Anticoagulation, delivered dose and outcomes in CRRT: The program to improve care in acute renal disease (PICARD).

Delivered dialysis dose by continuous renal replacement therapies (CRRT) depends on circuit efficacy, which is influenced in part by the anticoagulation strategy. We evaluated the association of anticoagulation strategy used on solute clearance efficacy, circuit longevity, bleeding complications, and mortality. We analyzed data from 1740 sessions 24 h in length among 244 critically ill patients, with at least 48 h on CRRT. Regional citrate, heparin, or saline flushes was variably used to prevent or attenuate filter clotting. We calculated delivered dose using the standardized Kt/Vurea . We monitored filter efficacy by calculating effluent urea nitrogen/blood urea nitrogen ratios. Filter longevity was significantly higher with citrate (median 48, interquartile range [IQR] 20.3-75.0 hours) than with heparin (5.9, IQR 8.5-27.0 hours) or no anticoagulation (17.5, IQR 9.5-32 hours, P < 0.0001). Delivered dose was highest in treatments where citrate was employed. Bleeding complications were similar across the three groups (P = 0.25). Compared with no anticoagulation, odds of death was higher with the heparin use (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.02-3.32; P = 0.033), but not with citrate (OR 1.02 95% CI 0.54-1.96; P = 0.53). Relative to heparin or no anticoagulation, the use of regional citrate for anticoagulation in CRRT was associated with significantly prolonged filter life and increased filter efficacy with respect to delivered dialysis dose. Rates of bleeding complications, transfusions, and mortality were similar across the three groups. While these and other data suggest that citrate anticoagulation may offer superior technical performance than heparin or no anticoagulation, adequately powered clinical trials comparing alternative anticoagulation strategies should be performed to evaluate overall safety and efficacy.

Toward the optimal dose metric in continuous renal replacement therapy.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Extracorporeal ultrafiltration vs. conventional diuretic therapy in advanced decompensated heart failure.

Compared with conventional diuretic (CD) therapy, ultrafiltration (UF) is associated with greater weight loss and fewer re-hospitalizations in patients admitted with decompensated heart failure (HF). Concerns have been raised regarding its safety and efficacy in patients with more advanced heart failure. The authors conducted a single-center, prospective, randomized controlled trial in patients with advanced HF admitted to an intensive care unit for hemodynamically guided therapy, comparing UF (n=17) with CD (n=19) at admission. The primary end point was the time required for pulmonary capillary wedge pressure (PCWP) to be maintained at a value of ≤18 mm Hg for at least 4 consecutive hours. Secondary end points included levels of cytokines and neurohormones, as well as several clinical outcomes. In our study cohort, the time to achieve the primary end point was lower in the UF group but did not reach statistical significance (P = .08). UF resulted in greater weight reduction, higher total volume removed, and shorter hospital length of stay. There were no differences in kidney function, biomarkers, or adverse events. In patients with advanced HF under hemodynamically tailored therapy, UF can be safely performed to achieve higher average volume removed than CD therapy without leading to adverse outcomes.

Predictive models for acute kidney injury following cardiac surgery.

BACKGROUND: Accurate prediction of cardiac surgery-associated acute kidney injury (AKI) would improve clinical decision making and facilitate timely diagnosis and treatment. The aim of the study was to develop predictive models for cardiac surgery-associated AKI using presurgical and combined pre- and intrasurgical variables. STUDY DESIGN: Prospective observational cohort. SETTINGS & PARTICIPANTS: 25,898 patients who underwent cardiac surgery at Cleveland Clinic in 2000-2008. PREDICTOR: Presurgical and combined pre- and intrasurgical variables were used to develop predictive models. OUTCOMES: Dialysis therapy and a composite of doubling of serum creatinine level or dialysis therapy within 2 weeks (or discharge if sooner) after cardiac surgery. RESULTS: Incidences of dialysis therapy and the composite of doubling of serum creatinine level or dialysis therapy were 1.7% and 4.3%, respectively. Kidney function parameters were strong independent predictors in all 4 models. Surgical complexity reflected by type and history of previous cardiac surgery were robust predictors in models based on presurgical variables. However, the inclusion of intrasurgical variables accounted for all explained variance by procedure-related information. Models predictive of dialysis therapy showed good calibration and superb discrimination; a combined (pre- and intrasurgical) model performed better than the presurgical model alone (C statistics, 0.910 and 0.875, respectively). Models predictive of the composite end point also had excellent discrimination with both presurgical and combined (pre- and intrasurgical) variables (C statistics, 0.797 and 0.825, respectively). However, the presurgical model predictive of the composite end point showed suboptimal calibration (P < 0.001). LIMITATIONS: External validation of these predictive models in other cohorts is required before wide-scale application. CONCLUSIONS: We developed and internally validated 4 new models that accurately predict cardiac surgery-associated AKI. These models are based on readily available clinical information and can be used for patient counseling, clinical management, risk adjustment, and enrichment of clinical trials with high-risk participants.

