Objective To determine the normal value range of glomerular diameter in Chinese adults and to investigate the measurement methods. Methods One hundred patients with minor glomerular abnormalities or thin basement membrane nephropathy diagnosed by renal biopsies from 1998 to 2008 with normal body weight and serum glucose were selected for the determination of normal value range of glomerular diameter. The maximal profile diameter of glomerular capillary loops was measured by Motic Med 6.0 image analysis system in the following ways: (1) direct measurement: two perpendicular longest diameters of each glomerulus were measured. (2) indirect measurement: the area of each glomerular capillary loop was measured, then its diameter was calculated by formula. Ten patients with minimal change disease, 10 with focal segmental glomerulosclerosis, and 10 with membranous nephropathy, who all had normal body weight and serum glucose, were also selected for the measurement of glomerular diameter, whose results were then compared with normal values. Results The results obtained from the direct and indirect measurements were not significantly different. The gender and age had no significant effects on glomerular size. The normal value ranges of glomerular maximal profile diameter were as follows: (1) the glomeruli with pole(s) which maximal profiles were with vascular pole and/or urinary pole: the diameter range measured by the direct method was 101.3-182.9 μm, and by the indirect method was 100.3-181.5 μm. (2) the glomeruli with pole(s) and the glumeruli without pole which maximal profiles were without vascular pole or urinary pole, but were bigger than those in smallest glomeruli with pole(s):the diameter range measured by the direct method was 108.5-182.9 μm, and by the indirect method was 107.6-183.2 μm. In addition, the glomerular maximal profile diameters of 30 patients with glomerular diseases were all in the normal value range. Conclusions Direct and indirect measurement methods are both available. The normal value range of glomerular diameter obtained from this study may be used for Chinese adults.

Objective To evaluate the efficacy and safety of low-dose cyclosporine A(CsA) combined with low-dose prednisone as induction therapy for patients with idiopathic membranous nephropathy (IMN) and compare with those of cyclophosphamide (CTX) combined with high-dose prednisone. Methods A prospective observational cohort study in 31 nephrotic patients with IMN was conducted. In CTX group, patients were treated with cyclophosphamide (oral 100 mg/d, accumulation about 8 g) combined with prednisone (0.6-1.0 mg•kg-1•d-1, tapered after 2-3 months). In CsA group, initial dose of CsA was 1.0-1.5 mg•kg-1•d-1 combined with prednisone 0.15-0.50 mg•kg-1•d-1 [(0.33±0.20) mg•kg-1•d-1, tapered after 3 months]. The dose of CsA was added gradually according to efficacy and the highest dose of cyclosporine was ≤2.5 mg•kg-1•d-1. Clinical parameters (urinary protein, serum albumin and serum creatinine) and adverse effects were estimated before and after therapy. Results In CTX group, twenty patients had been followed-up for (48±22) weeks and their remission was observed in 13 patients (65%, complete remission 6, partial remission 7). Nineteen patients were recruited in CsA group, including 8 patients who either had no response or relapsed after CTX therapy. In CsA group, two patients discontinued CsA therapy due to severe uncontrolled hypertension; the effective dose of CsA for remission was (2.1±0.4) mg•kg-1•d-1 (1.5-2.5 mg•kg-1•d-1); mean trough concentration of CsA was (92.5±23.5) μg/L (58-124 μg/L); remission was observed in 12 patients (70%, complete remission 6, partial remission 6) over a period of (44±15) weeks. There was no significant difference of remission rate between two groups. Liver dysfunction was common adverse effects during CTX therapy. Many adverse effects (increase of serum creatinine, hypertension, gum hyperplasia and hyperuricemia) occurred during CsA therapy, but could be easily controlled. Conclusions Low-dose CsA combined with low-dose prednisone has similar efficacy and safety to CTX combined with high-dose prednisone for majority of patients with IMN, including refractory patients to CTX regimens. Many adverse effects occur during CsA therapy, but can be easily controlled.

