Objectives To modify glomerular filtration rate (GFR) estimating equation (also called abbreviated MDRD equation) based on plasma creatinine (Pcr) and other demographic data from Chinese chronic kidney disease (CKD) population， and compare the diagnostic performance of the modified abbreviated MDRD equations with that of original abbreviated MDRD equation in different CKD stages. Methods Six hundred and eighty-four patients with CKD including 352 males and 332 females，with average (49.9±15.8) years，were collected from 9 renal institutes of university hospital located in 9 different geographic regions of China，and were enrolled in this study from June 2004 to September 2005. Four hundred and fifty-four cases were randomly selected to be included in the training samples， and the remaining 230 cases were used as testing samples. Using 99mTc-diethylene triamine pentaacetic acid(99mTc-DTPA) plasma clearance by dual plasma sampling method as reference GFR(rGFR)，the original abbreviated MDRD equation was modified by the following two methods. Firstly， a racial factor for Chinese was added to the original abbreviated MDRD equation. Secondly， multiple linear regression was applied to the training sample， and the coefficient associated with each variable in the original abbreviated MDRD equation was modified respectively. The modified equations were validated in the testing samples and were compared with the original abbreviated MDRD equation. Results Both modified abbreviated MDRD equations showed significant performance improvement in bias(the areas between the regression line of difference and a common distance along the zero difference line were 543.0， 677.2， and 2175.0 arbitrary units， respectively)， precision [the widths between the 95% limits of agreement for the regression line of difference were 57.5，56.5 and 60.7 ml&#8226;min^-1&#8226;(1.73 m²) ^-1， respectively]. Compared with the original abbreviated MDRD equation，the 30% accuracy of modified abbreviated MDRD equations was significantly higher(from 66.1% to 77.8% and 79.6%， P < 0.05). Conclusions Compared with original abbreviated MDRD equation，the modified abbreviated MDRD equations based on the Chinese CKD patients offer significantly advantages in different CKD stages. It can be applied to GFR estimation in substitution of original abbreviated MDRD equation.

Objective To evaluate the cost-effectiveness of intravenous and oral iron supplements in hemodialysis patients with chronic renal anemia. Methods Two hundred and thirty-five patients with renal anemia were enrolled and randomly divided into intravenous group(n=116) who received iron dextran injection and oral group (n=119) who received ferrous succinate tablets. The dosage of iron dextran was calculated for each patient and was given during each hemodialysis session. After total dosage was finished， 100 mg of maintenance dose was given periodically depending on the levels of ferritin and Hb. The oral group received ferrous succinate tablet equivalent to 200 mg element iron. Two hundred and twenty-six patients finished 26-week treatment and 113 patients in each group. HB and Hct were indexes to evaluate the efficacy of the treatment. The treatment cost included the direct medical costs in iron product， EPO， medical examination and adverse events， and indirect medical costs in traffic， nursing， nutriment and the loss of labor. Results The average treatment cost for each patient was 25 thousand yuan(RMB) and 24.1 thousand yuan(RMB) for intravenous and oral group respectively with no significant difference(P > 0.05). The effective rates were 88.5% and 71.68% for intravenous and oral group respectively with significant difference (P < 0.05). Therefore， average cost per patient for achieving effectiveness was 28.213 thousand yuan(RMB) and 33.683 thousand yuan(RMB) for intravenous and oral group respectively. Conclusions Intravenous iron therapy is more effective in the treatment of renal anemia. There is no significant difference in treatment cost between two groups. Therefore， intravenous iron dextran has greater cost-effectiveness than oral iron in renal anemia， and is worthy to be recommended to clinical application.

Objective To assess the efficacy of two antibiotic prophylactic regimens in a prospective randomized trial in 1 year for patients undergoing insertion of catheters， and to provide the evidence for uniform consensus existing on the timing， route， and choice of antibiotic. Methods During a period of 12 months， 78 patients， who consecutively entered the peritoneal dialysis programme， [45 women and 33 men， mean age (48.2±15.7)years] were included. The prophylactic regimens were a single dose of ceftriaxone (1.0 g) given intravenously 30 minutes before surgery (Group A) and given cefazolin (0.25 g/L) i.p. in the each dialysis bag for 3 days postoperatively (Group B). All operations were performed in one room. The wound was observed every day， and body temperature， Count of white blood corpuscle and type， dialysate were examined every day. Results In Group A and B， none of the patients showed peritonitis or wound infection during the post-operative period (within 10 days). One of 39 patients(2.5%) in the group A， and 2 of 39 patients (5.1%) in the group B had exit site infection (P > 0.05). Conclusions There is no significant difference in the incidence of peritonitis and wound infection between two groups. Prophylactic preoperative single-dose antibiotics intravenously do as well as antibiotics given intraperitoneally for peritoneal dialysis catheter insertion， but is much more convenient.

