FTO-mediated m6A mRNA demethylation aggravates renal fibrosis by targeting RUNX1 and further enhancing PI3K/AKT pathway.

Chronic kidney disease (CKD) is a global health burden, with ineffective therapies leading to increasing morbidity and mortality. Renal interstitial fibrosis is a common pathway in advanced CKD, resulting in kidney function and structure deterioration. In this study, we investigate the role of FTO-mediated N6-methyladenosine (m6A) and its downstream targets in the pathogenesis of renal fibrosis. M6A modification, a prevalent mRNA internal modification, has been implicated in various organ fibrosis processes. We use a mouse model of unilateral ureteral obstruction (UUO) as an in vivo model and treated tubular epithelial cells (TECs) with transforming growth factor (TGF)-ß1 as in vitro models. Our findings revealed increased FTO expression in UUO mouse model and TGF-ß1-treated TECs. By modulating FTO expression through FTO heterozygous mutation mice (FTO+/- ) in vivo and small interfering RNA (siRNA) in vitro, we observed attenuation of UUO and TGF-ß1-induced epithelial-mesenchymal transition (EMT), as evidenced by decreased fibronectin and N-cadherin accumulation and increased E-cadherin levels. Silencing FTO significantly improved UUO and TGF-ß1-induced inflammation, apoptosis, and inhibition of autophagy. Further transcriptomic assays identified RUNX1 as a downstream candidate target of FTO. Inhibiting FTO was shown to counteract UUO/TGF-ß1-induced RUNX1 elevation in vivo and in vitro. We demonstrated that FTO signaling contributes to the elevation of RUNX1 by demethylating RUNX1 mRNA and improving its stability. Finally, we revealed that the PI3K/AKT pathway may be activated downstream of the FTO/RUNX1 axis in the pathogenesis of renal fibrosis. In conclusion, identifying small-molecule compounds that target this axis could offer promising therapeutic strategies for treating renal fibrosis.

The application of new complex indicators in the detection of urine.

BACKGROUND: Accurate diagnosis and assessment of hematuria is crucial for the early detection of chronic kidney disease(CKD). As instability of urinary RBC count (URBC) often results with clinical uncertainty, therefore new urinary indexes are demanded to improve the accuracy of diagnosis of hematuria. In this study, we aimed to investigate the benefit of applying new complex indicators based on random urine red blood cell counts confirmed in hematuric kidney diseases. METHODS: All patients enrolled underwent renal biopsy, and their clinical information was collected. Urinary and blood biomedical indexes were implemented with red blood cell counts to derive complex indicators. Patients were divided into two groups (hematuria-dominant renal histologic lesions and non-hematuria-dominant renal histologic lesions) based on their renal pathological manifestations. The target index was determined by comparing the predictive capabilities of the candidate parameters for hematuric kidney diseases. Hematuria stratification was divided into four categories based on the scale of complex indicators and distributional features. The practicality of the new complex indicators was demonstrated by fitting candidate parameters to models comprising demographic information. RESULTS: A total of 1,066 cases (678 hematuria-dominant renal histologic lesions) were included in this study, with a mean age of 44.9 ± 15 years. In differentiating hematuria-dominant renal histologic lesion from the non-hematuria-dominant renal histologic lesion, the AUC value of "The ratio of the random URBC to 24-h albumin excretion" was 0.76, higher than the standard approach of Lg (URBC) [AUC = 0.744] (95% Confidence interval (CI) 0.712 ~ 0.776). The odds ratio of hematuria-dominant renal histologic lesion (Type I) increased from Q2 (3.81, 95% CI 2.66 ~ 5.50) to Q4 (14.17, 95% CI 9.09 ~ 22.72). The predictive model, composed of stratification of new composite indexes, basic demographic characteristics, and biochemical parameters, performed best with AUC value of 0.869 (95% CI 0.856-0.905). CONCLUSION: The new urinary complex indicators improved the diagnostic accuracy of hematuria and may serve as a useful parameter for screening hematuric kidney diseases.

Association of trimethylamine N-Oxide with cardiovascular and all-cause mortality in hemodialysis patients.

