SP689SERUM SOLUBLE CD163 LEVEL IN PATIENTS WITH RENAL TRANSPLANTATION: RELATION TO ALLOGRAFT FUNCTION AND SURVIVAL AND TO INSULIN RESISTANCE

Abstract

INTRODUCTIONANDAIMS: Renal transplantation is considered as the treatment of choice for patients with end stage renal disease who are medically suitable. Chronic allograft dysfunction describes long-term loss of function in transplanted organs. Both immunological and non-immunological factors may cause chronic allograft injury. Chronic allograft rejection is a clinico-pathological entity associated with chronic allograft loss. It is characterized by progressive interstitial fibrosis and tubular atrophy as well as microvascular and glomerular damage. Macrophages are key players in tissue homeostasis. They play an important role in the resolution of inflammation and wound healing. Macrophages are precusrsors of monocytes which are involved in the development and progression of kidney fibrosis. They are subdivided into different subpopulations by expression of surface antigens.CD163 expression seems to be a marker of monocyte subset down-regulating inflammatory process. SolubleCD163 comes fromCD163 molecules, which peel off the membrane ofmononuclear cells. It has been found that renal transplant patients had more liability of cardiovascular disease and diabetes than the normal populations. It could be associated with obesity and insulin resistance. This could be related to chronic use of immunosuppressive drugs such as corticosteroids and calcineurin inhibitors, and persistent low-grade inflammatory activity of viral infections.The aim of the study was to measure the serumlevel of soluble CD163 in living kidney transplant recipients and detect its ability to predict kidney allograft dysfunction and developping insulin resistance. METHODS: This study was performed in a cohort of 45 subjects who were divided into three groups; Group I: 15 healthy subjects served as control subjects, Group II: 15 patients with kidney transplantation and normal renal functions & Group III: 15 patients with kidney transplantation and chronic graft rejection. Serum creatinine and eGFR were measured to monitor renal functions. Serum soluble CD163 was measured by ELISA tecnique. Serum fasting insulin level and fasting blood glucose were measured to calculate homeostasis model assessment-estimated insulin resistance (HOMA-IR). Serum high sensitivity C-reactive protein was used as an inflammatory marker. RESULTS: Serum level of soluble CD163 was significantly higher in kidney transplant patients (797≥116340≥45 ng/ml) than in controls. It was also statistically higher in kidney transplant patients with chronic rejection than in kidney transplant patients with normal renal functions. In simple correlation analysis, in group III, serum soluble CD163 was correlated positively with serum creatinine (r=0≥467, P=0≥028) and negatively with Modification of Diet in Renal Disease (MDRD) (r=0≥6056, P = 0≥003). sCD163 correlated significantly with HOMA-IR (R=0.44), insulin (R=0.41), glucose (R=0.30), (All p<0.0001). sCD163 is positively correlated with high sensitivity CRP. CONCLUSIONS: Macrophage-specific sCD163 is strongly associated with chronic allograft rejection. Measuring serum soluble CD163 can be used to predict development of graft rejection. The induction of immunosuppressive CD163+ monocytes and downregulation of proinflammatory monocytes might play a protective role in the early phase after kidney transplantation. High serum sCD163 level is also strongly associated with developping insulin resistance and diabetes mellitus.