Plasma inflammatory and apoptosis markers are associated with dialysis dependence and death among critically ill patients receiving renal replacement therapy.

BACKGROUND: Survivors of critical illness complicated by acute kidney injury requiring renal replacement therapy (RRT) are at an increased risk of dialysis dependence and death but the mechanisms are unknown. METHODS: In a multicenter, prospective, cohort study of 817 critically ill patients receiving RRT, we examined association between Day 1 plasma inflammatory [interleukin (IL)-1ß, IL-6, IL-8, IL-10 and IL-18; macrophage migration inhibitory factor (MIF) and tumor necrosis factor]; apoptosis [tumor necrosis factor receptor (TNFR)-I and TNFR-II and death receptor (DR)-5]; and growth factor (granulocyte macrophage colony stimulating factor) biomarkers and renal recovery and mortality at Day 60. Renal recovery was defined as alive and RRT independent. RESULTS: Of 817 participants, 36.5% were RRT independent and 50.8% died. After adjusting for differences in demographics, comorbid conditions; premorbid creatinine; nephrotoxins; sepsis; oliguria; mechanical ventilation; RRT dosing; and severity of illness, increased concentrations of plasma IL-8 and IL-18 and TNFR-I were independently associated with slower renal recovery [adjusted hazard ratio (AHR) range for all markers, 0.70-0.87]. Higher concentrations of IL-6, IL-8, IL-10 and IL-18; MIF; TNFR-I and DR-5 were associated with mortality (AHR range, 1.16-1.47). In an analysis of multiple markers simultaneously, increased IL-8 [AHR, 0.80, 95% confidence interval (95% CI) 0.70-0.91, P < 0.001] and TNFR-I (AHR, 0.63, 95% CI 0.50-0.79, P < 0.001) were associated with slower recovery, and increased IL-8 (AHR, 1.26, 95% CI 1.14-1.39, P < 0.001); MIF (AHR, 1.18, 95% CI 1.08-1.28, P < 0.001) and TNFR-I (AHR, 1.26, 95% CI 1.02-1.56, P < 0.03) were associated with mortality. CONCLUSIONS: Elevated plasma concentrations of inflammatory and apoptosis biomarkers are associated with RRT dependence and death. Our data suggest that future interventions should investigate broad-spectrum immune-modulation to improve 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.

Intensity of renal support in critically ill patients with acute kidney injury.

BACKGROUND: The optimal intensity of renal-replacement therapy in critically ill patients with acute kidney injury is controversial. METHODS: We randomly assigned critically ill patients with acute kidney injury and failure of at least one nonrenal organ or sepsis to receive intensive or less intensive renal-replacement therapy. The primary end point was death from any cause by day 60. In both study groups, hemodynamically stable patients underwent intermittent hemodialysis, and hemodynamically unstable patients underwent continuous venovenous hemodiafiltration or sustained low-efficiency dialysis. Patients receiving the intensive treatment strategy underwent intermittent hemodialysis and sustained low-efficiency dialysis six times per week and continuous venovenous hemodiafiltration at 35 ml per kilogram of body weight per hour; for patients receiving the less-intensive treatment strategy, the corresponding treatments were provided thrice weekly and at 20 ml per kilogram per hour. RESULTS: Baseline characteristics of the 1124 patients in the two groups were similar. The rate of death from any cause by day 60 was 53.6% with intensive therapy and 51.5% with less-intensive therapy (odds ratio, 1.09; 95% confidence interval, 0.86 to 1.40; P=0.47). There was no significant difference between the two groups in the duration of renal-replacement therapy or the rate of recovery of kidney function or nonrenal organ failure. Hypotension during intermittent dialysis occurred in more patients randomly assigned to receive intensive therapy, although the frequency of hemodialysis sessions complicated by hypotension was similar in the two groups. CONCLUSIONS: Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour. (ClinicalTrials.gov number, NCT00076219.)

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.

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.

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, 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.

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.

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.

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.

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.

Severe renal dysfunction complicating cardiogenic shock is not a contraindication to mechanical support as a bridge to cardiac transplantation.