BACKGROUND: Trimethylamine-N-Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis (HD) patients. METHODS: Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death. RESULTS: We recruited 252 patients and divided them into a high-TMAO group (>4.73 µg/mL) and a low-TMAO group (≤4.73 µg/mL). The median follow-up time was 73.4 months (interquartile range: 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank: p = 0.006) and all-cause death (Log-Rank: p < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable: HR: 1.18, 95%CI: 1.07, 1.294, p < 0.001; TMAO as a dichotomous variable: HR: 3.44, 95%CI: 1.68, 7.08, p < 0.001) and all-cause mortality (TMAO as a continuous variable: HR: 1.14, 95%CI: 1.08, 1.21, p < 0.001; TMAO as a dichotomous variable: HR: 2.54, 95%CI: 1.71, 3.76, p < 0.001). CONCLUSIONS: High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients.

Delayed ischaemic preconditioning in the presence of galectin-9 protects against renal ischaemic injury through a regulatory T-cell dependent mechanism.

AIM: Renal ischaemia/reperfusion injury (IRI) is a complication of major surgeries. Regulatory T cells (Tregs) can suppress immunologic damage in the renal IR. Previous studies indicated that delayed ischaemic preconditioning (IPC) partially attenuates IR by inducing Treg expansion. Galectin-9 also attenuates inflammation-related organ injury by expanding Tregs, but it was not used in renal IR yet. Our aim was to test whether IPC combined with galectin-9 has an increased renoprotective effect. METHODS: Mice were divided into five treatment groups (n = 6 per group): (i) IR group: renal ischaemia/reperfusion group; (ii) IPC-IR group: IPC followed by renal IR; (iii) IPC-Gal9-IR group: Gal-9 injections during the time between IPC and IR; (iv) IPC-Gal9-PC61-IR group: anti-CD25 antibody administration apart from IPC, Gal-9 and IR; (v) sham-sham group. We assessed the renal function, histopathological scores, and percentages of Tregs and interferon-γ (IFN-γ) cells in peripheral bood, spleen, and kidney and compared these values among the different groups. RESULTS: Serum creatinine measured was significantly lower after IPC and even lower in combination with Gal-9 injection. The histopathological scores for tubulo-interstitial injury were decreased following IPC and markedly lower after the addition of Gal-9. The number of kidney infiltrating neutrophils and IFN-γ secreting CD4+ T cells was diminished in the IPC/Gal9 combination group, while the percentage of Treg cells in the peripheral blood, spleen, and kidney of animals from the IPC-Gal9-IR group was also markedly increased. CONCLUSION: The renoprotective effect of delayed IPC combined with galectin-9 was superior to IPC alone, through a mechanism related to expansion of regulatory T cells.

Lymphocyte depletion and subset alteration correlate to renal function in chronic kidney disease patients.

BACKGROUND: It is widely accepted that chronic renal failure is associated with severe alterations of immune system. However, few studies looked into the immune alteration in earlier stage of chronic kidney disease (CKD) patients. To characterize immune defect in CKD patients, we performed lymphocyte subset analysis and explored its relationship to renal function in this population. METHODS: 472 CKD patients were enrolled in this study. Lymphocyte subsets (CD19(+), CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD56(+)CD16(+)) were determined by flow cytometry. Clinical and laboratory data were collected. Patterns of immune cells in different stages of CKD were compared. Multivariate linear regression was used to evaluate the relationship between lymphocyte subset group and renal function. Correlation analysis was used to assess the relationship between lymphocyte subset and other clinical and laboratory data. RESULTS: Decreased lymphocyte counts occurred long before the end stage of renal disease. Increased NK cell percentage was negatively related to estimated glomerular filtration rate (eGFR) (r = -0.259, p < 0.001) while B cell percentage was positively related to eGFR (r = 0.249, p < 0.001). Further multivariate linear regression showed increased B cell percentage (ß = 16.470, 95%CI [1.018-31.922], p = 0.037) and decreased NK cell percentage (ß = -10.659, 95%CI [-20.063 to -1.254], p = 0.026) were independently correlated with higher eGFR, respectively. Patients with lower NK cell percentage and higher B cell percentage tended to have the best renal function. CONCLUSIONS: Lymphocyte depletion and subset alteration occurred during the progress of CKD. Further studies are needed to clarify the role of immune system in CKD and to expand our knowledge about the effect of uremia on the structure and function of immune system.

[Multi-center randomized control study on the effects of syndrome differentiated traditional Chinese medicine therapy on CKD 1-2 with chronic nephritis proteinuria].

