Skin tests have greater sensitivity and specificity than in vitro tests measuring serum venom-specific IgE (SSIgE) [39]. Levels of SSIgE and skin test responses do not correlate with clinical reactivity. Venom-specific IgE can also be measured GS-1101 research buy by a basophil activation test

(BAT), but the latter is currently a research tool and does not have significant advantages over routinely employed enzyme immunoassays. In patients with a history of moderate–severe SR reaction, plasma baseline tryptase should also be measured to screen for underlying disorders of mast cell overload, such as telangectasia macularis eruptiva perstans (TMEP) and other forms of cutaneous (urticaria pigmentosa) and systemic mastocytosis which may warrant further investigation, including bone marrow studies, tissue biopsy and appropriate management [45–50]. Elevated baseline tryptase is an important risk factor for anaphylaxis [45–50] and will have implications for VIT, as discussed in the following sections. Choice of venom for VIT.  This is dictated by clinical history and demonstration of venom-specific IgE. There is no significant cross-reactivity between clinically significant antigens of Apidae and Vespidae (honey bee and wasp/hornet) venoms [51–53]. Within the Vespidae family, there is significant overlap between wasps and hornet venoms [54–56]. However, there is little cross-reactivity

between wasps/hornet and paper wasps (not

encountered in the United Kingdom) [56]. These facts, as well as Tyrosine-protein kinase BLK knowledge of local entomology of hymenoptera insects, have to be taken into consideration carefully to make a correct ABT-199 choice of the venom for immunotherapy. For example, in a British patient with a history of hornet sting anaphylaxis during a visit to mainland Europe, the ideal choice for immunotherapy would be wasp venom, as the prevalence of wasps is greater in the United Kingdom and wasp venom immunotherapy will protect the patient from either insect sting. VIT protocols.  Different protocols (Example 1), including conventional, clustered, rush and ultra-rush, have been described in the literature. A conventional protocol involves weekly up-dosing, reaching the maintenance dose in 12 weeks [57–60]. Maintenance dose is reached in 4–7 days in a rush up-dosing [61–63] protocol and 1–2 days in an ultra-rush schedule [61,64,65]. A recent national audit in the United Kingdom has shown that more than 90% of allergy specialists employ the conventional protocol, as services in this country are primarily out-patient-based [66]. Accelerated protocols are popular in North America and Europe, and have been shown to be safe as well as efficacious [61,63,64,67–69]. The target maintenance dosage is 100 µg and this is administered at 4-, 6- and 8-weekly intervals during the maintenance phases of years 1, 2 and 3 respectively [37].

Expression of cytokines including IL-6 and tumour necrosis factor-α (TNF-α)21 was increased. Interestingly, transcripts for IL-10, IL-13, interferon-γ (IFN-γ) and IL-12p35 were increased but no production at the protein level was detected.10,21 Furthermore, LPS stimulation did not induce a change in IL-4 gene expression.20 However, T cells that had been exposed to antigen-pulsed MoDCs produced protein

for both IL-4 and IFN-γ.6 In contrast to MoDCs, however, very little information is available on maturation and activation of isolated BDCs following stimulation with LPS. Following their activation and maturation, DCs are known to drive GSK458 in vivo T-cell proliferation and to modulate the immune response towards a Th1, Th2, Th17 or T regulatory type of response.1,2 As a result of the limitations of studying T-cell

proliferation in outbred species, most studies in pigs have used mixed lymphocyte reactions6,10,12 and few have used autologous cells.16,21,22 In the present study, both MoDCs and BDCs were isolated from vaccinated pigs and co-cultured with autologous T cells to assess the induction of antigen-specific T-cell activation. We found that both MoDCs and BDCs were equally able to induce T-cell proliferation. However, PI3K inhibitor when stimulated with LPS, BDCs that were directly isolated from blood showed a greater increase in cytokine and chemokine expression, when compared with MoDCs. This study therefore provides further evidence that directly isolated BDCs represent an important cell population for studying DC biology in pigs. Further studies, however, are required to identify learn more the specific role of pDCs within the BDC population. Eight-week-old Dutch Landrace pigs purchased from Saskatoon Prairie Swine Centre, University of Saskatchewan were used in this study. The goal of this study was to directly compare MoDCs with isolated BDCs both phenotypically and functionally. Phenotypically, DC morphology was examined by Giemsa staining