Renal replacement therapy for acute renal injury: we need better therapy.

Dialytic support of patients with acute kidney injury (AKI) has taken on an important aspect of critical care medicine. Increased morbidity and mortality associated with the AKI syndrome and the lack of great improvement despite the addition of differing dialytic techniques (and intensity) speaks to the need for a re-evaluation of renal support. Continuous therapies have brought greater control of urea, volume, acid/base status and enhanced hemodynamic stability over the traditional intermittent approaches. However, the incremental efficiency achieved by intense dialysis has not improved outcome in patients with AKI. We need to move beyond urea-based decision-making and pursue clinically relevant goal-targeted therapies. The latter will invariably lead to re-evaluation of the timing, intensity and duration of therapy, which traditionally have been mainly solute driven. Whether this will be via specifically designed membrane extracorporeal support or focused drug or cell-based therapies is currently under consideration. Volume determination and variability remain another moving target for therapy. Machine-generated feedback mechanisms responding to specific endpoints or compartmental changes are also under development. Improved diagnostic criteria, especially in septic-induced renal dysfunction, may allow for specific adsorption techniques using a variety of membrane-imbedded substances from activated charcoal to polymyxin B to newer resins. Cascade apheretic techniques have been attempted in specific disease entities to capture a larger group of potential toxins, while nanoporous membranes have been developed to remove a specific sized entity. Bio-artificial systems utilizing functioning cells should help with the recovery of injured cell and cell protection in those yet viable. Simple maneuvers to reduce the cost of delivered therapy, and the development of a more robust severity scoring system to help address the futile use of technology would be of great help. Greater attention to elements lost during intervention which may require supplementation, as well as the development of on-line replacement technology and coagulation friendly systems, will help eliminate much of the current cost of therapy.

Model to predict mortality in critically ill adults with acute kidney injury.

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) requiring dialysis is associated with high mortality. Most prognostic tools used to describe case complexity and to project patient outcome lack predictive accuracy when applied in patients with AKI. In this study, we developed an AKI-specific predictive model for 60-day mortality and compared the model to the performance of two generic (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation II [APACHE II]) scores, and a disease specific (Cleveland Clinic [CCF]) score. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from 1122 subjects enrolled in the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study; a multicenter randomized trial of intensive versus less intensive renal support in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 VA- and university-affiliated centers. RESULTS: The 60-day mortality was 53%. Twenty-one independent predictors of 60-day mortality were identified. The logistic regression model exhibited good discrimination, with an area under the receiver operating characteristic (ROC) curve of 0.85 (0.83 to 0.88), and a derived integer risk score yielded a value of 0.80 (0.77 to 0.83). Existing scoring systems, including APACHE II, SOFA, and CCF, when applied to our cohort, showed relatively poor discrimination, reflected by areas under the ROC curve of 0.68 (0.64 to 0.71), 0.69 (0.66 to 0.73), and 0.65 (0.62 to 0.69), respectively. CONCLUSIONS: Our new risk model outperformed existing generic and disease-specific scoring systems in predicting 60-day mortality in critically ill patients with AKI. The current model requires external validation before it can be applied to other patient populations.

