interleukin-8 and Acute-Kidney-Injury

Renal dysfunction is common in urologic patients, especially in those undergoing nephrectomy for renal cancer. Partial nephrectomy better preserves renal function than radical nephrectomy, but is associated with acute kidney injury related to loss of nephrons and ischemic injury. Ischemic injury may not be reliably assessed using common clinical parameters, such as serum creatinine and urine output, which may delay detection of clinically-significant kidney damage. Molecular markers, such as cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), IL-18 and kidney injury molecule-1 (KIM-1), better quantify the extent of acute ischemic and/or tubular injury than other currently available tools. The use of these and/or other markers may facilitate research to improve outcomes following partial nephrectomy.

Topics: Acute Kidney Injury; Acute-Phase Proteins; Biomarkers; Cystatin C; Hepatitis A Virus Cellular Receptor 1; Humans; Interleukin-8; Kidney; Lipocalin-2; Lipocalins; Membrane Glycoproteins; Proto-Oncogene Proteins; Receptors, Virus; Sensitivity and Specificity

The pathophysiology of acute renal failure in sepsis is complex and includes intrarenal vasoconstriction, infiltration of inflammatory cells in the renal parenchyma, intraglomerular thrombosis, and obstruction of tubuli with necrotic cells and debris. Attempts to interfere pharmacologically with these dysfunctional pathways, including inhibition of inflammatory mediators, improvement of renal hemodynamics by amplifying vasodilator mechanisms and blocking vasoconstrictor mechanisms, and administration of growth factors to accelerate renal recovery, have yielded disappointing results in clinical trials. Interruption of leukocyte recruitment is a potential promising approach in the treatment of septic acute renal failure, but no data in humans are presently available. Activated protein C and steroid replacement therapy have been shown to reduce mortality in patients with sepsis and are now accepted adjunctive treatment options for sepsis in general.

Topics: Acute Kidney Injury; Anticoagulants; Antineoplastic Agents; Antithrombins; Endothelins; Growth Substances; Humans; Interleukin-8; Lipoproteins; Natriuretic Peptides; Nitric Oxide Synthase; Platelet Activating Factor; Protein C; Sepsis; Steroids; Tumor Necrosis Factor-alpha

Whether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated. We examined follow-up data from a large clinical trial to prospectively investigate the long-term outcomes associated with the timing of RRT initiation in such patients. We extended the follow-up of patients in the Early Versus Delayed Initiation of RRT in Critically Ill Patients with AKI (ELAIN) Trial from 90 days to 1 year after randomization for 230 (99.6%) patients. The primary outcome was a composite of major adverse kidney events (persistent renal dysfunction, dialysis dependence, and mortality) at 1 year. Secondary outcomes included inflammatory markers. Overall, 72 of 111 (64.9%) and 106 of 119 (89.1%) patients met the primary outcome in the early (stage 2 AKI) and delayed (stage 3 AKI) initiation groups, respectively (odds ratio [OR] with early initiation, 0.23; 95% confidence interval [95% CI], 0.11 to 0.45;

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Biomarkers; Critical Illness; Follow-Up Studies; Humans; Inflammation; Interleukin-10; Interleukin-18; Interleukin-6; Interleukin-8; Interleukins; Intramolecular Oxidoreductases; Macrophage Migration-Inhibitory Factors; Mortality; Recovery of Function; Renal Insufficiency, Chronic; Renal Replacement Therapy; Time Factors; Time-to-Treatment

We attempted to explore the effect of Dex on renal function in patients with cardiac valve replacement under cardiopulmonary bypass (CPB).. We designed a prospective, randomized, placebo-controlled, single-center, parallel-arm double-blind trial.. Operating room.. Seven-two eligible patients were randomly divided into Dex group and placebo group.. Dexmedetomidine (Dex) (0.6μg·kg. The levels of serum urea nitrogen (BUN), creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), urine interleukin-8 (IL-18) and superoxide dismutase (SOD) activity were tested before anesthesia induction (T1) and after operation at 0, 12h, 24h and 72h (T2-5). The urine output during operation and the post-operative complication of acute kidney injury (AKI) were recorded.. The levels of BUN and Cr were significantly increased at T5, and similar findings were found in the levels of NGAL and urine IL-18 at T3 and T4. The SOD activity was significantly declined at T2 and T3 in the two groups. The levels of BUN and Cr at T5 and the NGAL level at T3 and T4 were significantly lower in Dex group, comparable to placebo group. The intraoperative urine output was significantly increased and the postoperative incidence of AKI was significantly lower in Dex group.. Dex may attenuate the renal injury and decrease the incidence of AKI in patients undergoing cardiac valve replacement under CPB.

Topics: Acute Kidney Injury; Adrenergic alpha-2 Receptor Agonists; Adult; Aged; Biomarkers; Blood Urea Nitrogen; Cardiopulmonary Bypass; Creatinine; Dexmedetomidine; Double-Blind Method; Drug Administration Schedule; Female; Heart Valve Prosthesis Implantation; Humans; Interleukin-8; Lipocalin-2; Male; Middle Aged; Perioperative Care; Prospective Studies; Superoxide Dismutase; Urination; Young Adult

AKI is common following liver transplantation and is associated with significant morbidity and mortality. Biomarkers of AKI have not been well established in this setting but are needed to help guide patient care and facilitate development of novel therapeutics.. Serum creatinine, cystatin C, IL-6, and IL-8 and urine IL-18, NGAL, IL-6, and IL-8 were measured before and within 24 hours after liver transplantation in 40 patients. AKI was defined as a ≥50% sustained increase in creatinine above pre-operative values occurring within 24 hours of transplantation and persisting for at least 24 hours.. Seven patients met criteria for AKI (17.5%), with mean creatinines of 0.81 mg/dL pre-operatively and 1.75 mg/dL post-operatively. While pre-operative biomarker levels in patients with AKI were similar to those in patients without AKI, differences were seen between the groups with regard to median post-operative serum IL-8 (pg/mL) (242.48 vs. 82.37, p = 0.0463) and urine NGAL (ng/mL) (386.86 vs. 24.31, p = 0.0039), IL-6 (pg/mL) (52 vs. 7.29, p=0.0532), IL-8 (pg/mL) (14.3 vs. 0, p = 0.0224), and IL-18 (pg/mL) (883.09 vs. 0, p = 0.0449). The areas under receiver operating characteristic (ROC) curves were 0.749 for urine IL-18, 0.833 for urine NGAL, 0.745 for urine IL-6, 0.682 for serum IL-6, 0.773 for urine IL-8, and 0.742 for serum IL-8. Post-operative cystatin C was not significantly different between AKI and no AKI groups.. Serum IL-8 and urine IL-18, NGAL, IL-6, and IL-8 are elevated in AKI within the first 24 hours following liver transplantation.

Topics: Acute Kidney Injury; Acute-Phase Proteins; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Colorado; Comorbidity; Female; Humans; Incidence; Interleukin-18; Interleukin-8; Lipocalin-2; Lipocalins; Liver Transplantation; Male; Middle Aged; Postoperative Complications; Proto-Oncogene Proteins; Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Young Adult

To evaluate the effect and timing of continuous blood purification (CBP) in treatment of acute renal failure (ARF) following cardiac-vascular surgery.. Twenty-five patients with ARF following cardiac-vascular surgery were divided into systematic inflammatory response syndrome (SIRS) Group (n = 13) and multiple organ dysfunction syndrome (MODS) Group (n = 12) according to the illness state prior to CBP and were divided into Group A (n = 5, with the APACHEIII score prior to CBP 90). All of the 25 patients underwent continuous veno-venous hemofiltration (CVVH). Before and 24h after the CVVH APACHEIII score was calculated and [peripheral; blood samples were collected to detect the levels of blood urea nitrogen (BUN) and serum creatinine (Scr) and the plasma levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha).. The APACHEIII score, BUN, Scr, IL6, IL8, and TNFalpha 24 h after the CBP of the 25 patients were 61 +/- 15 mmol/L, (19 +/- 5) mmol/L, (312 +/- 87) micromol/L, (544 +/- 154) ng/L, (18 +/- 7) ng/L, and (43 +/- 15) ng/L respectively, all significantly lower than those before CBP (81 +/- 20, 26 +/- 5 mmol/L, 458 +/- 107 micromol/L, (842 +/- 132) ng/L, (25 +/- 8) ng/L, and (59 +/- 17) ng/L respectively, all P = 0.000). The survival rate of SIRS Group was 84.62%, significantly higher than that of MODS Group (41.67%, P < 0.05). The APACHEIII score, and the levels of BUN, Scr, IL6, IL8, and TNF-alpha of Group MODS were significantly higher than those of Group SIRS. The higher the level of Scr, IL6, IL8, and TNF-alpha and the APACHEIII score the lower the survival rate.. CBP has a positive effect on ARF following cardiac-vascular surgery. The APACHEIII score 60 to 90 reflects an opportunity to treat the ARF following cardiac-vascular surgery using CBP.