Objective To determine the incidence, risk factor and outcome of acute kidney injury (AKI) after living donor liver transplantation (LDLT). Methods Clinical data of adult patients undergone LDLT first were retrospectively analyzed. Acute Kidney Injury Net (AKIN) criteria was applied to define and classify the postoperative AKI. Logistic regression analysis was used to determine the risk factor of AKI. Kaplan-Meier survival curve was used to investigate the association between AKI stage and survival rate. Results Of 220 patients during the period of investigation, 94 patients received LDLT. Of these 94 patients, 56 patients presented AKI. The incidence of AKI after LDLT was 59.6%, and the percentages of stage I, stage II and stage III AKI were 31.9%, 12.8% and 14.9% respectively. Two patients with AKI (3.6%) needed the renal replacement therapy (RRT). One year survival rate of AKI patients was much lower than that of non-AKI patients (65.0% vs 96.7%, P<0.05). Multivariate Logistic regression analysis showed that preoperative acute physiology and chronic health evaluation II (APACHE II) score (OR=5.126), the change of mean artery pressure (△MAP) during anhepatic phase (OR=5.564) and colloid transfusion in operation(OR=1.650) were independent risk factors for stage I AKI. Preoperative prothrombin international normalized ratio (INR) (OR=4.940), preoperative proteinuria (OR=3.385) and RBC transfusion during operation(OR=1.752) were independent risk factors for stage II-III AKI. Conclusions Incidence of AKI after LDLT is quite high and the prognosis is poor. Paying close attention to the potential risk factors of AKI may be beneficial to the prognosis of patients.

Objective To investigate the morbidity of peripheral arterial occlusive disease (PAOD) in dialysis patients and the associated risk factors of PAOD. Methods Two hundred patients including 95 on hemodialysis, 55 on peritoneal dialysis and 50 with stage 2-3 chronic kidney disease (CKD) in Peking Union Medical College Hospital were enrolled in this study. Brachial-ankle pulse wave velocity (baPWV) and ankle-brachial BP index (ABPI) were detected by device (VP1000, Japan Colin). Clinical data of these patients were collected. Plasma CRP, Scr, BUN, Hb, Ca, P, iPTH, Alb, Palb, Cho, TG, LDL, HDL were measured. Lower extremity arteries ultrasonography and CT angiography (CTA) were performed in the patients with ABPI<0.9. Results (1) The morbidity of PAOD（ABPI<0.9）was significantly higher in dialysis patients as compared to CKD patients (11.33% vs 0, P=0.016), and was also significantly higher in CAPD patients as compared to HD patients (20.0% vs 6.3%, P=0.011). Superficial femoral artery, anterior tibial artery and posterior tibial artery were common occlusive sites. 23.1% patients complained the intermittent claudications. (2) Correlation analysis revealed that ABPI was associated with dialysis mode (χ2=6.491, P=0.011), age (r=-0.338, P=0.000), TC (r=-0.185, P=0.028), HDL(r=0.179, P=0.035), Scr(r=0.244, P=0.003), BUN (r=0.280, P= 0.001), Kt/V (r=-0.275, P=0.001), nPCR (r=0.269, P=0.001), DBP of upper limb(r=0.267, P=0.001), MAP (r=0.225, P=0.006), SBP of lower limb (r=0.593, P=0.000), DBP of lower limb (r=0.215, P=0.009), PWV (r=0.202, P=0.014). (3) Multiple linear regression revealed that dialysis mode, HDL, Alb, DBP of upper limb, SBP of lower limb and baPWV were independent risk factors of ABPI. Conclusions The morbidity of PAOD in dialysis patients is significantly higher than that in CKD patients. Malnutrition, dyslipidemia, hypertension and arterial stiffness are independent risk factors of PAOD in dialysis patients.

Objective To analyze the distribution of adults pathoglycemia in Zhengzhou urban area and its relation to chronic kidney disease. Methods Data were gathered from the survey of chronic kidney disease and its risk factors of Zhengzhou adults. A total of 1593 subjects (men 659, women 934) with complete data were enrolled in this study. Pathoglycemia and CKD were diagnosed according to associated definition. Results The crude prevalence of pathoglycemia and diabetes mellitus was 30.26% and 6.15% respectively, while the standardized rate was 30.76% and 6.20%. Men had higher prevalence of pathoglycemia than women (34.14% vs 27.52%, χ2=8.040, P = 0.005), and the prevalence of pathoglycemia was increased with age (χ2=5.571, P=0.018). The prevalence of albuminuria, hematuria, reduced eGFR and CKD was 5.64%, 6.3%, 1.59% and 11.51% respectively after the adjustment of age and gender component. The subjects with pathoglycemia or diabetes mellitus had higher prevalence of albuminuria and CKD (P＜0.05), which both increased with the course of disease (χ2=37.263, P＜0.01). Conclusions Prevalence of pathoglycemia and diabetes mellitus is quite high in adults of Zhengzhou city, whose standardized rate is 30.76% and 6.20% respectively. Pathoglycemia and diabetes mellitus are associated with the prevalence of CKD.

