Chronic low-grade inflammation is involved in late renal transplant dysfunction. Recent studies suggest a role for hemopexin, an acute phase protein, in kidney damage. We investigated whether hemopexin activity (Hx) predicts graft failure in renal transplant recipients (RTRs). In 557 RTRs with functioning grafts for >or=1 year, Hx was measured in citrate-plasma. RTRs were divided according to Hx into two groups; A: sextile 1-5 (464 RTRs, 83%) and B: sextile 6 (92 RTRs, 17%). Hx [median (IQR) 11.1 (3.3-19.1) arbitrary units] was measured at 6.0 (2.6-11.5) years post-transplant. RTRs with high Hx (group B) had significantly higher urinary protein excretion (UP) and diastolic blood pressure than group A, despite significantly more prevalent use of renin-angiotensin-aldosterone system inhibitors. After follow-up [4.6 (3.8-5.2) years], incidence of graft failure in group A was 25 (5%) and in group B 14 (15%,P = 0.0009) After adjustment for high-sensitivity C-reactive protein (hsCRP), UP and other potential confounders, Hx remained an independent predictor of graft failure [HR = 2.5 (95% CI 1.2-5.3), P = 0.01]. In conclusion, elevated Hx predicts late graft failure in RTRs, independent of hsCRP and UP. This suggests that Hx measurement, next to measurement of creatinine clearance and UP, could be of value for the identification of RTRs at risk for graft failure.