Topics: Acute Kidney Injury; APACHE; Blood Urea Nitrogen; Cardiac Surgical Procedures; Humans; Interleukin-6; Interleukin-8; Multiple Organ Failure; Postoperative Complications; Renal Dialysis; Survival Analysis; Systemic Inflammatory Response Syndrome; Treatment Outcome; Tumor Necrosis Factor-alpha

To compare the hemodynamic and biological effects of high-adsorption continuous veno-venous hemofiltration (CVVH) with standard CVVH in septic shock.. In a randomized cross-over clinical trial twelve patients with septic shock and multiple organ failure were enrolled at a tertiary intensive care unit. Patients were allocated to either 9 hours of high-adsorption hemofiltration (CVVH with 3 hourly filter change using AN69 hemofilters - 3FCVVH) or 9 hours of standard hemofiltration (CVVH without filter change - 1F-CVVH).. Changes in hemodynamic variables, dose of noradrenaline required to maintain a mean arterial pressure greater than 75 mmHg and plasma concentrations of cytokines (IL-6, IL-8, IL-10 and IL-18) were measured. A 9-hour period of 3F-CVVH was associated with greater reduction in noradrenaline dose than a similar period of 1F-CVVH (median reduction: 16 vs. 3.5 microg/min, p=0.036; median percentage reduction: 48.1% vs. 17.5%, p=0.028). Unlike 1F-CVVH, 3F-CVVH was associated with a reduction in the plasma concentration of IL-6, IL-10 and IL-18 at 9 hours and a significant decrease 30 minutes after additional filter changes (IL-6: p<0.01, p<0.01; IL-10: p=0.03, p=0.016 and IL-18: p=0.016, p<0.01, respectively). Both, 3F-CVVH and 1F-CVVH were associated with decreased plasma concentrations of IL-8 at 9 hours (p<0.01, p<0.01, respectively). In a confirmatory ex-vivo experiment IL-6 concentrations substantially decreased during 3F-CVVH (at baseline 511 pg/mL and at end: 21 pg/mL) whereas IL-6 concentrations increased in control blood (at baseline 511 pg/mL and at end: 932 pg/mL).. High-adsorption CVVH appears more effective than standard CVVH in decreasing noradrenaline requirements and plasma concentrations of cytokines in septic shock patients.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Blood Pressure; Female; Heart Rate; Hemofiltration; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Norepinephrine; Renal Dialysis; Shock, Septic

Precision medicine aims to change treatment from a "one-size-fits-all" approach to customized therapies based on the individual patient. Applying a precision medicine approach to a heterogeneous condition, such as the cardiopulmonary bypass (CPB)-induced inflammatory response, first requires identification of homogeneous subgroups that correlate with biological markers and postoperative outcomes. As a first step, we derived clinical phenotypes of the CPB-induced inflammatory response by identifying patterns in perioperative clinical variables using machine learning and simulation tools. We then evaluated whether these phenotypes were associated with biological response variables and clinical outcomes.. This single-center, retrospective cohort study used Cleveland Clinic registry data from patients undergoing cardiac surgery with CPB from January 2010 to March 2020. Biomarker data from a subgroup of patients enrolled in a clinical trial were also included. Patients undergoing emergent surgery, off-pump surgery, transplantation, descending thoracoabdominal aortic surgery, and planned ventricular assist device placement were excluded. Preoperative and intraoperative variables of patient baseline characteristics (demographics, comorbidities, and laboratory data) and perioperative data (procedural data, CPB duration, and hemodynamics) were analyzed to derive clinical phenotypes using K-means-based consensus clustering analysis. Proportion of ambiguously clustered was used to assess cluster size and optimal cluster numbers. After clusters were formed, we summarized perioperative profiles, inflammatory biomarkers (eg, interleukin [IL]-6 and IL-8), kidney biomarkers (eg, urine neutrophil gelatinase-associated lipocalin [NGAL] and IL-18), and clinical outcomes (eg, mortality and hospital length of stay). Pairwise standardized difference was reported for all summarized variables.. Of 36,865 eligible cardiac surgery cases, 25,613 met inclusion criteria. Cluster analysis derived 3 clinical phenotypes: α, β, and γ. Phenotype α (n = 6157 [24%]) included older patients with more comorbidities, including heart and kidney failure. Phenotype β (n = 10,572 [41%]) patients were younger and mostly male. Phenotype γ (n = 8884 [35%]) patients were 58% female and had lower body mass index (BMI). Phenotype α patients had worse outcomes, including longer hospital length of stay (mean = 9 days for α versus 6 for both β [absolute standardized difference {ASD} = 1.15] and γ [ASD = 1.08]), more kidney failure, and higher mortality. Inflammatory biomarkers (IL-6 and IL-8) and kidney injury biomarkers (urine NGAL and IL-18) were higher with the α phenotype compared to β and γ immediately after surgery.. Deriving clinical phenotypes that correlate with response biomarkers and outcomes represents an initial step toward a precision medicine approach for the management of CPB-induced inflammatory response and lays the groundwork for future investigation, including an evaluation of the heterogeneity of treatment effect.

Topics: Acute Kidney Injury; Biomarkers; Cardiopulmonary Bypass; Female; Humans; Interleukin-18; Interleukin-8; Lipocalin-2; Male; Phenotype; Renal Insufficiency; Retrospective Studies

The prevalence, prediction and impact of acute kidney injury (AKI) in alcohol-related hepatitis (AH) is uncertain.. We aimed to determine AKI incidence; association with mortality; evaluate serum biomarkers and the modifying effects of prednisolone and pentoxifylline in the largest AH cohort to date.. Participants in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial with day zero (D0) creatinine available were included. AKI was defined by modified International Club of Ascites criteria; incident AKI as day 7 (D7) AKI without D0-AKI. Survival was compared by Kaplan-Meier; mortality associations by Cox regression; associations with AKI by binary logistic regression; biomarkers by AUROC analyses.. D0-AKI was present in 198/1051 (19%) participants; incident AKI developed in a further 119/571 (21%) with available data. Participants with D0-AKI had higher 90-day mortality than those without (32% vs. 25%, p = 0.008), as did participants with incident AKI compared to those without D0-AKI or incident AKI (47% vs. 25%, p < 0.001). Incident AKI was associated with D90 mortality adjusted for age and discriminant function (AHR 2.15, 1.56-2.97, p < 0.001); D0-AKI was not. Prednisolone therapy reduced incident AKI (AOR 0.55, 0.36-0.85, p = 0.007) but not mortality. D0 bilirubin and IL-8 combined, miR-6826-5p, and miR-6811-3p predicted incident AKI (AUROCs 0.726, 0.821, 0.770, p < 0.01).. Incident AKI is associated with 90-day mortality independent of liver function. Prednisolone therapy was associated with reduced incident AKI. IL-8 and several miRNAs are potential biomarkers to predict AKI. Novel therapies to prevent incident AKI should be evaluated in AH to reduce mortality.

Topics: Acute Kidney Injury; Biomarkers; Hepatitis, Alcoholic; Humans; Interleukin-8; MicroRNAs; Patient Acuity; Pentoxifylline; Prednisolone

Patients with cardiac surgery-associated acute kidney injury are at risk of renal replacement therapy and in-hospital death. We aimed to develop and validate a novel predictive model for poor in-hospital outcomes among patients with cardiac surgery-associated acute kidney injury.. A total of 196 patients diagnosed with cardiac surgery-associated acute kidney injury were enrolled in this study as the training cohort, and 32 blood cytokines were measured. Least absolute shrinkage and selection operator regression and random forest quantile-classifier were performed to identify the key blood predictors for in-hospital composite outcomes (requiring renal replacement therapy or in-hospital death). The logistic regression model incorporating the selected predictors was validated internally using bootstrapping and externally in an independent cohort (n = 52).. A change in serum creatinine (delta serum creatinine) and interleukin 16 and interleukin 8 were selected as key predictors for composite outcomes. The logistic regression model incorporating interleukin 16, interleukin 8, and delta serum creatinine yielded the optimal performance, with decent discrimination (area under the receiver operating characteristic curve: 0.947; area under the precision-recall curve: 0.809) and excellent calibration (Brier score: 0.056, Hosmer-Lemeshow test P = .651). Application of the model in the validation cohort yielded good discrimination. A nomogram was generated for clinical use, and decision curve analysis demonstrated that the new model adds more net benefit than delta serum creatinine.. We developed and validated a promising predictive model for in-hospital composite outcomes among patients with cardiac surgery-associated acute kidney injury and demonstrated interleukin-16 and interleukin-8 as useful predictors to improve risk stratification for poor in-hospital outcomes among those with cardiac surgery-associated acute kidney injury.

Topics: Acute Kidney Injury; Cardiac Surgical Procedures; Creatinine; Hospital Mortality; Hospitals; Humans; Interleukin-16; Interleukin-8; Risk Assessment

To investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis.. A retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI.. The level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p < 0.01). The ROC analysis showed the combined detection of urine IL-8, NGAL and KIM-1 at 12 h had a larger area under curve (AUC) than a single marker (0.997, 95% CI: 0.991-0.998), and the sensitivity and specificity were 98.2% and 96.7%, respectively. Pearson correlation analysis showed that the levels of urine NGAL at 4, 12, 24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18 (p < 0.01).. AKI could be quickly recognized by the elevated level of urine IL-8, NGAL and KIM-1 in patients with URL-related urosepsis. Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance, which may be an important reference for the early diagnosis of AKI.

Topics: Acute Kidney Injury; Biomarkers; Early Diagnosis; Hepatitis A Virus Cellular Receptor 1; Humans; Interleukin-18; Interleukin-8; Lipocalin-2; Lithotripsy; Retrospective Studies; Ureteroscopy

Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common complications of cardiac surgery procedures. In this study, the authors attempt to provide new data regarding the application of novel kidney injury biomarkers in the early diagnostics of CSA-AKI. 128 adult patients undergoing elective cardiac surgery procedures with the use of cardiopulmonary by-pass (CPB) were enrolled in this study. Novel kidney injury biomarkers were marked in the plasma and urine 6 h after weaning from the CPB. A significant difference in the postoperative biomarkers' concentration between the AKI and no-AKI group was found, regarding plasma IL-8, plasma TNF-α and urine NGAL, normalized for creatinine excretion (NGAL/Cr). These were also independent predictors of CSA-AKI. An independent risk factor for CSA-AKI proved to be preoperative CKD. Plasma IL-8 and TNF-α, as well as urine NGAL/Cr, are independent early indicators of CSA-AKI and pose a promising alternative for creatinine measurements. The cut-off points for these biomarkers proposed in this investigation should be confronted with more data and revised to achieve a suitable diagnostic value.

