In vivo and in vitro performance of a China-made hemodialysis machine: a multi-center prospective controlled study.

OBJECTIVE: To evaluate the in vivo and in vitro performance of a China-made dialysis machine (SWS-4000). METHODS: This was a multi-center prospective controlled study consisting of both long-term in vitro evaluations and cross-over in vivo tests in 132 patients. The China-made SWS-4000 dialysis machine was compared with a German-made dialysis machine (Fresenius 4008) with regard to Kt/V values, URR values, and dialysis-related adverse reactions in patients on maintenance hemodialysis, as well as the ultrafiltration rate, the concentration of electrolytes in the proportioned dialysate, the rate of heparin injection, the flow rate of the blood pump, and the rate of malfunction. RESULTS: The Kt/V and URR values at the 1st and 4th weeks of dialysis as well as the incidence of adverse effects did not differ between the two groups in cross-over in vivo tests (P > 0.05). There were no significant differences between the two groups in the error values of the ultrafiltration rate, the rate of heparin injection or the concentrations of electrolytes in the proportioned dialysate at different time points under different parameter settings. At weeks 2 and 24, with the flow rate of the blood pump set at 300 mL/min, the actual error of the SWS-4000 dialysis machine was significantly higher than that of the Fresenius 4008 dialysis machine (P < 0.05), but there was no significant difference at other time points or under other settings (P > 0.05). The malfunction rate was higher in the SWS-4000 group than in the Fresenius 4008 group (P < 0.05). CONCLUSIONS: The in vivo performance of the SWS-4000 dialysis machine is roughly comparable to that of the Fresenius 4008 dialysis machine; however, the malfunction rate of the former is higher than that of the latter in in vitro tests. The stability and long-term accuracy of the SWS-4000 dialysis machine remain to be improved.

Comparison of two fluid solutions for resuscitation in a rabbit model of crush syndrome.

BACKGROUND: Crush syndrome is a common injury, the main characteristics of which include acute kidney injury. However, there is still lack of reliable animal model of crush syndrome, and it also remains controversial as to which type of fluid should be chosen as a more appropriate treatment option for prevention and treatment of acute kidney injury. METHODS: The rabbits were crushed at the lower limbs for 6 h with 36 times the body weight, which means the pressure of each leg was also 36 times the body weight. Fluid resuscitation was performed from 1 h prior to the end of the crush treatment until 24 h after the reperfusion. Tissue, blood and urine samples were collected at predetermined time points before and after reperfusion. Twelve rabbits in each group were taken for survival observation for 72 h. RESULTS: The model group showed elevated serum creatine kinase, aspartate aminotransferase, alanine aminotransferase, and K(+) level, reduced serum Ca(2+) level and Na(+) level, and increased serum creatinine and blood urea nitrogen levels, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 (p < 0.05). The 0.9 % normal saline (SAL) group and SAL plus 6 % hydroxyethyl starch 130/0.4 SAL/HES group showed reduced serum creatinine and blood urea nitrogen levels (p < 0.05). The SAL/HES group also showed reduced serum IL-6 and IL-10 levels (p < 0.05). The 72 h survival rate of the SAL/HES group was higher than that of the model group (p < 0.05). CONCLUSION: The rabbit model of crush syndrome showed clinical features consistent with those of crush syndrome. There was no significant difference in the ability of preventing AKI after a crush injury between the two fluid solutions, while SAL/HES can improve the survival rate.

The aldosterone receptor antagonist spironolactone prevents peritoneal inflammation and fibrosis.

Peritoneal fibrosis is a complication of patients with long-term continuous ambulatory peritoneal dialysis (CAPD). Reports have indicated that angiotensin (Ang) II may correlate with the development of peritoneal fibrosis. However, it is unknown whether aldosterone also has a role in the development of peritoneal inflammation and fibrosis. The aim of the present study was to clarify the role of aldosterone in peritoneal inflammation and fibrosis. A rat model of peritoneal inflammation and fibrosis was established by daily intraperitoneal injection of dialysates and lipopolysaccharide in a 4-day interval over a period of 7 days. The animals were randomly assigned to five groups as follows: control (C); peritoneal dialysis (PD); peritoneal dialysis-spironolactone (PD-S); peritoneal dialysis-cilazapril (PD-C); and peritoneal dialysis-spironolactone-cilazapril (PD-SC). After 30 days, the TGF-ß1 concentration in dialysates from all treatment groups was determined by ELISA. The histopathology of the parietal peritoneum was examined, and the expression of MCP-1, c-Jun, fibronectin (FN) and TGF-ß1 in the abdominal membrane was determined by immunohistochemistry. Mineralocorticoid receptor (MR), 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) and CYP11B2 (aldosterone synthase) were analyzed by real time-PCR. Collagen deposition was significantly higher in PD compared with the other groups. The expression of MR, 11ß-HSD2 and CYP11B2 was significantly higher in PD compared with the other groups. Spironolactone and/or cilazapril treatment partially ablated the increase in monocyte chemoattractant protein (MCP)-1, p-c-Jun, transforming growth factor (TGF)-ß1, FN, MR, 11ß-HSD2 and CYP11B2. Furthermore, treatment with spironolactone and/or cilazapril also reduced the infiltration of CD-4- and ED-1-positive cells in rat peritoneal tissues after peritoneal fibrosis. Exogenous aldosterone may have a key role in the development of peritoneal inflammation and fibrosis. Spironolactone decreased peritoneal inflammation and fibrosis, which was associated with reduced secretion from peritoneal macrophages, inactivation of the c-Jun N-terminal kinase (JNK) pathway and subsequent downregulation of the expression of TGF-ß1.

