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ABSTRACT: There is no consensus on the optimal method to measure delivered dialysis dose in patients with acute kidney injury (AKI). The use of direct dialysate-side quantification of dose in preference to the use of formal blood-based urea kinetic modeling and simplified blood urea nitrogen (BUN) methods has been recommended for dose assessment in critically-ill patients with AKI. We evaluate six different blood-side and dialysate-side methods for dose quantification.
We examined data from 52 critically-ill patients with AKI requiring dialysis. All patients were treated with pre-dilution CVVHDF and regional citrate anticoagulation. Delivered dose was calculated using blood-side and dialysis-side kinetics. Filter function was assessed during the entire course of therapy by calculating BUN to dialysis fluid urea nitrogen (FUN) ratios q/12 hours.
Median daily treatment time was 1,413 min (1,260-1,440). The median observed effluent volume per treatment was 2,355 mL/h (2,060-2,863) (p<0.001). Urea mass removal rate was 13.0 ± 7.6 mg/min. Both EKR (r²=0.250; p<0.001) and KD (r²=0.409; p<0.001) showed a good correlation with actual solute removal. EKR and KD presented a decline in their values that was related to the decrease in filter function assessed by the FUN/BUN ratio.
Effluent rate (mL/kg/h) can only empirically provide an estimated of dose in CRRT. For clinical practice, we recommend that the delivered dose should be measured and expressed as KD. EKR also constitutes a good method for dose comparisons over time and across modalities.
The International journal of artificial organs 03/2012; 35(6):413-24. · 1.86 Impact Factor
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ABSTRACT: Studies examining dose of continuous renal replacement therapy (CRRT) and outcomes have yielded conflicting results. Most studies considered the prescribed dose as the effluent rate represented by ml/kg per hour and reported this volume as a surrogate of solute removal. Because filter fouling can reduce the efficacy of solute clearance, the actual delivered dose may be substantially lower than the observed effluent rate.
Data were examined from 52 critically ill patients with acute kidney injury (AKI) requiring dialysis. All patients were treated with predilution continuous venovenous hemodiafiltration (CVVHDF) and regional citrate anticoagulation. Filter performance was monitored during the entire course of therapy by measuring blood urea nitrogen (BUN) and dialysis fluid urea nitrogen (FUN) at initiation and every 12 hours. Filter efficacy was assessed by calculating FUN/BUN ratios every 12 hours of filter use. Prescribed urea clearance (K, ml/min) was determined from the effluent rate. Actual delivered urea clearance was determined using dialysis-side measurements.
Median daily treatment time was 1413 minutes (1260 to 1440) with a total effluent volume of 46.4 ± 17.4 L and urea mass removal of 13.0 ± 7.6 mg/min. Prescribed clearance overestimated the actual delivered clearance by 23.8%. This gap between prescribed and delivered clearance was related to the decrease in filter function assessed by the FUN/BUN ratio.
Effluent volume significantly overestimates delivered dose of small solutes in CRRT. To assess adequacy of CRRT, solute clearance should be measured rather than estimated by the effluent volume.
Clinical Journal of the American Society of Nephrology 11/2010; 6(3):467-75. · 5.23 Impact Factor
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ABSTRACT: 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.
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.
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%.
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.
Nephrology Dialysis Transplantation 09/2009; 25(1):102-7. · 3.40 Impact Factor
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ABSTRACT: Acute renal failure (ARF) in the critically ill is associated with extremely high mortality rates. Understanding the changing spectrum of ARF will be necessary to facilitate quality improvement efforts and to design successful interventional trials.
We conducted an observational cohort study of 618 patients with ARF in intensive care units at five academic medical centers in the United States. Participants were required to sign (or have a proxy sign) informed consent for data collection. A comprehensive data collection instrument captured more than 800 variables, most on a daily basis, throughout the course of ARF. Patient characteristics, dialysis status, and major outcomes were determined and stratified by clinical site.
The mean age was 59.5 years, 41% were women, and 20% were of minority race or ethnicity. There was extensive comorbidity; 30% had chronic kidney disease, 37% had coronary artery disease, 29% had diabetes mellitus, and 21% had chronic liver disease. Acute renal failure was accompanied by extrarenal organ system failure in most patients, even those who did not require dialysis. Three hundred and ninety-eight (64%) patients required dialysis. The in-hospital mortality rate was 37%, and the rate of mortality or nonrecovery of renal function was 50%. The median hospital length of stay was 25 days (26 days, excluding patients who died).
There is a changing spectrum of ARF in the critically ill, characterized by a large burden of comorbid disease and extensive extrarenal complications, obligating the need for dialysis in the majority of patients. There is wide variation across institutions in patient characteristics and practice patterns. These differences highlight the need for additional multicenter observational and interventional studies in ARF.
Kidney International 11/2004; 66(4):1613-21. · 6.61 Impact Factor
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Edith M Simmons,
Jonathan Himmelfarb,
M Tugrul Sezer,
Glenn M Chertow,
Ravindra L Mehta,
Emil P Paganini, Sharon Soroko,
Stephanie Freedman,
Karen Becker,
Daniel Spratt,
Yu Shyr,
T Alp Ikizler
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ABSTRACT: Critically ill patients with acute renal failure (ARF) experience a high mortality rate. Animal and human studies suggest that proinflammatory cytokines lead to the development of a systemic inflammatory response syndrome (SIRS), which is temporally followed by a counter anti-inflammatory response syndrome (CARS). This process has not been specifically described in critically ill patients with ARF.
