The prevention and control of chronic kidney disease(CKD)and end-stage renal disease(ESRD)has become an important public health problem.This article has outlined the status,hazards,and problems in prevention of CKD and ESRD,briefly described the work having been done by the Chinese Society of Nephrology of the Chinese Medical Association,and proposed countermeasures for future prevention and treatment of ESRD,aiming at improving knowledge of the urgency of combating ESRD by the society,government,public,and medical staff in order to improve the prevention and treatment of ESRD in China.

Alterations in the balance between synthesis and degradation of extracellular matrix (ECM) and its remodeling may result in an accumulation of ECM molecules and lead to glomerulosclerosis. Recent studies have focused on the role of degradative systems, especially the roles of plasminogen activators/plasminogen activator inhibitors (PA/PAI), matrix metalloproteinases, and their inhibitors[GK2*4/5!2*4/5] (MMP/TIMP) in the initiation and pathogenesis of renal diseases. Previously, attention has been paid to the study of inhibitors of ECM degrading enzymes, such as PAI and TIMP. Recent researchs showed that there existed complex dynamic expressions of enzymes and their inhibitors. Although many studies have tried to elucidate the pathogenesis of renal diseases, the exact underlying mechanisms are still not completely understood. For better understanding of the mechanism of chronic progressive renal diseases, the underlying genetic and molecular regulation of each component of PA/PAI and MMP/TIMP systems should be elucidated in different renal physiological and pathophysiological processes. Future studies are needed to manipulate activity or expression of these proteinases in order to treat and/or prevent glomerular diseases.

Objective To introduce the current development of nephrology during the period of "Eleventh-Five-Year Plan" in PLA medical circles,to serve as a reference for the further development of nephrology in PLA.Methods Literature concerning nephrology published domestically and abroad in past 5years were retrieved,and the progresses,achieved domestically and abroad,especially in PLA,on new concept,diagnoses and therapy of common nephropathy,and clinical applications of new drugs and techniques were emphatically analyzed.Results Great progresses have been made during the period of "Eleventh-Five-Year Plan" on basic researches,clinical applications and substitution therapy in nephrology,and outstanding achievements have been acquired on basic and clinical researches of chronic nephropathy and acute renal injury,drug treatment of renal diseases and continuous renal replacement therapy.The PLA medical personnel participated in the formulation of "Diagnostic and Therapeutic Standard of Renal Diseases" ,furthered the academic exchanges between the military and civilian circles,both domestically and abroad.The academic level of PLA in nephrology was raised markedly with obvious features and preponderance.Conclusion During the period of "Twelfth-Five-Year Plan" ,the focus of nephropathy researches should be put on the enhancement of the ability of military health service,integrated control and comprehensive remedy of acute renal injury induced by combat wound,trauma and stress injuries.It is important to stably retain the superiority on basic and clinical researches of chronic nephropathy,acquire more achievements,make greater contributions to raising the professional level of diagnosis and treatment of kidney diseases.

Animal model of aged rat nephrotoxicity was induced by i. p. administrationof gentamycin in a dose of 140mg/kg/day. Part of those rats were treated with CordycepsSinensis(CS), Epimedium(Ep) and Astragalus Membranaccus (AM) in form of decoc-tion per Os and others seryed as control. The results were summarized as. 1. The nephro-toxicity of gentamycin was aggrevated with age. CS, Ep and AM are effective drugs inpreventing the tdeular damage caused by gentamycin in rats. The pathological changes ofrenal tuoules of the rat groups which treated with CS, Ep and AM were less severe thanthat of the control. 2. CS, Ep and AM could prevent the decline of renal cortical Na~+-K~+-ATPase activity of aged rat induced by gentamycin.

Chronic kidney disease(CKD)is increasingly recognized as a global public health problem.Uncontrolled complications of CKD,especially cardiovascular diseases,contribute greatly to the premature death and unfavorable prognosis.Recent evidence shows that CKD complications may occur earlier than previously thought.CKD complications deserve early detection and active treatment.Periodical follow-up and regular check should be done to adjust the therapeutic condition.Clinical practice guideline or recommendation based on evidence-based medicine is essential for management of CKD complications.Personalized treatment should be considered to improve survival and quality of life,and to make patient return to society.