Objective To explore the distribution of dendritic cells(DCs) and the expression of adhesion molecules in rat kidney with unilateral ureteral obstruction(UUO)，as well as the regulatory effect of anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) on adhesion， maturation and function of human DCs cultured in vitro. Methods UUO rat models were established， which were divided into sham group(n=6)，untreated group(n=18)and treated group with PsL-EGFmAb(n=18). DCs were analyzed with Axioplan 2 microscopy， while P-selectin being observed by immunohistochemistry. CD34+ stem cells were isolated from cord blood and cultured in 20%IMDM medium with SCF， GM-CSF， TGF-β1， Flt-3L and TNF-α in vitro. During development， PsL-EGFmAb was added and IL-10 served as control. FACS was performed to detect the expression of HLA-DR， CD1a， CD11c， CD54，CD83， CD80， CD86， CD209 (DC-SIGN) and CD62-P，-E，-L(P-，E-，L-selectin) on DCs. RT-PCR was performed to detect the expression of NF-κB P50， P65 mRNA. MLR was performed to detect the stimulatory effect of DCs on T cell proliferation and ELISA to determine IL-12p70 amount. Results Comparing with Sham group， the expression of P-selectin was up-regulated among tubulointerstitium mainly on renal tubular epithelial cell after unilateral ureteral obstruction on day 1， while CD1a+CD80+DCs being also found in renal interstitium. The expression of P-selectin and CD1a+CD80+DCs was increased evidently on day 7， and correlated with the degree of renal tubulointerstitial fibrosis closely. However， these changes became less conspicuous in rat treated with PsL-EGFmAb. In vitro experiment showed on day 5 after cultured with the induction of TNF-α， immature DCs highly expressed C-type lectin DC-SIGN of pattern recognition receptors； the expression of co-stimulatory molecules such as CD11c，CD83，CD80 and CD86 on mature DCs was up-regulated in paralleling with the mRNA level of NF-κB；the secretion of IL-12 was enhanced， as well as displaying the features of antigen-presenting cells with a higher ability to induce proliferation of T lymphocytes in vitro. In addition， L-selectin expressed highly on immature DCs， but lowly on mature DCs， neither of two DCs expressed P- and E-selectin. Compared with the IL-10 treated group， PsL-EGFmAb had an inhibitory effect on DC-SIGN of DCs with down-regulating the mRNA level of NF-κB. PsL-EGFmAb could also inhibited CD11c， CD83， CD80， CD86 expression， reduced secretion of IL-12， and inhibited T cell proliferation stimulated by DCs in vitro. Conclusion DCs may play a critical role on initiating the inflammatory injury of renal tubulointerstitium， and the inhibitory effect of PsL-EGFmAb on DC maturation and function correlated with the inhibition of DC-SIGN， which is mainly mediated through NF-κB signaling pathway.

Objective To investigate the role of overexpression of Smad7， the inhibitory factor of TGF-β/Smads signaling，in epithelial-mesenchymal transition(EMT) of peritoneal mesothelial cells. Methods Peritoneal fibrosis rat model was built by daily intraperitoneal injection with 4.25% Dineal (100 ml/kg) and lipopolysaccharide(LPS)(0.6 mg/kg) at day 8， 10， 12， 22， 24， 26. Smad7 or control empty vectors was transferred at day 0，14 and was induced by doxycline in the daily drinking water(200 mg/L). Rats were sacrificed on day 28 and the expression of TGF-beta/Smads， α-SMA and E-cadherin was examined. Results Compared with normal rats， empty vector rats showed higher expression of phosphorylated Smad2/3. α-SMA expression was elevated but E-cadherin was reduced. Under electron microscope，the mesothelial cells removed to submesothelial zone and showed large bundles of actin microfilaments and dense bodies within the cytoplasm. Basement membrane was broken. After induction of Smad7 in peritoneal fibrosis rats， the morphology of mesothelial cells normalized partly， phosphorylated Smad2/3 was reduced. Moreover， expression of E-cadherin was increased， expression of α-SMA was dramatically reduced. Conclusion Inhibition of TGF-β/Smad signaling by Smad7 overexpression may inhibit the epithelial-mesenchymal transition of mesothelial cell， which may provide a new therapeutic method for peritoneal fibrosis by overexpression of Smad7.

