Preliminary Report on the Association of Apolipoprotein E Polymorphisms, with Postoperative Peak Serum Creatinine Concentrations in Cardiac Surgical Patients

Background: Renal dysfunction after cardiac surgery occurs in up to 8% of patients and is associated with major increases in morbidity, mortality, and cost. Genetic polymorphisms have been implicated as a factor in the progression of chronic renal disease, but a genetic basis for the development of acute renal impairment has not been investigated. The authors therefore tested the hypothesis that apolipoprotein E alleles are associated with different postoperative changes in serum creatinine after cardiac surgery.

Methods: The authors performed a prospective observational study with use of data from 564 coronary bypass surgical patients who were enrolled in an ongoing investigation of apolipoprotein E genotypes and organ dysfunction at a university hospital between 1989-1999. Renal function was assessed among apolipoprotein E genotype groups by comparisons of preoperative (CrPre), peak in-hospital postoperative (CrMax) and perioperative change (DCr) in serum creatinine values.

Results: The [epsilon]4 allele grouping (E2 = 2/2,2/3,2/4; E3 = 3/3; E4 = 3/4,4/4) was associated with a smaller increase in postoperative serum creatinine (perioperative change: E4, +0.17; E3, +0.26; E4, +0.27 mg/dl) and a lower peak postoperative creatinine than the [epsilon]2 and [epsilon]3 in univariate and multivariate analysis (peak in-hospital postoperative serum creatinine multivariate P = 0.015 vs. [epsilon]3, P = 0.038 vs. [epsilon]2). There was no difference in baseline creatinine among allele groups.     

Preliminary report on the interaction of apolipoprotein E polymorphism with aortic atherosclerosis and acute nephropathy after CABG

Background

Renal dysfunction is a serious complication of cardiac surgery that is highly associated with short- and long-term adverse outcome. While the apolipoprotein E (APOE) ?4 allele has been linked to the occurrence of both postcardiac surgery acute renal injury (?4 favorable) and ascending aortic arteriosclerosis (?4 unfavorable), the role of ?4 in the relationship between these two conditions is unknown. We hypothesized that patients with and without the ?4 allele (E4/non-E4) would have different associations between atheroma burden and postoperative renal dysfunction.

Methods

Ascending, arch, and descending aorta atheromatous burden and APOE status were evaluated for 130 coronary bypass patients. Multivariable analyses were performed for aortic regions to assess the relationship of atheroma burden and APOE ?4 status with peak in-hospital postoperative serum creatinine. All p < 0.05 were considered significant.

Results

We found an interaction between E4 status (E4/non-E4; 24/106) and atheroma burden, with a much greater predicted peak in-hospital postoperative serum creatinine for increases in ascending aorta atheroma load for non-E4 patients versus E4 patients (beta coefficient −0.13; p = 0.002). We also confirmed the association between ascending aorta atheroma and peak creatinine (beta coefficient 0.11; p = 0.0008), after controlling for E4 status, preoperative creatinine, and the E4-atheroma interaction.

Conclusions

Equivalent ascending aortic atheroma burden is associated with a greater susceptibility to postoperative renal injury among patients undergoing cardiac operation who lack the APOE ?4 allele. Findings may be attributable to APOE-related differences in inflammation, susceptibility to atheroma detachment (eg, during operative aortic manipulation), or renal vulnerability to embolic injury.     

Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery

BACKGROUND: There has been increasing recognition of adverse neurodevelopmental sequelae in some children after repair of congenital heart defects. Even among children with the same cardiac defect, significant interindividual variation exists in developmental outcome. Polymorphisms of apolipoprotein E have been identified as a risk factor for worse neurologic recovery after central nervous system injury. METHODS: A single-institution prospective study of patients 相似文献   

Apolipoprotein E epsilon4 allele and neurobehavioral status after on-pump coronary artery bypass grafting

Abstract Background and Aim: The presence of apolipoprotein E epsilon4 allele is being considered as a risk factor for cognitive decline after cardiac surgery. We sought the effect of apolipoprotein E epsilon4 allele on neurobehavioral status after on-pump coronary artery bypass grafting. Methods: Prior to the operation, neurologic examination and neurobehavioral cognitive status test (COGNISTAT) were performed. Both procedures were repeated on the day of discharge and 3 months after surgery. Apolipoprotein E epsilon4 allele positive and apolipoprotein E epsilon4 allele negative patients' performance on COGNISTAT were compared. Results: There was no statistically significant demographic and operative data difference between two groups. No neurological impairment was observed on examinations. There was no statistically significant neurocognitive decline difference between two groups' postoperative performances. Conclusions: It seems that apolipoprotein E epsilon4 allele may not affect neurobehavioral status in the intermediate period after on-pump coronary artery bypass grafting.     

Influence of apolipoprotein E polymorphisms on serum creatinine levels and predicted glomerular filtration rate in healthy subjects.

