P0652THYMOSIN BETA 4 AND KIDNEY FUNCTION: AN INVERSE RELATIONSHIP?

Abstract

Abstract Background and Aims Thymosin β4 (Tβ4) is an abundant peptide in urine and plasma, involved in multiple processes including cell morphology, wound healing, and inflammation. A major, yet not well defined role of Tβ4 was described in the context of kidney and cardiovascular disease. Knock out of Tβ4 resulted, among others, in increased albuminuria in a nephrotoxic nephritis model. In animal models it has been shown that Tβ4 can modify renal and cardiovascular disease, fibrosis and inflammation. However, most of the data are derived from animal models and the relevance of Tβ4 in human is less clear. As a first step towards investigating the potential relevance of Tβ4 in chronic kidney disease (CKD) in human, we investigated the abundance of Tβ4 in human urine. Method We investigated human urine in 2240 subjects with a wide spread of kidney function for the presence of Tβ4 using capillary-electrophoresis coupled mass spectrometry (CE-MS) and tandem mass spectrometry. In addition, we evaluated the presence of Tβ4 abundance in hemodialysis fluid of 10 subjects. Results The full length acetylated Tβ4 peptide could be identified in human urine in high abundance (molecular mass 4960.485 Da). In addition, an oxidized isoform could also be observed at high abundance. When investigating the distribution of both isoforms in control subjects and patients at different stages of CKD, a highly significant inverse association of the abundance of Tβ4 with eGFR could be observed for both, with rho -0.388 for the non-oxidized and -0.387 for the oxidized isoform, p<0.0001 in each case. In hemodialysate, Tβ4 is found as the most abundant peptide in 2 of the 10 analyzed subjects, on average the second most abundant peptide, with β2 microglobuline being the most abundant one. Conclusion Tβ4 is highly significantly inversely associated with kidney function, suggesting a role of Tβ4 in kidney disease and/or its complications. Based on the experimental data published from animal models, the increase in Tβ4 may reflect a potential physiological mechanism to counteract CKD and its complications. Investigation of association of Tβ4 levels with progression in CKD, cardiovascular complications and death may inform on a potentially beneficial effect of Tβ4, is currently ongoing in longitudinal datasets and will be presented.