Sepsis-induced acute kidney injury

Acute kidney injury (AKI) is a common sequel of sepsis in the intensive care unit. It is being suggested that sepsis-induced AKI may have a distinct pathophysiology and identity. Availability of biomarkers now enable us to detect AKI as early as four hours after it''s inception and may even help us to delineate sepsis-induced AKI. Protective strategies such as preferential use of vasopressin or prevention of intra-abdominal hypertension may help, in addition to the other global management strategies of sepsis. Pharmacologic interventions have had limited success, may be due to their delayed usage. Newer developments in extracorporeal blood purification techniques may proffer effects beyond simple replacement of renal function, such as metabolic functions of the kidney or modulation of the sepsis cascade.     

Effects of Honokiol on Sepsis-Induced Acute Kidney Injury in an Experimental Model of Sepsis in Rats

Acute kidney injury (AKI) is a severe complication of sepsis, which largely contributes to the high mortality rate of sepsis. Honokiol, a natural product isolated from Magnolia officinalis (Houpo), has been shown to exhibit anti-inflammatory and antioxidant properties. Here, we investigated the effects of honokiol on sepsis-associated AKI in rats subjected to cecal ligation and puncture (CLP). We found that the administration of honokiol improved the survival of septic rats. Periodic acid-Schiff stain revealed that the morphological changes of kidney tissues in CLP rats were restored after honokiol treatment. Furthermore, honokiol reduced CLP-induced oxidative stress and inflammatory cytokine production. The levels of nitric oxide (NO) and inducible NO synthetase (iNOS) were attenuated by honokiol in septic rats. Finally, honokiol inhibited CLP-induced activation of NF-κB signaling in CLP rats. Our findings suggest that honokiol might be used as a potential therapeutic agent for complications of sepsis, especially for sepsis-induced AKI.     

Determinants of hepcidin levels in sepsis-associated acute kidney injury: Impact on pAKT/PTEN pathways?

The antimicrobial β-defensin-like role of hepcidin (HEPC) has been increasingly investigated for its potential role in acute kidney injury (AKI). In sepsis-induced AKI, there is a complex interplay between positive and negative regulation of HEPC, with consequently altered distributions of iron caused by changes in HEPC levels. The aim of the current research was to assess serum HEPC levels in a cohort of septic patients with AKI and investigate the regulatory impact of hypoxia-inducing factor (HIF)-1α, erythropoietin (EPO) and inflammation on HEPC levels and related signal cascades in these patients. Baseline, higher levels of SCr (2.3-fold), blood urea nitrogen (BUN) (1.8-fold), uric acid (2.3-fold) and white blood cell (2.3-fold) were noted in septic AKI patients, along with decreased levels of albumin (15.7%), creatinine (44.7%) and BUN/creatinine ratios (23.8%), compared to in normal subjects. These hosts also had increased serum levels of TNFα (4.4-times) and TGFβ1 (3.2-times) compared to controls (p?相似文献   

Protective Effects of Growth Arrest-Specific Protein 6 (Gas6) on Sepsis-Induced Acute Kidney Injury

Acute kidney injury (AKI) is a serious complication of sepsis, which has a high mortality rate. Growth arrest-specific protein 6 (Gas6), the protein product of the growth arrest specific gene 6, has been shown to have an anti-apoptotic effect as well as pro-survival capability. Here, we investigated the effects of Gas6 on sepsis-associated AKI in mice subjected to cecal ligation and puncture (CLP). We found that the administration of rmGas6 significantly reduced serum urea nitrogen and creatinine and improved the survival of septic mice. Furthermore, the renal pathological damage induced by CLP was attenuated by rmGas6 treatment. Finally, rmGas6 reduced the renal tissue apoptotic index and the expression of Bax, while it upregulated the expression of Bcl-2. The data suggest that rmGas6 might be used as a potential therapeutic agent for sepsis-induced AKI.     