Objective To study the effect of injured podocytes on glomerular maturation and its underlying mechanism in neonatal mice. Methods Single i.p.injection with puromycin aminonucleoside (PA， 0.1 mg/g BW) was given to ICR neonatal mice at day 1 after birth (1 dpp). Littermates injected with normal saline (NS) were used as control. Animals were examined for urine protein， blood pressure， kidney weight/body weight (KW/BW)， renal histology at 2， 4， 8， 12， 30， 60 and 90 dpp (n=6~9 for each group). Immunohistochemistry and quantitative RT-PCR were performed to examine the expression of WT-1， CD31， VEGF， Flk-1， Ang-1， Ang-2， Tie-1 and Tie-2. Results Mice with PA injection had lower kidney weight and body weight at all time points as well as lower KW/BW at 4， 8， 12 dpp when compared with NS controls. Electron microscopy revealed nearly complete foot process effacement and segmental microvillous transformation as early as 1 day after PA injection. PA-injected kidneys showed fewer capillary loops and decreased maturation index as well as less CD31-positive endothelium in cortical glomeruli at 12 dpp. Glomerular mesangial injury and developing glomerulosclerosis along with proteinuria were noted in PA-injected kidneys starting from 30 dpp. Significantly increased systolic blood pressure was detected at 60 dpp in PA mice. Compared with NS injection， PA injection significantly induced decreased mRNA expression of Flk-1 and Tie-2 as well as increased expression of Ang-1，without obvious changes of VEGF at 2 dpp. Conclusions Podocytes in neonatal kidney of ICR mice are susceptible to PA. Such podocyte injury can alter the expression of VEGF and angiopoietin system in glomeruli， leading to abnormal development of glomerular capillaries， and subsequent proteinuria， hypertension and glomerulosclerosis.

Objective To observe the role of rosiglitazone in unclipped kidneys of two-kidney- one-clip hypertensive rats and examine its relationship to angiotensin Ⅱ receptors. Methods Two-kidney-one-clip hypertensive rats were divided randomly into 4 groups as follows: positive control group (CONT)， traditional antihypertensive drugs group (TAHD， reserpine 50 µg·kg^-1·d^-1， dihydralazine 6.25 mg·kg^-1·d^-1 and hydrochlorothiazide 6.25 mg·kg^-1·d^-1， regular-dose rosiglitazone group (RRGL， rosiglitazone 5 mg·kg^-1·d^-1)， and high-dose rosiglitazone group (HRGL， rosiglitazone 20 mg·kg^-1·d^-1). Sham operation rats were as negative controls. Each group had 8 rats. Animals were monitored and sacrificed at 10th week. Results Blood systolic pressure in TAHD group and HRGL group was significantly lower than that in CONT group [TAHD(137±27 ) mm Hg and HRGL(143±16) mm Hg vs CONT (191±25) mm Hg， P < 0.05]， but no significant difference between the former two groups was found. Nor did the blood systolic pressure between RRGL group [(176±18) mm Hg] and CONT group. At 10th week， rats in SHAM group and treated groups had lower urinary urinary protein excretion rate， glomerular injury score and wall-to-lumen ratio of arteriole than those in CONT group[vs CONT urinary protein excretion rate (44.60±17.40) mg/24 h， P < 0.05； vs CONT glomerular injury score 60.85±33.05， P < 0.05； vs CONT wall-to-lumen ratio of arteriole 2.33±1.01， P < 0.01，except TAHD group]. Though with the similar level of blood pressure， blood glucose and lipid， HRGL， compared with TAHD group showed lower urinary protein excretion rate [HRGL (16.78±3.50) mg/24 h vs TAHD (27.94±12.79) mg/24 h， P < 0.05]， decreased glomerular injury score (HRGL 18.04±7.76 vs TAHD 27.92±6.39， P < 0.05) and wall-to-lumen ratio of arteriole (HRGL 1.75±0.38 vs TAHD 2.16±0.90， P < 0.05) in the cortexes of unclipped right kidneys. The expression of type 1 angiotensin Ⅱ receptor (AT1R) mRNA was no difference in HRGL group and TAHD group， but the expression of type 2 angiotensin Ⅱ receptor (AT2R) mRNA was more intensive in HRGL group. Conclusion Rosiglitazone can protect the kidneys from hypertensive injury， especially in high dose. The beneficial effects seem incompletely dependent on the metabolism modulating and reduction of blood pressure， but in relationship to the upregulation of AT2R mRNA.

