Vancomycin associated acute kidney injury in patients with infectious endocarditis: a large retrospective cohort study.

Background: Vancomycin remains the cornerstone antibiotic for the treatment of infective endocarditis (IE). Vancomycin has been associated with significant nephrotoxicity. However, vancomycin associated acute kidney injury (AKI) has not been evaluated in patients with IE. We conducted this large retrospective cohort study to reveal the incidence, risk factors, and prognosis of vancomycin-associated acute kidney injury (VA-AKI) in patients with IE. Methods: Adult patients diagnosed with IE and receiving vancomycin were included. The primary outcome was VA-AKI. Results: In total, 435 of the 600 patients were enrolled. Of these, 73.6% were male, and the median age was 52 years. The incidence of VA-AKI was 17.01% (74). Only 37.2% (162) of the patients received therapeutic monitoring of vancomycin, and 30 (18.5%) patients had reached the target vancomycin trough concentration. Multiple logistic regression analysis revealed that body mass index [odds ratio (OR) 1.088, 95% CI 1.004, 1.179], duration of vancomycin therapy (OR 1.030, 95% CI 1.003, 1.058), preexisting chronic kidney disease (OR 2.291, 95% CI 1.018, 5.516), admission to the intensive care unit (OR 2.291, 95% CI 1.289, 3.963) and concomitant radiocontrast agents (OR 2.085, 95% CI 1.093, 3.978) were independent risk factors for VA-AKI. Vancomycin variety (Lai Kexin vs. Wen Kexin, OR 0.498, 95% CI 0.281, 0.885) were determined to be an independent protective factor for VI-AKI. Receiver operator characteristic curve analysis revealed that duration of therapy longer than 10.75 days was associated with a significantly increased risk of VA-AKI (HR 1.927). Kidney function was fully or partially recovered in 73.0% (54) of patients with VA-AKI. Conclusion: The incidence of VA-AKI in patients with IE was slightly higher than in general adult patients. Concomitant contrast agents were the most alarmingly nephrotoxic in patients with IE, adding a 2-fold risk of VA-AKI. In patients with IE, a course of vancomycin therapy longer than 10.75 days was associated with a significantly increased risk of AKI. Thus, closer monitoring of kidney function and vancomycin trough concentrations was recommended in patients with concurrent contrast or courses of vancomycin longer than 10.75 days.

Salvianolic Acid B Prevents Iodinated Contrast Media-Induced Acute Renal Injury in Rats via the PI3K/Akt/Nrf2 Pathway.

Contrast-induced acute renal injury (CI-AKI) has become a common cause of hospital-acquired renal failure. However, the development of prophylaxis strategies and approved therapies for CI-AKI is limited. Salvianolic acid B (SB) can treat cardiovascular-related diseases. The aim of the present study was to assess the effect of SB on prevention of CI-AKI and explore its underlying mechanisms. We examined its effectiveness of preventing renal injury in a novel CI-AKI rat model. Compared with saline, intravenous SB pretreatment significantly attenuated elevations in serum creatinine and the histological changes of renal tubular injuries, reduced the number of apoptosis-positive tubular cells, activated Nrf2, and lowered the levels of renal oxidative stress induced by iodinated contrast media. The above renoprotection of SB was abolished by the PI3K inhibitor (wortmannin). In HK-2 cells, SB activated Nrf2 and decreased the levels of oxidative stress induced by hydrogen peroxide and subsequently improved cell viability. The above cytoprotection of SB was blocked by the PI3K inhibitor (wortmannin) or siNrf2. Thus, our results demonstrate that, due to its antioxidant properties, SB has the potential to effectively prevent CI-AKI via the PI3K/Akt/Nrf2 pathway.

Mechanism of miR?21 in delayed ischemia preconditioning and its protection against subsequent ischemia reperfusion injury in kidney / 中华肾脏病杂志

Objective To investigate the molecular mechanism of protection of ischemia preconditioning on renal ischemia reperfusion injury. Methods Male C57/BL6N mice were randomly divided into two groups: in IR group, 35 min ischemia was induced by occlusion of both renal pedicles followed by 24 h perfusion (I/R). 15 min ischemia was induced 4 days before I/R in IPC group. Blood sample and kidney were collected in IR and IPC group after 24 h perfusion. Serum creatinine (Scr) and histological changes were used to evaluate the renal injury. PHD2 and HIF-1αwere evaluated by Western blotting, miR-21 expression was confirmed by real-time PCR. In vitro, hypoxic model was established by 1% O2 in HK-2 cells. Knockdown of miR-21 in hypoxic model was perfermed by locked nucleic acid modified-anti-miR-21 transfection. The levels of miR-21, HIF-1α and PHD2 mRNA were confirmed by real-time PCR. The levels of HIF-1α and PHD2 proteins were tested by Western blotting. Results In vivo, Compared with IR group, the renal function and histological changes were improved in IPC group (P<0.01). Compared with IR group, the expression of miR-21(P<0.01) and HIF-1α(P<0.05) were increased in IPC group, while PHD2 was reduced (P<0.01). In vitro, hypoxia reduced miR-21. The inhibition of miR-21 could increased the expression of PHD2 (P<0.05). Conclusions Ischemia preconditioning may exert protection against renal ischemia reperfusion injury by inhibiting PHD2.