To determine whether increased expressions of gelatinase A(MMP-2) and gelatinase B(MMP-9) occur in vivo in autoimmune MRL/lpr mice model and to investigate the modulation effects of "shenle." Shenle (4g?kg -1 ?d -1 ,orally) or methylprednisolone(MPS,25mg?kg -1 ?d -1 ,ip)was administered daily to MRL/lpr mice at the age of 8 weeks. The activities of MMP-2/9 by gelatin zymography were compared in kidney protein extracts and urine. After treatment for 20 weeks, a progressive reduction in positive proteinuria number/total mice (40% vs.33 3% vs.80%, proteinuria over 300 mg/dl as positive) and an elevated survival rate (70% vs.80% vs. 50%) were found in "shenle" and MPS groups compared with the control group. Histological analysis of kidney tissues indicated that both "shenle" and MPS could inhibit the mesangial proliferation and renal sclerosis. Using SDS-PAGE gelatin zymography, we have identified increased expressions of both latent and activated form enzymes of MMP-2/9 in urine and kidney extraction. Immunohistochemical staining showed both MMP-2 and MMP-9 were obviously up-regulated within glomerulus in control group. "Shenle" as well as MPS suppressed the expression of both latent and activated form of MMP-2/9. These in vivo results suggested that MMP-2/9 expressions might play an important role in murine lupus nephritis. "Shenle" delayed the development of glomerulonephritis and improved survival in MRL/lpr mice probably by suppressing the expressions and activities of MMP-2/9.

To determine thrombin activation and fibrin deposition in the development of lupus nephritis in MRL lpr/lpr mice and the inhibitory effects of "shenle". "Shenle" (4g/(kg?d) orally) was administered daily to MRL lpr/lpr mice at the age of 8 weeks. After treatment for 20 weeks, we compared thrombin receptor (Protease Activated Receptor-1, PAR-1) expression with immunohistochemistry and fibrin deposition with MSB(Martius-Scarlet-Blue)staining in renal sections. PAR-1 mRNA expression was analyzed with RT-PCR method in the two groups. With the development of murine lupus nephritis, we observed an increase in thrombin receptor mRNA and severe fibrin deposition in renal tissue in the control group, while thrombin receptor protein expression was strikingly downregulated, suggesting its continuous activation and degradation. "Shenle" inhibited PAR-1 activation significantly and it was correlated with reduced fibrin deposition. These results suggested that thrombin activation may play an important role in the development of glomerulonephritis in MRL-lpr mice. "Shenle" ameliorated the murine renal lesions probably by inhibiting thrombin receptor activation and fibrin deposition.

To explore the effects of angiotensin Ⅱ on plasminogen activator inhibitor 1 (PAI 1) gene expression in human glomerular mesangial cells.Glomerular mesangial cells (GMCs) were cultured from a healthy adult human kidney (unsuitable for renal transplantation) and then treated with angiotensin Ⅱ at concentration of 10 -9 ,10 -8 , 10 -7 and 10 -6 mol/L, respectively. The mRNA expressions of angiotensinⅡAT1 and AT2 receptor, and PAI I were examined with RT PCR and Northern blot analysis, respectively. Plasminogen activator activity in the supernatants of the GMCs was measured with fibrin plate method. After the GMCs were stimulated by angiotensin Ⅱ, the mRNA level of the AT1 receptor was markedly enhanced, but the AT2 receptor mRNA level was still undetectable as that in normal condition. When GMCs were treated with angiotensin Ⅱ for 48 hours, PAI 1 mRNA expression was increased in a dose dependent manner. The plasminogen activator activity was significantly reduced in the supernatants of the angiotensinⅡ treated GMCs. the results suggested that angiotensinⅡ promote PAI 1 gene expression of the GMCs possibly through its AT1 receptor.

To observe the high glucose concentration on proliferation and fibronectin (FN) synthesis of glomerular mesangial cells (GMC),a culture of human GMC was established and the cell proliferation was assessed using MTT method and cell counting, and the changes in FN was analyzed with RT PCR and ELISA. It was found that high glucose concentration inhibited GMC proliferation and increased FN synthesis in dose and time dependent manner.The results suggest that hyperglycemia may have important role in the development of diabetic nephropathy.

To explore expressions of ? smooth muscle actin (? SMA), plasminogen activator inhibitor 1 (PAI 1), matrix metalloproteinase 9 (MMP 9)and tissue type inhibitor of metalloproteinase 1 (TIMP 1) in renal vessels of 38 patients with immunoglobulin A nephropathy (IgAN), immunohistochemistry method was used to detect abundances of the above proteins. The results showed that ? SMA staining was found mainly in vascular smooth muscle cells (SMCs); apparent PAI 1 staining was also shown by vascular SMCs; MMP 9 expressed considerably in vascular both SMCs and endothelial cells; TIMP 1 was located only in vascular endothelial cells. In renal tissues of IgAN patients at Lee IV V grade, vascular expressions of ? SMA?PAI 1 and MMP 9 were significantly higher than those at Lee I III grade ( P