Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI.

Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes.

Cisplatin is a widely used chemotherapeutic agent used to treat solid tumours, such as ovarian, head and neck, and testicular germ cell. A known complication of cisplatin administration is acute kidney injury (AKI). The development of effective tumour interventions with reduced nephrotoxicity relies heavily on understanding the molecular pathophysiology of cisplatin-induced AKI. Rodent models have provided mechanistic insight into the pathophysiology of cisplatin-induced AKI. In the subsequent review, we provide a detailed discussion of recent advances in the cisplatin-induced AKI phenotype, principal mechanistic findings of injury and therapy, and pre-clinical use of AKI rodent models. Cisplatin-induced AKI murine models faithfully develop gross manifestations of clinical AKI such as decreased kidney function, increased expression of tubular injury biomarkers, and tubular injury evident by histology. Pathways involved in AKI include apoptosis, necrosis, inflammation, and increased oxidative stress, ultimately providing a translational platform for testing the therapeutic efficacy of potential interventions. This review provides a discussion of the foundation laid by cisplatin-induced AKI rodent models for our current understanding of AKI molecular pathophysiology.

https://www.mdpi.com/1422-0067/20/12/3011/pdf

Recent Advances in Models, Mechanisms, Biomarkers, and Interventions in Cisplatin-Induced Acute Kidney Injury.

Acute kidney injury (AKI) due to renal ischemia reperfusion (IR) is a major clinical problem without effective therapy and is a significant and frequent cause of morbidity and mortality during the perioperative period. Although the pathophysiology of ischemic AKI is not completely understood, several important mechanisms of renal IR-induced AKI have been studied. Renal ischemia and subsequent reperfusion injury initiates signaling cascades mediating renal cell necrosis, apoptosis, and inflammation, leading to AKI. Better understanding of the molecular and cellular pathophysiological mechanisms underlying ischemic AKI will provide more targeted approach to prevent and treat renal IR injury. In this review, we summarize important mechanisms of ischemic AKI, including renal cell death pathways and the contribution of endothelial cells, epithelial cells, and leukocytes to the inflammatory response during ischemic AKI. Additionally, we provide some updated potential therapeutic targets for the prevention or treatment of ischemic AKI, including Toll-like receptors, adenosine receptors, and peptidylarginine deiminase 4. Finally, we propose mechanisms of ischemic AKI-induced liver, intestine, and kidney dysfunction and systemic inflammation mainly mediated by Paneth cell degranulation as a potential explanation for the high mortality observed with AKI.

Mechanisms and therapeutic targets of ischemic acute kidney injury.

Acute kidney injury (AKI) is a common complication in patients undergoing major abdominal surgery. Various recent studies using modern standardized classifications for AKI reported a variable incidence of AKI after major abdominal surgery ranging from 3 to 35%. Several patient-related, procedure-related factors and postoperative complications were identified as risk factors for AKI in this setting. AKI following major abdominal surgery has been shown to be associated with poor short- and long-term outcomes. Herein, we provide a contemporary and critical review of AKI after major abdominal surgery focusing on its incidence, risk factors, pathogeny and outcomes.

/pdf/acute-kidney-injury-in-major-abdominal-surgery-incidence-37oznx0cns.pdf

Acute kidney injury in major abdominal surgery: incidence, risk factors, pathogenesis and outcomes.

The incidence of acute kidney injury (AKI) in the intensive care unit (ICU) has increased during the past decade due to increased acuity as well as increased recognition. Early epidemiology studies were confounded by erratic definitions of AKI until recent consensus guidelines (RIFLE and AKIN) standardized its definition. This paper discusses the incidence of AKI in the ICU with focuses on specific patient populations. The overall incidence of AKI in ICU patients ranges from 20% to 50% with lower incidence seen in elective surgical patients and higher incidence in sepsis patients. The incidence of contrast-induced AKI is less (11.5%–19% of all admissions) than seen in the ICU population at large. AKI represents a significant risk factor for mortality and can be associated with mortality greater than 50%.

/pdf/epidemiology-of-acute-kidney-injury-in-the-intensive-care-17063oyvrn.pdf

Epidemiology of Acute Kidney Injury in the Intensive Care Unit

https://downloads.hindawi.com/archive/2013/538642.pdf

Role of obesity in asthma control, the obesity-asthma phenotype.

Hypertension (HTN) is a modifiable, highly prevalent risk factor for cardiovascular morbidity and renal dysfunction worldwide. In the United States, HTN affects one in three adults, contributes to one out of every seven deaths and to nearly half of all cardiovascular disease-related deaths. HTN is considered resistant when the blood pressure remains above goal despite lifestyle modification and administration of three antihypertensive agents of different classes including a diuretic. Large population-based studies have suggested that obstructive sleep apnea (OSA) is a risk factor for resistant HTN. The mechanism proposed is a pattern of intermittent hypoxia associated with hyperaldosteronism, increased sympathetic tone, endothelial dysfunction, and inflammation. In this review we discuss the association between OSA and resistant HTN, the physiologic mechanisms linking OSA with resistant HTN, and the effect of continuous positive airway pressure therapy (CPAP) on blood pressure in patients with resistant HTN. While the reduction in blood pressure with CPAP is usually modest in patients with OSA, a decrease of only a few mmHg in blood pressure can significantly reduce cardiovascular risk. Patients presenting to a center specializing in management of hypertension should be screened and treated for OSA as a potentially modifiable risk factor.

/pdf/resistant-hypertension-and-obstructive-sleep-apnea-11t83s402k.pdf

Resistant hypertension and obstructive sleep apnea

Acute kidney injury (AKI) frequently occurs in the setting of critical illness and its management poses a challenge for the intensivist. Optimal management of volume status is critical in the setting of AKI in the ICU patient. The use of urine sodium, the fractional excretion of sodium (FeNa), and the fractional excretion of urea (FeUrea) are common clinical tools used to help guide fluid management especially further volume expansion but should be used in the context of the patient’s overall clinical scenario as they are not completely sensitive or specific for the finding of volume depletion and can be misleading. In the case of oliguric or anuric AKI, diuretics are often utilized to increase the urine output although current evidence suggests that they are best reserved for the treatment of volume overload and hyperkalemia in patients who are likely to respond to them. Management of volume overload in ICU patients with AKI is especially important as volume overload has several negative effects on organ function and overall morbidity and mortality.

/pdf/volume-management-in-the-critically-ill-patient-with-acute-3y35l9bg17.pdf

Supriya Khan

Papers

Epidemiology of Acute Kidney Injury in the Intensive Care Unit

Role of obesity in asthma control, the obesity-asthma phenotype.

Resistant hypertension and obstructive sleep apnea

Volume Management in the Critically Ill Patient with Acute Kidney Injury