Topics: Acute Kidney Injury; Acute-Phase Proteins; Adult; Biomarkers; Cardiac Surgical Procedures; Creatinine; Humans; Interleukin-8; Kidney; Lipocalin-2; Lipocalins; Predictive Value of Tests; Proto-Oncogene Proteins; Tumor Necrosis Factor-alpha

Acute kidney injury (AKI) is the most common complication of sepsis. The current incidence of sepsis is high (0.3% of total population) worldwide, and septic AKI may cause death in patients. Long non‑coding (lnc)RNAs serve important roles in the pathogenesis of AKI. Therefore, the present study investigated the mechanism underlying lncRNA plasmacytoma variant translocation 1 (PVT1)‑mediated regulation of pyroptosis in septic AKI. Septic kidney injury was induced in mice using the caecal ligation and puncture method, and lipopolysaccharide (LPS)‑induced HK‑2 cell models were also established. Haematoxylin‑eosin staining was performed to assess pathological alterations of kidney tissues in the mice. The levels of IL‑1β, IL‑18 and lactate dehydrogenase were determined by conducting ELISAs. Reverse transcription‑quantitative PCR was used to detect the expression levels of PVT1 and microRNA (miR)‑20a‑5p. To assess pyroptosis, the protein expression levels of nucleotide‑binding oligomerization domain‑like receptor protein 3 (NLRP3), IL‑1β, IL‑18, apoptosis‑associated speck‑like protein containing a CARD and cleaved caspase‑1 were measured via western blotting. Flow cytometry was performed to assess the rate of cell pyroptosis. Dual luciferase reporter assays were used to assess the binding relationships of PVT1/miR‑20a‑5p and miR‑20a‑5p/NLRP3. PVT1 expression was significantly increased, whereas miR‑20a‑5p expression was significantly decreased in sepsis model mice and LPS‑induced HK‑2 cells compared with sham mice and control HK‑2 cells, respectively. PVT1 knockdown significantly suppressed cell pyroptosis and downregulated the expression of inflammatory factors in LPS‑induced HK‑2 cells. The results also indicated that PVT1 served as a sponge of miR‑20a‑5p, and miR‑20a‑5p directly targeted NLRP3. miR‑20a‑5p knockdown significantly promoted LPS‑induced cell pyroptosis. Moreover, PVT1 knockdown inhibited LPS‑induced cell pyroptosis by targeting the miR‑20a‑5p/NLRP3 signalling pathway. The results of the present study suggested that PVT1 modulated NLRP3‑mediated pyroptosis in septic AKI by targeting miR‑20a‑5p, which might suggest significant potential therapeutic targets for septic AKI.

Topics: Acute Kidney Injury; Animals; Caspase 1; Cecum; Cell Line; Gene Expression Regulation; Humans; Interleukin-1beta; Interleukin-8; Ligation; Mice; MicroRNAs; NLR Family, Pyrin Domain-Containing 3 Protein; Punctures; Pyroptosis; RNA, Long Noncoding; Sepsis

Acute kidney injury (AKI) remains a major global healthcare problem, and there is a need to develop human-based models to study AKI in vitro. Toward this goal, we have characterized induced pluripotent stem cell-derived human kidney organoids and their response to cisplatin, a chemotherapeutic drug that induces AKI and preferentially damages the proximal tubule. We found that a single treatment with 50 µM cisplatin induces hepatitis A virus cellular receptor 1 (

Topics: Acute Kidney Injury; Antineoplastic Agents; Cells, Cultured; Cisplatin; DNA Damage; Dose-Response Relationship, Drug; Hepatitis A Virus Cellular Receptor 1; Histones; Humans; Interleukin-8; Kidney Tubules, Proximal; Organic Cation Transporter 2; Organoids; Time Factors

To study the natural course of patients with acute pancreatitis (AP) with acute kidney injury (AKI) and their cytokine profile.. Natural course of patients with AP and AKI was studied in 97 individuals. Levels of TNFα, IL-6, IL-10, IL-8 and IL-1β were measured at presentation and at 72 h in patients who developed AKI.. Amongst the entire cohort, 16.4% patients developed AKI (persistent AKI - 11 patients, transient AKI - 5 patients). Mortality rate was 25% amongst patients with AKI. Levels of IL-6 (p = 0.035) and IL-8 (p = 0.002) were found to be significantly higher in the AKI group. On multivariate analysis, IL-8 levels at baseline were found to be an independent predictor of AKI. AKI group had significant rise of TNF-α (P < 0.001), IL-6 (P < 0.001) and IL- 1β (P < 0.001) on day 3 whereas persistent-AKI group had significant rise of TNF-α (p = 0.031), IL-6 (p = 0.001) and IL-1β on day 3 and significant decline of IL-10 (p = 0.015). Using a cut-off of 105 pg/ml, IL-8 levels at baseline could predict AKI with a sensitivity of 87.5% and specificity of 59.2%, with area under the curve being 0.744 (p = 0.002).. AP patients developing AKI have poor prognosis. IL-8 levels can predict AKI in patients with AP.

Topics: Acute Kidney Injury; Adult; Cytokines; Female; Humans; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Pancreatitis; Prospective Studies; Tumor Necrosis Factor-alpha

The aim of this study was to explore the effect of micro ribonucleic acid (miR)-133 on kidney injury in rats with diabetic nephropathy (DN) through the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway.. The model of DN was first established in rats. Blood glucose, renal index, urinary micro-albumin (UMA), and creatinine clearance rate (CCr) were detected. Meanwhile, the protein expression levels of miR-133, kidney injury molecule-1 (KIM-1) and anti-inflammatory cytokine interleukin-8 (IL-8) were measured using Western blotting. Human renal proximal tubular epithelial cell line human kidney-2 (HK-2) was treated with high glucose to simulate DN cells in vivo. Subsequently, Western blotting was performed to detect the protein expression of KIM-1. After HK-2 cells were treated with high glucose and silenced miR-133 for 24 h, the expression changes in KIM-1 was evaluated.. In DN group, blood glucose, renal index, UMA, and CCr were all markedly higher than those of control group. This indicated the successful establishment of DN model in rats. The expression level of miR-133 was significantly up-regulated in DN model rats. Meanwhile, the downstream protein phosphorylated-EPK (p-EPK) showed a significantly increasing trend as well. Additionally, the protein expressions of KIM-1 and IL-8 were notably elevated. High-glucose-treated HK-2 cells showed significantly up-regulated expression levels of miR-133, KIM-1, and IL-8. After 24 h of combined treatment with high glucose and miR-133 silence, the expressions of KIM-1 and IL-8 were markedly down-regulated.. MiR-133 may be related to the occurrence and development of DN. The silence of miR-133 inhibits kidney injury in DN via the MAPK/ERK signaling pathway. Our findings suggest that miR-133 may be an effective target for the treatment of DN.

Topics: Acute Kidney Injury; Animals; Cell Line; Diabetic Nephropathies; Disease Models, Animal; Hepatitis A Virus Cellular Receptor 1; Humans; Interleukin-8; Male; MicroRNAs; Mitogen-Activated Protein Kinases; Rats; Rats, Sprague-Dawley

MLKL is a central mediator for necroptosis. Its knockout significantly relieves acute kidney injury (AKI). However, its upstream regulatory mechanism in AKI has not been fully elucidated. We recently reviewed how microRNAs (miRNAs), a type of well-studied epigenetic regulator, play critical roles in AKI. Here, we evaluated miRNAs that potentially target MLKL and evaluated their function in human tubular epithelial cells in response to toxic and ischemic insults. TargetScan analysis showed that miR-194-5P, miR-338-3P, miR-500a-3P, and miR-577 had MLKL binding sites. Although all 4 miRNAs are reduced in AKI, our data show that only hsa-miR-500a-3P was significantly suppressed in cisplatin-treated human tubular epithelial (HK2) cells. We further found that hsa-miR-500a-3P alleviated cisplatin-induced HK2 cell death, which was confirmed by transmission electron microscopy and flow cytometry. In addition, overexpression of hsa-miR-500a-3P decreased kidney injury molecule-1 mRNA and protein levels. Real-time PCR, ELISA, and immunofluorescence data show that hsa-miR-500a-3P protected against inflammatory response, evidenced by decreased monocyte chemotactic protein-1 and proinflammatory cytokines TNF-α and IL-8. Further, hsa-miR-500a-3P attenuated P65 NF-κB phosphorylation and promoter activity. Mechanistically, luciferase reporter assay showed that hsa-miR-500a-3P bound the 3'UTR of MLKL, thereby suppressing phosphorylation and membrane translocation of MLKL. In agreement with these findings, we identified that overexpression of hsa-miR-500a-3P attenuated cell injury and the inflammatory response in response to sodium azide treatment in an in vitro model. Results show that circulating exosomes from patients with AKI down-regulated miR-500a-3P, which suppressed cell injury and inflammation in HK2 cells. hsa-miR-500a-3P alleviated toxic and ischemic insults that were triggered by cell necroptosis and the inflammatory response in human HK2 cells by targeting MLKL. This may serve as a novel therapeutic target for treatment of AKI.-Jiang, L., Liu, X.-Q., Ma, Q., Yang, Q., Gao, L., Li, H.-D., Wang, J.-N., Wei, B., Wen, J., Li, J., Wu, Y.-G., Meng, X.-M. hsa-miR-500a-3P alleviates kidney injury by targeting MLKL-mediated necroptosis in renal epithelial cells.

Topics: 3' Untranslated Regions; Acute Kidney Injury; Apoptosis; Cell Line; Down-Regulation; Epithelial Cells; Exosomes; Humans; Inflammation; Interferon-alpha; Interleukin-8; Kidney; MicroRNAs; Necrosis; Promoter Regions, Genetic; Protein Kinases; RNA, Messenger

Cardiopulmonary bypass causes detrimental effects on remote organs due to inflammatory response. One of these organs is kidney that is frequently affected by cardiac surgery. Acute kidney injury is a post-cardiopulmonary bypass complication, which may result in increased post-operative morbidity and mortality. Post-cardiopulmonary bypass inflammatory response may contribute to remote organ dysfunction. In the present study, we investigated the relation between cytokines including interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α, and renal function tests such as creatinine and blood urea nitrogen (BUN).. In total, 91 patients between the ages of 4 and 60 months were enrolled for elective cardiac surgery with cardiopulmonary bypass after informed consent. Data regarding renal function tests and clinical outcomes were carefully recorded until 24 hours after admission to intensive care unit and analyzed.. Our findings support that there is a direct correlation between cytokines including interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α and cardiopulmonary bypass time, duration of operation, and intensive care unit stay. Longer cardiopulmonary bypass time was associated with higher interleukin-8 at cross-clamp removal and 24 hours post- intensive care unit as well as higher interleukin-10 at declamp time. Higher interleukin-6 at declamp time was directly correlated with higher post-operative BUN. Interleukin-8 level after anesthesia induction was directly correlated with intensive care unit stay duration. Higher blood interleukin-6 and tumor necrosis factor-α levels following 24 hours of admission to intensive care unit were associated with longer mechanical ventilation time.. Higher circulatory pro-inflammatory cytokine level is associated with adverse outcomes such as increased intensive care unit stay and longer mechanical ventilation time in pediatric patients. It is also correlated with unfavorable biochemical parameter of renal function, BUN. Findings hint that proper control of the inflammatory response is vital for the control of unfavorable clinical and pathological outcomes.