Objective To examine the association of aldosterone-mineralocorticoid receptor (Ald-MR) expression with vascular calcification in the radial artery in uremic patients. Methods Sixty uremic patients undergone arteriovenous fistula surgery for hemodialysis treatment and 8 patients undergone splenectomy after acute trauma were enrolled in the study as uremia group and control group, respectively. About 0.5 cm segment of distal radial artery was harvested as sample. Fasting venous blood was collected for the measurement of serum creatinine, calcium, phosphorus, parathyroid hormone (PTH), lipid profile, high sensitivity C-reactive protein (CRP), alkaline phosphatases (ALP) and albumin. Vascular calcification was evaluated by van Kossa staining and categorized as non-calcified, mild-to-moderate calcified and severe calcified group (group A, B, C). The expression of vascular 11β-HSD2, MR, Cbfα1, OPN, ColⅠwas detected by immunohistochemistry staining, and vascular CYP11B2 mRNA expression was determined by in situ hybridization assay. The associations among MR expression, vascular calcification and osteogenic proteins expressions were analyzed by ANOVA, Spearman correlation analysis. Results The total calcification rate of radial artery was 31.67% in uremia group and the number of patients in A, B, C group was 41, 11, 8 respectively. No vascular calcification was found in control group. Arteries from control group did not express MR and 11β-HSD2. Arteries from uremia group expressed these two Ald-MR system components obviously. MR expression in C group was significantly higher than that in other two groups (1288±223 vs 728±84, 806±133, P<0.05), however, 11β-HSD2 expression in C group was significantly lower than that in B group (1607±300 vs 3110±373, P<0.01). Uremia group presented a pattern of co-expression of Cbfα1, OPN and ColI, whose expression increased significantly in C group as compared to A group (9405±1701 vs 4563±480, 1125±592 vs 553±102, 3754±1871 vs 1821±241, P<0.01). Statistical analysis showed that MR expression was positively correlated with vascular calcification and expression of OPN, Cbfα1, ColⅠ, whose correlation coefficients were 0.469 (P<0.01), 0.312 (P<0.05), 0.413 (P<0.01), 0.379 (P<0.01), respectively. According to in situ hybridization assay, all the arteries from uremia and control groups did not express CYP11B2 mRNA. Conclusions Arterial MR expression in uremic patients increases and is positively correlated with vascular calcification and expression of OPN, Cbfα1, ColⅠ. The increment of Ald-MR system activity may play an important role in vascular calcification of uremic patients.

Objective To investigate the effect of celecoxib (CXB) on extracellular matrix (ECM) remodeling in a model of autosomal dominant polycystic kidney (ADPKD). Methods Fifty seven Han: SPRD heterozygous (Cy/+) rats were randomly divided into 3 groups: control group, small dosage CXB group (3 mg&#8226;kg-1&#8226;d-1) and large dosage CXB group (10 mg&#8226;kg-1&#8226;d-1). Renal cystic index(CT), fibrosis index and inflammatory cells infiltration in interstitium were analyzed. The mRNA expression of typeⅣ collagen (COLⅣ), matrix matalloproteinase-2 (MMP-2), metalloproteinase-2 tissue inhibitor (TIMP-2) and transforming growth factor β1 (TGF-β1) was detected by real-time PCR. The co-expression of COLⅣ, MMP-2, TIMP-2, TGF-β1 and proliferating cell nuclear antigen (PCNA) was analyzed by double immunofluorescence labeling technique and laser scanning confocal microscopy. The protein expression of TGF-β1 was detected by Western blotting. Results CT (42.90±6.56 & 47.10±7.28 vs 64.80±6.71, all P<0.05), fibrosis index (11.20±2.63 & 10.10±3.30 vs 16.30±4.16, all P<0.05) and inflammatory cells infiltration (2.60±0.26 & 2.80±0.31 vs 3.70±0.33, all P<0.05） in interstitium all decreased in small and large dosage group compared to control group. COLⅣ，TIMP-2 and TGF-β1 mRNA level decreased in both small and large dosage groups as well. Contrarily MMP-2 mRNA level increased in both groups(all P<0.05). The co-expression of COLⅣ distributed widely in tubulointerstitial area in control group but only few in small (20.30±5.11 vs 61.40±4.51, P<0.01) and large dosage group (27.50±6.73 vs 61.40±4.51, P<0.05）. MMP-2/TIMP-2 ratio increased in smalll dosage group (4.88±1.52 vs 0.35±0.13, P<0.05) and large dosage group (3.63±1.67 vs 0.354±0.13, P<0.05) as compared to control group. Western blotting showed the expression of TGF-β1 decreased in both small and large dosage groups (all P<0.05). Conclusion CXB can inhibit tubulointerstitial fibrosis in Han:SPRD rats by inhibiting the expression of TGF-β1, promoting COLⅣ degradation and increasing MMP-2/TIMP-2 ratio.