Does early initiation of continuous renal replacement therapy affect outcome: experience in a tertiary care center.

BACKGROUND: Acute kidney injury (AKI) requiring dialysis commonly occurs in critically ill patients and is associated with high mortality. Factors impacting outcomes of individuals with AKI who underwent continuous renal replacement therapy (CRRT), including early versus late initiation and duration of CRRT, were examined. METHODS: Survival and recovery of renal function for patients with AKI in the intensive care unit were retrospectively examined over a 7-year period. Factors associated with mortality and renal recovery were analyzed based on severity of illness as defined by Cleveland Clinic Foundation (CCF) score. Univariate and multivariate logistic regression analysis with backward elimination was performed to determine the most significant risk factors. RESULTS: Of patients who underwent CRRT, 230/330 met inclusion criteria. During index admission 112/230 (48.7%) patients died. Median survival was 15.5 days [95% confidence interval (12.0, 18.0)]. Among survivors, renal recovery occurred in 84/118 (71.2%). Renal recovery overall was observed in 90/230 subjects (39.13%). A higher baseline CCF score correlated with higher mortality and lower probability of renal recovery. Patients initiated on CRRT > 6 days after AKI diagnosis had significantly higher mortality compared with those initiated earlier (odds ratio = 11.66, p = 0.0305). Patients receiving CRRT >10 days had a higher mortality rate compared with those with shorter exposure (71.3% vs. 45.5%, respectively, p = 0.012). CONCLUSIONS: CRRT remains an important dialysis modality in hemodynamically unstable patients with AKI. Mortality in these patients continues to be high. Renal recovery is high in survivors. Delay in initiation and length of CRRT exposure may portend poorer prognosis.

Hypophosphatemia during continuous hemodialysis is associated with prolonged respiratory failure in patients with acute kidney injury.

BACKGROUND: Hypophosphatemia is common in critically ill patients and has been associated with generalized muscle weakness, ventilatory failure and myocardial dysfunction. Continuous renal replacement therapy causes phosphate depletion, particularly with prolonged and intensive therapy. In a prospective observational cohort of critically ill patients with acute kidney injury (AKI), we examined the incidence of hypophosphatemia during dialysis, associated risk factors and its relationship with prolonged respiratory failure and 28-day mortality. METHODS: This is a single-center prospective observational study. Included in the study were 321 patients with AKI on continuous dialysis as initial treatment modality. RESULTS: Four per cent of the patients had a phosphate level <2 mg/dL at initiation and 27% during dialysis. Low baseline phosphate was associated with older age, female gender, parenteral nutrition, vasopressor support, low calcium, and high urea, bilirubin and creatinine, whereas hypophosphatemia during dialysis correlated with the ischemic acute tubular necrosis etiology of renal failure, intensive dose and longer therapy. Serum phosphate decline during dialysis was associated with higher incidence of prolonged respiratory failure requiring tracheostomy [odds ratio (OR) = 1.81; 95% confidence interval (CI) = 1.07-3.08], but not 28-day mortality (OR = 1.16; 95% CI = 0.76-1.77) in multivariable analysis. CONCLUSIONS: Hypophosphatemia occurs frequently during dialysis, particularly with long and intensive treatment. Decline in serum phosphate levels during dialysis is associated with higher incidence of prolonged respiratory failure requiring tracheostomy, but not 28-day mortality.

Sepsis as a cause and consequence of acute kidney injury: Program to Improve Care in Acute Renal Disease.