BACKGROUND: There are conflicting results regarding the effect of apolipoprotein (ApoE) polymorphisms on the progression of a variety of renal diseases. However, there are no data on the possible effect of the ApoE alleles on serum creatinine levels and predicted glomerular filtration rate (GFR) in healthy subjects. METHODS: 290 apparently healthy individuals were studied. ApoE genotyping was performed by the polymerase chain reaction; the Modification of Diet in Renal Disease equation (MDRD) predicted the GFR. RESULTS: ApoE2 was associated with lower levels of total cholesterol, low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol, as well as with higher levels of triglycerides in our population. Furthermore, the ApoE2 allele was associated with increased serum creatinine levels compared with both the E3 and E4 alleles (1.04+/-0.13 vs 0.92+/-0.13 vs 0.88+/- 0.11 mg/dl, respectively, P = 0.0077), while the MDRD-predicted GFR was decreased in ApoE2 carriers compared with both E3 and E4 carriers (80.3+/-10.2 vs 88.1+/-9.6 vs 89.3+/-9.7 ml/min/1.73 m(2), respectively, P = 0.031). These observations remained significant statistically even if the effect of ApoE polymorphisms on age- and body-mass index-adjusted serum creatinine and MDRD-predicted GFR was separately analysed in both men and women. Although, ApoE4 carriers tended to exhibit lower levels of serum creatinine and higher values of predicted GFR compared with the E3 carries, these differences did not reach statistical significance. CONCLUSIONS: ApoE2 allele seems to be associated with increased serum creatinine levels and decreased MDRD-predicted GFR in healthy subjects.     

Apolipoprotein E genotype and cognitive dysfunction after noncardiac surgery

BACKGROUND: Apolipoprotein E is important in recovery after neuronal damage. The epsilon4 allele of the apolipoprotein E gene has been shown as a risk factor for Alzheimer disease, poor outcome after cerebral injury, and accelerated cognitive decline with normal aging. The authors hypothesized that patients with the epsilon4 allele would have an increased risk of postoperative cognitive dysfunction (POCD) after noncardiac surgery. METHODS: In a multicenter study, a total of 976 patients aged 40 yr and older undergoing noncardiac surgery were tested preoperatively and 1 week and 3 months after surgery with a neuropsychological test battery comprising seven subtests. POCD was defined as a decline in test performance of more than 2 SD from the expected. Apolipoprotein E genotypes were determined by blood sample analysis at a central laboratory. Multivariate logistic regression analysis with POCD as the dependent variable assessed presence of the epsilon4 allele (yes/no) and other possible risk factors. RESULTS: The epsilon4 allele was found in 272 patients. One week after surgery, the incidence of POCD was 11.7% in patients with the epsilon4 allele and 9.9% in patients without the epsilon4 allele (P = 0.41). Three months later, POCD was found in 10.3% of patients with the epsilon4 allele and in 8.4% of patients without the epsilon4 allele (P = 0.40). Multivariate logistic regression analysis did not identify the epsilon4 allele as a risk factor at 1 week (P = 0.33) or 3 months (P = 0.57). CONCLUSIONS: The authors were unable to show a significant association between apolipoprotein E genotype and POCD, but statistical power was limited because of a lower incidence of POCD than expected.     

Renal dysfunction after cardiac surgery with normothermic cardiopulmonary bypass: incidence,risk factors,and effect on clinical outcome

Renal dysfunction is a frequent and severe complication after conventional hypothermic cardiac surgery. Little is known about this complication when cardiopulmonary bypass (CPB) is performed under normothermic conditions (e.g., more than 36 degrees C). Thus, we prospectively studied 649 consecutive patients undergoing coronary artery bypass surgery or valve surgery with normothermic CPB. The association between renal dysfunction (defined as a > or =30% preoperative-to-maximum postoperative increase in serum creatinine level) and perioperative variables was studied by univariate and multivariate analysis. Renal dysfunction occurred in 17% of the patients. Twenty-one (3.2%) patients required dialysis. Independent preoperative predictors of this complication were: advanced age, ASA class >3, active infective endocarditis, radiocontrast agent administration <48 h before surgery, and combined surgery. When all the variables were entered, active infective endocarditis, radiocontrast agent administration, postoperative low cardiac output, and postoperative bleeding were independently associated with renal dysfunction. The in-hospital mortality rate was 27.5% when this complication occurred (versus 1.6%; P < 0.0001). Furthermore, postoperative renal dysfunction was independently associated with in-hospital mortality (odds ratio, 4.1 [95% confidence interval, 1.3-12.8]). We conclude that advanced age, active endocarditis, and recent (within 48 h) radiocontrast agent administration, as well as postoperative hemodynamic dysfunction, are more consistently predictive of postoperative renal dysfunction than CPB factors. IMPLICATIONS: We found that postoperative renal dysfunction was a frequent and severe complication after normothermic cardiac surgery, independently associated with poor outcome. Independent predictors of this complication were advanced age, active endocarditis, and recent (within 48 h) radiocontrast agent administration (the only preoperative modifiable factor), as well as postoperative hemodynamic dysfunction.     

