Inflammatory Markers and Outcomes in Kidney Transplant Recipients

Increased levels of TNF-α and IL6 are associated with inflammation and cardiovascular disease among patients with normal kidney function. However, little is known about their association with outcomes in kidney transplant recipients.

We collected sociodemographic, clinical and laboratory parameters, medical and transplant history from 977 prevalent kidney transplant recipients enrolled in the Malnutrition-Inflammation in Transplant-Hungary study. Serum cytokine levels were measured at baseline. Associations between serum TNF-α and IL6 values and death with a functioning graft over a 6-year follow-up period were examined in unadjusted and adjusted models.

The mean ± SD age of the study population was 51 ± 13 years, 57% were men, 21% were diabetics. Median serum TNF-α and IL6 concentrations were significantly higher in patients who died with a functioning graft as compared with those who did not die during the follow-up period (TNF-α: median, 1.92 pg/mL; interquartile range [IQR], 1.43-2.67 pg/mL vs median, 2.25 pg/mL; IQR, 1.63-3.08 pg/mL, P < 0.001; and for IL6: median, 1.91 pg/mL; IQR, 1.21-3.02 pg/mL vs median, 2.81 pg/mL; IQR, 1.65-4.97 pg/mL, P < 0.001). Higher serum TNF-α and IL6 levels were associated with higher mortality risk in both unadjusted and fully adjusted models: TNF-α: hazard ratios (HRs)(1 pg/ml increments), 1.24; 95% confidence interval (CI), 1.13-1.36 and HRs(1 pg/ml increments), 1.19; 95% CI, 1.08-1.32; IL6: HRs(1 pg/ml increments), 1.06; 95% CI, 1.03-1.09 and HRs(1 pg/ml increments), 1.03; 95% CI, 0.99-1.06, respectively. Compared with patients whose serum TNF-α or IL6 levels were in the lowest tertile, those in the middle tertile had similar mortality risk (TNF-α: HR, 1.09; 95% CI, 0.74-1.61; IL6: HR, 1.05; 95% CI, 0.68-1.62), but patients in the highest tertile reported higher risk of mortality: TNF-α: HR, 1.45; 95% CI, 1.01-2.09; IL6: HR, 1.55; 95% CI, 1.04-2.32 in multivariable adjusted models.

In prevalent kidney transplant recipients, serum TNF-α and IL6 were independently associated with death with a functioning graft.