Efficacy and safety of Changfu peritoneal dialysis solution: a multi-center prospective randomized controlled trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A multi-center large scale study is needed to confirm the efficacy and safety of domestic peritoneal dialysis (PD) solutions. Some researchers believe that 6 L/d is enough for adequate dialysis, but there is no multi-center prospective study on Chinese population to confirm this. In this study, we evaluated the efficacy and safety of domestic PD solution (Changfu) and its difference between 6 L and 8 L dosage.</p><p><b>METHODS</b>Adult PD patients who had taken PD therapy for at least one month were selected and divided into four groups according to two dialysis solution brands and two dialysis dosages, i.e., 6 L dose with Changfu dialysis solution, 6 L dose with Baxter dialysis solution, 8 L dose with Changfu dialysis solution, and 8 L dose with Baxter dialysis solution. After 48 weeks, the changes of primary and secondary efficacy indices were compared between different types and different dosages. We also analyzed the changes of safety indices.</p><p><b>RESULTS</b>Changes of Kt/V from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of creatinine clearance rate (Ccr). Normalized protein catabolic rate (nPCR) from baseline to 48 weeks between Changfu and Baxter showed no statistical differences; so did those of net ultrafiltration volume (nUF) and estimated glomerular filtration rate (eGFR). Changes of nPCR from baseline to 48 weeks between 6 L and 8 L showed no statistical differences; so did those of nUF and eGFR. The decline of Kt/V from baseline to 48 weeks in 6 L group was more than that in 8 L group. Change of Ccr was similar. During the 48-week period, the mean Kt/V was above 1.7/w, and mean Ccr was above 50 L×1.73 m(-2)×w(-1). More adverse events were found in Changfu group before Changfu Corporation commenced technology optimization, and the statistical differences disappeared after that.</p><p><b>CONCLUSIONS</b>The domestic PD solution (Changfu) was proven to be as effective as Baxter dialysis solution. During 48-week period, a dosage of 6 L/d was enough for these patients to reach adequate PD. Clinical study promotes technological optimization, further helps to improve the safety indices of the medical products.</p>

Prevalence, awareness, treatment, and control of hypertension in the non-dialysis chronic kidney disease patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Data on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.</p><p><b>METHODS</b>The survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.</p><p><b>RESULTS</b>The analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).</p><p><b>CONCLUSIONS</b>The prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.</p>

Effects of non-bioartificial liver support system on Gc-globulin in patients with liver failure / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effects of artificial liver support system(plasma exchange combined with continuous veno - venous hemodiafiltration, PE + CVVHDF) on Gc globulin in patients with liver failure.</p><p><b>METHODS</b>81 patients with liver failure were divided into 4 groups according to the treatment protocols and indicators such as liver function and clinical symptoms. Totally 29 effective cases and 14 ineffective cases in the ALSS group versus 15 effective cases and 23 ineffective cases in the medical group were included. Finally the changes of Gc globulin were observed in four subgroups before and after treatment. The correlation between Gc globulin and IL-10, IL-4, IL-18, TNFa, endotoxin, NO, sVCAM-1and sICAM-1were analyzed by Pearson correlation analysis.</p><p><b>RESULTS</b>The effectiveness rate was 67.44% in ALSS group and 34.21% in the medical treatment (P less than 0.01). Gc globulin, one of liver cell protection proteins was notably increased following the artificial liver treatment as compared with the increase in the medical treatment (P less than 0.01). The time-response curve of Gc globulin level had a significant upward trend in the effective group as compared to no significant rise in the ineffective group. Moreover, the Gc globulin was negatively correlated with IL-4, IL-18, TNFa, SVCAM-1, SICAM-1 and NO. In contrast, no correlation existed between Gc globulin and IL-10. The treatment with artificial liver can improve the outcome of the patients with liver failure. The level of Gc globulin was correlated with the curative effect and thus may be used as a potential indicator for curative effect forcast in the patients with liver failure.</p>

