Clinical Relevance Of Peripheral Blood Soluble CXCL16with Chronic Kidney Disease

BackgroundChronic kidney disease (CKD) is a growing public health epidemic and Patientswith CKD not only have an augmented atherogenic lipid profles but also have evidenceof chronic infammation and oxidative stress. Animal and clinical studies indicate thatoxidized. There was a consensus that hyperlipidemia is an independent risk factors ofrenal injury. The available experimental proof of the low-density lipoprotein (LDL),oxidized low-density lipoprotein (ox-LDL), can also damage the kidney mesangial cells,endothelial cells and podocytes. Animal and clinical studies have shown that oxidizedlow-density lipoprotein (ox-LDL), can be directly involved in the pathological processof inflammation and oxidative stress lead to CKD.Number of studies suggest CXCL16(CXC chemokine ligand16) plays animportant role in the onset and progression of renal disease process and its effect maybe mediated by ox-LDL uptake and lipidcytotoxicity, chemotaxis of inflammatory cellsinfiltration. Proinflammatory cytokines can promote CXCL16were up-regulated in therenal vascular endothelial cells. IFN-γ and TNF-α, IL-1β can induce the increasedexpression of CXCL16and mediate cells uptake ox-LDL, proliferation and migration inthe studies of cultured human mesangial cells. Podocyte play an important role in theglomerular filtration barrier. There is also evidence that CXCL16in the surface ofpodocytes upregulated and combinated ox-LDL as scavenger receptors in CKD. Thepositive correlation and common space point of CXCL-16and ox-LDL was found inRenal tissue of diabetic patients by double immunofluorescence and it further confirmedthe role of CXCL-16in podocytes injury. Expression of CXCL16in renal interstitialwas significantly increased more than the control group in a rat model of urinary tractobstruction that induced renal interstitial fibrosis. Intervention of anti-CXCL16antibody can significantly reduce the renal tissue inflammatory cell infiltration and tissue damage; the mechanism may reduce inflammatory cell infiltration of the renaltissue in Animal models of nephritis mediated by anti-glomerular basement membraneantibody. These researches mentioned above suggest that CXCL-16may be thepotential targeted molecule of the treatment to CKD.The relationship between CXCL16and CKD in clinical level is still known poorlythough there are some studies have shown that CXCL16was related to the developmentof chronic kidney disease. Can CXCL16be a biomarker and even a new therapeutictarget in chronic kidney disease? More studies are needed.ObjectiveTo detect peripheral blood soluble CXCL16levels and study its correlation withvarious clinical indicators of Minor lesion patients, pre-dialysis CKD patients, andlong-term hemodialysis patients in order to explore the clinical correlation andpredictability of CXCL16in kidney disease.Methods86Minor lesion patients,147pre-dialysis CKD patients,83long-term hemodialysispatients, and44health controls were enrolled. The peripheral blood soluble CXCL16levels of patients were tested by ELISA，meanwhile, Clinical data and lab tests werecollected from inpatient case history and dialysis data department. Then analysisvarious factors with level of soluble CXCL16by single factor correlation analysis andmultiple stepwise regression analysis.Results1. Minor lesion patients: the level of CXCLl16is positively correlated with24-hoururine protein, Scr and CHO and LDL；urinary albumin, serum albumin, systolic blood pressure, diastolic blood pressure is negatively correlated；immunosuppressive drugs is positively correlated；sex is not correlated (p <0.05).2. Pre-dialysis CKD patients: The level of CXCL16is positively correlated withsystolic blood pressure, diastolic blood pressure, duration (months), CHO,calcium-phosphate product and Scr; hemoglobin, serum albumin, and GFR isngatively correlated with the level of CXCL16; the antihypertensive drugs, historyof CVD is positively correlated (p <0.05).3. Long-term hemodialysis patients: The level of CXCL16is negatively correlatedwith plasma albumin and positively correlated with LVMI (p <0.05).4. Compare CXCL16among4groups of people：the level of CXCL16，health controls＜Pre-dialysis CKD patients（p＜0.05）＜Minor lesion patients（p＜0.05）＝long-term hemodialysis patients（p＝0.087）.Conclusions1. The level of peripheral blood soluble CXCL16in Minor lesion patients,pre-dialysis CKD patients, and long-term hemodialysis patients is higher than inhealthy people;2. CXCL16level of the Minor lesion patients is correlated with hypoalbuminemia,urinary protein excretion and the use of immunosuppressive agents, it mayindicate activity and prognosis of kidney disease;3. CXCL16level of the Pre-dialysis CKD patients is related to lost of renal function,duration of disease, and hypoalbuminemia. High CXCL16level may indicate theacceleration of CKD progress;4. CXCL16level of the long-term hemodialysis patients is related tohypoalbuminemia and LVMI. High CXCL16level may indicate malnutrition,micro-inflammatory state, and Long-term cardiovascular disease events. 5. The long-term hemodialysis patients are not statistically different to Minor lesionpatients in CXCL16level and relatively higher than Pre-dialysis CKD patients. Itmay suggest CXCL16is derived from different tissue and involved in differentprocess of pathophysiology in different period of kidney disease. Advancedresearch should be taken.