Elevated Post-transplant Levels of Neopterin are Associated with Poorer long-term Graft Outcome

Abstract

Abstract Chronic allograft nephropathy (CAN) and death with functioning graft due to cardiovascular disease (CVD) are the key determinants for long-term renal allograft survival. Chronic allograft nephropathy and cardiovascular disease are seen as manifestations of a single disease entity with a common pathogenesis including inflammation and accelerated atherogenesis. Therefore we investigated the relation between early post-transplant inflammatory burden and long-term graft survival. In 64 consecutive renal transplant patients the acute phase reactants serum amyloid A (SAA) and serum C-reactive protein (S-CRP) as well as the macrophage product neopterin in urine (U-NEOP) and serum (S-NEOP) were determined daily during the immediate postoperative period (mean p.o.obs. χ = 29.2 ± 8.7 days, total of Σ = 1869 days). SAA and CRP were measured with high-sensitive assays (in mg/1; immune nephelometry, Dade Behring Co., Marburg, Germany), NEOP was measured with ELISA-technique (Brahms, Berlin, Germany) and related to serum and urine creatinine levels, resp. (in μπιοΐ/mol creatinine). The association between the mean values of these parameters and the survival distribution function of the 64 patients was tested using the log rank test and the Wilcoxon-test. In this analysis graft loss was defined as either resumption of dialysis treatment or patient death with functioning graft. The 1- and 5- year graft survival rates in our patients were 93% and 76%, resp. The markers showed the following mean post-transplant levels: S-CRP χ = 21.3 ± 16.1 mg/1, SAA χ = 10.1 ± 6.5 mg/1, U-NEOP χ = 602 ± 427 mmol/mol creatinine and S-NEOP χ = 81 ± 60 μπιοΐ/mol creatinine. Both log rank test and Wilcoxon-test provided evidence that the graft survival is negatively related to the post-transplant levels of U-NEOP (p = 0.009 and ρ = 0.027, resp.). The markers S-NEOP (p = 0.074 and ρ = 0.116, resp.), SAA (p = 0.599 and ρ = 0.294, resp.), and S-CRP (p = 0.059 and ρ = 0.358, resp.) did not reach statistical significance. These findings support the impact of the inflammatory burden on graft survival. In particular, elevated post-transplant neopterin values, reflecting activated innate and adaptive responses, are predictive for long-term graft outcome.