Topics: Acute Kidney Injury; Cardiopulmonary Bypass; Child, Preschool; Cross-Sectional Studies; Female; Heart Defects, Congenital; Humans; Infant; Interleukin-10; Interleukin-6; Interleukin-8; Kidney; Male; Treatment Outcome; Tumor Necrosis Factor-alpha

Inflammation, reflected by high plasma interleukin-6 concentration, is associated with acute kidney injury (AKI) in septic patients. Neutrophil activation has pathophysiological significance in experimental septic AKI. We hypothesized that neutrophil activation is associated with AKI in critically ill sepsis patients.. We measured plasma (n = 182) and urine (n = 118) activin A (a rapidly released cytosolic neutrophil protein), interleukin-8 (a chemotactic factor for neutrophils), myeloperoxidase (a neutrophil biomarker released in tissues), and interleukin-6 on intensive care unit admission (plasma and urine) and 24 hours later (plasma) in sepsis patients manifesting their first organ dysfunction between 24 hours preceding admission and the second calendar day in intensive care unit. AKI was defined by the Kidney Disease: Improving Global Outcomes criteria.. Plasma admission interleukin-8 (240 [60-971] vs 50 [19-164] pg/mL, P < .001) and activin A (845 [554-1895] vs 469 [285-862] pg/mL, P < .001) were but myeloperoxidase (169 [111-300] vs 144 [88-215] ng/mL, P = .059) was not higher among patients with AKI compared with those without. Urine admission interleukin-8 (50.4 [19.8-145.3] vs 9.5 [2.7-28.7] ng/mL, P < .001) and myeloperoxidase (7.7 [1.5-12.6] vs 1.9 [0.4-6.9] ng/mL, P < .001) were but activin A (9.7 [1.4-42.6] vs 4.0 [0.0-33.0] ng/mL, P = .064) was not higher in AKI than non-AKI patients. Urine myeloperoxidase correlated with urine interleukin-8 (R = .627, P < .001) but not with plasma myeloperoxidase (R = .131, P = .158).. Interleukin-8 in plasma and urine was associated with septic AKI. Elevated plasma activin A indicates intravascular neutrophil activation in septic AKI. Concomitant plasma and urine myeloperoxidase measurements suggest neutrophil accumulation into injured kidneys.

Topics: Activins; Acute Kidney Injury; Aged; Female; Humans; Interleukin-8; Male; Middle Aged; Neutrophil Activation; Peroxidase; Sepsis

Topics: Acute Kidney Injury; Area Under Curve; Biomarkers; Cardiopulmonary Bypass; Child; Child, Preschool; Disease Progression; Fatty Acid-Binding Proteins; Female; Humans; Infant; Infant, Newborn; Interleukin-8; Male; Postoperative Complications; Prospective Studies

Topics: Acute Kidney Injury; Biomarkers; Child; Humans; Interleukin-8; Lipocalins; Tumor Necrosis Factors

Topics: Acute Kidney Injury; Cardiac Surgical Procedures; Child; Humans; Interleukin-8; Tumor Necrosis Factor-alpha

Topics: Acute Kidney Injury; Biomarkers; Critical Care; Early Diagnosis; Humans; Interleukin-8; Predictive Value of Tests; Risk Factors; Severity of Illness Index

Heme is a ubiquitous compound of human tissues, and it is involved in cellular physiology and metabolism. Once released from the cell, free heme oxidizes to the ferric state (hemin). High levels of hemin can cause oxidative stress and inflammation if not neutralized immediately by specialized scavenger proteins. Human alpha1-antitrypsin (A1AT), an acute-phase glycoprotein and important inhibitor of neutrophil proteases, is also a hemin-binding protein. A short-term exposure of freshly isolated human blood neutrophils to 4 µM hemin results in cell spreading, surface expression of filament protein, vimentin, free radical production, expression of heme oxygenase-1 (HO-1), release of IL-8, and enhanced neutrophil adhesion to human endothelial cells. Consequently, the phosphorylation of protein kinase C (PKC) occurs after 25 min. Under the same experimental conditions, addition of 1 mg/ml A1AT markedly reduces or abolishes neutrophil-activating effects of hemin and prevents PKC phosphorylation. In a mouse model of acute kidney injury (AKI) plus injection of hemin, monotherapy with 4 mg/mouse A1AT significantly lowered serum levels of free hemin at 2 h after surgery. Moreover, a tendency toward lower AKI scores, reduced infiltration of neutrophils, and lower levels of serum chemokine [CXCL1/keratinocyte-derived chemokine (KC)] was observed. Our findings highlight A1AT as a potential serum scavenger of hemin and suggest that the commercial preparations of human plasma A1AT might prove to be useful therapeutics in conditions associated with hemolysis.

Topics: Acute Kidney Injury; alpha 1-Antitrypsin; Animals; Disease Models, Animal; Heme Oxygenase-1; Hemin; Hemolysis; Humans; Interleukin-8; Mice; Neutrophil Activation; Neutrophils; Oxidation-Reduction; Protein Kinase C

Inflammation is a key component of both acute kidney injury (AKI) and response to cardiopulmonary bypass. Because AKI poses risks to children after cardiac surgery, we investigated the value of inflammatory biomarkers interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFα) for predicting AKI and other complications.. We enrolled 412 children between the ages of 1 month and 18 years undergoing cardiopulmonary bypass for cardiac surgery. We collected blood both preoperatively and postoperatively (within 6 hours post-surgery) and measured plasma IL-8 and TNFα.. IL-8 and TNFα did not predict AKI in children <2 years, but were strongly associated with AKI in children ≥2 years. There were significant associations between biomarker levels and age (<2 or ≥2 years). In children ≥2 years, patients in the highest tertile of preoperative IL-8 and postoperative TNFα had 4.9-fold (95% CI: 1.8-13.2) and 3.3-fold (95% CI: 1.2-9.0) higher odds of AKI compared with those in the lowest tertile. Children <2 years with higher biomarker levels also had higher odds of AKI, but the difference was not significant. We also found that postoperative TNFα levels were significantly higher in patients with longer hospital stays, and that both postoperative IL-8 and TNFα levels were significantly higher in patients with longer ventilation lengths. There was no evidence that biomarker levels mediated the association between AKI and length of ventilation; they appear to be independent predictors.. Preoperative IL-8 and postoperative TNFα are significantly associated with higher odds of AKI and greater lengths of hospital stays and ventilator use in children 2 years and older.

Topics: Acute Kidney Injury; Adolescent; Biomarkers; Cardiac Surgical Procedures; Child; Child, Preschool; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Interleukin-8; Male; Postoperative Complications; Prognosis; Prospective Studies

Dogs with leptospirosis show similar organ manifestations and disease course as human patients, including acute kidney injury and pulmonary hemorrhage, making this naturally-occurring infection a good animal model for human leptospirosis. Expression patterns of cytokines and enzymes have been correlated with disease manifestations and clinical outcome in humans and animals. The aim of this study was to describe mRNA expression of pro- and anti-inflammatory mediators in canine leptospirosis and to compare it with other renal diseases to identify patterns characterizing the disease and especially its pulmonary form.. The mRNA abundance of cytokines (IL-1α, IL-1β, IL-8, IL-10, TNF-α, TGF-β) and enzymes (5-LO, iNOS) was measured prospectively in blood leukocytes from 34 dogs with severe leptospirosis and acute kidney injury, including 22 dogs with leptospirosis-associated pulmonary hemorrhages. Dogs with leptospirosis were compared to 14 dogs with acute kidney injury of other origin than leptospirosis, 8 dogs with chronic kidney disease, and 10 healthy control dogs. Canine leptospirosis was characterized by high 5-LO and low TNF-α expression compared to other causes of acute kidney injury, although the decreased TNF-α expression was also seen in chronic kidney disease. Leptospirosis-associated pulmonary hemorrhage was not characterized by a specific pattern, with only mild changes noted, including increased IL-10 and decreased 5-LO expression on some days in affected dogs. Fatal outcome from pulmonary hemorrhages was associated with low TNF-α, high IL-1β, and high iNOS expression, a pattern possibly expressed also in dogs with other forms of acute kidney injury.. The patterns of cytokine and enzyme expression observed in the present study indicate a complex pro- and anti-inflammatory response to the infection with leptospires. The recognition of these signatures may be of diagnostic and prognostic relevance for affected individuals and they may indicate options for newer therapies targeting the identified pathways.