Objective To explore the effect of low protein diet on the expression of ammonia transporters, rhesus type B glycoprotein(Rhbg) in kidney of rats. Methods The expression of Rhbg in cortex, outer medullar and inner medulla of the kidnty was detected by Western blotting. The expression of Rhbg in principal cells and intercalated cells of cortical collecting duct (CCD), outer medullary collecting duct(OMCD) and inner medullary collecting duct(IMCD) was detected by single-labeling immunohistochemistry, double-labeling immunohistochemistry and quantitative immunohistochemistry. Results Western blotting results showed that low protein diet significantly increased the protein expression of Rhbg in the cortex of rat kidney but not in outer medulla and inner medulla. Rhbg immunoreactivity in principal cells and intercalated cells of CCD increased significantly in low protein diet group as compared to control group(1310±357 vs 896±154; 1550±497 vs 926±251, all P<0.05). Rhbg immunoreactivity had no change in principal and intercalated cells of OMCD and IMCD. Conclusion Low protein diet increases Rhbg expression in the cortex, which is consistence with more distinct difference in basolateral Rhbg immunoreactivity, especially in the principal cells and intercalated cells of CCD.

Objective To study the effect and underlying mechanism of pioglitazone(PPARγ ligand) on increased extracellular matrix(ECM) production in rat peritoneal mesothelial cells(RPMCs) induced by high glucose． Methods RPMCs were isolated and subcultured by enzymatic disaggregation． The cells were randomly divided into groups as follows: normal control group，high glucose group (2.5%glucose), PDTC group (NF-κB inhibitor, 25 μmol/L and 50 μmol/L+2.5%glucose), curcumin group(activator protein-1 inhibitor, 15 μmol/L and 30 μmol/L+2.5%glucose) and pioglitazone group(10 μmol/L and 20 μmol/L+2.5%glucose)． RT-PCR was used to detect the mRNA expression of fibronectin(FN), collagen Ⅰ(COLⅠ), plasminogen activator inhibitor-1 (PAI-1), c-fos and c-jun． The protein expression of p-IκBα, IκBα, p-p65, NF-κBp65 was estimated by Western blotting． Concentrations of FN, COLⅠand PAI-1 in culture medium were examined by ELISA． Results The expressions of FN, COLⅠand PAI-1 in RPMCs were significantly increased after treatment with high glucoce (P<0.01) and significantly decreased after treatment with pioglitazone(P<0.01). High glucose up-regulated the phosphoralation of IκBα, NF-κBp65 and the expression of c-fos and c-jun mRNA． Both PDTC and curcumin reduced the protein expression of FN and PAI-1 in RPMCs induced by high glucose(P<0.01), not PDTC but curcumin decreased the protein expression of COLⅠ(P<0.01)． Pioglitazone partially reversed the effect of high glucose on the phosphoralation of IκBα, NF-κBp65 and the mRNA expression of c-fos and c-jun(P<0.01)． Conclusion Pioglitazone can suppress the increased ECM production in RPMCs induced by high glucose, and this effect might be related to the inhibitory effects on activation of NF-κB and activator protein-1 pathways．