Objective To investigate the effect of 12-lipoxygenase(12-LO) on the angiotensin Ⅱ type 1 receptor(AT1R) expression in mesangial cells (MC). Methods p38 MAPK activation and ECM protein expression were determined using AngⅡ-stimulated MC derived from normal and 12-LO knockout mice. AT1R expression was determined using 12-LO product 12(S)-HETE-stimulated MC， MC transfected with 12-LO gene and microdissected glomeruli derived from 12-LO knockout mice. RT-PCR and Western blot were used for evaluating mRNA and protein expression respectively. Results AngⅡ stimulation increased p38 MAPK activation and ECM protein expression in normal MC， but not in MC derived from 12-LO knockout mice. Time-dependent and dose-dependent experiment showed that 12(S)-HETE increased AT1R protein′expression in MC. Similarly， 12(S)-HETE increased AT1R mRNA expression in MC compared with control MC(P < 0.01). Furthermore， AT1R expression was lower in glomeruli derived from 12-LO knockout mice relative to genetic controls(P < 0.01) and MC stably overexpressing 12-LO had greater AT1R protein and mRNA expression relative to control MC(P < 0.01). Conclusion 12-LO activation can upregulate AT1R expression in MC.

Objective To initially investigate the mechanism of COX-2 inhibitor inducing cell apoptosis through the observation of celecoxib(CXB)， a specific COX-2 inhibitor，inducing apoptosis of cyst lining epithelial cells of human polycystic kidney. Methods (1)Primarily cultured cell was divided into control group and CXB group to evaluate the proliferative state by Brdu assay.(2)The cell apoptosis was observed by transmitted electronic microscope after being cultured in CXB 2×10^-5 mol/L for 24，48 hours.(3)The cell apoptosis and apoptotic rate were detected by TUNEL assay.(4)The cell apoptotic rate were measured by AnnexinV， PI-labeled flow cytometry after being cultured in CXB 2×10^-5 mol/L for 0， 24， 48 hours.(5)Protein expression of Bax，Bcl-2，caspase 3 was examined by Western blotting. Results (1)The Brdu assay revealed that CXB inhibited cell growth in a concentration-dependent manner， with the maximum growth inhibition ratio of 63.9% when treated by CXB 2×10^-5 mol/L for 24 h.(2)Typical morphological changes of apoptotic cell were apoptotic body， nuclear concentration，chromatin aggregation， endochylema vacuolization and ravinement under eletrou microscope. (3)TUNEL assay showed that the apoptotic rate was (2.8±0.2)% in control group， and (28.5±1.6)%， (48.5±1.2)% in CXB group for 24，48 hours respectively，with significant differences to control group(P < 0.05). (4) AnnexinV， PI-labeled flow cytometry showed that，in 0，0.5，1，2×10^-5 mol/L CXB group，the apoptotic rates were(3.15±0.05)%，(7.15±0.11)%，(7.76±0.08)%，(12.15±0.07)% for 24 hours respectively，and(13.53±0.21)%，(18.36±0.17)%，(24.87±0.25)%，(53.66±0.32)% for 48 hours respectively. Significant differences were found among corresponding groups(all P < 0.01). (5) Extracted total cell protein in every group and more protein of Bax，Bcl-2 expressed in CXB-treated group was detected by Western blotting than that in control group.Conclusions CXB can inhibit the proliferation of cyst liner epithelial cells in a time- and concentration-dependent manner， and induce cell apoptosis through increasing the ratio of Bax/Bcl-2. CXB is hopeful to become an effective drug to treat ADPKD.