OBJECTIVE: To determine the effects of Syndrome Differentiated Chinese Medicine (TCM) Therapy on (CKD) 1-2 stage chronic kidney disease with proteinuria. METHODS: A prospective randomized control study was undertaken in 11 centers. A total of 396 chronic nephritis patients were divided into a treatment group (n=297) and a control group (n=99). Their TCM syndrome was classified as "Qi and Yin Deficiency of spleen and kidney" or "Qi and Yang Deficiency of spleen and kidney", with accompanying syndromes showing as "water and dampness", "damp-heat", and "blood stasis". Patients in the treatment group took a dose of Chinese medicine daily in response to their syndromes, while the controls took 50 mg/d losartan. The course of treatment was 24 weeks. Changes of 24-hour urinary protein excretion and glomerular filtration rate (eGFR) before and after treatments (4, 8, 12, 16, 20, 24 weeks), as well as clinical efficacy (after 4, 16, 24 weeks treatments) were measured. RESULTS: 361 patients were included in the final program participants comply analysis (PPS). Patients in the treatment group showed gradual decreased 24-hour urinary protein excretion, whereas the controls remained unchanged. Significant differences in 24-hour urinary protein excretion appeared between the experimental and control group at week 20 and 24 (P<0.05). eGFR decreased in all of the patients after treatments (P=0.0014). At three follow-up points, patients in the treatment group had higher eGFR than the controls, but without statistical significance (P>0.05). Significant differences in clinical remission rate, marked effect rate and total effective rate were observed between the treatment and control groups at week 24 (P<0.001). CONCLUSION: Syndrome differentiated TCM therapy can reduce the level of proteinuria in CKD 1-2 nephritis patients, promoting clinical effectiveness and protecting renal functions.

Efficacy and safety of Abelmoschus manihot for primary glomerular disease: a prospective, multicenter randomized controlled clinical trial.

BACKGROUND: Abelmoschus manihot, a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess its efficacy and safety in patients with primary glomerular disease. STUDY DESIGN: Prospective, open-label, multicenter, randomized, controlled, clinical trial. SETTING & PARTICIPANTS: From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. INTERVENTIONS: A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50mg/d. The duration of intervention was 24 weeks. OUTCOMES & MEASUREMENTS: The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. RESULTS: Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot, losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2, respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of -508, -376, and -545 mg/d, respectively (P=0.003 for A manihot vs losartan and P<0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups (P>0.05), and there were no severe adverse events in any group. LIMITATIONS: Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. CONCLUSIONS: A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.

Rapamycin reduces renal hypoxia, interstitial inflammation and fibrosis in a rat model of unilateral ureteral obstruction.

PURPOSE: The purpose of this study was to explore effects of rapamycin on renal hypoxia, interstitial inflammation and fibrosis, and the expression of transforming growth factor ß1 (TGF-ß1), vascular endothelial growth factor (VEGF), Flk-1 and Flt-1 in a rat model of unilateral ureteral obstruction (UUO). METHODS: Male Sprague-Dawley rats (n=36) were randomly divided into three groups (n=12 per group): sham surgery, UUO and UUO plus rapamycin (0.2 mg/kg/d). Serum creatinine (Scr), blood urea nitrogen, uric acid, triglycerides, cholesterol and 24-h urine protein levels were measured. The extent of interstitial fibrosis was determined by Masson's trichrome staining. ED-1 positive macrophages, type III collagen, hypoxia, TGF-1, VEGF, Flk-1, and Flt-1 mRNA and protein expressions were detected using immunohistochemical staining, real-time PCR and Western blot. RESULTS: UUO induced an elevation in Scr, renal hypoxia, inflammation, interstitial fibrosis, TGF-ß1, VEGF, Flk-1, and Flt-1 mRNA and protein expression levels (P < 0.05). Rapamycin alleviated the UUO-induced renal hypoxia, infiltration of inflammatory cells and tubulointerstitial fibrosis (at days 3 and 7). Rapamycin also down-regulated the UUO-induced elevated expression levels of TGF-ß1 and Flt-1 mRNA and protein (P < 0.05). Rapamycin decreased VEGF mRNA and protein expression at day 3, and increased Flk-1 mRNA and protein expression at day 7, compared with the UUO group (P < 0.05). CONCLUSION: Rapamycin shows beneficial effects by reducing UUO-induced renal hypoxia, inflammation and tubulointerstitial fibrosis.

ELISA examining urinary angiotensinogen as a potential indicator of intrarenal renin-angiotensin system (RAS) activity: a clinical study of 128 chronic kidney disease patients.