PURPOSE: Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI. METHODS: We analyzed data from 618 critically ill patients enrolled in a multicenter observational study of AKI (PICARD). Patients were stratified according to their sepsis status and timing of incident sepsis relative to AKI diagnosis. RESULTS: We determined the associations among sepsis, clinical characteristics, provision of dialysis, in-hospital mortality, and length of stay (LOS), comparing outcomes among patients according to their sepsis status. Among the 611 patients with data on sepsis status, 174 (28%) had sepsis before AKI, 194 (32%) remained sepsis-free, and 243 (40%) developed sepsis a median of 5 days after AKI. Mortality rates for patients with sepsis developing after AKI were higher than in sepsis-free patients (44 vs. 21%; p < 0.0001) and similar to patients with sepsis preceding AKI (48 vs. 44%; p = 0.41). Compared with sepsis-free patients, those with sepsis developing after AKI were also more likely to be dialyzed (70 vs. 50%; p < 0.001) and had longer LOS (37 vs. 27 days; p < 0.001). Oliguria, higher fluid accumulation and severity of illness scores, non-surgical procedures after AKI, and provision of dialysis were predictors of sepsis after AKI. CONCLUSIONS: Sepsis frequently develops after AKI and portends a poor prognosis, with high mortality rates and relatively long LOS. Future studies should evaluate techniques to monitor for and manage this complication to improve overall prognosis.

Effluent volume in continuous renal replacement therapy overestimates the delivered dose of dialysis.

BACKGROUND AND OBJECTIVES: 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

INTRODUCTION: Serum 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. METHODS: In 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. RESULTS: The 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. CONCLUSIONS: In 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.

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.

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.

Alkalemia during continuous renal replacement therapy and mortality in critically ill patients.

OBJECTIVE: Acid-base disorders are common in critically ill patients. Once continuous renal replacement therapy (CRRT) is initiated, it becomes a major determinant of acid-base status. We hypothesized that therapy-induced alkalemia and alkalosis is associated with increased mortality. PATIENTS: The CCF-ARF Registry (1995-01) was used to identify 405 patients supported with bicarbonate based continuous hemodialysis. Proportion of days with an elevated pH to the number of days with normal pH was used to assess the association of alkalemia and the number of days with alkalemia, and mortality. Multivariable analyses were used to adjust for days with acidosis, and other relevant covariates. MAIN RESULTS: Serum bicarbonate and pH levels plateau after 48 hrs of CRRT. Study subjects had on average 1.5 +/- 2.9 days where pH was greater than 7.45, and .4 days where serum bicarbonate level was greater than 28 mmol/L, during a median of 9 days of CRRT. Daily dialysis dose was inversely associated with the number of days with a low serum bicarbonate level, but was not associated with increased frequency of an elevated pH or serum bicarbonate level. Increasing proportion of days with elevated pH or serum bicarbonate was not associated with increased mortality in multivariable analysis. CONCLUSIONS: Alkalemia and alkalosis occur frequently during CRRT, but they are not associated with increased mortality. Persistent acidosis and acidemia while on CRRT was a strong predictor of poor outcome.

Dosing intermittent haemodialysis in the intensive care unit patient with acute renal failure--estimation of urea removal and evidence for the regional blood flow model.

BACKGROUND: Blood-side dosing methods may overestimate urea removal in comparison to dialysate-side measurements during intermittent HD (IHD) for acute renal failure (ARF). The present study sought to quantify this mass balance error (MBE) and explore potential explanatory factors. METHODS: Prospective, formal, blood-side urea kinetic modelling was performed in serial sessions (n = 42) in 18 intensive care unit ARF patients. Three blood-side estimates of urea removal were calculated and these were compared to urea removal derived from fractional dialysate sampling and use of an on-line urea monitor. We also examined urea rebound in these patients, as expressed by the intercompartmental urea clearance (Kc), and in a subset of patients examined the relation of Kc to cardiac output and systemic vascular resistance (SVR). RESULTS: The mean % MBE (MBE = blood - dialysate-estimated urea removal) was about 9% using conventional two-pool modelling based on a 60-min post-dialysis blood urea nitrogen (BUN) with or without the use of one or more intra-dialytic BUN values. The extent of MBE could not be explained by the clinical or dialytic variables that were measured. Part of the MBE error was due to overestimation of the intradialytic BUN profile, because model-independent profiling of intra-dialytic BUN values to compute urea removal reduced the MBE to approximately 6%. The log Kc was correlated with cardiac output and showed trends towards an inverse correlation with SVR. CONCLUSIONS: Classical, two-pool, blood-side UKM produces a modest overestimate of urea removal in IHD for critically ill ARF patients. The source of this small, residual MBE is unknown. The amount of urea rebound, as reflected by Kc, varied among patients and associated with cardiac output and SVR, as predicted by the regional blood flow model.