and the expression of cell surface markers was examined by flow cytometry. Functionally, endocytic ability was examined by flow cytometry, changes in transcript expression and the production of cytokines in response to stimulation with LPS were investigated using quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunsorbent assay (ELISA), respectively, and lastly for their ability to stimulate autologous T-cell proliferation, thymidine uptake assays were performed. Studies were performed as per the ethical guidelines of the University of Saskatchewan and the Canadian Council for Animal Care. Blood was collected by heart puncture using ethylenediaminetetraacetic acid (EDTA) -coated syringes and blood mononuclear cells were isolated using a 60% Ficoll-Paque™ Plus gradient (GE Healthcare, Uppsala, Sweden). Monocytes were isolated using magnetic beads [magnetic antibody cell sorting (MACS); Miltenyi Biotec, Auburn, CA] and human anti-CD14 (TÜK4) microbeads (Miltenyi Biotec).

4B, compare lanes 2, 3 and 4). On the other hand, the elevated basal activity of JNK in thymocytes from LckCre-Cyldflx9/flx9 mice was Liproxstatin-1 not reduced by the concomitant

inactivation of Ikk2 (Supporting Information Fig. 3). These findings indicate that the developmental defect of CyldΔ9 thymocytes is due to excessive activation of IKK2-dependent NF-κB activity. One of the striking observations in LckCre-Cyldflx9/flx9 mice was the dramatic reduction of CD4+ and CD8+ T cells in the periphery as assessed by their enumeration in mesenteric lymph nodes and spleen. LckCre-Cyld+-Ikk2flx/flx mice showed a 20% reduction in peripheral CD4 cells and a 50% reduction in peripheral CD8 cells in accordance with previous observations (Fig. 5A–D). Surprisingly, LckCre-Cyldflx9/flx9-Ikk2flx/flx mice showed a severe reduction in both CD4 and CD8 peripheral, which exceeded the defect seen in LckCre-Cyld+-Ikk2flx/flx peripheral T cells. Most of the remnant peripheral T cells in LckCre-Cyldflx9/flx9-Ikk2+/+ mice possessed CD44hiCD62Llo effector-like phenotype (Fig. 5E), which is consistent with lymphopenia-induced expansion as described in other lymphopenic states 24, 25. Interestingly, while the peripheral T cells isolated from LckCre-Cyld+-Ikk2flx/flx mice showed reduced expression of CD44 as previously reported

19, the peripheral T cells isolated from the LckCre-Cyldflx9/flx9-Ikk2flx/flx mice showed an intermediate phenotype since they have almost 50% more CD44hiCD62Llo T cells when compared with control mice buy PLX-4720 and 50% less CD44hiCD62Llo T cells when compared with LckCre-Cyldflx9/flx9-Ikk2fl+/+ (Fig. 5E). These findings are consistent with a function of CYLD in the establishment of physiological peripheral T-cell populations which is IKK2 independent. Oxaprozin The implication of the deubiquitinating activity of CYLD in the regulation of thymocyte positive selection in an NEMO-dependent manner

and the ambiguity that surrounds the role of NF-κB in this process prompted an investigation into the specific function of IKK2-dependent NF-κB activity in Cyld-dependent regulation of thymocyte development. For this purpose, a conditional gene targeting approach was employed which permitted the concomitant inactivation of CYLD’s activity and IKK2 from the early stages of thymocyte development by crossing LckCre-Cyldflx9/flx9 to Ikk2flx/flx mice. Thymocyte-specific ablation of IKK2 does not affect the development of thymocytes but results in a mild phenotype in the periphery, which is manifested by a small reduction of CD4+ peripheral T cells and a 50% reduction of CD8+ peripheral T cells (19 and Fig. 5). The observation that the concomitant inactivation of IKK2 and CYLD leads to normal thymocyte development establishes the improper regulation of NF-κB activity as the main cause of defective development of thymocytes with inactive CYLD.