In the current study, we measured urinary angiotensinogen (AGT) through enzyme-linked immunoadsordent assay (ELISA) and analyzed its correlation with intrarenal renin-angiotensin system (RAS) activity in 128 chronic kidney disease (CKD) patients. Urinary and plasma renin activity, AGT, angiotensin II (Ang II) and aldosterone levels were also measured by radioimmunoassay (RIA) or ELISA in these participants. Further, the expression level of intrarenal renin, AGT, Ang II and Ang II receptors were examined by immunohistochemistry staining (IHCS) in 72 CKD patients. Their correlations with urinary AGT were also analyzed. We found that the urinary AGT level was positively correlated with hypertension (ρ = 0.28, P < 0.01), urinary protein (r = 0.38, P < 0.01), urinary Ang II (r = 0.29, P < 0.05), urinary type IV collagen (Col IV) (r = 0.56, P < 0.01), and was negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.28, P < 0.01), urinary sodium (r = -0.22, P < 0.05) and serum AGT (r = -0.27, P < 0.01). Multiple regression analysis indicated low serum AGT (P < 0.01), high urinary protein (P < 0.01), high urinary Ang II (P < 0.05) and high urinary Col IV (P < 0.01) were correlated significantly with high urinary AGT. Urinary AGT level was positively correlated with intrarenal expression level of AGT (ρ = 0.46, P < 0.01), Ang II (ρ = 0.56, P < 0.01) and Ang II type 1 receptor (ρ = 0.32, P < 0.01), as detected by IHCS. Together, these data suggest that urinary AGT might be a potential biomarker of intrarenal RAS and Ang II activities in CKD patients.

Analysis of early kidney damage in hospitalized patients with chronic kidney disease: a multicenter study.

BACKGROUND: To identify the risk factors for early kidney damage in hospitalized Chinese patients with chronic kidney disease (CKD). METHODS: A total of 12 multicenter cross-sectional studies were conducted between January 2005 and January 2006 in Chinese CKD patients with estimated glomerular filtration rate (eGFR) equal to or more than 30 mL/min/1.73 m2 in Shanghai. CKD was defined according to the K/DOQI guideline. GFR was estimated by the simplified modification of diet in renal disease equation. The demographic, clinical, and laboratory data were collected through a questionnaire and analyzed among eligible patients stratified by three different CKD groups (CKD stages 1, 2, and 3). The relevant clinical and laboratory risk factors for early kidney damage with a GFR < 90 mL/min/1.73 m2 were determined by logistic regression. RESULTS: A total of 822 CKD patients were enrolled in this study. There were significant differences in age and gender among patients with CKD stages 1, 2, and 3. The prevalence of hypertension, cardiovascular disease, cerebral vascular disease, anemia, and hyperuricemia increases when the eGFR declines. Logistic analysis showed that age, hypertension, anemia, and hyperuricemia were independently associated with early kidney damage. CONCLUSIONS: In CKD patients, we have identified only age, hypertension, anemia, and hyperuricemia as the risk factors for early kidney damage. Risk factors should be managed to prevent accelerated kidney damage in CKD patients.

[The risk factors and prognosis of acute kidney injury after cardiac surgery: a prospective cohort study of 4007 cases].

OBJECTIVE: To investigate the risk factors and prognosis influential factors of acute kidney injury (AKI) after cardiac surgery. METHODS: The clinical data of patients who were hospitalized and underwent cardiac surgery from April 2009 to May 2011 were collected prospectively. Demographic characteristics, types of surgeries, preoperative renal function, pre- and intra-operative conditions and clinical outcomes, etc were recorded. RESULTS: A total of 4007 patients underwent cardiac surgery were recruited. The overall incidence of AKI was 31.2% (1250/4007). The incidence of AKI requiring renal replacement treatment (AKI-RRT) was 2.6% (104/4007). The overall hospital mortality was 1.9% (77/4007), and was significantly higher in AKI group than in non-AKI group (5.4% vs 0.3%, P < 0.01). The hospital mortality of AKI-RRT group was 36.5% (38/104). Grouped by type of surgery, cardiac transplantation had the highest AKI incidence (73.0%) and highest in-hospital mortality (18.9%), followed by coronary artery bypass grafting (CABG) combined with valve surgery (AKI incidence 57.8%, in-hospital mortality 6.1%) and aneurysm surgery (AKI incidence 52.0%, in-hospital mortality 5.5%). Multivariate logistic regression analysis showed that man, age, BMI, hypertension, chronic heart failure, pre-operative serum creatinine (SCr) > 106.0 µmol/L, intra-operative cardiopulmonary bypass time, intra-operative hypotension and aneurysm surgery were the risk factors of AKI after cardiac surgery. Multivariate logistic regression analysis showed that pre-operative SCr > 106.0 µmol/L and intra-operative hypotension were independent risk factors of renal recovery after cardiac surgery while recovery of urine output was the favorable factor. CONCLUSIONS: Cardiac surgery usually induces high AKI incidence and poor prognosis, which closely associated with many risk factors in peri-operative stage. The incidence of AKI is related to a number of perioperative risk factors. Heart transplantation, aneurysm surgery, CABG combined valve surgery are high risk surgeries.

