Inflammation in renal transplantation

Abstract

Background and objectives: Renal transplant recipients experience premature cardiovascular disease and death. The association of inflammation, all-cause mortality, and cardiovascular events in renal transplant recipients has not been examined in a large prospective controlled trial.

Design, setting, participants, & measurements: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5- to 6-yr trial were offered open-label fluvastatin in a 2-yr extension to the original study. The association between inflammation markers, high-sensitivity C-reactive protein (hsCRP), and IL-6 on cardiovascular events and all-cause mortality was investigated.

Results: The baseline IL-6 value was 2.9 +/- 1.9 pg/ml (n = 1751) and that of hsCRP was 3.8 +/- 6.7 mg/L (n = 1910). After adjustment for baseline values for established risk factors, the hazard ratios for a major cardiac event and all-cause mortality for IL-6 were 1.08 [95% confidence interval (CI), 1.01 to 1.15, P = 0.018] and 1.11 (95% CI, 1.05 to 1.18, P < 0.001), respectively. The adjusted hazard ratio for hsCRP for a cardiovascular event was 1.10 (95% CI, 1.01 to 1.20, P = 0.027) and for all-cause mortality was 1.15 (95% CI, 1.06 to 1.1.25, P = 0.049).

Conclusions: The inflammation markers IL-6 and hsCRP are independently associated with major cardiovascular events and all-cause mortality in renal transplant recipients.

Figure 1.

Association between (A) all-cause death, (B) major cardiovascular events, and (C) cerebrovascular events for quartiles of high-sensitivity C-reactive protein (hsCRP) over the whole range of hsCRP. (D) Association between all-cause death, (E) major cardiovascular events, and (F) cerebrovascular events for quartiles of hsCRP below 5 mg/dl. x-axis represents follow-up time in years. y-axis represents cumulative survival.

Figure 2.

Association between (A) all-cause death, (B) major cardiovascular events, and (C) cerebrovascular events with IL-6 for quartiles of IL-6. x-axis represents follow-up time in years. y-axis represents cumulative survival.