Acute kidney injury (AKI) is associated with progression to advanced chronic kidney disease (CKD). We tested whether patients who survive AKI and are at higher risk for CKD progression can be identified during their hospital admission, thus providing opportunities to intervene. This was assessed in patients in the Department of Veterans Affairs Healthcare System hospitalized with a primary diagnosis indicating AKI (ICD9 codes 584.xx). In the exploratory phase, three multivariate prediction models for progression to stage 4 CKD were developed. In the confirmatory phase, the models were validated in 11,589 patients admitted for myocardial infarction or pneumonia during the same time frame that had RIFLE codes R, I, or F and complete data for all predictor variables. Of the 5351 patients in the AKI group, 728 entered stage 4 CKD after hospitalization. Models 1, 2, and 3 were all significant with ‘c’ statistics of 0.82, 0.81, and 0.77, respectively. In model validation, all three were highly significant when tested in the confirmatory patients, with moderate to large effect sizes and good predictive accuracy (‘c’ 0.81–0.82). Patients with AKI who required dialysis and then recovered were at especially high risk for progression to CKD. Hence, the severity of AKI is a robust predictor of progression to CKD.
Kidney International (2011) 79, 1361–1369; doi:10.1038/ki.2011.42; published online 23 March 2011
Most important would be identification of clinical characteris- tics and biomarkers of patients who are likely to have progressive kidney disease leading to ESRD.
Figure 3 | Fluid and haemodynamic management after the initial phase of critical illness. Throughout this pathway a clinically appropriate arterial blood pressure is targeted using vasopressors, if required. In addition to fluid overload, in AKI, RRT may be required for other indications including hyperkalaemia, acidaemia, or severe uraemia. *Increased vasopressor requirement, new or worsening organ dysfunction, tachycardia, lactic acidosis or clinical examination. ‡Measure cardiac index, stroke volume, ejection volume, oxygen delivery or venous saturation of oxygen. Ensure oxygen delivery is adequate to clinical need. §Clinical examination, serial weights, cumulative fluid balance, chest X-ray or ventilation parameters. Lung ultrasound, echocardiography, abdominal pressure measurements and bioimpedance analysis may provide added information. ||Based on relative fluid overload, haemodynamic stability and expected speed of vascular refilling. ¶Maintenance intravenous fluid is rarely needed where no large ongoing fluid losses are present and feeding established. Replacement should be titrated to volume and expected composition of fluid losses. #Interpretation of stroke volume, pulse pressure, corrected aortic systolic flow time, intrathoracic blood volume index, low central venous or pulmonary artery pressure, echocardiography, or fluid responsiveness to passive leg raises or fluid challenges.
At a target MAP of 75 mm Hg, renal DO2 (13 %), GFR (27 %) and urine flow were higher and renal O2Ex was lower (–7.4 %) compared with a target MAP of 60 mm Hg.
Background: Recent studies have suggested that early goal-directed resuscitation of patients with septic shock and conservative fluid management of patients with acute lung injury (ALI) can improve outcomes. Because these may be seen as potentially conflicting practices, we set out to determine the influence of fluid management on the outcomes of patients with septic shock complicated by ALI.
Methods: A retrospective analysis was performed at Barnes-Jewish Hospital (St. Louis, MO) and in the medical ICU of Mayo Medical Center (Rochester, MN). Patients hospitalized with septic shock were enrolled into the study if they met the American-European Consensus definition of ALI within 72 h of septic shock onset. Adequate initial fluid resuscitation (AIFR) was defined as the administration of an initial fluid bolus of > 20 mL/kg prior to and achievement of a central venous pressure of > 8 mm Hg within 6 h after the onset of therapy with vasopressors. Conservative late fluid management (CLFM) was defined as even-to- negative fluid balance measured on at least 2 consecutive days during the first 7 days after septic shock onset.