OBJECTIVES: This study investigated outcomes in patients with cardiogenic shock and severe renal dysfunction treated with ventricular assist devices (VAD) as a bridge to cardiac transplantation. BACKGROUND: Previous reports have documented poor survival in patients with cardiogenic shock and severe renal dysfunction treated with VAD. METHODS: We surveyed 215 consecutive patients who received a VAD from 1992 to 2000 and selected patients who had a serum creatinine > or =3.0 mg/dl at the time of VAD placement. Demographic, laboratory, and clinical outcome data were collected. RESULTS: Eighteen patients met the inclusion criteria. Mean serum creatinine at the time of VAD placement was 4.0 +/- 0.7 mg/dl (range 3.0 to 5.2 mg/dl). Seven patients required temporary renal support with continuous venovenous hemodialysis (CVVHD). Eleven patients underwent cardiac transplantation. At six months post-transplantation, mean serum creatinine was 2.0 +/- 0.6 mg/dl (range 1.3 to 3.5 mg/dl). None of the transplanted patients required subsequent renal support. Seven patients died with a VAD before transplantation. Three died early (<1 month) after VAD placement, and all three required CVVHD until death. Four patients survived for >1 month after VAD placement; all four had resolution of renal dysfunction with mean serum creatinine of 1.9 +/- 1.2 mg/dl (range 0.8 to 3.6 mg/dl) without the need for renal support. Overall 30-day and six-month survival after VAD placement, survival to transplantation, and survival one year post-transplantation were similar to patients without severe renal dysfunction. CONCLUSIONS: Contemporary use of VAD leads to resolution of severe renal dysfunction in most cardiogenic shock patients and comparable long-term outcomes to patients without renal dysfunction.

A randomized controlled trial comparing intermittent with continuous dialysis in patients with ARF.

BACKGROUND: Despite the widespread use of continuous renal replacement therapy in critically ill patients with acute renal failure (ARF), there are few data supporting its benefits over conventional intermittent hemodialysis (IHD). We sought to analyze differences in survival between modalities in a study that compared continuous venovenous hemodialysis (CVVHD) with IHD. METHODS: Eighty critically ill patients with ARF requiring dialysis were randomized after stratification by severity of illness to treatment with CVVHD or IHD. RESULTS: There were no differences in survival or renal recovery between groups. In patients who died, mean survival time was 10.7 +/- 11.2 days for the IHD group versus 14.3 +/- 16.1 days for the CVVHD group (P = not significant). There was greater net volume removal in the CVVHD group during 72 hours. Declines in urine output during 72 hours were similar between groups. Mean arterial pressure off and on dialysis therapy was analyzed retrospectively. There was a significant decrease in mean arterial pressure for patients on IHD therapy not seen in those on CVVHD therapy, but this did not lead to a survival advantage. CONCLUSION: Despite greater volume control, CVVHD did not lead to an improvement in survival, preservation of urine output, or renal recovery compared with IHD in patients with ARF.

Dialyzer fiber bundle volume and kinetics of solute removal in continuous venovenous hemodialysis.

The relationship between dialyzer fiber bundle volume (FBV), dialyzer life span, and small-solute clearance has yet to be clearly defined in continuous venovenous hemodialysis (CVVHD). This study sought to define this relationship using novel ultrasound dilution technology. We studied 55 sessions in 31 intensive care unit patients on CVVHD therapy. A session was defined as the life span of a single dialyzer. The following variables were assessed every 6 hours throughout each session, starting within 1 hour of initiation of that session: FBV, access recirculation, extracorporeal blood flow rate, effluent (EUN) to blood urea nitrogen (BUN) concentration ratio, effluent creatinine to blood creatinine concentration ratio, and urea nitrogen and creatinine clearances. Data were analyzed using random-effects linear models to estimate trends. Several dialysis-related and solute-removal parameters were analyzed for association with each other. Systemic or dialysis circuit heparin was administered in 28 of 55 sessions. One hundred seventy sets of FBV, 101 sets of urea clearance, and 102 sets of creatinine clearance measurements were performed. There was a declining trend for FBV (0.8 mL/h), heart rate (0.25 beats/min/h), and measured blood flow (0.33 mL/min/h; P < 0.05). Apart from dialysate inflow rate (P = 0.044), there was no significant correlation with EUN-BUN ratio. Session duration was associated with dialysis access site; the femoral access provided longer dialysis sessions than subclavian and internal jugular accesses (P = 0.029). We conclude that small-solute removal remains stable over the course of our CVVHD system life spans despite significant loss of hemodialyzer FBV.

ARF after open-heart surgery: Influence of gender and race.