Proliferation of renal mesangial cells induced by very low density lipoprotein is mediated by p42/44 mitogen activated protein kinase / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The plasma concentration of very low density lipoprotein (VLDL) is negatively correlated to renal function in glomerular diseases. Effects of VLDL on renal function have been partially attributed to the proliferation of mesangial cells. This study examined the potential role of the p42/44 mitogen activated protein kinase (MAPK) in mesangial cell proliferation induced by VLDL.</p><p><b>METHODS</b>Mesangial cells were treated with VLDL at different concentrations or for different time. The cell cycle of the mesangial cells was analyzed by XTT assay and flow-cytometry; MAPK activity was also assayed. In some experiments, cells were treated with VLDL together with or without 0.1 µmol/L PD 98059.</p><p><b>RESULTS</b>Ten to 500 µg/ml VLDL stimulated the proliferation of mesangial cells cultured in vitro in a concentration-dependent manner. The effect was associated with an increase in p42/44 MAPK activity. Increased proliferation of mesangial cells by VLDL was significantly attenuated by PD98059, a specific p42/44 MAPK inhibitor.</p><p><b>CONCLUSION</b>These results indicate that the p42/44 MAPK pathway is an important regulator of mesangial cell proliferation and of renal functions.</p>

Parathyroid hormone-mitogen-activated protein kinase axis exerts fibrogenic effect of connective tissue growth factor on human renal proximal tubular cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Enhanced and prolonged expression of connective tissue growth factor (CTGF) is associated with kidney fibrosis. Parathyroid hormone (PTH) is involved in the genesis of disturbed calcium/phosphate metabolism and ostitis fibrosa in renal failure. PTH activated mitogen-activated protein kinase (MAPK) signaling pathway is present in renal tubular cells. The aim of this study was to identify the mechanism how the signal is transduced to result in extracellular signal-regulated protein kinase (ERK) activation, leading to upregulation of CTGF.</p><p><b>METHODS</b>The levels of CTGF mRNA and protein in human kidney proximal tubular cells (HK-2) treated with PTH in the presence or absence of the MAPK inhibitor PD98059 were analyzed by quantitative real-time polymerase chain reaction (RT-PCR) and immunoblotting assay. The activation of the CTGF promoter in HK-2 cells was determined by the dual-luciferase assay. The effects of the protein kinase A (PKA) activator 8-Br-cAMP and protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) on MAPK phosphorylation, and the effects of the PKA inhibitor H89 and PKC inhibitor calphostin C on MAPK phosphorylation and CTGF expression were detected by immunoblotting assay.</p><p><b>RESULTS</b>PD98059 inhibited the PTH stimulated expression of CTGF, which strongly suggested that the MAPK signaling pathway plays an important role in the PTH-induced CTGF upregulation in renal tubular cells. A PKA activator as well as PKC activators induced MAPK phosphorylation, and both PKA and PKC inhibitors antagonized PTH-induced MAPK phosphorylation and CTGF expression.</p><p><b>CONCLUSION</b>CTGF expression is upregulated by PTH through a PKC/PKA-ERK-dependent pathway.</p>

