Josée Bouchard

Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury

Fluid accumulation is associated with adverse outcomes in critically ill patients. Here, we sought to determine if fluid accumulation is associated with mortality and non-recovery of kidney function in critically ill adults with acute kidney injury. Fluid overload was defined as more than a 10% increase in body weight relative to baseline, measured in 618 patients enrolled in a prospective multicenter observational study. Patients with fluid overload experienced significantly higher mortality within 60 days of enrollment. Among dialyzed patients, survivors had significantly lower fluid accumulation when dialysis was initiated compared to non-survivors after adjustments for dialysis modality and severity score. The adjusted odds ratio for death associated with fluid overload at dialysis initiation was 2.07. In non-dialyzed patients, survivors had significantly less fluid accumulation at the peak of their serum creatinine. Fluid overload at the time of diagnosis of acute kidney injury was not associated with recovery of kidney function. However, patients with fluid overload when their serum creatinine reached its peak were significantly less likely to recover kidney function. Our study shows that in patients with acute kidney injury, fluid overload was independently associated with mortality. Whether the fluid overload was the result of a more severe renal failure or it contributed to its cause will require clinical trials in which the role of fluid administration to such patients is directly tested.

Fluid accumulation, recognition and staging of acute kidney injury in critically-ill patients

IntroductionSerum creatinine concentration (sCr) is the marker used for diagnosing and staging acute kidney injury (AKI) in the RIFLE and AKIN classification systems, but is influenced by several factors including its volume of distribution. We evaluated the effect of fluid accumulation on sCr to estimate severity of AKI.MethodsIn 253 patients recruited from a prospective observational study of critically-ill patients with AKI, we calculated cumulative fluid balance and computed a fluid-adjusted sCr concentration reflecting the effect of volume of distribution during the development phase of AKI. The time to reach a relative 50% increase from the reference sCr using the crude and adjusted sCr was compared. We defined late recognition to estimate severity of AKI when this time interval to reach 50% relative increase between the crude and adjusted sCr exceeded 24 hours.ResultsThe median cumulative fluid balance increased from 2.7 liters on day 2 to 6.5 liters on day 7. The difference between adjusted and crude sCr was significantly higher at each time point and progressively increased from a median difference of 0.09 mg/dL to 0.65 mg/dL after six days. Sixty-four (25%) patients met criteria for a late recognition to estimate severity progression of AKI. This group of patients had a lower urine output and a higher daily and cumulative fluid balance during the development phase of AKI. They were more likely to need dialysis but showed no difference in mortality compared to patients who did not meet the criteria for late recognition of severity progression.ConclusionsIn critically-ill patients, the dilution of sCr by fluid accumulation may lead to underestimation of the severity of AKI and increases the time required to identify a 50% relative increase in sCr. A simple formula to correct sCr for fluid balance can improve staging of AKI and provide a better parameter for earlier recognition of severity progression.

Oliguria is an early predictor of higher mortality in critically ill patients

Oliguria is a valuable marker of kidney function and a criterion for diagnosing and staging acute kidney injury (AKI). However, the utility of urine output as a specific metric for renal dysfunction is somewhat controversial. To study this issue further we tested whether urine output is a sensitive, specific, and early measure for diagnosing and staging AKI in 317 critically ill patients in a prospective observational study. Urine output was assessed every hour and serum creatinine every 12 to 24  h. The sensitivity and specificity of different definitions of oliguria for the diagnosis of AKI were compared with the Acute Kidney Injury Network serum creatinine criterion. The incidence of AKI increased from 24%, based solely on serum creatinine, to 52% by adding the urine output as a diagnostic criterion. Oliguric patients without a change in serum creatinine had an intensive care unit mortality rate (8.8%) significantly higher than patients without AKI (1.3%), and similar to oliguric patients with an increase in serum creatinine (10.4%). The diagnosis of AKI occurred earlier in oliguric than in non-oliguric patients. Oliguria of more than 12  h and oliguria of 3 or more episodes were associated with an increased mortality rate. Thus, urine output is a sensitive and early marker for AKI and is associated with adverse outcomes in intensive care unit patients.

