Renal Histopathology During Experimental Septic Acute Kidney Injury and Recovery*

Langenberg, Christoph; Gobé, Glenda C.; Hood, Sally G.; May, Clive; Bellomo, Rinaldo

doi:10.1097/ccm.0b013e3182a639da

Cited by 114 publications

(76 citation statements)

References 26 publications

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“…18 Despite more patients with septic AKI required RRT when compared with non-septic AKI, they had better renal recovery. This finding is actually similar to that reported by Cruz et al and Bagshaw et al, 8,19 signifying a difference in the pathophysiology [20][21][22] between septic and non-septic AKI. Instead, Singer et al proposed the cell cycle arrest hypothesis and mentioned that multiorgan failure induced by critical illness is primary a functional, rather than structural abnormality.…”

Section: Discussionsupporting

confidence: 92%

Septic acute kidney injury in critically ill patients – a single-center study on its incidence, clinical characteristics, and outcome predictors

et al. 2016

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Purpose The objective of this study is to examine the incidence, clinical characteristics, and outcome (90-day mortality) of critically ill Chinese patients with septic AKI. Methods Patients admitted to the ICU of a regional hospital from 1 January 2011 to 31 December 2013 were included, excluding those on chronic renal replacement therapy. AKI was defined using KDIGO criteria. Patients were followed till 90 days from ICU admission or death, whichever occurred earlier. Demographics, diagnosis, clinical characteristics, and outcome were analyzed. Results In total, 3687 patients were included and 54.7% patients developed AKI. Sepsis was the most common cause of AKI (49.2%). Compared to those without AKI, AKI patients had higher disease severity, more physiological and biochemical disturbance, and carried significant co-morbidities. Ninety-day mortality increased with severity of AKI (16.7, 27.5, and 48.3% for KDIGO stage 1, 2, and 3 AKI, p < 0.001). Full renal recovery was achieved in 71.6% of AKI patients. Compared with non-septic AKI, septic AKI was associated with higher disease severity and required more aggressive support. Non-recovery of renal function occurred in 2.5% of patients with septic AKI, compared with 6.4% in non-septic AKI (p < 0.001). Cox regression analysis showed that age, emergency ICU admission, post-operative cases, admission diagnosis, etiology of AKI, disease severity score, mechanical ventilation, vasopressor support, and blood parameters (like albumin, potassium and pH) independently predicted 90-day mortality. Conclusions AKI, especially septic AKI is common in critically ill Chinese patients and is associated with poor patient outcome. Etiology of AKI has a significant impact on 90-day mortality and may affect renal outcome. ARTICLE HISTORY

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Section: Discussionsupporting

confidence: 92%

Septic acute kidney injury in critically ill patients – a single-center study on its incidence, clinical characteristics, and outcome predictors

et al. 2016

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“…This provides evidence that AGs might stop endothelial and cellular signals at the origin of sepsis-related AKI (35).…”

Section: Discussionmentioning

confidence: 79%

“…Recent pharmacological concepts of AGs administration, such as the once-daily dose schedule for AG administration, which result in a decrease on AG-associated AKI (9) have been respected in the present study, as shown by the use of once-daily doses of gentamicin and amikacin during a short course achieving a correct rate of target obtention (Table 3). A physiological mechanism has also been suggested by several authors (33)(34)(35). Lipcsey et al compared four groups of pigs (endotoxinemia plus tobramycin, endotoxinemia plus saline, saline plus tobramycin, and saline alone) and suggested that sepsis-induced hypoperfusion was predominant over specific AG toxicity for AKI occurrence (34).…”

Section: Discussionmentioning

confidence: 89%

Propensity-Based Study of Aminoglycoside Nephrotoxicity in Patients with Severe Sepsis or Septic Shock