Cathelicidin protects mice from Rhabdomyolysis-induced Acute Kidney Injury

Background: Cathelicidins are ancient and well-conserved antimicrobial peptides (AMPs) with intriguing immunomodulatory properties in both infectious and non-infectious inflammatory diseases. In addition to direct antimicrobial activity, cathelicidins also participate in several signaling pathways inducing both pro-inflammatory and anti-inflammatory effects. Acute kidney injury (AKI) is common in critically ill patients and is associated with high mortality and morbidity. Rhabdomyolysis is a major trigger of AKI.Objectives: Here, we investigated the role of cathelicidins in non-infectious Acute kidney Injury (AKI).Method: Using an experimental model of rhabdomyolysis, we induced AKI in wild-type and cathelicidin-related AMP knockout (CRAMP^-/-) mice. Results: We previously demonstrated that CRAMP^-/- mice, as opposed wild-type mice, are protected from AKI during sepsis induced by cecal ligation and puncture. Conversely, in the current study, we show that CRAMP^-/- mice are more susceptible to the rhabdomyolysis model of AKI. A more in-depth investigation of wild-type and CRAMP^-/- mice revealed important differences in the levels of several inflammatory mediators.Conclusion: Cathelicidins can induce a varied and even opposing repertoire of immune-inflammatory responses depending on the subjacent disease and the cellular context.     

脓毒症继发急性肾损伤过程中的凝血变化

目的 脓毒症继发急性损伤是脓毒症患者死亡的重要原因之一,凝血变化是急性肾损伤重要因素.本研究旨在筛选脓毒症过程中同急性肾损伤相关的凝血指标.方法 本研究收集外科、急诊及呼吸重症监护室的脓毒症患者,纳入132例脓毒症患者,其中合并急性肾损伤64例,非急性肾损伤68例.收集各组患者一般资料及入ICU第1个24h内各项实验室...     

MIR210HG Aggravates Sepsis-Induced Inflammatory Response of Proximal Tubular Epithelial Cell via the NF-κB Signaling Pathway

PurposeAcute kidney injury (AKI) is a serious complication of sepsis and is characterized by inflammatory response. MicroRNA-210 host gene (MIR210HG) is upregulated in human proximal tubular epithelial cells under treatment of inflammatory cytokines. This study aimed to explore the role of MIR210HG in sepsis-induced AKI.Materials and MethodsCell viability was detected by a cell counting kit 8 assay. The levels of proinflammatory cytokines were detected by enzyme-linked immunosorbent assay kits. The protein levels of p65, IκBα, and p-IκBα were examined by western blot analysis. The nuclear translocation of nuclear factor kappa B (NF-κB) was detected by immunofluorescence assay. The histological changes of kidneys were analyzed by hematoxylin and eosin staining assay.ResultsLipopolysaccharide (LPS) treatment significantly inhibited cell viability and increased productions of proinflammatory cytokines in proximal tubular epithelial cells (HKC-8). Additionally, MIR210HG levels in HKC-8 cells were increased by LPS treatment. MIR210HG silencing inhibited the LPS-induced cell inflammatory response. MIR210HG activated the NF-κB signaling pathway by promoting the phosphorylation of IκBα and nuclear translocation of p65. Rescue assays revealed that the MIR210HG-induced increase of cytokines levels and decline of cell viability were rescued by QNZ treatment. Knockdown of MIR210HG decreased blood urea nitrogen, serum creatinine, and proinflammatory cytokine levels in AKI rats. Moreover, the knockdown of MIR210HG protected against AKI-induced histological changes of kidneys in rats.ConclusionMIR210HG promotes sepsis-induced inflammatory response of HKC-8 cells by activating the NF-κB signaling pathway. This novel discovery may be helpful for the improvement of sepsis-induced AKI.     

Sepsis-induced immunosuppression

The sepsis syndrome is characterized by the acute release of a variety of inflammatory mediators, which often result in detrimental effects to the host. The release of these mediators is regulated and counterbalanced by the coordinated expression of antiinflammatory molecules. It is the balance between the expression of pro- and anti-inflammatory mediators that often determines the magnitude of early tissue injury and subsequent risk of infectious complications. As our understanding of the pathophysiology of sepsis continues to evolve, we have gained a greater appreciation for the effects that sepsis and similar states of overwhelming stress have on host antimicrobial immunity. A number of functional defects in leukocytes isolated from sepsis patients have been characterized. These defects include diminished expression of important cell surface antigens, dysregulated cytokine production, alterations in antigen-presenting ability, and accelerated apoptosis. Impaired leukocyte function has important clinical ramifications, as high mortality rates have been observed in patients displaying evidence of sepsis-induced immune deactivation. In this article, we review the current literature supporting evidence of dysregulation of host immunity occurring during sepsis syndrome, characterize the underlying pathophysiology, and describe novel therapeutic interventions directed at augmenting host immunity during sepsis.     

