Marlies Ostermann

Acute kidney injury in the intensive care unit according to RIFLE

Objectives:To apply the RIFLE criteria “risk,” “injury,” and “failure” for severity of acute kidney injury to patients admitted to the intensive care unit and to evaluate the significance of other prognostic factors. Design:Retrospective analysis of the Riyadh Intensive Care Program database. Setting:Riyadh Intensive Care Unit Program database of 41,972 patients admitted to 22 intensive care units in the United Kingdom and Germany between 1989 and 1999. Patients:Acute kidney injury as defined by the RIFLE classification occurred in 15,019 (35.8%) patients; 7,207 (17.2%) patients were at risk, 4,613 (11%) had injury, and 3,199 (7.6%) had failure. It was found that 797 (2.3%) patients had end-stage dialysis-dependent renal failure when admitted to an intensive care unit. Interventions:None. Measurements and Main Results:Patients with risk, injury, and failure classifications had hospital mortality rates of 20.9%, 45.6%, and 56.8%, respectively, compared with 8.4% among patients without acute kidney injury. Independent risk factors for hospital mortality were age (odds ratio 1.02); Acute Physiology and Chronic Health Evaluation II score on admission to intensive care unit (odds ratio 1.10); presence of preexisting end-stage disease (odds ratio 1.17); mechanical ventilation (odds ratio 1.52); RIFLE categories risk (odds ratio 1.40), injury (odds ratio 1.96), and failure (odds ratio 1.59); maximum number of failed organs (odds ratio 2.13); admission after emergency surgery (odds ratio 3.08); and nonsurgical admission (odds ratio 3.92). Renal replacement therapy for acute kidney injury was not an independent risk factor for hospital mortality. Conclusions:The RIFLE classification was suitable for the definition of acute kidney injury in intensive care units. There was an association between acute kidney injury and hospital outcome, but associated organ failure, nonsurgical admission, and admission after emergency surgery had a greater impact on prognosis than severity of acute kidney injury.

Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

IntroductionAcute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI.MethodsWe performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection.ResultsModerate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method.ConclusionsTwo novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI.Trial registrationClinicalTrials.gov number NCT01209169.

Acute renal failure following cardiopulmonary bypass: a changing picture.

Objective: To assess the incidence of acute renal failure (ARF) developing perioperatively in adult patients requiring cardiopulmonary bypass surgery (CPB) and to make comparisons with data from the same institution published earlier. Design: Prospective, observational. Setting: Tertiary referral centre for cardiopulmonary medicine. Patients and participants: All patients admitted to the intensive care unit (ICU) who developed ARF perioperatively necessitating continuous veno-venous haemofiltration (CVVH) during the 24 months January 1997–December 1998. Interventions: None. Measurements and results: Of 2337 adult patients undergoing cardiac surgery, 47 (2.0 %) needed CVVH. Patients were excluded from analysis who underwent cardiac transplantation (n = 4), pericardial surgery (n = 3) or insertion of a left ventricular assist device (n = 1). Of the remaining 39, 21 patients died in ICU (53.8 % mortality). Relatively more non-survivors suffered from diabetes, hypertension and preoperative renal dysfunction. A previous report from our Unit revealed that, in 1989–90, 2.7 % of all patients undergoing CPB required CVVH with an in-hospital mortality of 83 %. The current study population were older (65.3 vs 56.0 years in 1990), and more severely ill as evidenced by a higher percentage of patients requiring redo (30 % vs 8.6 % in 1990) and emergency (50 % vs 25.7 % in 1990) surgery. Conclusions: The need for CVVH following CPB may be diminishing despite increased risk factors. ARF-associated mortality in these circumstances is falling.

The definition of acute kidney injury and its use in practice.