BACKGROUND: Both acute renal failure (ARF) and female sex are strongly associated with mortality after open-heart surgery. This study analyzes the effect of sex and race on the incidence of ARF after open-heart surgery and its influence on mortality. METHODS: A total of 24,660 patients underwent open-heart surgery at the Cleveland Clinic Foundation (Cleveland, OH) from 1993 to 2000. The primary outcome was ARF defined as ARF requiring dialysis, 50% or greater decline in glomerular filtration rate (GFR) not requiring dialysis, or 50% or greater decline in GFR relative to baseline or requirement of dialysis. The secondary outcome was all-cause hospital mortality. RESULTS: The overall frequency of ARF requiring dialysis after open-heart surgery was 1.82%. The frequency was greater in women (2.36%) than men (1.60%; P < 0.0001) and blacks (2.94%) than nonblacks (1.70%; P < 0.0001) by univariate analysis. By multivariate analysis, risk for ARF requiring dialysis in women was 1.61 (confidence interval [CI], 1.27 to 2.05; P < 0.0001), but race was not a risk factor. The overall postoperative mortality rate was 2.2%, and for patients with ARF requiring dialysis, it was 61.2% (women, 68.6% versus men, 56.5%; P = 0.01) with an odds ratio of 49.29, whereas in patients with ARF not requiring dialysis, it was 14.1% (women, 13.3% versus men 14.6%; P = 0.63) with an odds ratio of 7.18. CONCLUSION: Female sex is an independent risk factor for developing ARF after open-heart surgery. The influence of race on risk for ARF is less clear. Regardless of its definition, ARF is strikingly associated with a high risk for mortality.

Reasons for non-enrollment in a cohort study of ARF: the Program to Improve Care in Acute Renal Disease (PICARD) experience and implications for a clinical trials network.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Evaluation of the harmonized alert sensing technology device for hemodynamic monitoring in chronic hemodialysis patients.

The Harmonized Alert Sensing Technology (HASTE) device was developed to overcome the primary shortcomings of interval based noninvasive blood pressure (BP) monitoring. This study was conducted to assess the reliability of the HASTE system compared with standard cuff BP values in patients on hemodialysis. A total of 1,370 HASTE measurements were compared with oscillometric standard cuff systolic BP values in 42 sessions of 15 patients on hemodialysis. The average discrepancy between the HASTE and cuff systolic BP was 1.41 +/- 16.90 mm Hg. Compared with cuff measurements, 31% of systolic BP fell within a range of 5 mm Hg difference, 57% of systolic BP fell within 10 mm Hg, and 73% of systolic BP fell within a 15 mm Hg band. According to British Hypertension Society standards or Association for the Advancement of Medical Instrumentation criteria, the current HASTE method did not perform well. Technology to provide noninvasive hemodynamic monitoring is, however, in its developmental stage. The effort at continuous systolic pressure monitoring using existing, readily available, and frequently used techniques is exciting. Although the HASTE system as currently configured and calibrated did not adequately perform, variations in site analysis and conversion factors may increase pressure sensitivity and tracking over the course of a standard dialysis treatment.

Predicting acute renal failure after cardiac surgery: validation and re-definition of a risk-stratification algorithm.

BACKGROUND: Acute renal failure (ARF) after cardiac surgery is associated with significant morbidity and mortality, irrespective of the need for dialysis. Previous studies have attempted to identify predictors of ARF and develop risk stratification algorithms. This study aims to validate the algorithm in an independent cohort of patients that includes a significant proportion of female and black patients and compares two different definitions of renal outcome. METHODS: A large single center cardiac surgery database was examined (n, 24,660; 1993-2000) which included 29.9% females and 3.7% black patients. Post-operative ARF was defined as: a) ARF requiring dialysis, b) > 50% reduction in creatinine clearance relative to baseline or requiring dialysis. Clinical variables related to baseline renal function and cardiovascular disease were used in recursive partitioning analysis for both outcome definitions. Chi-square goodness of fit analysis was performed to validate the algorithm. RESULTS: The frequency of post-operative ARF requiring dialysis ranged between 0.5 and 15.5% based on the risk categories with the area under the receiver operating characteristic (ROC) curve of 0.78. Using the more inclusive definition of ARF, the frequency was significantly higher ranging from 2.6 to 25%(P < 0.001) with an area under ROC curve of 0.65. CONCLUSIONS: The renal risk stratification algorithm is valid in predicting post-operative ARF in an independent cohort of patients, well represented by differences in gender and race. Since the need for dialysis remains subjective, a more objective and inclusive definition of ARF may help in identifying a larger number of patients 'at-risk'.

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.