The Program to Improve Care in Acute Renal Disease (PICARD) is a prospective, multicenter cohort study designed to examine the natural history, practice patterns, and outcomes of treatment in critically ill patients with ARF. In a subset of 98 patients with ARF, we measured plasma proinflammatory cytokines [interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)], the acute-phase reactant C-reactive protein (CRP), and the anti-inflammatory cytokine IL-10 at study enrollment and over the course of illness.
When compared with healthy subjects and end-stage renal disease patients on maintenance hemodialysis, patients with ARF had significantly higher plasma levels of all measured cytokines. Additionally, the proinflammatory cytokines IL-6 and IL-8 were significantly higher in nonsurvivors versus survivors [median 234.7 (interdecile range 64.8 to 1775.9) pg/mL vs. 113.5 (46.1 to 419.3) pg/mL, P= 0.02 for IL-6; 35.5 (14.1 to 237.9) pg/mL vs. 21.2 (8.5 to 87.1) pg/mL, P= 0.03 for IL-8]. The anti-inflammatory cytokine IL-10 was also significantly higher in nonsurvivors [3.1 (0.5 to 41.9) pg/mL vs. 2.4 (0.5 to 16.9) pg/mL, P= 0.04]. For each natural log unit increase in the levels of IL-6, IL-8, and IL-10, the odds of death increased by 65%, 54%, and 34%, respectively, corresponding to increases in relative risk of approximately 30%, 25%, and 15%. The presence or absence of SIRS or sepsis was not a major determinant of plasma cytokine concentration in this group of patients.
There is evidence of ongoing SIRS with concomitant CARS in critically ill patients with ARF, with higher levels of plasma IL-6, IL-8, and IL-10 in patients with ARF who die during hospitalization. Strategies to modulate inflammation must take into account the complex cytokine biology in patients with established ARF.
Kidney International 05/2004; 65(4):1357-65. · 6.61 Impact Factor
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ABSTRACT: Acute renal failure (ARF) is associated strongly with in-hospital mortality and morbidity. Previous clinical trials of ARF have been hampered by the heterogeneous population affected, difficulty defining ARF, delays in identification of ARF, and significant comorbid conditions, among other factors.
The Program to Improve Care in Acute Renal Disease (PICARD) phase I was a multicenter cohort study aimed to identify clinical characteristics and practice patterns associated with adverse and favorable outcomes in patients with ARF in intensive care units. Although PICARD used no interventions, signed informed consent was required of all study subjects or their proxies.
Signed informed consent was obtained in 645 of 1,243 ARF episodes (52%). The fraction of patients not enrolled and reasons for non-enrollment varied widely across the 5 PICARD centers. Refusal by potential study subjects was infrequent, although the absence of family or proxy (15%) and refusal by family or proxy (18%) accounted for large fractions of non-enrolled subjects. Death (23%) and discharge (11%) before study personnel could evaluate patients were additional important reasons for non-enrollment.
Understanding reasons for non-enrollment may help rationalize mortality and other outcome differences seen in clinical trials and cohort studies that require informed consent compared with historic reports of "all comers" with ARF.
American Journal of Kidney Diseases 10/2003; 42(3):507-12. · 5.43 Impact Factor
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ABSTRACT: Acute renal failure is associated with high mortality and morbidity. Diuretic agents continue to be used in this setting despite a lack of evidence supporting their benefit.
To determine whether the use of diuretics is associated with adverse or favorable outcomes in critically ill patients with acute renal failure.
Cohort study conducted from October 1989 to September 1995.
A total of 552 patients with acute renal failure in intensive care units at 4 academic medical centers affiliated with the University of California. Patients were categorized by the use of diuretics on the day of nephrology consultation and, in companion analyses, by diuretic use at any time during the first week following consultation.
All-cause hospital mortality, nonrecovery of renal function, and the combined outcome of death or nonrecovery.
Diuretics were used in 326 patients (59%) at the time of nephrology consultation. Patients treated with diuretics on or before the day of consultation were older and more likely to have a history of congestive heart failure, nephrotoxic (rather than ischemic or multifactorial) origin of acute renal failure, acute respiratory failure, and lower serum urea nitrogen concentrations. With adjustment for relevant covariates and propensity scores, diuretic use was associated with a significant increase in the risk of death or nonrecovery of renal function (odds ratio, 1.77; 95% confidence interval, 1.14-2.76). The risk was magnified (odds ratio, 3.12; 95% confidence interval, 1.73-5.62) when patients who died within the first week following consultation were excluded. The increased risk was borne largely by patients who were relatively unresponsive to diuretics.
The use of diuretics in critically ill patients with acute renal failure was associated with an increased risk of death and nonrecovery of renal function. Although observational data prohibit causal inference, it is unlikely that diuretics afford any material benefit in this clinical setting. In the absence of compelling contradictory data from a randomized, blinded clinical trial, the widespread use of diuretics in critically ill patients with acute renal failure should be discouraged.
JAMA The Journal of the American Medical Association 12/2002; 288(20):2547-53. · 30.03 Impact Factor