KMUP-1 regulates the vascular calcification in chronic renal failure by mediating NO/cGMP/PKG signaling pathway.

OBJECTIVE: To explore the potential mechanism of KMUP-1 in the vascular calcification of chronic renal failure (CRF) through mediating NO/cGMP/PKG pathway, and provide novel insights into the CRF treatment. METHODS: CRF rats were treated by KMUP-1 with/without L-NNA (a NOS inhibitor) and then performed by ELISA, alizarin red staining, Von Kossa staining, Masson's trichrome, Sirius red staining and CD3 immunohistochemical staining. Simultaneously, vascular smooth muscle cells (VSMCs) were collected from rats to confirm the effect of KMUP-1 on vascular calcification in vitro via NO/cGMP/PKG pathway. Besides, protein and mRNA expressions were determined via Western blotting and qRT-PCR, respectively. RESULTS: CRF rats were elevated in 24-h urine protein, blood urea nitrogen (BUN), serum creatinine, Cys-C levels and inflammatory cytokines. Besides, CRF rats also showed increased calcium content and ALP level with up-regulated mRNA of osteogenic differentiation-related markers. Furthermore, the up-regulated expressions of eNOS and PKG, as well as down-regulated levels of NOx and cGMP were also found in CRF rats. However, renal failure and vascular calcification of CRF were improved significantly by KMUP-1 treatment via activation of NO/cGMP/PKG pathway. Moreover, KMUP-1 treatment attenuated calcified VSMCs, accompanied by the decreases in the calcified nodules, level of calcium and activity of ALP. In addition, either L-NNA treatment for CRF rats or the calcified VSMCs could antagonize the improving effect of KMUP-1. CONCLUSION: KMUP-1 can improve the renal function and vascular calcification in CRF rats at least in part by activating NO/cGMP/PKG pathway.

[Epidemiology of anticoagulation for hemodialysis patients: survey of 842 cases in seven hemodialysis centers].

OBJECTIVE: To investigate the anticoagulant methods and characters of hemodialysis patients in hospitals of Grade III Level A. METHODS: A questionnaire survey was conducted in 7 hemodialysis centers of class 3 first level general hospital in Beijing, Shenyang, Harbin, and Dalian, on the hemodialysis status, primary diseases, anticoagulation methods, and complications. RESULTS: 808 of the 842 patients (95.9%) underwent hemodialysis, and 34 patients (4.1%) were subjected to hemodialysis filtration. 606 hemodialysis patients (74.9%) used heparin as the anticoagulant, and the doses and using method were different among different centers. 223 patients (26.5%) used low molecular weight heparin (LMWH) with different kinds, doses and using methods. The underlying diseases included diabetes (15.1%), hypertension (9.4%), and other diseases (75.5%). There was no significant difference in the dosage of heparin among different diseases, while the dosage of LMWH was lower for the diabetes and hypertension patients. 171 patients (20.3%) had hemorrhagic tendency, and 67 patients (20.3%) suffered from thrombus. The dosage of heparin was lower in the patients with hemorrhagic tendency while no difference was found in the dosages of LMWH among the patients with different diseases. Antiplatelet agents were co-administrated in 172 hemodialysis patients (20.4%). The percentages of co-administration of antiplatelet for patients with thrombus and hemorrhagic tendency were 14% and 12.8% respectively. The dosages of heparin and LMWH were higher in the patients with co-administration than those without co-administration. Coagulation marker examination was conducted in only 385 patients (45.7%), and no difference in the frequency of coagulation marker examination was found among the patients with hemorrhagic tendency, thrombus, and other diseases. CONCLUSION: Heparin is the main anticoagulant in hemodialysis. The anticoagulant methodology in hemodialysis is still empirical without clotting monitor and standard for usage of anticoagulants.

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats.

BACKGROUND: This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. METHODS: 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. RESULTS: Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta (P < 0.05) and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. CONCLUSIONS: Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

Icariin ameliorates IgA nephropathy by inhibition of nuclear factor kappa b/Nlrp3 pathway.