Topics: Acute Kidney Injury; Animals; Arachidonate 5-Lipoxygenase; Disease Models, Animal; Disease Progression; Dogs; Female; Gene Expression Regulation; Hemorrhage; Humans; Interleukin-1alpha; Interleukin-1beta; Interleukin-8; Leptospirosis; Leukocytes, Mononuclear; Lung Injury; Male; Nitric Oxide Synthase Type II; RNA, Messenger; Severity of Illness Index; Signal Transduction; Survival Analysis; Syndrome; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Determining ultratrace amounts of protein biomarkers in patient samples in a straightforward and quantitative manner is extremely important for early disease diagnosis and treatment. Here, we successfully demonstrate the novel use of zinc oxide nanorods (ZnO NRs) in the ultrasensitive and quantitative detection of two acute kidney injury (AKI)-related protein biomarkers, tumor necrosis factor (TNF)-α and interleukin (IL)-8, directly from patient samples. We first validate the ZnO NRs-based IL-8 results via comparison with those obtained from using a conventional enzyme-linked immunosorbent method in samples from 38 individuals. We further assess the full detection capability of the ZnO NRs-based technique by quantifying TNF-α, whose levels in human urine are often below the detection limits of conventional methods. Using the ZnO NR platforms, we determine the TNF-α concentrations of all 46 patient samples tested, down to the fg per mL level. Subsequently, we screen for TNF-α levels in approximately 50 additional samples collected from different patient groups in order to demonstrate a potential use of the ZnO NRs-based assay in assessing cytokine levels useful for further clinical monitoring. Our research efforts demonstrate that ZnO NRs can be straightforwardly employed in the rapid, ultrasensitive, quantitative, and simultaneous detection of multiple AKI-related biomarkers directly in patient urine samples, providing an unparalleled detection capability beyond those of conventional analysis methods. Additional key advantages of the ZnO NRs-based approach include a fast detection speed, low-volume assay condition, multiplexing ability, and easy automation/integration capability to existing fluorescence instrumentation. Therefore, we anticipate that our ZnO NRs-based detection method will be highly beneficial for overcoming the frequent challenges in early biomarker development and treatment assessment, pertaining to the facile and ultrasensitive quantification of hard-to-trace biomolecules.

Topics: Acute Kidney Injury; Biomarkers; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-8; Microscopy, Electron, Scanning; Nanotubes; Tumor Necrosis Factor-alpha; Zinc Oxide

Hemolytic uremic syndrome (HUS), a vascular disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure, is caused by enterohemorrhagic Shiga toxin (Stx)-producing bacteria, which mainly affect children. Besides Stx, the inflammatory response mediated by neutrophils (PMN) is essential to HUS evolution. PMN can release neutrophil extracellular traps (NET) composed of DNA, histones, and other proteins. Since NET are involved in infectious and inflammatory diseases, the aim of this work was to investigate the contribution of NET to HUS. Plasma from HUS patients contained increased levels of circulating free-DNA and nucleosomes in comparison to plasma from healthy children. Neutrophils from HUS patients exhibited a greater capacity to undergo spontaneous NETosis. NET activated human glomerular endothelial cells, stimulating secretion of the proinflammatory cytokines IL-6 and IL-8. Stx induced PMN activation as judged by its ability to trigger reactive oxygen species production, increase CD11b and CD66b expression, and induce NETosis in PMN from healthy donors. During HUS, NET can contribute to the inflammatory response and thrombosis in the microvasculature and thus to renal failure. Intervention strategies to inhibit inflammatory mechanisms mediated by PMN, such as NETosis, could have a potential therapeutic impact towards amelioration of the severity of HUS.

Topics: Acute Kidney Injury; Anemia, Hemolytic; Apoptosis; Bacterial Infections; Cells, Cultured; Child; Endothelial Cells; Extracellular Traps; Hemolytic-Uremic Syndrome; Humans; Interleukin-6; Interleukin-8; Kidney; Neutrophil Activation; Neutrophils; Reactive Oxygen Species; Shiga Toxin; Thrombocytopenia

Immunocompromised patients who develop sepsis while neutropenic are at high risk for morbidity and mortality; however, it is unknown if neutropenic sepsis is associated with distinct clinical and biological characteristics.. We conducted a prospective cohort study of patients admitted to the medical intensive care unit of an academic medical center with severe sepsis. Patients were followed for the development of acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality. Plasma proteins, representing the host inflammatory response, anti-inflammatory response, and endothelial leak were measured in 30 % of subjects. Clinical characteristics and plasma protein concentrations of patients with neutropenia at enrollment were compared to patients without neutropenia.. Of 797 subjects enrolled, 103 (13 %) were neutropenic at ICU admission. The neutropenic subjects were more often in shock, admitted from the hospital ward, had higher APACHE III scores, and more likely bacteremic. Neutropenia was an independent risk factor for AKI (RR 1.28; 95 % CI 1.04, 1.57; p = 0.03), but not ARDS (RR 0.90; 95 % CI 0.70, 1.17; p = 0.42) or 30-day mortality (RR 1.05; 95 % CI 0.85, 1.31; p = 0.65). Neutropenic subjects had higher plasma interleukin (IL)-6 (457 vs. 249 pg/ml; p = 0.03), IL-8 (581 vs. 94 pg/ml; p <0.001), and granulocyte colony-stimulating factor (G-CSF) (3624 vs. 99 pg/ml; p <0.001). Angiopoietin-2 and IL-1 receptor antagonist concentrations did not differ between groups.. Neutropenic sepsis is associated with a higher AKI risk and concentrations of inflammatory mediators IL-6, IL-8, and G-CSF relative to non-neutropenic patients. These differences may have implications for future therapies targeting neutropenic sepsis.

Topics: Acute Kidney Injury; Adult; Aged; Angiopoietin-2; APACHE; Biomarkers; Chi-Square Distribution; Cohort Studies; Critical Illness; Female; Granulocyte Colony-Stimulating Factor; Humans; Intensive Care Units; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Neutropenia; Pennsylvania; Prospective Studies; Receptors, Interleukin-1; Respiratory Distress Syndrome; Sepsis

The aim of this study was to investigate the role of cytokine genes in the susceptibility to Candida infection. A total of 275 consecutive patients diagnosed with Candida infection were selected between May 2010 and May 2011, along with 305 uninfected controls. Genotyping of the IL-1β gene polymorphisms (IL1β) rs1143634, IL1βrs16944, IL8 rs4073, IL10 rs1800872, and IL10 rs1800896 was carried out using a 384-well plate format on the Sequenom MassARRAY platform. Patients with invasive Candida infections were more likely to have had an immunocompromised state, hematopoietic stem cell transplantation, solid organ transplant, solid tumor, chemotherapy within the past three months, neutropenia, surgery within the past 30 days, acute renal failure, liver failure, and/or median baseline serum creatinine. Conditional logistic regression analyses found that individuals with the rs1800896 GG genotype were associated with a higher risk of invasive Candida infections than those carrying the AA genotype (odds ratio = 0.61, 95% confidence interval = 0.37-0.94). From the results of this case-control study, we suggest that the cytokine IL-10 gene rs1800896 polymorphism might play a role in the etiology of invasive Candida infections.

Topics: Acute Kidney Injury; Adult; Aged; Alleles; Candida; Candidiasis, Invasive; Case-Control Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Immunocompromised Host; Interleukin-10; Interleukin-1beta; Interleukin-8; Liver Failure; Logistic Models; Male; Middle Aged; Neoplasms; Polymorphism, Single Nucleotide

This study aimed to explore the effect and mechanisms of rhein on sepsis-induced acute kidney injury by injecting lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in vivo, and on LPS-induced HK-2 cells in vitro. For histopathological analysis, rhein effectively attenuated the severity of renal injury. Rhein could significantly decrease concentration of BUN and SCr and level of TNF-α and IL-1β in two different mouse models of experimental sepsis. Moreover, rhein could markedly attenuate circulating leukocyte infiltration and enhance phagocytic activity of macrophages partly impaired at 12 h after CLP. Rhein could enhance cell viability and suppresse the release of MCP-1 and IL-8 in LPS-stimulated HK-2 cells Furthermore, rhein down regulated the expression of phosphorylated NF-κB p65, IκBα and IKKβ stimulated by LPS both in vivo and in vitro. All these results suggest that rhein has protective effects on endotoxin-induced kidney injury. The underlying mechanism of rhein on anti-endotoxin kidney injury may be closely related with its anti-inflammatory and immunomodulatory properties by decreasing NF-κB activation through restraining the expression and phosphorylation of the relevant proteins in NF-κB signal pathway, hindering transcription of NF-κB p65.These evidence suggest that rhein has a potential application to treat endotoxemia-associated acute kidney injury.

Topics: Acute Kidney Injury; Animals; Anthraquinones; Blood Urea Nitrogen; Cell Line; Creatine; Disease Models, Animal; I-kappa B Kinase; I-kappa B Proteins; Immunohistochemistry; Interleukin-1beta; Interleukin-8; Kidney; Lipopolysaccharides; Macrophages; Mice; Mice, Inbred BALB C; NF-kappa B; NF-KappaB Inhibitor alpha; Phosphorylation; Sepsis; Signal Transduction; Transcription Factor RelA; Transcription, Genetic; Tumor Necrosis Factor-alpha

The kidney is a major target for drug-induced toxicity, and the renal proximal tubule is frequently affected. Nephrotoxicity is typically detected only late during drug development, and the nephrotoxic potential of newly approved drugs is often underestimated. A central problem is the lack of preclinical models with high predictivity. Validated in vitro models for the prediction of nephrotoxicity are not available. Major problems are related to the identification of appropriate cell models and end points. As drug-induced kidney injury is associated with inflammatory reactions, we explored the expression of inflammatory markers as end point for renal in vitro models. In parallel, we developed a new cell model. Here, we combined these approaches and developed an in vitro model with embryonic stem-cell-derived human renal proximal tubular-like cells that uses the expression of interleukin (IL)-6 and IL-8 as end points. The predictivity of the model was evaluated with 41 well-characterized compounds. The results revealed that the model predicts proximal tubular toxicity in humans with high accuracy. In contrast, the predictivity was low when well-established standard in vitro assays were used. Together, the results show that high predictivity can be obtained with in vitro models employing pluripotent stem cell-derived human renal proximal tubular-like cells.