Results: The study cohort was made up of 212 patients with ALI complicating septic shock. Hospital mortality was statistically lowest for those achieving both AIFR and CLFM and higher for those achieving only CLFM, those achieving only AIFR, and those achieving neither (17 of 93 patients [18.3%] vs 13 of 31 patients [41.9%] vs 30 of 53 patients [56.6%] vs 27 of 35 [77.1%], respectively; p < 0.001).
Conclusions: Both early and late fluid management of septic shock complicated by ALI can influence patient outcomes. (CHEST 2009; 136:102–109)
Summary
Background and objectives Management of volume status in patients with acute kidney injury (AKI) is com- plex, and the role of diuretics is controversial. The primary objective was to elucidate the association be- tween fluid balance, diuretic use, and short-term mortality after AKI in critically ill patients.
Design, setting, participants, & measurements Using data from the Fluid and Catheter Treatment Trial (FACTT), a multicenter, randomized controlled trial evaluating a conservative versus liberal fluid-manage- ment strategy in 1000 patients with acute lung injury (ALI), we evaluated the association of post-renal in- jury fluid balance and diuretic use with 60-day mortality in patients who developed AKI, as defined by the AKI Network criteria.
Results 306 patients developed AKI in the first 2 study days and were included in our analysis. There were 137 in the fluid-liberal arm and 169 in the fluid-conservative arm (P 0.04). Baseline characteristics were similar between groups. Post-AKI fluid balance was significantly associated with mortality in both crude and adjusted analysis. Higher post-AKI furosemide doses had a protective effect on mortality but no signif- icant effect after adjustment for post-AKI fluid balance. There was no threshold dose of furosemide above which mortality increased.
Conclusions A positive fluid balance after AKI was strongly associated with mortality. Post-AKI diuretic therapy was associated with 60-day patient survival in FACTT patients with ALI; this effect may be medi- ated by fluid balance.
Conclusions
In this post-hoc analysis, a positive fluid balance after in-hospital AKI carried a strong and consistent association with mortality in patients with ALI, independent of liberal or conservative fluid management. Higher diuretic dose after AKI onset had a protective effect on survival, with no observed threshold dose above which mortality increased; this relationship appeared to be mediated by post-AKI fluid balance. With the caveat that these data were ob- tained in a randomized clinical trial of patients with ALI, clinicians may be reassured that, in the appropriate pa- tient, diuretics may not be contraindicated. Future ran- domized clinical trials focused on diuretic administration and fluid balance in critically ill patients with AKI are clearly warranted.
IT IS WELL KNOWN THAT AMONG THE KEY PROBLEMS OF RRT IN THE CRITICALLY ILL, THE NEED FOR PROLONGED ANTICOAGULATION IS A POTENTIAL DRAWBACK OF CRRT. THEREFORE, THE ADOPTION OF AN APPROPRIATE ANTICOAGULATION STRATEGY REPRESENTS A KEY POINT FOR A SAFE AND EFFECTIVE CRRT TREATMENT.
Abstract
Despite advances in renal replacement therapy, the mortal- ity of acute kidney injury (AKI) has remained high, especially when associated with distant organ dysfunction such as acute lung injury (ALI). Mortality rates for combined AKI/ALI reach 80% in critically ill patients. While the clinical presen- tation of AKI-associated ALI is characterized by increased pulmonary edema, a defining feature of the syndrome, the AKI-induced lung effects extend beyond simple volume overload. Furthermore, ALI and associated mechanical ven- tilation frequently lead to a decline in renal hemodynam- ics, structure and function. New experimental data have emerged in recent years focusing on the interactive effects of kidney and lung dysfunction, and these studies have high- lighted the pathophysiological importance of proinflamma- tory and proapoptotic pathways as well as the complex na- ture of interorgan crosstalk. This review will examine our current understanding of the deleterious kidney-lung cross- talk in the critically ill.
