Objective The abnormal proliferation of renal cells underlies the pathology of progressive glomerulosclerosis.Cell proliferation is regulated by cell regulatory proteins.This study aims to investigate the expression of cyclin-dependent kinase inhibitor P16INK4a in renal tissue of patients with primary mesangial proliferative glomemlonephritis(MsPGN)and its clinical significance.Methods Paraffinembedded renal biopsy renal tissue sections from 36 patients with MsPGN were detected by immunohistochemical staining.Normal renal ti8.Sue sections from 6 nephrectomized patients with trauma were used as controls.Possible correlation between p16 positive area and sclerotic and crescentic glomeruli,blood pressure,serum creatinine,endogenous creatinine clearance rate,and total proteinuria were evaluated.Resuits There were very few expression of P16INK4a in normal glomemli and renal tubular-interstitial.Compared to the normal comrol group,the expression of P16INK4a in 36 renal biopsy specimens with MsPG'N was significantly higher(P<0.01),especially in sclerotic and crescentic glomeruli,and it had wild expression of the same components in no sclerotic and crescentic glomeruli.There was a statistic difference(P<0.01).No statistic difference was found between the expression of P16 INK4a in renal tubular-interstitial of two groups(P>0.05).Therewag positive correlation among P16 INK4a of glomeruli without use of glucocorticoid/immunoinlfibitors and ACEI/ARB(r=0.774,0.497,P<0.01),also blood pressure and 8ul～m creatinine(r=0.64,0.473,P<0.01).It was negstively correlated with endogenous creatinine clearance rate and total proteinuria(r=-0.487,-0.694,P<0.01).There is no correlation between P16INK4s and clinical data in renal tubular-interstitial.Conclusion This study demonstrated that overexpression of P16INK4a in renal tissue with MsPGN may promote the regression ofabnormal proliferation and senescence cells,and induce sclerotic and crescentic glomeruli.The expression level of P16 INK4a not only reflected the degree of renal function,but also hypertension and proteinuria.In brief,expression of P16INK4a may be an important marker in renal sclerotic or crescentic glomeruli of MsPGN.Some drugs may prevent the expression of P16INKa.