The Role Of Complement C3a, C5a In The Pathogenesis Of Diabetic Nephropathy

Background：Diabetic nephropathy (DN) is considered to be one of the most common reasonsin the western nations leading to the end stage renal disease (ESRD)requiring dialysis.And in our country more and more people are suffering from this disease. However,the accurate pathogenesis of diabetic nephropathy is unknown. Recently，a fewstudies have shown that complement activation might be involved in the pathogenesisof diabetic nephropathy. As is known that complement C3a and C5a were products ofcomplement activation. It was reported that complement C3a and C5a could amplifypro-inflammatory and involve in the pathogenesis of many inflammatory andautoimmune diseases. In this study, we detect the expressions of the receptors ofcomplementC3a and C5a (C3aR, C5aR)， investigate the concentrations ofcomplement C3a and C5a in serum and urine from diabetic nephropathy patients, andexplore the potential role of C3a and C5a in the pathogenesis of diabetic nephropathy(DN).Objective:(1)To detect the expressions of the receptors of complement C3a, C5a (C3aR,C5aR) in the kidney of diabetic nephropathy patients, and investigate theconcentration of complement C3a and C5a in serum and urine from diabetic nephropathy patients.(2)To explore the relationship between complement C3a, C5a and diabeticnephropathy.Subjects and Methods:We selected forty-five diabetic nephropathy patients who were diagnosed byrenal biopsy which was conducted in Department of Nephrology, the First AffiliatedHospital of Zheng zhou University. The selected patients were considered to be DNgroup and they were divided into three small groups (13patients at I+II stage,21patients at III stage and11patients at IV stage),according to the PathologicClassification of Diabetic Nephropathy published in JASN in2010.At the same time,normal renal tissue coming from10nephrectomy patients with kidney neoplasm wasselected as control group. The expressions of C3aR and C5aR in the kidney tissuewere investigated by immunohistochemical staining. Meanwhile, in order toinvestigate the condition of C3a and C5a during diabetic nephropathy patients,wecollected serum and urine samples of13diabetic nephropathy patients. At the sametime, serum and urine samples from10healthy volunteers were collected as normalcontrol group and10sepsis patients as positive control group. The concentrations ofC3a and C5a in serum and urine from different groups were detected by ELISA,respectively.Result:(1) The expressions of C3aR and C5aR in DN groups were obviously higherthan those in control groups (P<0.05).And the worsen diabetic nephropathy patientswere, the higher the expressions of C3aR and C5aR in the kidney of diabeticnephropathy patients.(2) Corrections were found between some clinical test results (such as:24hurine protein、Scr、BUN、CRP) and the expressions of C3aR and C5aR in the kidneyof diabetic nephropathy patients(P<0.05).(3) The concentration of C3a and C5a in serum and urine from diabetic nephropathy patients and sepsis patients were significantly higher than those fromhealthy volunteers(P<0.05)，especially the concentration of C5a in urine fromdiabetic nephropathy patients.Conclusion:（1）There may be activation of complement both in system and local kidney indiabetic nephropathy patients.（2）C3a and C5a play an important role in kidney injury and make contributions tothe progression of diabetic nephropathy.