Background. Despite the frequent use of renal replace- ment therapy (RRT) for patients with acute kidney injury (AKI) in the intensive care unit (ICU), there is no accepted consensus on the optimal indications and timing. Methods. The aim of this paper is to identify optimal trig- gers for RRT in critically ill patients with AKI. Results. We examined data from 2 randomized controlled trials, 2 prospective studies and 13 retrospective trials and found large variation in the different parameters and cut- offs for initiation of RRT. No single biochemical parameter was adequate to define the optimal indication and time to commence RRT. Degree of fluid overload, oliguria and associated non-renal organ failure appeared to be more appropriate parameters for initiation of RRT. We propose a clinical algorithm based on regular assessment of the patient’s condition and trends in these parameters. It is intended to aid the process of deciding when to start RRT in critically ill adult patients with AKI. Conclusion. Available evidence suggests that the decision when to start RRT in critically ill patients with AKI should be based on trends in the patient’s severity of illness, pres- ence of oliguria and fluid overload and associated non-renal organ failure rather than specific serum creatinine or urea values.
Sepsis initiates a brisk inflammatory response that directly and indirectly causes widespread tissue injury. Shownhere are key components of this process and their interactions at the level of the microvasculature of a representa- tive vital organ. Gram-positive and gram-negative bacteria, viruses, and fungi have unique cell-wall molecules called pathogen-associated molecular patterns that bind to pattern-recognition receptors (toll-like receptors [TLRs]) on the surface of immune cells. The lipopolysaccharide of gram-negative bacilli binds to lipopolysaccharide-binding pro- tein, CD14 complex. The peptidoglycan of gram-positive bacteria and the lipopolysaccharide of gram-negative bacte- ria bind to TLR-2 and TLR-4, respectively. Binding of TLR-2 and TLR-4 activates intracellular signal-transduction pathways that lead to the activation of cytosolic nuclear factor κB (NF-κB). Activated NF-κB moves from the cyto- plasm to the nucleus, binds to transcription initiation sites, and increases the transcription of cytokines such as tu- mor necrosis factor α (TNF-α), interleukin-1β, and interleukin-10. TNF-α and interleukin-1β are proinflammatory cytokines that activate the adaptive immune response but also cause both direct and indirect host injury. Interleu- kin-10 is an antiinflammatory cytokine that inactivates macrophages and has other antiinflammatory effects. Sepsis increases the activity of inducible nitric oxide synthase (iNOS), which increases the synthesis of nitric oxide (NO), a potent vasodilator. Cytokines activate endothelial cells by up-regulating adhesion receptors and injure endothelial cells by inducing neutrophils, monocytes, macrophages, and platelets to bind to endothelial cells. These effector cells release mediators such as proteases, oxidants, prostaglandins, and leukotrienes. Key functions of the endothe- lium are selective permeability, vasoregulation, and provision of an anticoagulant surface. Proteases, oxidants, pros- taglandins, and leukotrienes injure endothelial cells, leading to increased permeability, further vasodilation, and al- teration of the procoagulant–anticoagulant balance. Cytokines also activate the coagulation cascade.
The results of this study showed that septic plasma induced different injurious effects on cultured TEC by favouring PMN adhesion, inducing cell apoptosis and altering cell polarity and function. All these biological effects are related to the presence of circulating inflammatory mediators that can be efficiently removed by unselective resin adsorption with a conse- quent limitation of tubular cell injury. Whether non- selective removal of cytokines may have a protective or therapeutic role in human sepsis-associated AKI is an attractive possibility which needs further investigation.
INDEED, IS GENERALLY RECOGNIZED THAT ACUTE RENAL FAILURE IS A HIGH BLEEDING RISK CONDITION AND THAT CLINICALLY IMPORTANT BLEEDING SIGNIFICANTLY INCREASES MORTALITY RISK, WITH AN ADJUSTED ODDS RATIO OF DEATH OF MORE THAN 2.5 IN HEMORRHAGIC PATIENTS.