Diagnosis of Acute Kidney Injury Using Functional and Injury Biomarkers: Workgroup Statements from the Tenth Acute Dialysis Quality Initiative Consensus Conference

Acute kidney injury (AKI) commonly occurs in hospitalized patients and is independently and strongly associates with morbidity and mortality. The clinical benefits of a timely and definitive diagnosis of AKI have not been fully realized due to limitations imposed by the use of serum creatinine and urine output to fulfill diagnostic criteria. These restrictions often lead to diagnostic delays, potential misclassification of actual injury status, and provide little information regarding underlying cause. Novel biomarkers of damage have shown ability to reflect ongoing kidney injury and help further refine existing Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN) diagnostic criteria. A comprehensive review of the published literature to date was performed using previously published methodology of the Acute Dialysis Quality Initiative (ADQI) working group to establish consensus statements regarding (i) the overall implementation of injury biomarkers in the concept of AKI diagnosis, (ii) their clinical use, and (iii) future research. On the basis of published data on the ability of novel damage biomarkers to provide diagnostic and prognostic information on AKI, we recommend that novel damage biomarkers may, in the appropriate clinical setting and context (situation consistent with AKI), be used to diagnose AKI even in the absence of changes in serum creatinine or the presence of oliguria as described in the existing RIFLE/AKIN criteria for diagnosis of AKI. Adding injury biomarkers as a criterion for AKI will complement the ability of RIFLE/AKIN to define AKI. Promising diagnostic injury markers include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18) and liver-type fatty acid binding protein (L-FABP). However, there are currently insufficient data on damage biomarkers to support their use for AKI staging. Rigorous validation studies measuring the association between the novel damage biomarker(s) and clinically relevant outcomes are needed.

Renal recovery following acute kidney injury.

Purpose of reviewRenal recovery after acute kidney injury (AKI) is an important outcome, most commonly defined as dialysis independence at hospital discharge. This review focuses on the epidemiology of renal recovery after AKI and provides a framework for determining the relationship of a lack of renal recovery and subsequent outcomes including the development of chronic kidney disease. Recent findingsThe majority of studies addressing renal recovery includes only critically ill patients requiring dialysis and considers renal recovery as dialysis independency at hospital discharge. However, a significant proportion of AKI patients are not in the ICU, are not dialyzed, and may require alternate definitions for assessing renal recovery. There is emerging evidence that an AKI episode can lead to chronic kidney disease and can accelerate the progression to end stage renal disease. Patients that survive after AKI present a higher long-term mortality risk, especially those with partial renal recovery. SummaryPatients with incomplete renal recovery after AKI are underrepresented in most epidemiologic studies and the precise effect on the incidence and prevalence of end stage renal disease population has yet to be determined. A standardized definition for renal recovery is needed and the influence of an AKI episode on long-term outcomes needs to be better evaluated.

Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury.

Acute kidney injury (AKI) is associated with pro-longed hospitalization, substantial health care re-source consumption, high mortality, and can lead toprogressive chronic kidney disease (CKD), includingchronic kidney failure, in survivors. The CanadianSociety of Nephrology (CSN) believes there is a needto develop clinical practice guidelines for patientswith AKI; however, efforts to synthesize knowledgefrom clinical studies evaluating the prevention andtreatmentofAKIandtogenerateguidelineshavebeenlimited. One barrier has been the absence of consen-sus on the definition of AKI, with more than 35definitionsofAKIpublishedtodate.Further,thereisaperceivedlackofeffectiveprophylacticandtreatmentstrategies for AKI, and it is challenging to developguidelines that involve multiple stakeholders fromdiversedisciplinesincludingnephrology,criticalcare,and radiology, all of which are important end users ofguidelines forAKI. In this context, the KDIGO (Kid-neyDisease:ImprovingGlobalOutcomes)AKIwork-ing group has recently published new criteria for thedefinition and classification of AKI, as well as aclinicalpracticeguidelineaddressingbothAKIpreven-tion and treatment.

Comparison of methods for estimating glomerular filtration rate in critically ill patients with acute kidney injury

BACKGROUND In critically ill patients with acute kidney injury, estimates of kidney function are used to modify drug dosing, adjust nutritional therapy and provide dialytic support. However, estimating glomerular filtration rate is challenging due to fluctuations in kidney function, creatinine production and fluid balance. We hypothesized that commonly used glomerular filtration rate prediction equations overestimate kidney function in patients with acute kidney injury and that improved estimates could be obtained by methods incorporating changes in creatinine generation and fluid balance. METHODS We analysed data from a multicentre observational study of acute kidney injury in critically ill patients. We identified 12 non-dialysed, non-oliguric patients with consecutive increases in creatinine for at least 3 and up to 7 days who had measurements of urinary creatinine clearance. Glomerular filtration rate was estimated by Cockcroft-Gault, Modification of Diet in Renal Disease, Jelliffe equation and Jelliffe equation with creatinine adjusted for fluid balance (Modified Jelliffe) and compared to measured urinary creatinine clearance. RESULTS Glomerular filtration rate estimated by Jelliffe and Modification of Diet in Renal Disease equation correlated best with urinary creatinine clearances. Estimated glomerular filtration rate by Cockcroft-Gault, Modification of Diet in Renal Disease and Jelliffe overestimated urinary creatinine clearance was 80%, 33%, 10%, respectively, and Modified Jelliffe underestimated GFR by 2%. CONCLUSION In patients with acute kidney injury, glomerular filtration rate estimating equations can be improved by incorporating data on creatinine generation and fluid balance. A better assessment of glomerular filtration rate in acute kidney injury could improve evaluation and management and guide interventions.