Intrarenal activation of renin angiotensin system in the development of cyclosporine A induced chronic nephrotoxicity / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The relationship between cyclosporine-induced chronic nephrotoxicity (CAN) and renin-angiotensin II in humans is still contradictory. This study was conducted to detect the levels of renin and angiotensin II (ANGII) both in renal tissue and plasma from kidney transplantation patients suffering from CAN.</p><p><b>METHODS</b>Twenty-six patients with allograft biopsy-proven CsA-related chronic nephrotoxicity (CAN group) and chronic rejection (control group) were enrolled in this study. Renal tissues were subjected to immunohistochemical staining with renin and ANGII antibodies. Renin and ANGII plasma levels were measured when the biopsy was performed. The relationship between expression of renin or ANGII and clinicopathological manifestations were also investigated. The cyclosporine plasma level was obtained 2 hours after morning dose (C2). In vitro, human umbilical vein endothelial cells (HUVEC) and rat mesangial cells (MC) were incubated with different concentrations of CsA (0, 250, 500, 1000 microg/L) for 24 hours. Secretion and expression of renin and ANGII was measured by radioimmunoassay or immunohistochemical staining.</p><p><b>RESULTS</b>Renal pathological scores for renin and ANGII expression were significantly higher in specimens of CAN than in controls (P < 0.05). The plasma levels of renin, ANGII and C(2) in the CAN group were higher than the control group, but no significant difference was found ((0.37 +/- 0.12) ng x ml(-1)x h(-1) vs (0.20 +/- 0.10) ng x ml(-1) x h(-1), P = 0.076; (122.69 +/- 26.73) pg/ml vs (121.88 +/- 36.35) pg/ml, P = 0.977; (719.04 +/- 55.89) ng/ml vs (658.80 +/- 90.78) ng/ml, P = 0.196, respectively). In vitro, renin as well as ANGII expression increased significantly in both HUVEC and MC after the cells were incubated with CsA for 24 hours (P < 0.05). CsA also stimulated the secretion of ANGII in HUVEC and MC in a dose-dependent manner.</p><p><b>CONCLUSIONS</b>Renal allograft biopsy is important to differentiate chronic CsA-related nephropathy from chronic rejection. The intrarenal renin angiotensin system plays an important role in CsA-related chronic nephropathy. The histological lesions of CsA nephrotoxicity fail to correspond spontaneously to either the change of C2 level or the change of renin and ANGII plasma level. CsA stimulates the secretion of ANGII and the expression of renin and ANGII in HUVEC and MC. Blockage of RAS may be helpful for therapeutic intervention in the progression of CsA-related chronic nephropathy.</p>

Expressions of homeobox transcription factor-2 and E-cadherin in gastric carcinoma and their clinical significance / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expressions of homeobox transcription factor-2 (CDX(2)) and E-cadherin and their relations to the clinicopathological characteristics of gastric carcinoma.</p><p><b>METHODS</b>Immunohistochemistry was performed on 83 human gastric carcinoma specimens and 40 normal gastric mucosa specimens for examining the expressions of CDX(2) and E-cadherin, and the relations of their expression with the tumor differentiation, infiltration and metastasis were analyzed.</p><p><b>RESULTS</b>According to the LaurAn classification, the positive expression rate of CDX(2) in intestinal type of gastric carcinoma was 56.86%, and 34.38% in the diffuse type, showing significant difference between the two types (P<0.05). The positivity rate of E-cadherin was also significantly different between the two types (66.67% vs 28.13%, P<0.01). In regard to tumor differentiation, the positivity of CDX(2) and E-cadherin expressions was significantly different between moderately to well differentiated tumors and poorly differentiated ones (P<0.01). The tumors infiltrating mucosal and submucosal layers were significantly different from those infiltrating the muscular and serous membrane layer in the positivity of CDX(2) and E-cadherin expressions (P<0.01), which were also different for the presence of lymph node metastasis (P<0.05). Regression analysis did not reveal significant correlations between CDX(2) and E-cadherin expression in gastric carcinoma (P>0.05).</p><p><b>CONCLUSION</b>The abnormal expression of CDX(2) and E-cadherin plays an important role in the development of gastric carcinoma, especially the intestinal type. CDX(2) and E-cadherin may serve as useful markers to predict the prognosis of patients with gastric carcinoma.</p>