[The prevalence and risk factors of kidney disease in type 2 diabetic patients in rural Shanghai].

OBJECTIVE: To identify the prevalence and etiology of kidney disease and the related risk factors in type 2 diabetic patients in rural Shanghai. METHODS: A cross-sectional study in type 2 diabetic patients was conducted in a community of Shanghai. Questionnaire, clinical examination and laboratory tests were completed to collect the information about sociodemographic and healthcare characteristics. RESULTS: A total of 1421 eligible patients with complete information were screened from 1487 type 2 diabetic patients between November 2008 and March 2009. Of them, 40.75% were men, 59.25% were women, aged 37 - 86 (61.33 ± 9.65) years old, with diabetic duration of 0.25 - 43.92 (7.85 ± 6.34) years. Among them, 43.42% had diabetic retinopathy, 21.18% had neuropathy; 69.95% met the screening definition for hypertension, 76.07% for hyperlipidemia, 15.55% for hyperuricemia and 23.65% for cardiovascular disease. The control rates of fasting blood glucose, glycosylated hemoglobin, blood pressure and serum cholesterol were 57.71%, 33.99%, 14.22% and 2.46%, respectively. The prevalence of kidney disease, diabetic nephropathy and non-diabetic renal disease was 41.31%, 18.51% and 13.44%, respectively; and 9.36% were diagnosed as renal insufficiency of unknown reasons. Age, diabetic duration, hyperuricemia, diabetic retinopathy and poor control of blood pressure were independently associated with kidney disease; age and poor control of blood pressure were independently associated with diabetic nephropathy; age and hyperuricemia were independent risk factors of renal insufficiency in patients with diabetic nephropathy. CONCLUSIONS: Although the diabetic duration of these subjects is relatively short, the prevalence of complications including diabetic nephropathy is high. The high prevalence of non-diabetic renal disease shows the importance of further screening and diagnoses for prevention. Strict control of blood glucose, blood pressure, serum cholesterol and serum uric acid are key points of cutting down the prevalence of diabetic nephropathy and chronic kidney disease.

[Effects of hypoxic preconditioning on the migration of bone marrow derived mesenchymal stem cells].

OBJECTIVE: To explore the effects and probable mechanism of CoCl2-induced hypoxic preconditioning on the migration of bone marrow derived mesenchymal stem cells (BMSC). METHODS: BMSC were cultured by whole bone marrow adherence and identified by surface markers (CD29, CD90 and CD45) with flow cytometry (FCM). The methods of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and FCM were applied to establish the model of CoCl2-induced hypoxic preconditioning. The migratory capacity of BMSC with hypoxic preconditioning was analyzed by the assays of scratch wound healing and transwell migration. The protein and mRNA expressions of HIF-1α and CXCR4 of BMSC were detected by Western blot and real-time polymerase chain reaction (PCR). After silencing HIF-1α by siRNA technique and blocking CXCR4 by its antagonist AMD3100, the changes of migratory capacity of BMSC were also tested. RESULTS: Cultured BMSC were uniformly positive for CD29 and CD90 and negative for CD 45. According to the results of MTT and FCM, 200 µmol/L CoCl2 and 24 h culture time was the ideal hypoxic preconditioning model of BMSC. The migratory capacity of BMSC in hypoxic preconditioning group was higher than the one in control group (scratch wound healing assay: (0.396 ± 0.018) mm vs (0.200 ± 0.011) mm, transwell migration assay: 21.0 ± 4.5 vs 8.5 ± 1.7, both P < 0.05). The protein and mRNA levels of HIF-1α and CXCR4 of BMSC in hypoxic preconditioning group were significantly higher than in control group. After silencing HIF-1α or blocking CXCR4 by AMD3100, the migratory capacity of BMSC in hypoxic preconditioning group decreased and had no difference with the control group. CONCLUSIONS: Hypoxic preconditioning may enhance the migratory capacity of BMSC in vitro. And it is partially attributable to the up-regulation of HIF-1α/CXCR4 axis after preconditioning.

