronic kidney disease stage 5 have high comorbidity and are prone to inflammation that may contribute to the high cardiovascular mortality risk.

Study Design

Three-month observational cohort study of prevalent hemodialysis patients.

Settings & Participants

228 hemodialysis patients (44% women) were included, median age of 66 years, median time on dialysis therapy of 29 months.

Predictors & Outcomes

In part 1, comorbidity and intercurrent illness were predictors and C-reactive protein (CRP) level was the outcome. In part 2, serial CRP values were predictors and survival was the outcome.

Measurements

High-sensitivity CRP was measured weekly and interleukin 6 (IL-6), tumor necrosis factor α, and IL-10 were measured monthly. Data for comorbidity were collected from patient records to calculate Davies comorbidity score, and self-reported clinical events were recorded weekly.

Results

Median baseline CRP level was 6.7 mg/L (25th to 75th percentiles, 2.5 to 21 mg/L). Baseline CRP level correlated with time-averaged CRP (Spearman ρ = 0.76) and individual median of serial CRP values (ρ = 0.78; both P < 0.001). Part 1: comorbidity score was significantly associated with greater CRP and IL-6 levels. Age, sex, comorbidity, and 7 of 12 clinical events had significant effects on CRP level variation. Part 2: during a mean follow-up of 29 months, 38% of patients died. Median and mean serial CRP levels were associated with a greater hazard ratio for death (1.013; 95% confidence interval, 1.004 to 1.022) and 1.012 (95% confidence interval, 1.004 to 1.020) than baseline, maximum, and minimum CRP values during the study. Other significant covariates were age, Davies risk group, dialysis vintage, and albumin level.

Limitations

The study is based on observational data for prevalent dialysis patients.

Conclusions

Comorbidity and clinical events are strongly associated with inflammation in hemodialysis patients. Despite variability over time, inflammation assessed by using CRP level is a strong predictor of mortality. Serial measurements provide additional information compared with a single measurement.

Index Words: Chronic kidney disease, comorbidity, C-reactive protein, hemodialysis, inflammation, survival