The prevalence and risk factors of kidney disease in type 2 diabetic patients in rural Shanghai / 中华内科杂志

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 low molecular weight iron dextran and iron sucrose on oxidative stress in chronic renal failure of subtotal nephrectomized rats / 中华肾脏病杂志

Objective To investigate the effects of repeated low dose intravenous infusion of low molecular weight iron dextran and iron sucrose on oxidative stress in chronic renal failure (CRF) rats. Methods CRF model was established by 5/6 subtotal nephrectomy (5/6 Nx). Four weeks after removing the right kidney, successful rats were randomly divided into low molecular weight iron dextran group, sucrose iron group and CRF control group. The sham group was established simultaneously. The dose of iron administrated in each rat was similar in iron dextran group and sucrose iron group. There were 6 rats in each group. Animals were observed for 6weeks, then the blood, urine and renal tissue samples were collected, and indexes of renal function,anemia, iron status and oxidative stress were investigated. Results The hemoglobulin (Hb) level in iron groups was significantly higher as compared to control group (P＜0.05) but was not significantly different between two iron groups. The levels of serum iron, ferritin and saturation rate of transferring (TS) were obviously lower in control group as compared to sham group (P＜0.05).Levels of above 3 indexes were significantly higher in two iron groups as compared to control group (P＜0.05), but were not significantly different between two iron groups. Concentration of plasma advanced oxidation protein products (AOPP) was obviously higher in two iron groups than that in control group [(127.84±21.19) μmol/L, (134.21±29.38) μmol/L vs (81.83±19.93) μmol/L, P＜0.05]. Plasma malonaldehyde (MDA) was significantly higher in iron sucrose group than that in iron dextran group [(6.06±0.73) nmol/L vs (4.99i0.80) nmol/L, P＜0.05]. Serum levels of superoxide dismutase (SOD) and total anti-oxidant capacity (TAOC) had no significant differences among three CRF groups. Concentration of plasma glutathione peroxidase (GSH-Px) was significantly decreased in three CRF groups as compared to sham group (P＜0.05), while plasma GSH-Px was significantly lower in sucrose iron group than that in iron dextran group and control group [(2123.11±74.78)nmol ·ml-1 ·min-1 vs (2352.84±163.90) nmol· ml-1 ·min-1, (2310.23±125.99) nmol ·ml-1 ·min-1, P＜0.05]. Conclusions Injection of intravenous iron can partially improve the anemia and the iron status indexes in 5/6 Nx CRF rats. Repeated low dose intravenous infusion of iron dextran and iron sucrose can aggravate the oxidative stress state in CRF rats, and the iron sucrose is worst.

Serum concentrations of tumor markers in patients with chronic kidney diseases and the analysis of related factors / 中国实用内科杂志

Objective Our study intended to check whether there are any changes of serum concentrations of tumor markers in patients with chronic kidney disease,and to determine the related factors.Methods Atotal of 232 hospitalized patients in Nephrology Department in Zhongshan Hospital of Fudan University from March to June in 2005 were divided into groups respectively according to their levels of Ccr,Upro and Salb.Then Kruskal-Wallis test was applied to confirm the relationships among Ccr,Upro,Salb and serum tumor markers.Furthermore,multielement logistic regression was used to analyze the independent effect of age,Ccr,effusion in serous cavity,the levels of proteinuria and serum albumin on the levels of these markers in CKD patients.Results The serum levels of CEA,CA 199,NSE and SCC in different Ccr groups,the levels of CA 199,CA125,NSE and SCC in different Salb groups,the levels of CA 125,NSE and SCC in different Upro groups,had significant statistical differences.Age was the risk factor of the increased levels of CEA and PSA;effusion in serous cavity was the risk factor of increased levels of CA 125.The decreased level of Ccr was the risk factor of CA 125 and SCC.The elevated Upro was the risk factor of SCC.The decreased Salb was the risk factor of CA 199,CA 125 and NSE.Conclusion When we diagnose some tumors according to their serum levels of tumor markers such as CEA,CA 199,CA 125,NSE,SCC and PSA,we must note that whether the patients are aged or have complications such as large proteinuria,hypoalbuminemia,effusion in serous cavity or decreased kidney function.