The Expression And Its Significance Of Cathepsin B And Cystatin C In Patients With Chronic Renal Disease

Objective: To elucidate the role of cathepsin B (CB) and cystatin C (CC) in the genesis of renal fibrosis and to evaluate the indirect diagnosis value of serum and urine CC concentration on the renal fibrosis. Methods: Fifty-six chronic renal disease patients received renal biopsy were divided into three groups according to the glomerular sclerosis and renal interstitial fibrosis score: no fibrosis group(score=0), light fibrosis group(score=1 to 2), and middle fibrosis group(score≥3). Other fifteen chronic renal failure (CRF) patients and ten health control people without renal biopsy were also observed. We examined the expression of CB, CC and type IV collagen in the renal biopsy specimens using immunohistochemical staining and compute image analysis system. The relationship between the expression of CB and CC in kidneys and the degree of glomerulosclerosis and tubulointerstitial injury was analyzed. The serum and urine CC concentration in all patients and ten health people were measured by enzyme linked immunosorbent assay (ELISA). Results: (1) The CB and CC of no fibrosis group expressed strongest in renal proximal tubular epithelial cells. (2) The expression of CB was significantly decreased in light fibrosis group and middle fibrosis group compared with that of no fibrosis group(P<0.01). The expression of CB was significantly negatively correlated with the degree of glomerulosclerosis and tubulointerstitial injury. (3) The expression of type IV collagen and CC in renal tissue of light fibrosis group and middle fibrosis group was significantly higher than that of no fibrosis group (P<0.01). The renal expression of type IV collagen was positively correlated with the degree of glomerulosclerosis and tubulointerstitial injury. The renal CC expression was positively correlated with the degree of tubulointerstitial injury. (4) The serum CC concentration of four groups of chronic renal disease patients was significantly higher than that of health control group (P<0.05). The serum concentration of CC was significantly positively correlated with the degree of glomerulosclerosis and tubulointerstitial injury. (5)The urine CC concentration of light fibrosis group, middle fibrosis group and CRF group was significantly higher than that of health group and no fibrosis group (P<0.05). The urine concentration of CC was significantly positively correlated with the degree ofglomerulosclerosis and tubulointerstitial injury.Conclusion: (1) The CB and CC was chiefly expressed in proximal tubular epithelial cells. (2) The expression of CB was significantly negatively correlated with the degree of glomerulosclerosis and tubulointerstitial injury . The expression of renal CC was positively correlated with the degree of tubulointerstitial injury. The disturbance of CB and /or CC expression had something to do with the ECM degradation, and contributed to the formation of renal fibrosis. (3) Serum and urine CC concentration positively correlated with the renal expression of CC and the degree of glomerulosclerosis and tubulointerstitial injury. The serum and urine CC concentration might be diagnosis index for renal fibrosis under the condition that other organ chronic disease could be excluded, especially suitable for those patients who could not receive renal biopsy.