[Goal-directed renal replacement therapy for acute kidney injury after cardiac surgery].

OBJECTIVE: To compare the efficacy and safety of goal-directed renal replacement therapy(GDRRT) and daily high volume hemofiltration (dHVHF) in the treatment of acute kidney injury (AKI) after cardiac surgery. METHODS: Clinical data from 128 patients received either GDRRT (n = 64) or dHVHF (n = 64) for AKI after cardiac surgery were analyzed retrospectively. parameters examined included: urea nitrogen, serum creatinine (SCr, before and after treatment), heart rate, mean artery pressure (MAp, recorded within 72 hours after the initiation of renal replacement therapy). The hospital mortality, day-28 mortality, renal function recovery rate, and the incidence of adverse events in the two groups were also compared. RESULTS: The hospital mortality was 43.75% for both GDRRT and dHVHF treated patients (group). The day-28 mortality in GDRRT group were slightly lower, but the difference was not significant (43.75% vs. 57.81%, P = 0.055). Also no significant difference was found between the two groups in hospital stay. The patients received dHVHF had longer intensive care unit (ICU) stay (hours) and duration of mechanical ventilation (days) as compared to the patients received GDRRT [356.5 (176.3, 554.6) vs. 238.3 (119.6, 440.9), P = 0.023; 8.0 (5.0, 16.0) vs. 6.0 (3.0, 13.5), P = 0.042]. The logistic regression analyses showed that complete renal function recovery rate in GDRRT group was significantly higher (39.1% vs. 18.8%, P < 0.01). The partial renal function recovery rate in GDRRT group was slightly lower but not statistically different from dHVHF group (3.1% vs. 9.4%, P > 0.05). In dHVHF group, the maximum SCr during the treatment, and the SCr before discharge were both significantly higher than GDRRT group (µmol/L: SCr maximum 559.0 ± 236.0 vs. 440.4 ± 192.0, SCr before discharge 381.4 ± 267.0 vs. 271.2 ± 164.4, both P < 0.01). No significant difference was found between the two groups in incidence of hypotension (35.9% vs. 37.5%) and MAP (mm Hg, 1 mm Hg=0.133 kPa, 82 ± 13 vs. 81 ± 15) 72 hours into the therapy (both P > 0.05). The incidence of tachycardia, and incidence of blood coagulation were both higher in dHVHF group (78.1% vs. 59.4%, 35.9% vs. 20.3%, both P < 0.05). However, the hospitalization expense (thousand yuan) was significantly higher for dHVHF group (15.00 ± 2.80 vs. 9.85 ± 3.00, P < 0.01). CONCLUSION: For patients with post-cardiac surgery AKI, GDRRT and dHVHF are very similar in terms of short-term survival rate and safety. But GDRRT is superior for renal function recovery and cost saving.

[A multi-center survey of hypertension and its treatment in patients with maintenance hemodialysis in Shanghai].

OBJECTIVE: To study the prevalence, treatment policy and control of hypertension in patients with maintenance hemodialysis, and to analyze the influencing factors of hypertension control. METHODS: We studied the current status of 1382 patients with maintenance hemodialysis in 11 dialysis centers in Shanghai, among them 809 were male, and 573 were female. Hypertension was defined as systolic blood pressure (SBP)≥140 and/or diastolic blood pressure (DBP)≥90 mm Hg (1 mm Hg=0.133 kPa). Those who had a history of hypertension and requiring antihypertensive therapy were also diagnosed as hypertension though their blood pressure was within normal range during the survey. Hypertension control was defined as blood pressure<140/90 mm Hg before each dialysis session. RESULTS: The prevalence of hypertension in the hemodialysis patients was 86.3%. The treatment rate and control rate in those patients were 96.8% and 25.5% respectively. More than half (50.4%) of patients were treated with only one kind of anti-hypertensive drug, and 34.4% with 2 kinds, 14.2% with 3 kinds, 1.0% with 4 kinds or more. Calcium channel blocker (CCB) was the most frequently prescribed drug (61.0%), followed by angiotensin II receptor blockers (56.4%), centrally acting anti-hypertensive agent (26.4%), beta blockers and alpha, beta-blockers (14.0%). The control rate of hypertension in those hemodialysis people was aggravated by the existence of coronary artery disease. The patients who need more kinds of antihypertensive agents have a poorer control rate of hypertension. The hypertension control rate elevated significantly with the adequate hemodialysis. CONCLUSIONS: There is a very high prevalence of hypertension in maintenance hemodialysis patients. Although the treatment rate is high, the control rate is unsatisfactory. So the control of hypertension in hemodialysis patient is still a clinical challenge. Appropriate dialysis adequacy, reasonable use of erythropoietin, treatment of heart disease and judicious use of antihypertensive drugs may be helpful to improve the clinical outcome.