Renal safety of a single dose of gentamicin in patients with sepsis in the emergency department

ObjectivesTo determine the effect of a single dose of gentamicin on the incidence and persistence of acute kidney injury (AKI) in patients with sepsis in the emergency department (ED).MethodsWe retrospectively studied patients with sepsis in the ED in three hospitals. Local antibiotic guidelines recommended a single dose of gentamicin as part of empirical therapy in selected patients in one hospital, whereas the other two hospitals did not. Multivariate analysis was used to evaluate the effect of gentamicin and other potential risk factors on the incidence and persistence of AKI after admission. AKI was defined according to the KDIGO (Kidney Disease Improving Global Outcomes) criteria.ResultsOf 1573 patients, 571 (32.9%) received a single dose of gentamicin. At admission, 181 (31.7%) of 571 of the gentamicin-treated and 228 (22.8%) of 1002 of the non–gentamicin-treated patients had AKI (p < 0.001). After admission, AKI occurred in 64 (12.0%) of 571 patients who received gentamicin and in 82 (8.9%) of 1002 people in the control group (p 0.06). Multivariate analysis showed that shock (odds ratio (OR), 2.72; 95% CI, 1.31–5.67), diabetes mellitus (OR, 1.49; 95% CI, 1.001–2.23) and higher baseline (i.e. before admission) serum creatinine levels (OR, 1.007; 95% CI, 1.005–1.009) were associated with the development of AKI after admission, but not receipt of gentamicin (OR, 1.29; 95% CI, 0.89–1.86). Persistent AKI was rare in both the group that received gentamicin (16/260, 6.2%) and the group that did not (15/454, 3.3%, p 0.09).ConclusionsWith regard to renal function, a single dose of gentamicin in patients with sepsis in the ED is safe. The development of AKI after admission was associated with shock, diabetes mellitus and higher baseline creatinine level.     

Decoding the potential role of regulatory T cells in sepsis-induced immunosuppression

Sepsis, a multiorgan dysfunction with high incidence and mortality, is caused by an imbalanced host-to-infection immune response. Organ-support therapy improves the early survival rate of sepsis patients. In the long term, those who survive the “cytokine storm” and its secondary damage usually show higher susceptibility to secondary infections and sepsis-induced immunosuppression, in which regulatory T cells (Tregs) are evidenced to play an essential role. However, the potential role and mechanism of Tregs in sepsis-induced immunosuppression remains elusive. In this review, we elucidate the role of different functional subpopulations of Tregs during sepsis and then review the mechanism of sepsis-induced immunosuppression from the aspects of regulatory characteristics, epigenetic modification, and immunometabolism of Tregs. Thoroughly understanding how Tregs impact the immune system during sepsis may shed light on preclinical research and help improve the translational value of sepsis immunotherapy.     

Acute Kidney Injury in Hematopoietic Cell Transplantation Patients Receiving Vancomycin and Piperacillin/Tazobactam Versus Vancomycin and Cefepime

