C-Reactive Protein and Risk of ESRD: Results From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)

Abstract

Background: To better understand a potential association of elevated C-reactive protein (CRP) level with progression of chronic kidney disease (CKD), we examined the relationship of CRP level with the development of end-stage renal disease (ESRD) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).

Study design: Post hoc analysis of a randomized controlled trial.

Setting & participants: 4,038 patients with type 2 diabetes, CKD, and anemia in TREAT.

Predictor: Baseline serum CRP concentrations.

Outcomes: The primary outcome was development of ESRD; secondary outcomes included doubling of serum creatinine level, a composite of ESRD/serum creatinine doubling, and a composite of death or ESRD.

Measurements: We fit unadjusted and adjusted Cox regression models to test the association of baseline CRP level with time to the development of the outcomes of interest.

Results: Mean age of participants was 67 years, 43% were men, and 64% were white. Approximately half (48%) the patients had CRP levels > 3.0mg/L; 668 patients developed ESRD, and 1,270 developed the composite outcome of death or ESRD. Compared with patients with baseline CRP levels ≤ 3.0mg/L, those with moderately/markedly elevated CRP levels (≥6.9mg/L; 24% of patients) had a higher adjusted risk for ESRD (HR, 1.32; 95% CI, 1.07-1.63) and the composite outcome of death or ESRD (HR, 1.41; 95% CI, 1.21-1.64). Although nonsignificant, similar trends were noted in competing-risk models.

Limitations: Results may not be generalizable to nondiabetic CKD or diabetic CKD in the absence of anemia.

Conclusions: Elevated baseline CRP levels are common in type 2 diabetic patients with anemia and CKD and are associated with the future development of ESRD and the composite of death or ESRD.

Keywords: C-Reactive protein (CRP); anemia; biomarker; chronic kidney disease (CKD); disease progression; end-stage renal disease (ESRD); inflammation; kidney function trajectory; mortality; risk factor; serum creatinine; type 2 diabetes mellitus (T2DM).