We measured proliferative responses to these two peptides in another cohort of patients with RA or osteoarthritis: positive responses were found in 28% of RA, but also in 11% of osteoarthritis patients and these responses could be blocked by anti-MHC class II Ab. Remarkably, the presence of 117/120–133-specific T cells was significantly associated with active disease in RA patients, and bone

Silmitasertib datasheet erosion appeared to be more common in T-cell positive patients. These data suggest involvement of hnRNP-A2 specific cellular autoimmune responses in RA pathogenesis. Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology characterized by chronic synovial inflammation in multiple joints leading to cartilage and bone damage and disability. The prevalence A-769662 cell line of RA is about 1% in the industrialized world and the major genetic contribution involves HLA class II alleles dominated by HLA DR*0101, DR*0401, and DR*0404 molecules in Caucasian

populations 1. These alleles share a highly homologous amino acid sequence at positions 67–74 of the third hypervariable region of the DRβ chain, termed the shared epitope 2, affecting peptide binding and T-cell recognition. Synovial tissue of inflamed joints is characterized by massive infiltration of T cells mostly of the Th1 subset, B cells, macrophages, and mast cells 3. Based on the abundance of T cells and the association of RA susceptibility with certain MHC class II Bupivacaine genotypes, it has been hypothesized that disease-associated

HLA-DR alleles present arthritogenic peptides leading to the stimulation and expansion of autoantigen-specific T cells in the joints and/or draining lymph nodes. Humoral and/or cellular immune responses against multiple autoantigens have been detected in arthritic patients or murine arthritis models. These include joint-specific proteins such as collagen, cartilage proteoglycan, cartilage oligomeric matrix protein, cartilage gp39, as well as ubiquitously expressed proteins such as heterogeneous nuclear ribonucleoprotein A2 (hnRNP-A2), keratin/filaggrin, fibrinogen, the stress protein BiP, and glucose 6-phosphate isomerase 4. These antigens have been studied mostly at the level of Ab production. Thus, some autoantibodies such as rheumatoid factor and Ab against deiminated (citrullinated) antigens have considerable diagnostic significance in RA 4. Although some of these autoantigens have been shown to induce T-cell reactivity 4, 5, information regarding autoantigen-specific T-cell responses in patients is limited and even contradictory 6. Moreover, the identification of autoantigenic T-cell epitopes has remained scarce and the role of T-cell responses in RA pathogenicity is still unresolved 5.

2/8H5 (Enzo Life Sciences (UK) Ltd, Exeter, UK; Mouse clone: 9H10, eBioscience). IgG isotype control antibodies were from Abcam plc, Cambridge, UK, or eBioscience. The selective ELISA for human sCTLA-4 used the anti-CTLA-4 murine mAb clone