Empiric antimicrobials are frequently utilized in the pre-engraftment phase after hematopoietic cell transplantation (HCT). Recent evidence suggests an increased risk of acute kidney injury (AKI) from combination of vancomycin with piperacillin/tazobactam; however, this has not specifically been evaluated in the HCT population. A single-center, retrospective review was conducted from 2011 to 2017 on 110 autologous and 60 allogeneic HCT patients with the primary objective of comparing incidence of AKI for those who received vancomycin with piperacillin/tazobactam versus vancomycin with cefepime in the pre-engraftment phase. Demographics and outcomes were compared for all patients who received vancomycin with piperacillin/tazobactam versus vancomycin with cefepime as well as within the autologous and allogeneic subgroups. The primary endpoint of incidence of AKI, defined as increase in serum creatinine by .3?mg/dL or?>50% from baseline (whichever was larger), was significantly higher for those who received vancomycin with piperacillin/tazobactam versus cefepime for the overall cohort (68% versus 27%; P?<?.001) resulting in an odds ratio (OR) of 5.16 (95% confidence interval [CI], 2.5 to 10.5) when adjusting for hypotension. Results were similar within the autologous (59% versus 22%; P?<?.001; OR, 4.63; 95% CI, 1.85 to 11.6) and allogeneic (79% versus 39%; P?=?.0021; OR, 5.41; 95% CI, 1.60 to 18.3) subgroups. Within the overall cohort between those who received vancomycin with piperacillin/tazobactam versus cefepime the time to onset of AKI was more commonly within 48 hours of concomitant antimicrobial use (53% versus 26%; P?=?.012), whereas resolution of AKI by discharge date was not different (39% versus 26%; P?=?.23). No difference in percentage of patients requiring at least 1 session of dialysis, duration of hospital stay, or 30-day mortality was found between overall cohorts. Further studies of HCT patients are warranted to fully elucidate the risk of various combination antimicrobial regimens on renal outcomes.     

Acute kidney injury after trauma: Prevalence, clinical characteristics and RIFLE classification

Background:

Acute kidney injury (AKI) is an uncommon but serious complication after trauma. The objective of this study was to evaluate the prevalence, clinical characteristics and outcome of AKI after trauma.

Patients and Methods:

This was a retrospective study performed from January 2006 to January 2008 in an emergency specialized hospital in Fortaleza city, northeast of Brazil. All patients with AKI admitted in the study period were included. Prevalence of AKI, clinical characteristics and outcome were investigated.

Results:

Of the 129 patients admitted to the intensive care unit (ICU), 52 had AKI. The mean age was 30.1 ± 19.2 years, and 79.8% were males. The main causes of AKI were sepsis in 27 cases (52%) and hypotension in 18 (34%). Oliguria was observed in 33 cases (63%). Dialysis was required for 19 patients (36.5%). Independent risk factors associated with AKI were abdominal trauma [odds ratio (OR) = 3.66, P = 0.027] and use of furosemide (OR = 4.10, P = 0.026). Patients were classified according to RIFLE criteria as Risk in 12 cases (23%), Injury in 13 (25%), Failure in 24 (46%), Loss in 1 (2%) and End-stage in 2 (4%). Overall in-hospital mortality was 95.3%. The main cause of death was sepsis (24%). Mortality was 100% among patients with AKI.

Conclusions:

AKI is a fatal complication after trauma, which presented with a high mortality in the studied population. A better comprehension of factors associated with death in trauma-associated AKI is important, and more effective measures of prevention and treatment of AKI in this population are urgently needed.     

Lectin binding patterns of alveolar epithelium and subepithelial seromucous glands of the bronchi in sepsis and controls – an approach to characterize the non-specific immunological response of the human lung to sepsis

A delayed or deficient immunological protection as well as an overstimulation of the mucosal immune system may act as possible additional promoters of sepsis-induced lung injury in patients suffering from a severe septic condition. Lectin-binding patterns in pulmonary tissue samples obtained at autopsy from septic patients and control individuals were studied using 11 carbohydrate-specific lectins (Con A, UEA, GSA I, GSA II, MPA, PNA, Jac, WGA, MAA, LPA, and SNA). There were no differences in the secretory product of serous parts of bronchial glands detectable in the two study groups, whereas lectin binding patterns of alveolar epithelium and mucous parts of subepithelial seromucous glands were different in sepsis cases when compared to controls. Apart from differences in binding sites for alpha-mannose, N-acetyl-neuraminic acid and alpha-(2-6)-galactose (as detected by different expression for Con A, MAA and SNA) in the two study groups, the main finding was that no binding sites for alpha-N-acetyl-galactosamine (as investigated by MPA immunoreactivity) could be detected on alveolar epithelial cells and mucous parts of subepithelial seromucous glands in sepsis cases in contrast to the presence of such binding sites in the control cases. We hypothesize that the finding of an altered secretory product of alveolar epithelial cells and bronchial glands in sepsis may be a result of specific carbohydrate deprivation or consumption, respectively, possibly due to direct bacterial effects or pathogenetic events in response to bacterial toxins during the complex cascade of the host's systemic inflammatory response in sepsis. The altered type of mucus glycoprotein physiologically secreted by alveolar epithelium and mucous parts of subepithelial seromucous glands of the bronchi with subsequent loss of a considerable proportion of protection of the mucosal barrier in sepsis may play an important additional role in the development of sepsis-induced lung injury.     

