Pai-1 And Vitronectin Expression In Chronic Allograft Kidney Damage And Preliminary Study On The Induced Fibrosis

BackgroundChronic allograft injury (CAI) is the major cause of loss of renal allografts. Progressive kidney disease is characterized by accumulation of extracellular matrix (ECM) in glomeruli and tubulointerstitium. Some researches show plasminogen activator inhibitor-1(PAI—1) and vitronectin play an important role in renal fibrosis. However, there are few studies related to the functional cooperation between PAI-1 and vitronectin in human CAI. We therefore studied the expression of these molecules in CAI.Methods8 transplant recipients who have successful renal transplantation with normal renal function and histology, served as control group. 16 tansplant recipients who have typical clinical changes and histology assigned to two groups with 8 in each group: acute reject group, CAI group. PAI-1 and vitronectin immunostaining was assessed in glomeruli and tubulointerstitium, as well as PAS and masson. We also collected normal characteristic information and creatinine of recipients in control and CAI group.ResultsGlomerular PAI-1 and vitronectin staining scores were markedly increased in CAI (49.10±6.51, 42.30±8.23, respectively) compared wit control (6. 35±2. 90,21.14±1.80, respectively, P<0. 05) and acute reject (28.66±4.70, 28.44±9.46, respectively, P<0.05). Tubulointerstitial PAI-1 and vitronectin staining scores were also markedly increased in CAI (15.13±1.45, 12.29±2.36, respectively) compared wit control (3.53±2.20, 3.95±1.46, respectively, P<0. 05) and acute re ject (8.81±2.20, 5.53 + 1.83, respectively, P<0.05). Glomerulosclerosis index in CAI was 2.80±0.49 compared with 0.91±0.23 in control. Interstitial fibrosis index in CAI was 2.50±0.27 compared with 0.44±0.224 in control. Tubular injury index in CAI was 2.49±0.29 compared with 0.65±0.32 in control. The portion of ECM in the glomerulus correlated with PAI-1 and vitronectin (R=0.944, R=0.815, respectively, P<0.01), which was dramatically increased in CAI (0.50±0.07) compared with control (0. 14±0. 03). PAI-1 and votronectin also correlated with each other (R=0. 826, P<0. 01), co-expressed in the same site. Creatinine correlated with PAI-1 and vitronectin (R=0.858, R=0.860, respectively, P<0.01), and creatinine clearance also correlated with PAI-1 and vitronectin (R=-0.730, R=-0.708, respectively, P<0.05). Creatinine in PAI-1 positive group was significantly higher than negative group (P<0. 05). In PAI-1 positive group, there are two recipients lost their renal allografts.ConclusionsPAI-1 and vitronectin are both increased in CAI, also co-expressed in the same site. We speculate that PAI-1 and vitronectin interact with each other, inhibit matrix degradation through the production of plasmin or not, promote the accumulation of ECM, lead to the progressive of allograft fibrosis eventually.