Efficacy and safety of renal tubule cell therapy for acute renal failure.

The mortality rate for patients with acute renal failure (ARF) remains unacceptably high. Although dialysis removes waste products and corrects fluid imbalance, it does not perform the absorptive, metabolic, endocrine, and immunologic functions of normal renal tubule cells. The renal tubule assist device (RAD) is composed of a conventional hemofilter lined by monolayers of renal cells. For testing whether short-term (up to 72 h) treatment with the RAD would improve survival in patients with ARF compared with conventional continuous renal replacement therapy (CRRT), a Phase II, multicenter, randomized, controlled, open-label trial involving 58 patients who had ARF and required CRRT was performed. Forty patients received continuous venovenous hemofiltration + RAD, and 18 received CRRT alone. The primary efficacy end point was all-cause mortality at 28 d; additional end points included all-cause mortality at 90 and 180 d, time to recovery of renal function, time to intensive care unit and hospital discharge, and safety. At day 28, the mortality rate was 33% in the RAD group and 61% in the CRRT group. Kaplan-Meier analysis revealed that survival through day 180 was significantly improved in the RAD group, and Cox proportional hazards models suggested that the risk for death was approximately 50% of that observed in the CRRT-alone group. RAD therapy was also associated with more rapid recovery of kidney function, was well tolerated, and had the expected adverse event profile for critically ill patients with ARF.

Improved survival in acute kidney injury after cardiac surgery.

BACKGROUND: The overall incidence of acute kidney injury (AKI) or mortality after cardiac surgery is low, but mortality in patients with AKI remains high. Effects of factors such as change in comorbid disease burden, intraoperative factors, or postoperative complications on trends in the incidence of AKI and associated mortality after cardiac surgery were not examined. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 34,562 cardiac surgeries were performed from 1993 to 2002; only the first surgical procedure was considered (N = 33,217). PREDICTOR, OUTCOMES, & MEASUREMENTS: AKI was defined as a composite outcome of a 50% or greater decrease in postoperative glomerular filtration rate or requirement of dialysis (AKI-D). Mortality was defined as postoperative hospital mortality. We examined effects of the predictors AKI and year of surgery on mortality after accounting for preoperative risk factors and serious postoperative complications. RESULTS: Between the first and second halves of the study period (1993 to 2002), the incidence of AKI increased from 5.1% to 6.6%, but the associated mortality rate decreased from 32% to 23% (P < 0.0001). Similarly, the incidence of AKI-D also increased from 1.5% to 2.0%, with a decrease in associated mortality from 61% to 49% (P < 0.01). In a risk-adjusted model, mortality in patients with AKI significantly decreased over time. Patients with AKI-D and with other organ system failures did not show improvement in survival over time. A preoperative history of congestive heart failure was associated significantly with a decrease in mortality risk over time, particularly in patients requiring dialysis. LIMITATIONS: Single-center, retrospective, observational cohort design. CONCLUSION: The incidence of AKI after cardiac surgery has increased over time. Although the adjusted risk of mortality decreased in patients with AKI without other postoperative complications, it is unchanged in those with multiorgan system failure.

Machine-generated bicarbonate dialysate for continuous therapy: a prospective, observational cohort study.