Immunoglobulin A nephropathy (IgAN) is the most frequent form of glomerulonephritis, which is characterized by glomerular proliferation and renal inflammation. Icariin is a flavonoid from the Chinese herb Epimedium, and its anti-inflammatory effect has been reported. This study aimed to investigate the effects of icariin on the renal damage in IgAN rats and the mechanisms behind these effects. IgAN model was established in Sprague-Dawley rats by oral and intravenous immunization with bovine gamma-globulin for 12 weeks, and rats were treated with icariin from 12 to 18 weeks. At the end of experimental period, kidneys, urine, and blood samples were collected for further analysis. Our results showed that icariin ameliorated the increase in the levels of proteinuria, serum creatinine, and urea nitrogen without severe side effects. IgAN rats exhibited significantly increased IgA deposition, mesangial matrix expansion, and glomerular fibrosis, while icariin treatment markedly attenuated these alterations. Moreover, treatment with icariin also dramatically blocked nuclear factor kappa b (NF-κB) nuclear translocation and Nlrp3 inflammasome activation in IgAN rats, leading to reduced downstream proinflammatory cytokines production. Mechanistically, we found that icariin treatment inhibited IKKß and IκBα phosphorylation and IκBα degradation in IgAN rats. Our data demonstrate that icariin ameliorates renal damage in IgAN rats via inhibition of NF-κB-mediated Nlrp3 inflammasome activation. These findings provide insight into an application of icariin for the treatment of IgAN disease, and represent a novel mechanism behind these effects.

Influence of overexpression of SOCS2 on cells of DN rat.

OBJECTIVE: To explore the influence and mechanism of overexpression of SOCS2 on diabetic nephropathy (DN) rats and cells. METHODS: STZ was used to induce male SD rats and SOCS2 was injected into left renal vein. Rats were divided into DN group, DN-Ad-null group and DN-Ad-SOCS2 group. Glucose with high and normal concentration was used to culture HBZY-1 cells and then transfect Ad-SOCS2. HG group, HG-Ad-null group, HG-Ad-SOCS2 group, CG group, CG-Ad-null group, and CG-Ad-SOCS2 group were created. The expression of inflammatory cytokines (MCP-1, TNF-α and IL-6) in kidney tissue of rats, fibrosis related protein (FN, Collagen IV and TGF-ß) in kidney tissue and cells of rats, and JAK/STAT signaling pathway related proteins (p-JAK2 and p-STAT3) were tested by western blot. ELISA was used to test the expression of inflammatory cytokines (TNF-α and IL-6) in cells. RESULTS: The expression of inflammatory cytokines in DN rats (MCP-1, TNF-α and IL-6) and cell (TNF-α and IL-6) were increased (P < 0.01) significantly. However, SOCS2 could decrease the overexpression of mediated inflammatory cytokines in DN animal models and cell models (P < 0.01). The expression of fibrosis related protein in DN rats and cells increased while SOCS2 decreased the overexpression of mediated fibrosis related protein in DN model rats and cells (P < 0.01). The expression of JAK/STAT pathway related protein in both DN rats and cells increased and the JAK/STAT signaling pathway was activated. Yet, SOCS2 obviously suppressed the expression of the JAK/STAT signaling pathway as well as the related proteins (p-JAK2 and p-STAT3) in both DN rats and cells. CONCLUSIONS: The overexpression of SOCS2 can decrease the expression of inflammatory cytokines and fibrosis related proteins in DN rats and cells, and meanwhile suppress the activation of JAK/STAT signaling pathway mediated by DN.

Anticoagulation treatments related different types of vascular access on maintenance hemodialysis patient: A multicenter epidemiological investigation.

OBJECTIVE: The objective was to increase the understanding of vascular access in hemodialysis and evaluate hemodialysis-related anticoagulation treatments and the associated hemorrhagic or thrombotic complications. MATERIALS AND METHODS: In this study, an epidemiological investigation was conducted in 1175 patients who underwent hemodialysis in seven blood purification centers in northern Chinese. The patients were divided into two groups based on the vascular access they used: Arteriovenous fistula (AVF) group and central venous catheter (CVC) group. The similarities and differences of anticoagulation and hemorrhagic, thrombotic complications were compared between two groups. RESULTS: Arteriovenous fistula was the most frequently used vascular access, and heparin was the most commonly used anticoagulant. Patients in CVC group experienced significantly greater rates of low molecular weight heparin (LMWH) administration and had a higher rate in achieving thrombotic complications than those in AVF group. There were no significant differences in LMWH dosages in patients with thrombotic complications, as well as the proportion of patients who received anti-platelet drugs. Heparinized catheter lock solutions were excessively high in this study, which may lead to a risk of hemorrhage. CONCLUSION: Hemodialysis-related anticoagulation treatments in China require additional improvements, especially for the patients using CVC as vascular access. There is an urgent need to develop clinical evaluation studies of anticoagulation treatments for achieving more standardized and targeted treatments.