Acute kidney injury applying pRifle scale in Children of Hospital Universitario del Valle in Cali,Colombia: clinical features,management and evolution

Objective:

To know the epidemiology of Acute Kidney Injury (AKI) in the pediatric population at Hospital Universitario del Valle (HUV), a tertiary University Hospital in Cali, Colombia.

Methods:

We obtained a series of cases through daily surveillance for a seven-month period (June 1 to December 31, 2009) in patients older than 30 days and under 18 years at HUV. We excluded patients with previous diagnosis of chronic renal failure. The new pRIFLE scale was used to define AKI.

Results:

27 patients were detected, with mean age of 36 months. Incidence of AKI was 0.38% from pediatric admissions and 6.2% from the pediatric intensive care unit (pICU) admissions. The pRIFLE scale at study entrance was: Risk: 2 patients, Injury: 8, Failure: 17. Etiology of AKI was: pre-renal in 89%, primary renal disease in 3.7%, and post-renal in 7.4%. There was an association of AKI with sepsis in 66.7% and 48.2% progressed to septic shock. Six patients required renal replacement therapy, all required peritoneal dialysis. The AKI was multi-factorial in 59.3% and associated with systemic multi-organ failure in 59.3%. At study entry, 63% patients were in pICU. The average hospital stay was 21.3 ± 9.2 days. Six children died, 16 resolved AKI, and nine were left with renal sequelae.

Conclusions:

We recommended pRIFLE scale for early diagnosis of AKI in all pediatric services. Education in pRIFLE scale, prevention of AKI, and early management of sepsis and hypovolemia is recommended.     

Furosemide is associated with acute kidney injury in critically ill patients

Acute kidney injury (AKI) is common in critically ill patients. Diuretics are used without any evidence demonstrating a beneficial effect on renal function. The objective of the present study is to determine the incidence of AKI in an intensive care unit (ICU) and if there is an association between the use of furosemide and the development of AKI. The study involved a hospital cohort in which 344 patients were consecutively enrolled from January 2010 to January 2011. A total of 132 patients (75 females and 57 males, average age 64 years) remained for analysis. Most exclusions were related to ICU discharge in the first 24 h. Laboratory, sociodemographic and clinical data were collected until the development of AKI, medical discharge or patient death. The incidence of AKI was 55% (95%CI = 46-64). The predictors of AKI found by univariate analysis were septic shock: OR = 3.12, 95%CI = 1.36-7.14; use of furosemide: OR = 3.27, 95%CI = 1.57-6.80, and age: OR = 1.02, 95%CI = 1.00-1.04. Analysis of the subgroup of patients with septic shock showed that the odds ratio of furosemide was 5.5 (95%CI = 1.16-26.02) for development of AKI. Age, use of furosemide, and septic shock were predictors of AKI in critically ill patients. Use of furosemide in the subgroup of patients with sepsis/septic shock increased (68.4%) the chance of development of AKI when compared to the sample as a whole (43.9%)     

Differences in CVVH vs. CVVHDF in the management of sepsis-induced acute kidney injury in critically ill patients

We hypothesized that patients with sepsis and AKI, especially patients without preserved renal function, and treated with continuous veno-venous hemodiafiltration (CVVHDF), have lower risk for mortality than patients treated with continuous veno-venous hemofiltration (CVVH). Patients were included if they fulfilled the diagnosis of severe sepsis or septic shock, suffered AKI and received continuous renal replacement therapy (CRRT) in intensive care unit. There were 62 patients treated by CVVH and 75 treated by CVVHDF. Mean survival time was longer in CVVHDF group with oliguric/anuric patients than in CVVH group. CVVH, and not classic risk factors, was associated with higher overall mortality in oliguric/anuric patients. In the linear regression model, hourly urine output was the strongest and positive predictor of longer survival. CVVHDF is according to our results a CRRT modality of choice for the treatment and lower mortality of septic patients with AKI where renal function is no longer preserved. CRRT has been associated with improved renal recovery, but it should be started earlier in AKI evolution with still preserved hourly urine output which is the most sensitive and prognostic marker of survival in septic patients with AKI.     