BNI3 (2 μg/mL) as the capture reagent and biotinylated JMW-3B3 as the sCTLA-4–specific detection reagent using the same protocol described for the cytokine ELISA mentioned above. Measurement of murine sCTLA-4 by ELISA was conducted according to the same procedures as for human sCTLA-4, but with a hamster anti-mouse CTLA-4 capture Ab (clone: 9H10). Affinity purified sCTLA-4 was used to construct standard curves. Specific primers for sCTLA-4 mRNA were used to amplify a fragment of 93 bp. The reaction consisted R428 molecular weight of 3 μL cDNA, 1.5 μL of each primer (0.5 μM), 1 μL of the corresponding probe (0.2 μM), 10 μL of LightCycler 480 probes master (Roche), and distilled water up to a final volume of 20 μL. The sCTLA-4–specific primer and probe sequences were as follows: sCTLA-4F: 5′-CAT CTG CAA GGT GGA GCT CAT-3′ and sCTLA-4R: 5′-GGC TTC TTT TCT TTA GCA ATT ACA TAA ATC-3′; Rapamycin in vivo probe: 5′-ACC GCC ATA CTA CCT GGG CAT AGG CA -3′, labeled with FAM. Amplification was performed in a LightCycler 2.0 instrument (Roche Diagnostics Ltd, Burgess Hill, UK). A reference to the standard curve was included in each run, and all

samples were replicated once. Data from cells stimulated in vitro for 5 days at 37°C 5% CO2 with PPD, SEB, or anti-CD3 mAb were compared against nonstimulated

resting cell–derived mRNA. Human B7.1Ig or B7.2Ig (2 μg/mL, Axxora, Nottingham, UK) was bound to protein A magnetic beads and incubated with a sCTLA-4 positive serum in the presence of an isotype Ab control, pan-specific anti-CTLA-4 mAb, or JMW-3B3 mAb (all 5 μg/mL). Bound sCTLA-4 was then eluted with Glycine HCl (pH 3.2) and detected in a conventional anti-CTLA-4 ELISA. Analyses of Treg-cell Myosin lines or fractionated T-cell subsets were conducted by incubating cells for 4 h in the presence of Brefeldin A (Golgiplug, BD Biosciences), before staining for extracellular CD4 (FITC), CD25 (PE-Cy™7), and CD127 (Alexa Fluor®647) using a regulatory T-cell cocktail kit (BD Biosciences). Cells were subsequently fixed and permeabilized (BD Cytofix/Cytoperm fixation/permeabilization solution kit, BD Biosciences) before staining for intracellular FoxP3 (V450, BD Biosciences) and sCTLA-4 (clone: JMW-3B3, PE). Flow cytometry was performed with an LSR II flow cytometer (BD Biosciences) and data analyzed with FCS Express 3 software. Isotype controls were used to exclude nonspecific staining and to set gates. CD4+CD25+ and CD4+CD25− T cells were prepared using a Dynabeads® Regulatory CD4+CD25+ T-cell kit (Invitrogen) according to manufacturer’s instructions. Purity of fractionated cell populations was checked using flow cytometry.

Student’s t-test was used to assess statistical significance. A value of p<0.05 was considered significant. Statistics were calculated with Prism version 5.0c (GraphPad). Funding support was from the National Institutes of Health (NIH) for WRB (K08 AI080952), SJS and TRH (R01 AI061464). The authors would like to acknowledge Malinka Jansson-Hutson and Destry Taylor for technical assistance. Conflict of interest: The authors declare no financial or commercial conflict of interest. "
“The importance of Ca2+ influx via store-operated calcium channels (SOCs) leading to mast cell degranulation is well known in

allergic disease. However, the underlying mechanisms are not fully understood. With food-allergic rat model, the morphology of degranulated mast cell was

analysed by toluidine blue stain and electron microscope. Ca2+ influx via SOCs was checked by Ca2+ imaging confocal microscope. Furthermore, the https://www.selleckchem.com/products/Dasatinib.html mRNA and protein expression of 3-deazaneplanocin A solubility dmso SOCs subunits were investigated using qPCR and Western blot. We found that ovalbumin (OVA) challenge significantly increased the levels of Th2 cytokines and OVA-specific IgE in allergic animals. Parallel to mast cell activation, the levels of histamine in serum and supernatant of rat peritoneal lavage solution were remarkably increased after OVA treatment. Moreover, the Ca2+ entry through SOCs evoked by thapsigargin was increased in OVA-challenged group. The mRNA and protein expressions of SOC subunits, stromal interaction molecule 1 (STIM1) and Orail (calcium-release-activated calcium channel protein 1), were dramatically elevated under food-allergic condition. Administration of Ebselen, a scavenger of reactive oxygen species (ROS), significantly attenuated OVA sensitization-induced intracellular Pyruvate dehydrogenase Ca2+ rise and upregulation of SOCs subunit expressions. Intriguingly, pretreatment with PI3K-specific inhibitor (Wortmannin) partially abolished the production of ROS and subsequent