Picard

Bazin

Clouzeau

et al. 2014

Antimicrob Agents Chemother

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cTo assess the risk of acute kidney injury (AKI) attributable to aminoglycosides (AGs) in patients with severe sepsis or septic shock, we performed a retrospective cohort study in one medical intensive care unit (ICU) in France. Patients admitted for severe sepsis/septic shock between November 2008 and January 2010 were eligible. A propensity score for AG administration was built using day 1 demographic and clinical characteristics. Patients still on the ICU on day 3 were included. Patients with renal failure before day 3 or endocarditis were excluded. The time window for assessment of renal risk was day 3 to day 15, defined according to the RIFLE (risk, injury, failure, loss, and end-stage renal disease) classification. The AKI risk was assessed by means of a propensity-adjusted Cox proportional hazards regression analysis. Of 317 consecutive patients, 198 received AGs. The SAPS II (simplified acute physiology score II) score and nosocomial origin of infection favored the use of AGs, whereas a preexisting renal insufficiency and the neurological site of infection decreased the propensity for AG treatment. One hundred three patients with renal failure before day 3 were excluded. AGs were given once daily over 2.6 ؎ 1.1 days. AKI occurred in 16.3% of patients in a median time of 6 (interquartile range, 5 to 10) days. After adjustment to the clinical course and exposure to other nephrotoxic agents between day 1 and day 3, a propensity-adjusted Cox proportional hazards regression analysis showed no increased risk of AKI in patients receiving AGs (adjusted relative risk ‫؍‬ 0.75 [0.32 to 1.76]). In conclusion, in critically septic patients presenting without early renal failure, aminoglycoside therapy for less than 3 days was not associated with an increased risk of AKI.A minoglycosides (AGs) have bactericidal activity, which has been proven to be synergic with that of ␤-lactams. Although adding an AG to a standard antibiotic treatment did not translate into a reduction of mortality in Gram-negative-bacterial sepsis in subgroups of patients with globally moderate degrees of severity (1), a decrease in mortality was recently reported in a meta-analysis comparing a bitherapy to therapy with a ␤-lactam alone for patients with septic shock (2). In addition, AGs widen the spectrum of the antibiotic treatment, which should be advantageous in populations with an increased risk of resistant bacteria, such as intensive care unit (ICU) patients (3, 4). Empirical antibiotic treatments including AGs could be more appropriate in up to 15 to 20% of cases than a ␤-lactam alone (5, 6). In the ICU setting, modifications of the empirical antibiotic treatment or the addition of a new antibiotic occurs less frequently after bitherapy including an AG than after monotherapy (7).Unfortunately, nephrotoxicity is an important potential limitation of AGs. There is a consensus that AG-related nephrotoxicity has decreased over the years due to better consideration of both reduced duration of treatment and once-daily administration (8). However...

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“…These inflammation-derived reactions compromise the endothelial barrier function, activate coagulation system, and impair receptor-mediated vasoreactivity, which alter the intrarenal microcirculatory blood flow distribution, causing heterogeneous patchy micro-areas of ischemia, often in the absence of macrocirculation (renal blood flow) defect (reviewed in [4,5] ). Nitric oxide synthase overexpression (all isoforms) in the cortex during sepsis also contributes to the shunting of blood flow away from the medulla [6] , exacerbating ischemia. The areas of hypoxia are subject to reperfusion injury.…”

Section: Qianmentioning

confidence: 99%

Inflammation: A Key Contributor to the Genesis and Progression of Chronic Kidney Disease

Qian

2017

Expanded Hemodialysis: Innovative Clinical Approach in Dialysis

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It has become apparent that inflammation and inflammatory reactions can evoke renal injury and promote chronic kidney disease (CKD) progression. Under physiological condition, intrarenal vascular distribution is heterogeneous, and medulla is hypoxic. To avoid energy deprivation in the low pO 2 regions of the kidney, an array of hormones, autocoids, and vasoactive substances, including medullipin, prostaglandins, endothelins, nitric oxide, angiotensin II, kinins, and adenosine, tonically regulates the microvasculature to ensure a perfect match of the microcirculation (O 2 supply) and renal tubules (O 2 demand). Inflammation, systemic or intrarenal, not only can abolish the microvascular response to its regulators, but also induces an array of tubular toxins, including reactive oxygen species, leading to tubular injury, nephron dropout, and onset of CKD. Positive acid balance, electrolyte alterations, and intestinal dysbiosis can perpetuate CKD progression. Understanding the role of inflammation in the genesis and progression of CKD will foster the development of strategies to prevent and treat the underlying inflammation and improve CKD outcomes.

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Renal Histopathology During Experimental Septic Acute Kidney Injury and Recovery*

Cited by 114 publications

References 26 publications

Septic acute kidney injury in critically ill patients – a single-center study on its incidence, clinical characteristics, and outcome predictors

Septic acute kidney injury in critically ill patients – a single-center study on its incidence, clinical characteristics, and outcome predictors

Propensity-Based Study of Aminoglycoside Nephrotoxicity in Patients with Severe Sepsis or Septic Shock

Inflammation: A Key Contributor to the Genesis and Progression of Chronic Kidney Disease

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