AS REPORTED IN THE ATN STUDY, A POSSIBLE STRATEGY COULD BE TO AVOID ANTICOAGULATION IN HIGH BLEEDING RISK PATIENTS. AS YOU CAN SEE IN THE TABLE, CVVHDF HAS BEEN PERFORMED WITHOUT ANTICOAGULATION IN MORE THAN FIFTY PER CENT OF CRRT SESSIONS.
AMONG POSSIBLE ALTERNATIVES TO HEPARIN, REGIONAL CITRATE ANTICOAGULATION HAS BEEN SHOWN TO BE HIGHLY EFFECTIVE IN PROLONGING FILTER LIFE. BY REDUCING IONIZED CALCIUM INSIDE THE EXTRACORPOREAL CIRCUIT, CITRATE IS ABLE TO BLOCK COAGULATION CASCADE AT DIFFERENT LEVELS.
IN ORDER TO ACHIEVE REGIONAL ANTICOAGULATION, A) CITRATE IS INFUSED AT THE BEGINNING OF THE EXTRACORPOREAL CIRCUIT WITH A FLOW-RATE STRICTLY RELATED TO BLOOD FLOW, CITRATE SOLUTION CONCENTRATION AND TARGET CITRATE DOSE. B) CITRATE CHELATES IONIZED CALCIUM, REDUCING ITS CONCENTRATION BELOW THE INTENDED TARGET (GENERALLY 0.3 TO 0.4 MMOL PER LITER). C) POST-FILTER IONIZED CALCIUM IS PERIODICALLY CHECKED TO MODULATE CITRATE FLOW RATE AS NEEDED. D) CITRATE AND CALCIUM-CITRATE COMPLEX ARE SMALL MOLECULES AND ARE PARTIALLY LOST IN THE EFFLUENT IN RELATION TO DIALYSIS DOSE. E) CALCIUM CHLORIDE OR CALCIUM GLUCONATE INFUSION IS NEEDED TO REPLACE CALCIUM LOSS AND TO MAINTAIN SYSTEMIC IONIZED CALCIUM WITHIN PHYSIOLOGICAL VALUES. F) METABOLIC LOAD AND BUFFER SUPPLY DERIVE FROM THE QUOTE OF CITRATE AND CALCIUM-CITRATE COMPLEX RETURNING TO THE PATIENT.
EVIDENCE EMERGING FROM EARLY RANDOMIZED CLINICAL TRIALS, COMPARING CITRATE WITH STANDARD HEPARIN ANTICOAGULATION, SHOWED THAT THE USE OF CITRATE WAS ASSOCIATED WITH A MUCH LONGER FILTER LIFESPAN, WITH LOWER TRANSFUSION RATES AND WITH A LOWER RELATIVE RISK OF BLEEDING COMPLICATIONS.
IN THE SAME META-ANALYSIS, REGIONAL CITRATE ANTICOAGULATION WAS ASSOCIATED WITH A HIGHLY SIGNIFICANT REDUCTION OF BLEEDING RISK, WITH A RISK RATIO OF ABOUT 0.3 IF COMPARED WITH CONTROL GROUP.
IN OUR EXPERIENCE, REGIONAL CITRATE ANTICOAGULATION ALLOWED TO SIGNIFICANTLY PROLONG FILTER LIFE IN HIGH BLEEDING RISK CARDIAC SURGERY PATIENTS SWITCHED TO RCA FROM HEPARIN OR NO ANTICOAGULATION. IN PARTICULAR, REGIONAL CITRATE ANTICOAGULATION ALLOWED TO MINIMIZE CRRT DOWN-TIME WITH A MEAN DELIVERED DOSE AROUND NINETY PERCENT.
MOREOVER, THE USE OF REGIONAL CITRATE ANTICOAGULATION WAS ASSOCIATED WITH A SIGNIFICANT REDUCTION OF TRANSFUSION RATES AND WITH AN INCREASE OF PLATELET COUNT AND ANTITHROMBIN III ACTIVITY, REDUCING THE NEED FOR SUPPLEMENTATION.