elevation of SOCs activity and their subunit expressions. Taken together, these results imply that enhancement of SOC-mediated Ca2+ influx induces mast cell activation, contributing to the pathogenesis of OVA-stimulated food allergy. PI3K-dependent ROS generation involves in modulating the activity of SOCs by increasing the expressions of their subunit. During the last two decades, a dramatic increase in the occurrence of food allergy has been reported in worldwide [1-3]. The prevalence of food allergy to milk, eggs and peanuts is reported to be around 6–8% of children under the age of three [4, 5], while it is less common in adult population with a percentage of about 4% [6]. It has been documented that food allergy is primarily mediated by type I or Immunoglobulin E (IgE)-induced allergic reaction, although non-IgE-mediated allergy are gaining growing attention recently [7]. The role of mast cell in the pathogenesis of food allergy is well established.

[15] Headley et al.[37] noted significant increases in VO2peak and time to exhaustion, following a 48 week exercise intervention in which optional resistance exercises were offered to subjects at weeks 24–48. Similarly, significant improvements in exercise capacity and functional ability were reported in CKD stage 3–4 patients taking part in a renal rehabilitation exercise intervention

consisting of aerobic, resistance and balance training.[53] These data suggest that all forms of exercise are effective at improving exercise and functional capacities in pre-dialysis CKD patients, but more research is required to identify the optimal training methods. It is well established that patients with CKD are at greatly increased risk of developing cardiovascular Target Selective Inhibitor Library disease (CVD),[54, 55] and are, in fact, more likely to develop CVD than progress to dialysis.[56] The reasons behind this are multi-factorial, including high prevalence of traditional risk factors (hypertension, hyperlipidaemia and diabetes) as well as factors related to kidney check details disease itself (endothelial dysfunction, oxidative stress, inflammation and abnormal lipid patterns).[2, 55] Physical inactivity is itself

an important modifiable risk factor for the development of CVD[29, 57] and in other populations exercise has shown to ameliorate Carnitine palmitoyltransferase II several of the possible mediators, although this is not well established in CKD. Headley et al.[58] studied the acute effects of aerobic exercise on blood pressure in pre-dialysis CKD patients. Forty minutes of moderate walking exercise at 50–60% VO2peak reduced blood pressure for up to 60 min following exercise. However, evidence of exercise interventions reducing hypertension is inconclusive. Boyce et al.[20] trialled the effects of 4 months aerobic exercise on cardiorespiratory fitness (CRF) and blood pressure (BP) in pre-dialysis patients with hypertension. Exercise consisted of supervised walking

and cycling performed three times weekly at a target intensity of 70% heart rate reserve for up to 60 min. In addition to improvements in CRF, significant reductions in systolic and diastolic BP were noted following exercise, returning back to baseline values following 2 months of detraining. Mustata et al.[50] reported a significant reduction in arterial stiffness, as estimated by augmentation index, following 3 months mixed supervised and home based exercise, performed at 40–60% VO2peak for up to 60 min, despite no significant effect on blood pressure. Furthermore, Kosmadakis et al.[51] investigated the benefits of walking exercise in patients with CKD stages 4–5 not on dialysis. Exercise sessions included a minimum of 30 min walking performed 5 times per week at a rate of perceived exertion (RPE) of 12–14.