Clinical and pathological characteristics in patients with clinically presumed hypertensive nephrosclerosis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the clinical and pathological characteristics of patients with clinically presumed hypertensive nephrosclerosis (HN).</p><p><b>METHODS</b>Clinical data and renal biopsy results were obtained in 63 patients diagnosed clinically as HN (primary hypertension plus renal injury).</p><p><b>RESULTS</b>HN was confirmed by biopsy in 47 out of 63 patients (74.6%, 12 malignant nephrosclerosis and 35 benign nephrosclerosis). Primary nephritis (PN) was diagnosed by biopsy in 10 patients (7 IgA nephropathy, 2 mesangial proliferative nephritis, 1 chronic interstitial nephritis) and focal and segmental glomerulosclerosis (FSGS) in 6 patients. Blood pressure, body mass index, GFR and blood lipids were similar among groups. HN patients were related to higher age, more frequent family history of hypertension, longer hypertension duration, higher left ventricular mass index, lower serum creatinine and lower incidence of microscopic hematuria. Most patients with malignant nephrosclerosis and FSGS patients showed grades III and IV retinopathy.</p><p><b>CONCLUSION</b>Our results show that HN was misdiagnosed in nearly 25% patients in this cohort. Since the clinical features are similar between HN, PN and FSGS, renal biopsy is needed to establish the diagnosis of HN.</p>

Evaluating the adequacy of hemodialysis with neural calculating method / 第二军医大学学报

Objective: To study the feasibility of evaluating the adequacy of hemodialysis using neural calculating method. Methods: The adequacy of hemodialysis patients were evaluated using Daugirdas, TACurea and neural calculating method respectively, the results of the 3 method; were compared with the clinical assessment of the patients. Results: The coincidence rate among the 3 methods was 84.6%, coincidence rate between neural calculating method and the clinical outcome of the patients was 92.3%, which was significantly higher than that of Daugirdas method (76.9%) and of TACurea (80.8%). Conclusion: Neural calculating method has higher accuracy in assessing the adequacy of hemodialysis patients and is clinically practical.

Evaluating the adequacy of hemodialysis with neural calculating method / 第二军医大学学报

Objective: To study the feasibility of evaluating the adequacy of hemodialysis using neural calculating method. Methods: The adequacy of hemodialysis patients were evaluated using Daugirdas, TACurea and neural calculating method respectively, the results of the 3 method; were compared with the clinical assessment of the patients. Results: The coincidence rate among the 3 methods was 84.6%, coincidence rate between neural calculating method and the clinical outcome of the patients was 92.3%, which was significantly higher than that of Daugirdas method (76.9%) and of TACurea (80.8%). Conclusion: Neural calculating method has higher accuracy in assessing the adequacy of hemodialysis patients and is clinically practical.

Expression of Bcl-2 and Bax in renal tissues of patients with hepatitis B virus-associated glomerulonephritis / 第二军医大学学报

Objective:To investigate the expression of Bcl-2 and Bax in renal tissues of patients with hepatitis B virus- associated glomerulonephritis(HBV-GN).Methods:Twenty HBV-GN specimens with complete nephrology data and 10 normal renal specimens were randomly chosen for the present study.Cell apoptosis was detected by means of terminal deoxynucleotidyl transferase mediated d-UTP nick end labeling(TUNEL)and the apoptotic index was calculated;immunohistochemistry was used to detect the protein expression of Bax and Bcl-2.ResuLts:The apoptotic index in HBV-GN group was obviously higher than that of the control group;the apoptotic cells were mainly distributed in the proximal and distal renal tubules and the collecting duct epithelial cells,seldom seen in the glomerular cells.The expression of Bcl-2 in HBV-GN patients was predominately present in the renal tubular epithelia cells(positive in the plasma,membrane and nuclear);the expression of Bax was found in both glomerular cells and renal tubular cells,mainly in tubular epithelial cells,seldom seen in Bowman's capsule or glomerular mesangial region.Conclusion:Apoptosis in the kidney of HBV-GN patients mainly occurs in the renal tubular epithelial cells;expression of Bax and Bcl-2 is mainly in the renal tubular epithelial cells,suggesting that the injury of tubular interstitial damage may be one of the important factors for the development of HBV-GN.