Acute kidney injury (AKI) is a common syndrome that is independently associated with increased mortality. A standardized definition is important to facilitate clinical care and research. The definition of AKI has evolved rapidly since 2004, with the introduction of the Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) classifications. RIFLE was modified for pediatric use (pRIFLE). They were developed using both evidence and consensus. Small rises in serum creatinine are independently associated with increased mortality, and hence are incorporated into the current definition of AKI. The recent definition from the international KDIGO guideline merged RIFLE and AKIN. Systematic review has found that these definitions do not differ significantly in their performance. Health-care staff caring for children or adults should use standard criteria for AKI, such as the pRIFLE or KDIGO definitions, respectively. These efforts to standardize AKI definition are a substantial advance, although areas of uncertainty remain. The new definitions have enabled the use of electronic alerts to warn clinicians of possible AKI. Novel biomarkers may further refine the definition of AKI, but their use will need to produce tangible improvements in outcomes and cost effectiveness. Further developments in AKI definitions should be informed by research into their practical application across health-care providers. This review will discuss the definition of AKI and its use in practice for clinicians and laboratory scientists.

Correlation between the AKI classification and outcome

IntroductionThe Acute Kidney Injury Network proposed a new classification for acute kidney injury (AKI) distinguishing between three stages. We applied the criteria to a large intensive care unit (ICU) population and evaluated the impact of AKI in the context of other risk factors.MethodsUsing the Riyadh Intensive Care Program database, we applied the AKI classification to 22,303 adult patients admitted to 22 ICUs in the UK and Germany between 1989 and 1999, who stayed in the ICU for 24 hours or longer and did not have end-stage dialysis dependent renal failure.ResultsOf the patients, 7898 (35.4%) fulfilled the criteria for AKI (19.1% had AKI I 3.8% had AKI II and 12.5% had AKI III). Mortality in the ICU was 10.7% in patients with no AKI, 20.1% in AKI I, 25.9% in AKI II and 49.6% in AKI III. Multivariate analysis confirmed that AKI III, but not AKI I and AKI II, were independently associated with ICU mortality (odds ratio (OR) = 2.27). Other independent risk factors for ICU mortality were age (OR = 1.03), sequential organ failure assessment (SOFA) score on admission to the ICU (OR = 1.11), pre-existing end-stage chronic health (OR = 1.65), emergency surgery (OR = 2.33), mechanical ventilation (OR = 2.83), maximum number of failed organ systems (OR = 2.80) and non-surgical admission (OR = 3.57). Cardiac surgery, AKI I and renal replacement therapy were associated with a reduced risk of dying in the ICU. AKI II was not an independent risk factor for ICU mortality. Without renal replacement therapy as a criterion, 21% of patients classified as AKI III would have been classified as AKI II or AKI I. Renal replacement therapy as a criterion for AKI III may inadvertently diminish the predictive power of the classification.ConclusionsThe proposed AKI classification correlated with ICU outcome but only AKI III was an independent risk factor for ICU mortality. The use of renal replacement therapy as a criterion for AKI III may have a confounding effect on the predictive power of the classification system as a whole.

Acute kidney injury after cardiac surgery according to Risk/Injury/Failure/Loss/End-stage, Acute Kidney Injury Network, and Kidney Disease: Improving Global Outcomes classifications

PURPOSE The epidemiology of acute kidney injury (AKI) after cardiac surgery depends on the definition used. Our aims were to evaluate the Risk/Injury/Failure/Loss/End-stage (RIFLE) criteria, the AKI Network (AKIN) classification, and the Kidney Disease: Improving Global Outcomes (KDIGO) classification for AKI post-cardiac surgery and to compare the outcome of patients on renal replacement therapy (RRT) with historical data. METHODS Retrospective analysis of 1881 adults who had cardiac surgery between May 2006 and April 2008 and determination of the maximum AKI stage according to the AKIN, RIFLE, and KDIGO classifications. RESULTS The incidence of AKI using the AKIN and RIFLE criteria was 25.9% and 24.9%, respectively, but individual patients were classified differently. The area under the receiver operating characteristic curve for hospital mortality was significantly higher using the AKIN compared with the RIFLE criteria (0.86 vs 0.78, P = .0009). Incidence and outcome of AKI according to the AKIN and KDIGO classification were identical. The percentage of patients who received RRT was 6.2% compared with 2.7% in 1989 to 1990. The associated hospital mortality fell from 82.9% in 1989 to 1990 to 15.6% in 2006 to 2008. CONCLUSIONS The AKIN classification correlated better with mortality than did the RIFLE criteria. Mortality of patients needing RRT after cardiac surgery has improved significantly during the last 20 years.

Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of >90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD.

Correlation between parameters at initiation of renal replacement therapy and outcome in patients with acute kidney injury

IntroductionRenal replacement therapy (RRT) is a fully established treatment for critically ill patients with acute kidney injury (AKI) but there are no scientifically established criteria when to initiate it. Our objectives were to describe the epidemiology of critically ill patients with AKI receiving RRT and to evaluate the relationship between biochemical, physiological and comorbid factors at time of RRT and ICU mortality.MethodsRetrospective analysis of demographic and physiologic data of 1,847 patients who received RRT for AKI in 22 ICUs in UK and Germany between 1989 - 1999.Results54.1% of RRT patients died in ICU. ICU survivors were younger, had a lower APACHE II score and fewer failed organ systems on admission to ICU compared to non-survivors. Multivariate analysis showed that at time of initiation of RRT, independent risk factors for ICU mortality were mechanical ventilation [odds ratio (OR) 6.03], neurological failure (OR 2.48), liver failure (OR 2.44), gastrointestinal failure (OR 2.04), pre-existing chronic illnesses (OR 1.74), haematological failure (OR 1.74), respiratory failure (OR 1.62), oligoanuria (OR 1.6), age (OR 1.03), serum urea (OR 1.004) and cardiovascular failure (OR 1.3). A higher pH at initiation of RRT was independently associated with a better outcome. Failure to correct acidosis and development of more organ failure within 48 hours after initiation of RRT were also associated with an increased risk of dying in ICU.ConclusionsOligoanuria, acidosis and concomitant dysfunction of other organs at time of RRT were associated with poor survival. In contrast, serum creatinine and urea levels only had a weak correlation with outcome after RRT.

Bench-to-bedside review: Citrate for continuous renal replacement therapy, from science to practice

To prevent clotting in the extracorporeal circuit during continuous renal replacement therapy (CRRT) anticoagulation is required. Heparin is still the most commonly used anticoagulant. However, heparins increase the risk of bleeding, especially in critically ill patients. Evidence has accumulated that regional anticoagulation of the CRRT circuit with citrate is feasible and safe. Compared to heparin, citrate anticoagulation reduces the risk of bleeding and requirement for blood products, not only in patients with coagulopathy, but also in those without. Metabolic complications are largely prevented by the use of a strict protocol, comprehensive training and integrated citrate software. Recent studies indicate that citrate can even be used in patients with significant liver disease provided that monitoring is intensified and the dose is carefully adjusted. Since the citric acid cycle is oxygen dependent, patients at greatest risk of accumulation seem to be those with persistent lactic acidosis due to poor tissue perfusion. The use of citrate may also be associated with less inflammation due to hypocalcemia-induced suppression of intracellular signaling at the membrane and avoidance of heparin, which may have proinflammatory properties. Whether these beneficial effects increase patient survival needs to be confirmed. However, other benefits are the reason that citrate should become the first choice anticoagulant for CRRT provided that its safe use can be guaranteed.

Guidelines for the prevention and management of Mycobacterium tuberculosis infection and disease in adult patients with chronic kidney disease

Guidelines have been compiled by the Joint Tuberculosis Committee of the British Thoracic Society for the prevention and management of Mycobacterium tuberculosis infection and disease in patients with all grades of renal impairment.