Topics: Acute Kidney Injury; Biomarkers; Cell Line; Drug-Related Side Effects and Adverse Reactions; Embryonic Stem Cells; Humans; Inflammation; Interleukin-6; Interleukin-8; Kidney; Kidney Tubules, Proximal; Pharmaceutical Preparations

We examined the value of inflammatory and oxidative biomarkers in predicting acute kidney injury (AKI) following orthotopic liver transplantation (OLT).. Urinary excretion of tumour necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-10 (IL-10), superoxide dismutase (SOD), malondialdehyde (MDA), 6-keto prostaglandin F1α (6-keto-PGF1α), hydrogen peroxide (H2O2), and 8-keto prostaglandin F2α (8-iso-PGF2α), serum creatinine (SCr), blood urea nitrogen (BUN), urinary N-acetyl-beta-D-glucosaminidase (NAG), β2-microglobulin (β2-MG) and γ-glutamyl-transferase (γ-GT), were measured before surgery (baseline), at 2 h after graft reperfusion and 24 h after OLT in 28 liver transplantation patients.. The levels of TNF-α, IL-8, IL-10, SOD, MDA, 6-keto-PGF1α, H2O2 and 8-iso-PGF2α in urine were all significantly higher in patients who had AKI than in those who did not at 2 h after graft reperfusion and 24 h after OLT (p < 0.01).

Topics: 6-Ketoprostaglandin F1 alpha; Acute Kidney Injury; Adult; Biomarkers; Dinoprost; Female; Humans; Hydrogen Peroxide; Interleukin-10; Interleukin-8; Liver Transplantation; Male; Malondialdehyde; Middle Aged; Postoperative Period; Preoperative Period; Prognosis; ROC Curve; Superoxide Dismutase; Time Factors; Tumor Necrosis Factor-alpha

The underlying mechanism for amphotericin B-induced acute kidney injury (AKI) remains poorly understood and may be immunologically mediated. We assessed whether the development of nephrotoxicity is linked to a distinct cytokine profile in patients receiving amphotericin B deoxycholate (AmBD).. In 58 patients who received AmBD, circulating serum interleukin (IL)-6, IL-8 and IL-10 were measured at baseline, week 1 and week 2 of antifungal treatment and correlated to the development of renal impairment. The Cox proportional hazards model approach was adopted for analysis.. The P value was 0.026 for the overall effect of IL-6 on time to development of AKI. An increasing or non-receding IL-6 trend by week 1 of AmBD treatment (followed by a decreasing or non-receding IL-6 trend from week 1 to week 2) correlated with an increased likelihood of nephrotoxicity [hazard ratio (HR) 6.93, P value 0.005 and HR 3.46, P value 0.035, respectively]. Similarly, persistently increasing IL-8 levels were linked to a 3.84-fold increased likelihood of AKI.. In patients receiving AmBD, persistence of an elevated pro-inflammatory cytokine milieu is associated with a predisposition to drug-related kidney injury.

Topics: Acute Kidney Injury; Adult; Aged; Amphotericin B; Antifungal Agents; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Serum

Organ cross talk exists in many diseases of the human and animal models of human diseases. A recent study demonstrated that inflammatory mediators can cause acute kidney injury and neutrophil infiltration in a mouse model of dextran sodium sulfate (DSS)-colitis. However, the chemokines and their receptors that may mediate distant organ effects in colitis are unknown. We hypothesized that keratinocyte chemoattractant (KC)/IL-8 receptor chemokine (C-X-C motif) ligand 2 (CXCL2) mediates DSS-colitis-induced acute kidney injury. Consistent with our hypothesis, wild-type (WT) mice developed severe colitis with DSS treatment, which was associated with inflammatory cytokine and chemokine expression and neutrophil infiltration in the colon. DSS-colitis in WT was accompanied by acute kidney injury and enhanced expression of inflammatory cytokines in the kidney. However, CXCR2 knockout mice were protected against DSS-colitis as well as acute kidney injury. Moreover, the expression of cytokines and chemokines and neutrophil infiltration was blunted in CXCR2 knockout mice in the colon and kidney. Administration of recombinant KC exacerbated DSS-colitis-induced acute kidney injury. Our results suggest that KC/IL-8 and its receptor CXCR2 are critical and major mediators of organ cross talk in DSS colitis and neutralization of CXCR2 will help to reduce the incidence of acute kidney injury due to ulcerative colitis and Crohn's disease in humans.

Topics: Acute Kidney Injury; Animals; Chemokine CXCL1; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Inflammation Mediators; Interleukin-8; Kidney; Ligands; Mice; Mice, Knockout; Neutrophil Infiltration; Receptors, Interleukin-8B; Recombinant Proteins; Signal Transduction; Time Factors

Puumala hantavirus (PUUV) infection, also known as nephropathia epidemica, is the most common cause of hemorrhagic fever with renal syndrome (HFRS) in Europe. The pathogenesis of PUUV nephropathia epidemica is complex and multifactorial, and the risk factors for severe acute kidney injury (AKI) during acute PUUV infection are not well defined. We conducted a prospective study of hospitalized patients with PUUV infection in Tampere, Finland to identify acute illness risk factors for HFRS severity. Serial daily blood and urine samples were collected throughout acute illness and at 2 week and 6 month convalescent visits. By univariate analyses, the maximum white blood cell count during acute illness was a risk factor for severe AKI. There were no significant associations between PUUV-induced AKI severity and platelet counts, C-reactive protein, or alanine aminotransferase levels. Maximum plasma interleukin (IL)-6, urine IL-6, and urine IL-8 concentrations were positively associated with PUUV-induced AKI. Finally, the maximum urinary sediment GATA-3 mRNA level was positively correlated with the peak fold-change in serum creatinine, regardless of AKI severity classification. By multivariate analyses, we found that the maximum levels of leukocytes and urinary sediment GATA-3 mRNA during acute illness were independent risk factors for severe PUUV-induced AKI. We have identified novel acute illness risk factors for severe PUUV-induced AKI.

Topics: Acute Kidney Injury; Adult; Creatinine; Female; Finland; GATA3 Transcription Factor; Hemorrhagic Fever with Renal Syndrome; Humans; Interleukin-6; Interleukin-8; Length of Stay; Leukocytosis; Male; Middle Aged; Prospective Studies; Puumala virus; Risk Factors; RNA, Messenger

During continuous venovenous hemofiltration (CVVH) to replace renal function in acute kidney injury (AKI), anticoagulation of the filter is routinely required. A survival benefit for citrate has been reported, possibly due to reduced proinflammatory effects of the filter (bioincompatibility). We hypothesized that the type of anticoagulation modulates the immune response to, and clearance by CVVH of interleukin-6 (IL-6) and -8 (IL-8).. Three anticoagulation regimens were compared: trisodium citrate (n=17), unfractionated heparin (n=8) and no anticoagulation in case of bleeding tendency (n=13). Immediately before initiation of CVVH (cellulose triacetate membrane) pre-filter blood was drawn. Thereafter, at 10, 60, 180 and 720 min, samples were collected from the pre- and postfilter blood and from ultrafiltrate. IL-6 and IL-8 were determined by ELISA.. High inlet levels of IL-6 and IL-8, particularly in the no anticoagulation group, were associated with non-survival. The inlet concentrations and mass rates of IL-6 and IL-8 decreased during CVVH. The course of fluxes across the filter were similar for the groups, however. Although increasing in time for IL-6 in the no anticoagulation group, mass removal and adsorption of IL-6 and IL-8 were low and did not differ among the anticoagulation groups.. Blood to membrane contact, adsorption/clearance and anticoagulation do not increase nor attenuate high circulating levels of IL-6 and IL-8 during CVVH for AKI. This renders the hypothesis that the reported survival benefit for citrate anticoagulation is based on a reduction of bioincompatibility unlikely.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anticoagulants; Citrates; Female; Hemofiltration; Heparin; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Young Adult

To investigate the impact of a traditional Chinese medicinal compound known as Fufang Shenhua Tablet (SHP) on the expression of Toll-like receptors (TLRs) during renal ischemia-reperfusion injury (IRI)-induced acute kidney injury (AKI) in rats.. A total of 28 Wistar rats were randomly divided into five groups: (1) pseudo-operation control group, (2) ischemia-reperfusion model group, (3) Astragaloside group, (4) high-dose SHP group, and (5) low-dose SHP group. There were four rats in the pseudo-operation group and six rats in each of the other groups. The accepted ischemia-reperfusion model was established after a 7-day gavage intervention, and pathological changes and renal function were observed, using an enzyme-linked immunosorbent assay (ELISA) to detect interleukin 8 (IL-8) and interferon gamma (IFN-γ) levels, as well as immunohistochemical staining to detect altered levels of TLR2 and TLR4 expression in renal tissue.. After 24 h, renal pathological damage and the expression levels of serum creatinine (Scr), IL-8, IFN-γ, TLR2, and TLR4 were significantly higher in the model group as compared with the pseudo-operation group (P<0.05). In addition, at 24 h the above indicators decreased significantly in the Astragaloside group, high-dose SHP group and low-dose SHP group as compared with the ischemia-reperfusion model group (P< 0.05). TLR2 and TLR4 expression levels were significantly reduced in the SHP treatment and Astragaloside group as compared with the pseudo-operation group (P<0.05). Further, the high-dose SHP group showed significantly less renal damage score and decreased levels of TLR expression than those of low-dose SHP group and Astragaloside group (all P<0.05).. SHP can alleviate the renal structural and functional damage caused by IRI-induced AKI in rats by reducing the damage of renal pathology, which may reduce inflammatory cytokine levels by downregulating the expression of TLRs in renal tissue in a dose-dependent manner.

Topics: Acute Kidney Injury; Animals; Drugs, Chinese Herbal; Enzyme-Linked Immunosorbent Assay; Immunohistochemistry; Interferon-gamma; Interleukin-8; Kidney Tubules; Male; Rats; Rats, Wistar; Reperfusion Injury; Tablets; Toll-Like Receptor 2; Toll-Like Receptor 4

To investigate the effect of penehyclidine hydrochloride (PHC) in a rat model of renal injury induced by hemorrhagic shock and lipopolysaccharides (LPS).. Forty-five healthy Wistar rats were randomized into sham operated group, model group, and 3 penehyclidine hydrochloride (PHC) dose (1, 2 and 3 mg/kg) groups (PHC1, PHC2, and PHC3 groups, respectively). The arterial blood samples were collected to determine the concentrations of serum tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-1 (IL-1), urine creatinine (Cr) and blood urine nitrogen (BUN), and the renal tissues were collected to measure the expressions of ICAM-1 and nuclear factor-κB (NF-κB) and observe the pathological changes.. TNF-α, IL-8, IL-1, Cr, BUN, ICAM-1 and NF-κB in the 3 PHC groups were significantly lower than those in the model group (P<0.05). TNF-α, IL-8, IL-1, Cr and BUN were significantly lower in PHC1 (P<0.05) than in the PHC2 and PHC3 groups, and ICAM-1 and NF-κB were similar between 3 PHC groups (P>0.05). Compared with the model group, the 3 PHC groups showed lessened pathological changes in the renal tubules.. PHC has protective effects against renal injury induced by hemorrhagic-endotoxin shock in rats, and treatment with 1 mg/kg PHC produces the most significant protective effect.