Acute Kidney Injury in Patients with Sepsis and Septic Shock: Risk Factors and Clinical Outcomes

Purpose

The aim of this study was to investigate clinical characteristics and risk factors of acute kidney injury (AKI) in patients with sepsis and septic shock. Additionally, we explored whether the severity of AKI affects on the clinical outcomes.

Materials and Methods

Data were collected retrospectively in a single center. Among 5680 patients who visited emergency department from January to December 2010, 992 patients with sepsis and septic shock were enrolled. Patients were divided into two groups, patients who developed AKI or not, to compare the baseline characteristics, and laboratory and physiologic data. Patients with AKI were subdivided according to its stages for survival analysis.

Results

AKI was developed in 57.7% of patients. Multivariable logistic regression analysis revealed that development of septic AKI was associated with older age, pre-existing chronic kidney disease, use of angiotensin converting enzyme inhibitor or angiotensin receptor blocker, presence of shock, positive blood culture results, and low white blood cell and platelet counts. Hospital mortality was higher in AKI group. Crude Kaplan-Meier survival curves demonstrated reduced 30-day survival rate was significantly associated with the severity of acute kidney injury.

Conclusion

The development of septic AKI was associated with poor clinical outcomes. Furthermore, the severity of AKI was associated with increased mortality.     

Renal arterial infusion of tempol prevents medullary hypoperfusion,hypoxia, and acute kidney injury in ovine Gram-negative sepsis

Aim

Renal medullary hypoperfusion and hypoxia precede acute kidney injury (AKI) in ovine sepsis. Oxidative/nitrosative stress, inflammation, and impaired nitric oxide generation may contribute to such pathophysiology. We tested whether the antioxidant and anti-inflammatory drug, tempol, may modify these responses.

Methods

Following unilateral nephrectomy, we inserted renal arterial catheters and laser-Doppler/oxygen-sensing probes in the renal cortex and medulla. Noanesthetized sheep were administered intravenous (IV) Escherichia coli and, at sepsis onset, IV tempol (IVT; 30 mg kg⁻¹ h⁻¹), renal arterial tempol (RAT; 3 mg kg⁻¹ h⁻¹), or vehicle.

Results

Septic sheep receiving vehicle developed renal medullary hypoperfusion (76 ± 16% decrease in perfusion), hypoxia (70 ± 13% decrease in oxygenation), and AKI (87 ± 8% decrease in creatinine clearance) with similar changes during IVT. However, RAT preserved medullary perfusion (1072 ± 307 to 1005 ± 271 units), oxygenation (46 ± 8 to 43 ± 6 mmHg), and creatinine clearance (61 ± 10 to 66 ± 20 mL min⁻¹). Plasma, renal medullary, and cortical tissue malonaldehyde and medullary 3-nitrotyrosine decreased significantly with sepsis but were unaffected by IVT or RAT. Consistent with decreased oxidative/nitrosative stress markers, cortical and medullary nuclear factor-erythroid-related factor-2 increased significantly and were unaffected by IVT or RAT. However, RAT prevented sepsis-induced overexpression of cortical tissue tumor necrosis factor alpha (TNF-α; 51 ± 16% decrease; p = 0.003) and medullary Thr-495 phosphorylation of endothelial nitric oxide synthase (eNOS; 63 ± 18% decrease; p = 0.015).

Conclusions

In ovine Gram-negative sepsis, renal arterial infusion of tempol prevented renal medullary hypoperfusion and hypoxia and AKI and decreased TNF-α expression and uncoupling of eNOS. However, it did not affect markers of oxidative/nitrosative stress, which were significantly decreased by Gram-negative sepsis.