[Analysis of drug-induced acute renal failure in Shanghai].

OBJECTIVE: To investigate the incidence and prognosis of drug-induced acute renal failure (ARF) in Shanghai. METHODS: The registration forms of ARF patients admitted in 17 hospitals of and over the middle class in Shanghai from January 1, 2004 to December 31, 2006 were screened prospectively. The data, such as epidemiology, survival, mortality, and morbidity were analyzed. RESULTS: 347 of the 1200 ARF patients (28.9%), 224 males and 123 females, aged (58+/-20), suffered from drug-induced ARF. 51.0% of the 347 patients were older than 60. 60.2% of the drug-induced ARF in the non-surgical departments were community-acquired, while 55.7% of the drug-induced ARF in the surgical departments were hospital-acquired. Among the non-surgical departments, the incidence of hospital-acquired drug-induced ARF was the lowest in the department of nephrology (9.5%), while higher in the departments of hematology, cardiology, and neurology, and among the surgical departments, it was the lowest in department of renal surgery, while higher in the departments of liver transplantation, neurosurgery, and cardiovascular surgery. The most common complication was chronic kidney disease (CKD) (n=69, 19.9%), followed by cerebrovascular disease (n=59, 17.0%), diabetes mellitus (n=43, 12.4%), and hypertension (n=41, 11.8%). Renal biopsy showed acute tubular necrosis (18, 37.5%), acute interstitial nephritis (11, 22.9%), and acute infectious tubulo-interstitial nephritis (6, 12.5%). Antibiotics (47.8%) were the head causes of drug-induced ARF, especially aminoglycoside (17.0%) and cephalosporins (12.7%), followed by diuretics (22.2%) and radiocontrasts (13.3%). 22.5% of the drug-induced ARF patients had used two or more drugs. 119 patients (34.3%) needed renal replacement treatment. 100 of the 347 patients (28.8%) died. 188 of the surviving patients (54.2%) had their renal function recovered completely, the renal function of 42 of them (12.1%) was recovered partially, and 17 of then (4.9%) required dialysis when discharged. CONCLUSION: Drug-induced ARF is common with higher incidence in the patients with complications. Antibiotics, diuretic agents, and contrast medium are the main causes.

Preemptive renal replacement therapy in post-cardiotomy cardiogenic shock patients: a historically controlled cohort study.

BACKGROUND: The aim of the study was to evaluate whether the preemptive renal replacement therapy (RRT) might improve outcomes in post-cardiotomy cardiogenic shock (PCCS) patients. METHODS: In Period A (September 2014-April 2016), patients with PCCS received RRT, depending on conventional indications or bedside attendings. In Period B (May 2016-November 2017), the preemptive RRT strategy was implemented in all PCCS patients in our intensive care unit. The goal-directed RRT was applied for the RRT patients. The hospital mortality and renal recovery were compared between the two periods. RESULTS: A total of 155 patients (76 patients in Period A and 79 patients in Period B) were ultimately enrolled in this study. There were no significant differences in demographic characteristics and intraoperative and postoperative parameters between the two groups. The duration between surgery and RRT initiation was significantly shorter in Period B than in Period A [23 (17, 66) vs. 47 (20, 127) h, P<0.01]. The hospital mortality in Period B was significantly lower than that in Period A (38.0% vs. 59.2%, P<0.01). There were fewer patients with no renal recovery in Period B (4.1% vs. 19.4%, P=0.026). Patients in Period B displayed a significantly shorter time to completely renal recovery (12±15 vs. 25±15 d, P<0.05). CONCLUSIONS: Among PCCS patients, preemptive RRT compared with conventional initiation of RRT reduced mortality in hospital and also led to faster and more frequent recovery of renal function. Our preliminary study supposed that preemptive initiation of RRT might be an effective approach to PCCS with acute kidney injury (AKI).

Self-Care Behavior of Hemodialysis Patients With Arteriovenous Fistula in China: A Multicenter, Cross-Sectional Study.