Topics: Acute Kidney Injury; Animals; Intercellular Adhesion Molecule-1; Interleukin-1; Interleukin-8; Kidney; Kidney Tubules; Lipopolysaccharides; Male; NF-kappa B; Quinuclidines; Rats; Rats, Wistar; Shock, Hemorrhagic; Tumor Necrosis Factor-alpha

Acute kidney injury (AKI) is associated with high mortality rates. New biomarkers that can identify subjects with early AKI (before the increase in serum creatinine) are needed to facilitate appropriate treatment. The purpose of this study was to test the role of serum cytokines as biomarkers for AKI and prolonged mechanical ventilation.. This was a case-control study of children undergoing cardiac surgery. AKI was defined as a 50% increase in serum creatinine from baseline within 3 days. Levels of serum interleukin (IL)-1beta, IL-5, IL-6, IL-8, IL-10, IL-17, interferon (IFN)-gamma, tumor necrosis factor-alpha (TNF-alpha), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured using a bead-based multiplex cytokine kit in conjunction with flow-based protein detection and the Luminex LabMAP multiplex system in 18 cases and 21 controls. Levels of IL-6 and IL-8 were confirmed with single-analyte ELISA; IL-18 was also measured with single-analyte ELISA.. IL-6 levels at 2 and 12 hours after cardiopulmonary bypass (CPB) and IL-8 levels at 2, 12 and 24 hours were associated with the development of AKI using the Wilcoxon rank-sum test and after adjustment for age, gender, race, and prior cardiac surgery in multivariate logistic regression analysis. In patients with AKI, IL-6 levels at 2 hours had excellent predictive value for prolonged mechanical ventilation (defined as mechanical ventilation for more than 24 hours postoperatively) by receiver operator curve (ROC) analysis, with an area under the ROC curve of 0.95. IL-8 levels at 2 hours had excellent predictive value for prolonged mechanical ventilation in all patients. Serum IL-18 levels were not different between those with and without AKI.. Serum IL-6 and IL-8 values identify AKI early in patients undergoing CPB surgery. Furthermore, among patients with AKI, high IL-6 levels are associated with prolonged mechanical ventilation, suggesting that circulating cytokines in patients with AKI may have deleterious effects on other organs, including the lungs.

Topics: Acute Kidney Injury; Biomarkers; Cardiac Surgical Procedures; Case-Control Studies; Child, Preschool; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Humans; Interleukin-6; Interleukin-8; Male; Respiration, Artificial

Cardiopulmonary bypass (CPB) elicits an inflammatory response mediated partly by neutrophils, which are activated and recruited by interleukin-8 (IL-8). We hypothesized that acute kidney injury (AKI) following CPB might be mediated by IL-8 and examined the association of perioperative plasma IL-8 levels with AKI in a prospective cohort.. Plasma IL-8 was measured before, and 2, 24 and 48 h following CPB. Two AKI definitions, a serum creatinine increase of > or = 0.3 mg/dl or 50% (AKI Network [AKIN] stage-1) or > or = 50% alone (AKI-50%), within the first 72 h, were used. Area under the receiver operator characteristic curves (AUCs) were generated and multivariable logistic regression analyses performed.. A total of 143 patients were enrolled. The baseline mean serum creatinine was 1.1 mg/ dl (SD = 0.3), the CPB perfusion time was 112 min (SD = 43). Twenty-nine percent of the patients developed AKIN stage-1 and 13% AKI-50%. The plasma IL-8 level 2 h after CPB was higher in AKIN stage-1 (p = 0.03) and AKI-50% (p < 0.01), and predicted AKIN stage-1 (AUC = 0.62; p = 0.02) and AKI-50% (AUC = 0.72; p < 0.01). On multivariable analysis, the 2-hour plasma IL-8 level was associated with 1.36- and 1.59-fold higher odds for AKIN stage-1 and AKI-50%, respectively (p = 0.05).. Plasma IL-8 predicts the development of AKI following CPB, supporting a potential involvement for this chemokine in the pathogenesis of AKI.

Topics: Acute Kidney Injury; Aged; Biomarkers; Cardiopulmonary Bypass; Cohort Studies; Creatinine; Female; Humans; Interleukin-8; Male; Middle Aged; Postoperative Complications; Prospective Studies

Renal ischemic reperfusion injury (IRI) is unavoidable and is still one of the major problems in renal transplantation. The aim of this study was to investigate the effects of olprinone, a phosphodiesterase III inhibitor, on renal IRI.. After a right nephrectomy, renal IRI was induced in rats. Olprinone was given in two different ways: sustained systemic administration and transient local administration to the kidney. Control rats were treated with saline. Using a magnifying endoscope, the renal blood flow speed was measured at 23 h after reperfusion. Then, blood samples were collected, and kidney specimens were taken for histological study. In order to study the mechanism, we performed in vitro experiments, using human proximal renal tubular cells (HK-2) incubated with tumor necrosis factor (TNF)-alpha along with olprinone or saline, and interleukin (IL)-8 was measured in the culture supernatant.. In the saline group, the blood flow speed (BFS) was greatly reduced compared to that in normal kidneys. In both olprinone-treated groups, BFS of the renal microcirculation significantly increased, tubular damage and macrophage infiltration attenuated, and renal function greatly improved. Olprinone inhibited the increase in the IL-8 levels resulting from the incubation of HK-2 with TNF-alpha.. Our study successfully demonstrates that olprinone has renoprotective properties when applied locally as well as systemically. The results suggest that olprinone might be clinically useful in renal transplantation for the donor kidney, the recipient, and even in treating acute renal failure.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Acute Kidney Injury; Animals; Blood Flow Velocity; Blood Urea Nitrogen; Cells, Cultured; Cyclic Nucleotide Phosphodiesterases, Type 3; Disease Models, Animal; Humans; Imidazoles; Immunohistochemistry; Interleukin-8; Kidney Tubules, Proximal; Male; Microscopy, Video; Phosphodiesterase Inhibitors; Pyridones; Rats; Rats, Sprague-Dawley; Renal Circulation; Reperfusion Injury; Treatment Outcome

Critically ill patients with acute renal failure (ARF) experience a high mortality rate. Animal and human studies suggest that proinflammatory cytokines lead to the development of a systemic inflammatory response syndrome (SIRS), which is temporally followed by a counter anti-inflammatory response syndrome (CARS). This process has not been specifically described in critically ill patients with ARF.. The Program to Improve Care in Acute Renal Disease (PICARD) is a prospective, multicenter cohort study designed to examine the natural history, practice patterns, and outcomes of treatment in critically ill patients with ARF. In a subset of 98 patients with ARF, we measured plasma proinflammatory cytokines [interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)], the acute-phase reactant C-reactive protein (CRP), and the anti-inflammatory cytokine IL-10 at study enrollment and over the course of illness.. When compared with healthy subjects and end-stage renal disease patients on maintenance hemodialysis, patients with ARF had significantly higher plasma levels of all measured cytokines. Additionally, the proinflammatory cytokines IL-6 and IL-8 were significantly higher in nonsurvivors versus survivors [median 234.7 (interdecile range 64.8 to 1775.9) pg/mL vs. 113.5 (46.1 to 419.3) pg/mL, P= 0.02 for IL-6; 35.5 (14.1 to 237.9) pg/mL vs. 21.2 (8.5 to 87.1) pg/mL, P= 0.03 for IL-8]. The anti-inflammatory cytokine IL-10 was also significantly higher in nonsurvivors [3.1 (0.5 to 41.9) pg/mL vs. 2.4 (0.5 to 16.9) pg/mL, P= 0.04]. For each natural log unit increase in the levels of IL-6, IL-8, and IL-10, the odds of death increased by 65%, 54%, and 34%, respectively, corresponding to increases in relative risk of approximately 30%, 25%, and 15%. The presence or absence of SIRS or sepsis was not a major determinant of plasma cytokine concentration in this group of patients.. There is evidence of ongoing SIRS with concomitant CARS in critically ill patients with ARF, with higher levels of plasma IL-6, IL-8, and IL-10 in patients with ARF who die during hospitalization. Strategies to modulate inflammation must take into account the complex cytokine biology in patients with established ARF.

Topics: Acute Kidney Injury; Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Cohort Studies; Critical Illness; Cytokines; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Renal Dialysis; Systemic Inflammatory Response Syndrome

Blockade of tissue factor before lethal sepsis prevents acute lung injury and renal failure in baboons, indicating that activation of coagulation by tissue factor is an early event in the pathogenesis of acute lung injury and organ dysfunction. We hypothesized that blockade of tissue factor would also attenuate these injuries in established sepsis by prevention of further fibrin deposition and inflammation. Twelve male baboons received heat-killed Escherichia coli intravenously followed 12 hours later by live E. coli infusion. Six animals were treated 2 hours after the live bacteria with site-inactivated Factor VIIa, a competitive tissue factor inhibitor, and six animals were vehicle-treated sepsis control subjects. Animals were ventilated and monitored for 48 hours. Physiologic and hematologic parameters were measured every 6 hours, and pathologic evaluation was performed after 48 hours. Animals treated with site inactivated Factor VIIa had less severe lung injury, with preserved gas exchange, better lung compliance and histology scores, and decreased lung wet/dry weight. In treated animals, urine output was higher, metabolic acidosis was attenuated, and renal tubular architecture was protected. Coagulopathy was attenuated, and plasma interleukin-6, interleukin-8, and soluble tumor necrosis factor receptor-1 levels were significantly lower in the treated animals. These results show that blockade of coagulation attenuates acute lung and renal injury in established Gram-negative sepsis accompanied by antiinflammatory effects of therapy.