8 The expression of inhibitory receptors includes NKG2A, KIR2DL4, KIR2DL1, KIR2DL2/L3, and ILT-242,45–47

which might function to inhibit the cytotoxic potential of dNK cells, as discussed below. Although dNK cells are in close contact with fetal-derived Venetoclax cell line trophoblasts they do not exert cytolytic functions against trophoblast cells.48 Several studies have shown that the general cytotoxicity of dNK cells is reduced compared with peripheral blood NK cells,42,49 despite the fact that they express several activating receptors (as mentioned above), as well as high levels of perforin and granzyme A and B.27,42,50 The cytotoxic activity of dNK cells, although potentially low, is still preserved, as engagement of NKp46 (but not NKp30) in freshly isolated dNK cells induced intracalcium mobilization, perforin polarization, granule exocytosis and triggered apoptosis in target cells.45 Such existing killing potential of dNK cells might be important in case of uterine viral infection. Several different explanations for the lack of cytotoxicity toward trophoblast cells have been proposed. First, this phenomenon could be a result of inhibitory interactions MK-1775 nmr between the non-classical class I MHC- molecules HLA-G and HLA-E and the inhibitory receptors expressed on dNK cells, e.g. ILT-2, KIR2DL4 [32], and CD94/NKG2A.45,51 However, ILT-2,

the most dominant HLA-G binding NK inhibitory receptor is only expressed on ∼20% of dNK cells, and whether KIR2DL4 could interact with HLA-G and inhibit NK cell activity is still controversial.52 Second, it has been suggested by Ribose-5-phosphate isomerase Kopcow et al.44 that dNK cells are unable to form mature activating synapses and to polarize perforin. This might also not be the only explanation, because as mentioned above, NKp46 is cytotoxic in dNK cells.45 Vacca et al.42 provided another possible explanation according to which, the cytotoxic activity of dNK cells is inhibited by the receptor 2B4, which delivers inhibitory signals that correlate with low or absent signaling lymphocyte activation molecule-associated protein (SAP) expression in dNK cells. Finally, it seems, of course, reasonable that

interactions of dNK cells with neighboring immune and non-immune cells at the decidua further inhibit their ability to damage the local tissue. The decidual microenvironment probably encourages dNK cells to exert their constructive functions. The landmark studies of Croy’s group demonstrated the novel concept of constructive functions for mouse dNK cells in vivo at the fetal-maternal interface and their involvement in tissue homeostasis.53 Their work demonstrated that depletion of dNK cells in the mouse decidua resulted in abnormal implantation sites and inadequate remodeling of the decidual spiral arteries. Furthermore, they showed that these abnormalities were a result of dNK-derived IFN-γ, which positively regulates the diameter of the lumen of the spiral arteries during decidualization.

59 The menstrual regularity was maintained and women continued to have ovulatory cycles.60 No change in

bleeding profile was observed. With the approval of the Drugs Controller General of India and Institutional Ethics Committees, phase II efficacy trials were carried out with this vaccine in three major institutions: the All India Institute of Medical Sciences (AIIMS, New Delhi), Postgraduate Institute of Medical Education and Research (PGIMER, Chandigarh), and Safdarjung Hospital, New Delhi. A total of 148 sexually active women of proven fertility with two living children (of which one below 1 year to confirm their contemporary fertility) Ibrutinib mw were enrolled with their informed consent. Many of them had come to clinics earlier for medical termination of unwanted pregnancy. The available contraceptives in the family planning basket either did not

suit these women or were not used consistently. Their husbands were reluctant to use condoms. Primary immunization was given by three intramuscular injections of the HSD-TT/DT vaccine adsorbed on alum at monthly interval. Sodium phthalyl lipopolysaccharide (SPLPS), a non-pyrogenic derivative of LPS, was used at 1 mg in the first injection only. Vaccine with the TT or DT as carrier was given alternatively, Y 27632 so as to avoid carrier-induced suppression of antibody response to HSD. All women made antibodies reactive with hCG.4 However, 110 of the 148 immunized women had hCG bioneutralization titers above 50 ng/mL (a threshold fixed for testing protection against pregnancy) for 3 months or longer. All women continued to ovulate and had regular menstrual cycles. The antibody titers declined with time but booster injections raised the titers (Fig. 4). Eight women completed more than 30 cycles by voluntary intake of booster injections as and when required without becoming pregnant. Nine completed 24–29 cycles, 12 completed 18–23 cycles, 15 completed 12–17 cycles, and 21 women completed 6–11