Improving the level of arteriovenous fistula (AVF) self-care behavior by people receiving hemodialysis is an effective way to reduce the occurrence of complications and mortality. The aim of this study was to assess the self-care behavior of Chinese patients undergoing hemodialysis with arteriovenous fistula. The assessment of self-care behaviors with arteriovenous fistula in hemodialysis (ASBHD-AVF, Portuguese version) was translated into Chinese using Brislin's translation model. The content validity was evaluated by six experts. Then we involved 301 hemodialysis patients with AVF to explore the construct validity of the Chinese version of ASBHD-AVF. Ultimately 216 patients from eight dialysis centers of general hospitals in China were recruited to evaluate the patients' self-care behavior about AVF. Measures included demographic questionnaire, and the Chinese ASBHD-AVF. The Chinese ASBHD-AVF that included 12 items has a good internal consistency (α = 0.865) and content validity (CVI = 0.979). Principal component analysis generated two factors which explained 53.525% of the total variance. About 69.9% of hemodialysis patients' AVF self-care behavior were at a low or moderate level. The level of self-care behavior and knowledge need to be improved. Nurses should give specific guidance according to the patients' own characteristics and different influence factors, in order to improve the recipients' self-care behavior.

Liver support therapy with molecular adsorbents recirculating system in liver failure: a summary of 252 cases from 14 centers in China.

BACKGROUND: A liver support therapy, named molecular adsorbents recirculating system (MARS), has been used for more than 700 liver failure patients in China. We made here a summary to evaluate the effects of MARS treatment in different applications with emphasis on hepatitis B virus (HBV) based liver failure. METHODS: This report analyzed data of 252 patients (mean age (44.9+/- 12.7) years) in three groups: acute severe hepatitis (ASH), subacute severe hepatitis (SSH) and chronic severe hepatitis (CSH). The largest group was CSH (156 patients, 61.9%), and 188 patients (74.6%, 188/252) were infected with HBV. RESULTS: MARS treatments were associated with significant reduction of albumin bound toxins and water-soluble toxins. Most of the patients showed a positive response with a significant improvement of multiple organ function substantiated by a significant increase in prothrombin time activity (PTA) and median arterial pressure (MAP). There was a decrease in hepatic encephalopathy (HE) grade and Child-Turcotte-Pugh (CTP) scale. Thirty-nine of 188 HBV patients (20.7%) dropped out of the commendatory consecutive therapy ending with lower survival of 43.6% while the rest of the 149 patients had a survival rate of 62.4%. Survival within the ASH and SSH groups were 81.2% and 75.0%, respectively. In the CSH group, end stage patients were predominant (65/151, 43%), whereas the early and middle stage patients had a better prognosis: early stage survival, including orthotopic liver transplantation (OLT) survival of 91.7%, middle stage survival of 75%, end stage survival of 33.8%. CONCLUSIONS: MARS continues to be the most favorable extracorporeal treatment for liver support therapy in China for a wide range of conditions, including the majority of hepatitis B related liver failure conditions. The appropriate application of MARS for the right indications and stage of hepatic failure, as well as the fulfillment of prescribed treatments, will lead to the optimal therapeutic result.

Endoplasmic reticulum stress associated apoptosis as a novel mechanism in indoxyl sulfate­induced cardiomyocyte toxicity.

Indoxyl sulfate (IS), a typical uremic toxin, is of great importance in the development of chronic kidney disease. In addition to its nephrotoxicity, previous studies have provided increasing evidence for its cardiovascular toxicity. The mechanism underlying IS­induced cardiovascular toxicity has been elusive to date. The present study aimed to evaluate whether IS treatment could induce apoptosis of H9C2 cells, and used the endoplasmic reticulum (ER) stress­modulator 4­phenylbutyric acid (4­PBA) to evaluate whether IS­induced apoptosis is indeed associated with ERS. To evaluate whether IS induces apoptosis in H9C2 cardiomyocytes, cells were exposed to increasing concentrations of IS (500, 1,000, and 2,000 µM) for 24 h, and apoptosis was detected by flow cytometry. To determine whether IS­induced apoptosis is associated with ERS, cells were divided into 4 groups: control group, PBA group, IS group and PBA+IS group. IS dose­dependently induced apoptosis, and increased the expression of ER chaperones in H9C2 cells. Additionally, 4­PBA treatment decreased IS­induced apoptosis, and reduced ERS­associated protein expression induced by IS. Therefore, the mechanism may be associated with the CCAAT­enhancer­binding protein homologous protein and c­Jun N­terminal kinase signaling pathways.