Systemic anticoagulation and prevention of hemodialysis catheter malfunction.

Although chronic anticoagulation is commonly prescribed to prevent thrombosis and malfunction of hemodialysis tunneled cuffed catheters (TCC), there are only limited data regarding its efficacy. The aim of this prospective study was to evaluate whether anticoagulation with adjusted-dose warfarin targeting an international normalized ratio (INR) of 1.5–2.0 is associated with improved catheter outcome in long-term patients at high risk of TCC malfunction. Among the 65 patients included in the study, 35 were considered at high risk (i.e., patients with a history of previous TCC thrombosis requiring catheter replacement and/or with TCC malfunction occurring within 2 weeks after catheter insertion in the absence of mechanical problems) and were prescribed warfarin, whereas 30 low-risk patients did not receive anticoagulation. During follow-up, TCC malfunction, defined as the need for inversion of catheter lines and/or recombinant tissue-type plasminogen activator infusion, was observed in 61.5% of patients. Among patients receiving warfarin, 19 (54.3%) achieved adequate anticoagulation (i.e., > 80% of follow-up INR values and INR value at the time of malfunction within target range). Anticoagulation was considered inadequate in 16 patients (45.7%). Malfunction-free catheter survival at 9 months was 47.1% in patients with adequate anticoagulation compared with 8.1% in patients with inadequate anticoagulation (p = 0.01). This difference remained statistically significant after adjustment for aspirin intake. These results suggest that achieving adequate anticoagulation with target INR 1.5–2.0 may prevent TCC malfunction and improve catheter outcome.

Fluid accumulation and acute kidney injury: consequence or cause.

PURPOSE OF REVIEW Fluid accumulation and fluid overload are frequent findings in critically ill patients and in those suffering from severe acute kidney injury. This review focuses on the consequences associated with fluid overload in critically ill patients with or without associated acute kidney injury and discusses the potential mechanisms by which acute kidney injury can contribute to fluid overload and whether fluid overload can also contribute to kidney dysfunction. RECENT FINDINGS Fluid overload has recently been linked to adverse outcomes in critically ill patients suffering from acute kidney injury. However, whether significant fluid accumulation can contribute to acute kidney injury has not been investigated. SUMMARY Fluid overload is independently associated with increased mortality in patients with acute kidney injury and contributes to worsen outcomes in critically ill patients. Further studies are required to determine the influence of fluid overload on organ function and overall prognosis.

A Prospective International Multicenter Study of AKI in the Intensive Care Unit

BACKGROUND AND OBJECTIVES AKI is frequent and is associated with poor outcomes. There is limited information on the epidemiology of AKI worldwide. This study compared patients with AKI in emerging and developed countries to determine the association of clinical factors and processes of care with outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This prospective observational study was conducted among intensive care unit patients from nine centers in developed countries and five centers in emerging countries. AKI was defined as an increase in creatinine of ≥0.3 mg/dl within 48 hours. RESULTS Between 2008 and 2012, 6647 patients were screened, of whom 1275 (19.2%) developed AKI. A total of 745 (58% of those with AKI) agreed to participate and had complete data. Patients in developed countries had more sepsis (52.1% versus 38.0%) and higher Acute Physiology and Chronic Health Evaluation (APACHE) scores (mean±SD, 61.1±27.5 versus 51.1±25.2); those from emerging countries had more CKD (54.3% versus 38.3%), GN (6.3% versus 0.9%), and interstitial nephritis (7.0% versus 0.6%) (all P<0.05). Patients from developed countries were less often treated with dialysis (15.5% versus 30.2%; P<0.001) and started dialysis later after AKI diagnosis (2.0 [interquartile range, 0.75-5.0] days versus 0 [interquartile range, 0-5.0] days; P=0.02). Hospital mortality was 22.0%, and 13.3% of survivors were dialysis dependent at discharge. Independent risk factors associated with hospital mortality included older age, residence in an emerging country, use of vasopressors (emerging countries only), dialysis and mechanical ventilation, and higher APACHE score and cumulative fluid balance (developed countries only). A lower probability of renal recovery was associated with residence in an emerging country, higher APACHE score (emerging countries only) and dialysis, while mechanical ventilation was associated with renal recovery (developed countries only). CONCLUSIONS This study contrasts the clinical features and management of AKI and demonstrates worse outcomes in emerging than in developed countries. Differences in variations in care may explain these findings and should be considered in future trials.