cycles. The personal diary of women indicated without doubt that they were sexually active with a minimum of two sexual intercourses per week. The semen parameters of husbands were good with high counts of motile sperms. The fact that the women were prone to become pregnant Cyclic nucleotide phosphodiesterase is supported by the record of 26 pregnancies taking place in women at titers falling below 35 ng/mL bioneutralization capacity. Fig. 5 is an illustrative example of a 30-year-old subject with two living children and one MTP. After three primary injections of the vaccine, she took two boosters and remained protected against pregnancy for 13 cycles. In the immediate cycle, when her antibody titers had fallen below 20 ng/mL, she conceived and had a positive pregnancy test. Although most conceptions occurring at or below protective threshold were terminated at the behest of the subjects (Medical termination of pregnancy is legal in India), four women decided to continue with their pregnancy.

Screening based on title and abstract identified 56 citations for full-text review (Fig. 1). Additional five studies[25-27, 39, 53] were identified from reference lists of the identified articles and from other databases. Of the 56 potentially relevant articles,

32 were excluded for reasons given in Figure 1, leaving a total of 24 studies[24-47] that met the inclusion criteria. Twenty one studies[24-30, 32, 34-38, 40-47] reported associations Palbociclib in vitro between use of statins and AKI, and 14 studies[28, 31-35, 37, 39-41, 43-46] reported associations between use of statins and AKI requiring RRT. Five studies[24-28] used RCT design, and the rest applied a cohort design.[29-47] Only one RCT[28] defined AKI as the primary endpoint. The other four RCTs defined postoperative thrombocytosis,[24] postoperative inflammatory responses,[25]

postoperative myocardial injury,[26] and the number of postoperative endothelial progenitor cells[27] as primary endpoints. Among the cohort studies, only three used prospective design; the remaining studies were retrospective in design. As for the study population, two studies involved nation-wide populations, while most of the other studies were conducted at one single centre. Among the two population-based studies, one was conducted in Canada,[43] and the other in the USA.[47] We assessed the quality Protein Tyrosine Kinase inhibitor of included studies with the Jadad scale.[54] The study conducted by Prowle JR and colleagues[28]

had the highest score on the Jadad scale. The results were summarized in the Appendix 1 (Table App1). The studies varied in their types of surgery, mean age, and case definition (Table 1). The types of surgery were restricted to cardiac or vascular surgery in most studies. Specific type, dosage, and duration of preoperative statin therapy Farnesyltransferase were not available in most studies. In contrast to AKI defined by database codes, AKI defined by a pre-specified increase of serum creatinine level was regarded as ‘AKI defined by laboratory criteria’. Among these, there were seven studies[28, 37, 38, 41, 44-46] using AKIN or RIFLE criteria[48, 49] as the definition for AKI. In all studies, the definition of AKI requiring RRT was based on clinical judgment without additional objective laboratory criteria. Specific statin type available i Dosage and duration not available Increase of sCr level > 30% (AKIN stage 1) Atorvastatin 20 mg/day or simvastatin 20 mg/day for at least 6 months Started before surgery Type, dosage and duration not available At least one dose of statin between admission and surgery In the 21 studies reporting the association of statin use and AKI, the incidence of AKI ranged from 1.88%[43] to 52.17%[44] (Table 1). The pooled incidence of AKI for all 21 studies was 4.89%. The pooled incidence of AKI among statin user and nonstatin user were 6.13% and 4.28%, respectively (Table 2).