Topics: Acute Kidney Injury; Animals; Antigens, CD; Cytokines; Disease Models, Animal; Drug Monitoring; Escherichia coli Infections; Factor VIIa; Hemodynamics; Inflammation; Interleukin-6; Interleukin-8; Lung Compliance; Male; Papio; Pulmonary Gas Exchange; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Respiratory Distress Syndrome; Sepsis; Severity of Illness Index; Thromboplastin

Cellular damage and inflammation after ischemia contribute to sustained acute renal failure (ARF).. To quantify cellular damage and inflammation in postischemic ARF and identify markers of renal functional outcome, urine specimens from 40 renal allograft recipients, including 30 cadaveric (9 "sustained ARF" and 21 "recovery" subjects) and 10 living donor allografts ("LD"), were analyzed for actin, gamma-glutamyl transpeptidase (GGTP), lactate dehydrogenase (LDH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) during the first posttransplant week.. On day 0, urinary actin, GGTP, IL-6, and IL-8 were elevated in recipients destined to have sustained ARF compared with those destined to recover. Median values per gram of urine creatinine in the sustained ARF, recovery, and LD groups were 263.9, 0.0, and 0.0 microg for actin; 5000.0, 892.9, and 5555.6 U for GGTP; 193.1, 27.2, and 10.5 ng for IL-6; and 382.0, 17.8, and 18.5 ng for IL-8, respectively. In contrast, urinary LDH and TNF-alpha increased in recipients with recovering function compared with those who had sustained ARF. The corresponding median values were 36.7 and 16.3 U (recovery versus sustained ARF) for LDH, and 18.4 and 7.6 ng (LD versus sustained ARF) for TNF-alpha. Computational analyses using the Receiver Operating Characteristic Curve found that elevated urinary actin, IL-6, and IL-8 on day 0 were strong predictors of sustained ARF, where the calculated areas under the curve were 0.75, 0.91, and 0.82, respectively.. Increased urinary actin, IL-6, and IL-8 may be useful markers for the prediction of sustained ARF after ischemia.

Topics: Actins; Acute Kidney Injury; Adult; Biomarkers; Creatinine; Female; gamma-Glutamyltransferase; Humans; Interleukin-6; Interleukin-8; Ischemia; Kidney; Kidney Function Tests; Kidney Transplantation; L-Lactate Dehydrogenase; Male; Middle Aged; ROC Curve; Transplantation, Homologous; Tumor Necrosis Factor-alpha

Priming of the polymorphonuclear neutrophil (PMN) response has been implicated in the activation of oxidative burst and tissue injury in patients with septic shock and acute renal failure (ARF). This study evaluated whether hemofiltration (HF) removes substances able to enhance the oxidative burst of PMNs.. Chemiluminescence (CL) priming activity induced by sera and ultrafiltrates of seven patients with septic shock, multiorgan dysfunction syndrome, and ARF (ARF/HF group) and of 10 uremic stable patients (Control/HF group) was evaluated on normal human PMNs stimulated with bacterial formyl-methionyl-leucyl-phenylalanine (FMLP). Patients submitted to HF were studied by determining blood and ultrafiltrate interleukin-8 (IL-8), platelet-activating factor (PAF), and CL priming activity at the beginning (T0), and after four hours (T4) of treatment.. Preincubation of normal human PMNs with sera and ultrafiltrates from septic patients induced a potent priming of CL activity in subsequent FMLP stimulation. In the ARF/HF group, the prefilter blood concentrations of IL-8 and CL PMN-priming activity significantly decreased during the four hours of HF treatment, with a loss of IL-8 in the ultrafiltrate of 6930 (median, range 4292 to 9282) ng per four hours. PAF detected in the ultrafiltrate and associated with the membrane (7.3 ng, range 1.45 to 9.89) was minimal. In the ARF/HF group, a significantly positive correlation between CL PMN-priming activity and IL-8 concentrations was observed. The CL priming activity in blood and ultrafiltrates was reduced to 55 and 46% by preabsorption with monoclonal antibody (mAb) anti-IL-8. In contrast, the PAF receptor antagonist WEB 2170 did not affect CL priming activity. In the control/HF group, the CL PMN-priming activity was significantly lower than in the ARF/HF group and was independent of IL-8.. Sera from septic patients demonstrate an enhanced CL priming activity on PMNs. This activity is reduced by ultrafiltration and is due, at least in part, to ultrafiltered IL-8.

Topics: Acute Kidney Injury; Aged; Blood Physiological Phenomena; Hemofiltration; Humans; Interleukin-8; Luminescent Measurements; Middle Aged; Multiple Organ Failure; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Platelet Activating Factor; Reference Values; Respiratory Burst; Shock, Septic; Uremia

The Yucatan micropig has been used to develop an experimental model of chronic bacteremia. This animal exhibits clinical and biological characteristics that are close to those in humans, and the pharmacokinetic behaviours of many classes of drugs in this model are similar to those in man. Six adult female were intravenously inoculated with a mean Escherichia coli inoculum of 5.1 x 10(9) bacteria. During five days of spontaneous evolution, the medical follow-up includes biological, clinical and bacteriological parameters. A systemic inflammatory syndrome, a sepsis, an organ insufficiency and positive blood cultures mimic the human disease. In all animals there is an adynamia, a lack of motor coordination, an anorexia, a tachypnea, a fever, a leuconeutropenia followed by an hyperleucocytosis, an anemia, a thrombopenia, an acute tubulonephritis and an elevated sedimentation rate. In some cases, there is an increase of the C reactive protein, in others, an increase of IL-6 and IL-8. At day five, all animals are alive, and five micropigs have positive blood cultures. This chronic, reproducible model is thus suitable for further antibacterial treatments evaluations.

Topics: Acute Kidney Injury; Acute-Phase Reaction; Animals; Anorexia; Ataxia; Bacteremia; Chronic Disease; Disease Progression; Escherichia coli Infections; Fever; Hematologic Diseases; Interleukin-6; Interleukin-8; Models, Animal; Multiple Organ Failure; Nephritis, Interstitial; Reproducibility of Results; Swine, Miniature; Systemic Inflammatory Response Syndrome

Studies in experimental animals have suggested that platelet-activating factor (PAF) is a mediator of sepsis-associated acute renal failure (ARF). In the present study we have evaluated whether an increased concentration of PAF within circulation or urine of septic patients correlated with the worsening of renal function.. The concentration of PAF and selected cytokines (TNF, IL-1, IL-6, IL-8) was evaluated in blood and urine of 12 patients with septic shock and ARF for 4 consecutive days.. The data obtained indicate that blood and urinary concentrations of PAF and of IL-1, IL-6 and IL-8 were significantly higher in septic patients than in controls subjects and in patients with chronic renal failure. The concentration of TNF was significantly increased only in urine. A significantly positive correlation was found among blood concentration of PAF and heart rate (r = 0.4193, P < 0.017), serum creatinine (r = 0.3671, P < 0.038), serum IL-6 (r = 0.5475, P < 0.005) and urine excretion of IL-8 (r = 0.3984, P < 0.044), whereas a negative correlation was present with the number of circulating platelets (r = -0.4285, P < 0.018). Moreover, a positive correlation among the concentration of PAF in urine and the serum concentration of IL-6 (r = 0.5654, P < 0.006) and urine excretion of IL-6 (r = 0.6589, P < 0.0008) and IL-8 (r = 0.6371, P < 0.0004) were found.. These results demonstrate in humans during ARF associated with septic shock the production of PAF, a mediator that has been previously implicated in the pathogenesis of experimental endotoxin-induced shock and renal injury. The observation that blood and urinary concentrations of PAF correlated with some of the clinical and laboratory parameters related to the severity of ARF and sepsis suggests that PAF may contribute to the development of renal injury in septic patients.

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Animals; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Platelet Activating Factor; Sepsis; Tumor Necrosis Factor-alpha

To determine whether continuous venovenous hemodialfiltration (CVVHD) is associated with the extraction of interleukin-6 (IL-6) and interleukin-8 (IL-8) from the circulation of critically ill patients with septic acute renal failure. To quantitate their clearance and assess any possible effect of CVVHD on these cytokines' serum concentrations.. Prospective controlled study of IL-6 and IL-8 removal by CVVHD in patients with septic acute renal failure.. Intensive care unit of a tertiary institution.. Ten critically ill patients with sepsis, acute renal failure, and multiorgan failure. A control group of five patients experiencing an acute illness while undergoing chronic hemodialysis.. Collection of blood samples before CVVHD. Simultaneous collection of prefilter blood and ultradiafiltrate after 4 and 24 h of treatment. IL-8 concentrations were measured in blood and ultradiafiltrate. Their clearances and daily extractions were calculated.. IL-6 and IL-8 were detected in the blood of all patients with septic acute renal failure prior to CVVHD. The median IL-6 blood level was 103 pg/mL (range: 19 to 900) and the median IL-8 blood level was 200 (range: 32 to 2925). Both cytokines were cleared by the hemofilter during CVVHD. The median hemofilter clearance of IL-6 were 1.99 L/day (range: 0 to 8.5) and the median clearance of IL-8 was 3.95 L/day (range: 0.31 to 42.8). These blood levels and clearances resulted in median daily extraction rates of 194 ng of IL-6 (range: 0 to 9031) and of 915 ng of IL-8 (range 47.5 to 3562). Control patients had negligible amounts of either IL-6 or IL-8 in their ultrafiltrate. The rate of extraction for IL-6 correlated with its blood levels (p < 0.0001). This was not true for IL-8. A correlation between IL-6 levels and the patients' white cell counts was found after 24 h of hemofiltration.. CVVHD is associated with the extraction of IL-6 and IL-8 from the circulation of patients with septic multiorgan and renal failure. The biological significance of such extraction is undetermined, but such cytokine removal highlights the complexity of the effect of continuous hemofiltration on the soluble mediators of inflammation activated during human sepsis.

Topics: Acute Kidney Injury; APACHE; Case-Control Studies; Female; Hemodiafiltration; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Sepsis