Objective To investigate the role of genistein(Gen) in the expression of connective tissue growth factor (CTGF) induced by parathyroid hormone (PTH) in human renal tubular epithelia cells. Method Real time-PCR, Western blotting, and reporter gene assay were employed to detect the effect of Gen on the expression of CTGF induced by PTH in HK-2 cells. Inhibitor of MAPK signaling pathway was used to ascertain which signal pathway was involved. Results HK-2 cells had basic CTGF mRNA and protein expression, which increased significantly after treatment with PTH. The maximal level of luciferase activity increased 1.96-fold 12 hours after exposure to PTH (10-10 mol/L). Gen dose-dependently decreased the expression of CTGF induced by PTH. Low level of p-ERK1/2 existed in normal HK-2 cells and which increased significantly in response to PTH (10-10 mol/L) and became most remarkable at 30 min. ERK1/2 antagonist U0126 noticeably inhibited the expression of CTGF in HK-2 cells. Gen blunted the phosphorylation of ERK1/2 induced by PTH. Conclusion Gen regulates CTGF expression induced by PTH through inhibiting MAPK signaling pathway in human renal tubular epithelia cells.

Objective To explore the possible mechanism of prolyl hydroxylases inhibitor-dimethyloxallyl glycine (DMOG) in protecting human renal tubular cells (HKC) from hypoxia reoxygenation injury throngh stabilizing hypoxia inducible factor 1 (HIF-1). Methods Hypoxia reoxygenation injury and pretreatment with different concentrations of DMOG on HKC were studied. Cell activitiy and cell death were evaluated by trypan blue staining and lactate dehydrogenase (LDH) activity respectively. Cell apoptosis was detected by Annexin V/PI staining and flow cytometry. The expression of EPO, HSP70 and HO-1 were examined by real-time PCR. The expressions of HIF-1α, cleaved caspase-3 and Bcl-2 were examined by Western blotting. Results The expression of HIF-1α protein was very weak in normal HKC cells. Pretreatment with DMOG for 6 h, the expressions of HIF-1α and its target gene such as EPO, HSP70 and HO-1 were all significantly up-regulated in protein or mRNA levels (all P＜0.01), and these up-regulations were concentration- dependent. Cells pretreated with 500 μmol/L or 1 mmol/L DMOG exhibited less injury compared to hypoxia reoxygenation group, with elevated cell survival (95.6%±1.8% or 96.1%±1.0% vs 83.3%±3.1%), decreased LDH activity and reduced cell apoptosis ratio (8.6%±2.7% or 6.1%±2.3% vs 19.2%±4.0%) (all P＜0.01). In DMOG-treated cells, the protein expression of cleaved caspase-3 was significantly inhibited and the protein expression of Bcl-2 was obviously up-regulated (all P＜0.05). Conclusions Preconditioning with DMOG can stabilize HIF-1α and protect HKC from hypoxia reoxygenation injury. The mechanism may be via up-regulating the expression of HIF-1α and its target genes EPO, HSP70 and HO-1, suppressing the expression of cleaved caspase-3, increasing the expression of Bcl-2, and finally reduce cell apoptosis.

Objective To evaluate the effect of low-osmolar non-ionic contrast medium （iopamidol） on apoptosis of human proximal tubular epithelial cells (HK-2) in vitro and to elucidate its possible mechanism. Methods Cultured HK-2 cells were divided into blank control group and iopamidol treated group (1.16, 4.63, 18.5, 74, 296 gI/L) and treated for 6 h. Then the HK-2 cells were treated with iopamidol(296 gI/L) for 0, 2, 4, 6, 12 h, respectively. The proportion and morphologic change of apoptotic cells were examined by flow cytometry and Hoechst 33258 staining. The protein expression of caspase-3 was determined by Western blotting. ERK phosphorylation (p-ERK1/2)/ERK1/2 and p-p38MAPK/p38MAPK were examined by Western blotting 1 h after iopamidol treatment. The expression of caspase-3 and Bcl-2 was detected by Western blotting when HK-2 cells were pretreated with SB203580 (the inhibitor of p38MAPK). Results The proportion of apoptotic cells treated with iopamidol of 74 gI/L and 296 gI/L increased significantly (all P<0.05). Iopamidol induced the expression of caspase-3 in HK-2 cells in dose- and time-dependent manner. The levels of p-ERK had no significant change in different iopamidol concentrations (all P>0.05). Iopamidol increased the level of p38MAPK significantly and the inhibitor of p38MAPK (30 μmol/L) significantly inhibited the production of caspase-3, but increased the level of Bcl-2(P<0.05). Conclusion Iopamidol induces apoptosis of cultured HK-2 cells in dose- and time-dependent manner， which may be related to the activation of p38MAPK.