Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients

Abstract

Delayed graft function (DGF) increases the risk of acute allograft rejection and may affect long-term graft survival. We compared pre-transplant, early post-transplant, and late post-transplant serum creatinine (Cr) and plasma levels of neopterin, cytokines, and cytokine receptors/antagonists in patients with DGF (n = 39), slow graft function (SGF) (n = 43), or immediate graft function (IGF) (n = 30). Three and eight days post-transplant, plasma neopterin (p < 0.001; p < 0.001), Soluble Interleukin-6 (IL-6) receptor (R) (p = 0.002; p = 0.001), and IL-10 (p = 0.003; p = 0.001) were higher in DGF than IGF patients. One month post-transplant, plasma neopterin (p < 0.001) and IL-10 (p < 0.001) were higher in DGF than IGF patients. Three days post-transplant, the results indicated reduced sIL-1 receptor antognist (RA) production in DGF patients (p = 0.001). Simultaneously, plasma sIL-6R and IL-10 increased in DGF (p < 0.001; p = 0.003) and SGF (p = 0.007; p = 0.030) patients, indicating increased production of sIL-6R and IL-10. Lower sIL-1 production in DGF than IGF patients early post-transplant might promote the increased production of monocyte-derived neopterin, sIL-6R, and IL-10. This monocyte/macrophage activation might induce inflammation in the graft and subsequently cause an impairment of graft function. Blocking of monocyte activity after renal transplantation may be considered a potential approach for improving graft outcome.

Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-Organ Transplant Rejection and Other Conditions

“…Our results suggest an important role for activated pro-inflammatory monocytes in transplant rejection. This finding is consistent with recent reports that monocyte/macrophage activation might induce inflammation, leading to impairment of graft function in renal transplant patients [39] .…”

Increased soluble fms-like tyrosine kinase 1 after ischemia reperfusion contributes to adverse clinical outcomes following kidney transplantation

“…19,20 In addition, Onoue et al described higher plasma sFlt-1 levels in the renal vein than in the aorta of patients, thereby suggesting that renal sFlt-1 production may substantially contribute to circulating sFlt-1 levels. 20 Although activated monocytes and macrophages recruited into the kidneys during injury may also account for sFlt-1 production, 14,33 renal epithelial cells seem to be of great relevance, as shown by immunostaining and cell culture studies (unpublished data).…”

Cumulative Exposure to Gamma Interferon-Dependent Chemokines CXCL9 and CXCL10 Correlates with Worse Outcome After Lung Transplant

“…Hence, a significant number of samples were classified as not detected and this may have limited the ability to draw meaningful conclusions with respect to IL‐17. IL1‐RA represented an attractive potential biomarker as it demonstrated the most significant dynamic range of all the markers tested, prior work has demonstrated an inverse relationship between IL1‐RA and renal function in kidney transplantation (18) and drug therapy harnessing the anti‐inflammatory promise of IL1‐RA has been demonstrated in rheumatoid arthritis (19). In spite of the relative detectability of BALF IL‐1RA, its presence did not correlate with outcome in our study.…”