INDEED, CITRATE IS RAPIDLY METABOLIZED, MAINLY BY THE LIVER, WITH A HALF-LIFE OF ABOUT 5 MINUTES, GENERATING 3 MMOL OF BICARBONATE FOR EACH MMOL OF CITRATE. TO PREVENT ACCUMULATION, CITRATE LOAD SHOULD BE MAINTAINED LOW IN PATIENTS WITH SEVERE LIVER FAILURE AND/OR TISSUE HYPOPERFUSION.
THEREFORE, STRATEGIES FOR THE PREVENTION OF CITRATE ACCUMULATION IN PATIENTS WITH LIVER FAILURE OR WITH OTHER RISK FACTORS SHOULD BE TARGETED TO MAINTAIN A LOW CITRATE LOAD THROUGH A DECREASE OF CITRATE ADMINISTRATION, WHICH COULD BE OBTAINED BY THE USE OF A LOW BLOOD FLOW RATE ASSOCIATED WITH A HIGHER IONIZED CALCIUM TARGET, AND AN INCREASE OF CITRATE CLEARANCE THROUGH THE OPTIMIZATION OF CONVECTIVE AND/OR DIFFUSIVE DIALYSIS DOSE.
IF METABOLIC COMPLICATIONS REMAIN DESPITE THESE MEASURES, ALTERNATIVES TO CITRATE SHOULD BE CONSIDERED.
IN THIS TABLE ARE SUMMARIZED THE POTENTIAL ELECTROLYTE AND ACID-BASE COMPLICATIONS OF REGIONAL CITRATE ANTICOAGULATION. SHOULD BE UNDERLINED THAT THESE COMPLICATIONS ARE RARELY OBSERVED WITH A STRICT OBSERVANCE OF WELL-DESIGNED PROTOCOLS.
METABOLIC ALKALOSIS IS GENERALLY RELATED TO EXCESSIVE CITRATE LOAD OR TO INADEQUATE MATCHING OF SOLUTIONS ADOPTED, WHILE METABOLIC ACIDOSIS IS MORE COMMONLY DUE TO IMPAIRED CITRATE METABOLISM PREVENTING BICARBONATE GENERATION.
CALCIUM AND MAGNESIUM DERANGEMENTS ARE USUALLY DUE TO INADEQUATE OR EXCESSIVE REPLACEMENT. HYPERNATREMIA REPRESENTS A POTENTIAL BUT RARELY OBSERVED COMPLICATION RELATED TO THE USE OF HYPERTONIC CITRATE SOLUTIONS.
ACID-BASE STATUS AND SERUM PHOSPHATE LEVELS THROUGHOUT RCA-CVVH DAYS ARE DISPLAYED HERE. WITH THE NEW PROTOCOL, PHOSPHATEMIA HAS BEEN MAINTAINED IN A PROGRESSIVELY NARROWER RANGE, AROUND PHYSIOLOGICAL VALUES.
ADVANCES IN TECHNOLOGY MAY GIVE US THE OPPORTUNITY TO DRAMATICALLY IMPROVE SAFETY OF RCA-CRRT THROUGH THE DEVELOPMENT OF CUSTOMIZED DIALYSIS SYSTEM AND SOFTWARE FOR A NEAR-AUTOMATED DELIVERY OF REGIONAL CITRATE ANTICOAGULATION.
THE USE OF A CRRT MONITOR WITH DEDICATED RCA SOFTWARE MAY PROVIDE CLINICAL ADVANTAGES IN THE DAILY PRACTICE. FOR EXAMPLE, PATIENT CITRATE LOAD CAN BE ROUGHLY ESTIMATED IN RELATION TO CITRATE DOSE AND DIALYSIS DOSE AND THE EFFECTS OF DIFFERENT SETTINGS MAY BE EASILY VERIFIED AND TAILORED ACCORDING TO PATIENT’S CHARACTERISTICS.
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