BACKGROUND: In 1995, we described the technique of adapting a haemodialysis (HD) machine to produce a composition-adjustable, bicarbonate-based fluid (as our primary source for dialysate) for continuous HD in intensive care unit (ICU) patients with acute renal failure (ARF). The following studies the clinical effects, biochemical changes and economic costs of this practice in a large cohort of patients at a single centre over the last 10 years. METHODS: The CCF-ARF Support Registry (1995-2001) was used to identify 405 patients initially supported with bicarbonate continuous HD. The registry is a prospective, observational cohort database that captures demographic, dialysis therapy, laboratory and outcome data. All supported ARF patients were recorded from 1995-98, and then one in five patients from 1999 to 2001. We also reviewed records of the individual dialysis procedures, dialysate disposal, dialysate monitoring tests and specific costs. RESULTS: Continuous HD was performed for 1292 +/- 587 days from 1994 to 2004. Demographics [age 59.57 +/- 14.41 years, weight 84.2 +/- 24 kg, male 65%, chronic kidney disease (CKD) 34%] and ICU mortality (60.5%) were comparable to other reported series. Day 4 solute [BUN 52.3 mg/dl (95% CI 49.6-54.9), creatinine 2.79 mg/dl (95% CI 2.64-2.95)], electrolyte and acid-base balance [bicarbonate 24.12 mmol/l (95% CI 23.7-24.6)] were well controlled. Dialysate monitoring revealed no positive cultures or elevated endotoxin levels. Variable-composition dialysate was achieved and delivered to all patients without adverse consequences. The cost of dialysate actually declined over time (1995 = $0.91/l, 2005 = $0.67/l). CONCLUSION: We have demonstrated that ICU ARF patients can be safely, effectively and economically supported with continuous HD using this source.

Renal assist device and treatment of sepsis-induced acute kidney injury in intensive care units.

Acute kidney injury (AKI) is a frequent and serious complication of sepsis in ICU patients and is associated with a very high mortality. Despite the advent of sophisticated renal replacement therapies (RRT) employing high-dose hemofiltration and high-flux membranes, mortality and morbidity from sepsis-induced AKI remained high. Moreover, these dialytic modalities could not substitute for the important functions of renal tubular cells in decreasing sepsis-induced AKI biological dysregulations. The results from the in vitro and preclinical animal model studies were very intriguing and led to the development of a bioartificial kidney consisting of a renal tubule assist device containing human proximal tubular cells (RAD) added in tandem to a continuous venovenous hemofiltration circuit. The results from the phase I safety trial and the recent phase II clinical trial showed that the RAD not only can replace many of the indispensable biological kidney functions, but also modify the natural history of sepsis-induced AKI by ameliorating patient survival.

Effect of off-pump coronary artery bypass graft surgery on postoperative acute kidney injury and mortality.

OBJECTIVE: Risk of mortality after cardiac surgery is associated with severity of acute kidney injury. The aim of this study is to examine the effect of off-pump coronary artery bypass surgery on the risk of postoperative acute kidney injury and its association with mortality. DESIGN: Observational cohort study. SETTING: Tertiary care center. PATIENTS: Some 10,061 patients underwent coronary artery bypass surgery (1998-2002), of which 1,365 patients underwent off-pump surgery. INTERVENTIONS: Acute kidney injury was defined as either requirement of dialysis or >/=50% decline in postoperative glomerular filtration rate but not requiring dialysis. We compared on- and off-pump surgeries and used propensity score matching to examine the effect of off-pump surgery on acute kidney injury and mortality. MEASUREMENTS AND MAIN RESULTS: We found that 2.6% on-pump and 1.2% off-pump patients developed acute kidney injury requiring dialysis among the 2,370 matched subjects (relative risk, 2.06; 95% confidence interval [CI], 1.36-3.36); 5.0% of on-pump patients suffered a >/=50% decline in glomerular filtration rate compared with 2.5% in off-pump group (relative risk, 2.00; 95% CI, 1.48-2.82). The mortality rate in the matched cohort was 2.3% for on-pump group vs. 0.6% in off-pump group (relative risk, 3.88; 95% CI, 2.29-9.50). Among matched patients with acute kidney injury, the risk of mortality was 13.14 (95% CI, 8.43-30.50) in patients requiring dialysis and 9.33 (95% CI, 4.83-19.00) in those with >/=50% decline in glomerular filtration rate but not requiring dialysis. CONCLUSIONS: Off-pump surgery is associated with a lower risk of developing acute kidney injury (regardless of its definition). The risk of mortality is incremental with worsening degrees of acute kidney injury. Lower risk of acute kidney injury may be one of the factors that offer a survival advantage after off-pump surgery.