The association of lowest hematocrit during cardiopulmonary bypass with acute renal injury after coronary artery bypass surgery

BACKGROUND: Acute renal injury is a common serious complication of cardiac surgery. Moderate hemodilution is thought to reduce the risk of kidney injury but the current practice of extreme hemodilution (target hematocrit 22% to 24%) during cardiopulmonary bypass (CPB) has been linked to adverse outcomes after cardiac surgery. Therefore we tested the hypothesis that lowest hematocrit during CPB is independently associated with acute renal injury after cardiac surgery. METHODS: Demographic, perioperative, and laboratory data were gathered for 1,404 primary elective coronary bypass surgery patients. Preoperative and daily postoperative creatinine values were measured until hospital discharge per institutional protocol. Stepwise multivariable linear regression analysis was performed to determine whether lowest hematocrit during CPB was independently associated with peak fractional change in creatinine (defined as the difference between the preoperative and peak postoperative creatinine represented as a percentage of the preoperative value). A p value of less than 0.05 was considered significant. RESULTS: Multivariable analyses including preoperative hematocrit and other perioperative variables revealed that lowest hematocrit during CPB demonstrated a significant interaction with body weight and was highly associated with peak fractional change in serum creatinine (parameter estimate [PE] = 4.5; p = 0.008) and also with highest postoperative creatinine value (PE = 0.06; p = 0.004). Although other renal risk factors were significant covariates in both models, TM50 (an index of hypotension during CPB) was notably absent. CONCLUSIONS: These results add to concerns that current CPB management guidelines accepting extreme hemodilution may contribute to postoperative acute renal and other organ injury after cardiac surgery.     

Apolipoprotein E Genotype and Cognitive Dysfunction after Noncardiac Surgery

Background: Apolipoprotein E is important in recovery after neuronal damage. The [epsilon]4 allele of the apolipoprotein E gene has been shown as a risk factor for Alzheimer disease, poor outcome after cerebral injury, and accelerated cognitive decline with normal aging. The authors hypothesized that patients with the [epsilon]4 allele would have an increased risk of postoperative cognitive dysfunction (POCD) after noncardiac surgery.

Methods: In a multicenter study, a total of 976 patients aged 40 yr and older undergoing noncardiac surgery were tested preoperatively and 1 week and 3 months after surgery with a neuropsychological test battery comprising seven subtests. POCD was defined as a decline in test performance of more than 2 SD from the expected. Apolipoprotein E genotypes were determined by blood sample analysis at a central laboratory. Multivariate logistic regression analysis with POCD as the dependent variable assessed presence of the [epsilon]4 allele (yes/no) and other possible risk factors.

Results: The [epsilon]4 allele was found in 272 patients. One week after surgery, the incidence of POCD was 11.7% in patients with the [epsilon]4 allele and 9.9% in patients without the [epsilon]4 allele (P = 0.41). Three months later, POCD was found in 10.3% of patients with the [epsilon]4 allele and in 8.4% of patients without the [epsilon]4 allele (P = 0.40). Multivariate logistic regression analysis did not identify the [epsilon]4 allele as a risk factor at 1 week (P = 0.33) or 3 months (P = 0.57).     

Serum creatinine patterns in coronary bypass surgery patients with and without postoperative cognitive dysfunction

Renal dysfunction is common after coronary artery bypass graft (CABG) surgery. We have previously shown that CABG procedures complicated by stroke have a threefold greater peak serum creatinine level relative to uncomplicated surgery. However, postoperative creatinine patterns for procedures complicated by cognitive dysfunction are unknown. Therefore, we tested the hypothesis that postoperative cognitive dysfunction is associated with acute perioperative renal injury after CABG surgery. Data were prospectively gathered for 282 elective CABG surgery patients. Psychometric tests were performed at baseline and 6 wk after surgery. Cognitive dysfunction was defined both as a dichotomous variable (cognitive deficit [CD]) and as a continuous variable (cognitive index). Forty percent of patients had CD at 6 wk. However, the association between peak percentage change in postoperative creatinine and CD (parameter estimate = -0.41; P = 0.91) or cognitive index (parameter estimate = -1.29; P = 0.46) was not significant. These data indicate that postcardiac surgery cognitive dysfunction, unlike stroke, is not associated with major increases in postoperative renal dysfunction. IMPLICATIONS: We previously noted that patients with postcardiac surgery stroke also have greater acute renal injury than unaffected patients. However, in the same setting, we found no difference in renal injury between patients with and without cognitive dysfunction. Factors responsible for subtle postoperative cognitive dysfunction do not appear to be associated with clinically important renal effects.     

Increased prevalence of apolipoprotein E3/E4 genotype among Swedish renal transplant recipients.

There is increasing evidence that lipoproteins are involved in the progression of kidney diseases and in the deterioration of kidney transplant function, although the exact mechanism is still not known. Common polymorphisms of apolipoprotein E genotype associate with the variability of lipoprotein levels and composition. We have, therefore, determined the apolipoprotein E genotype in a group of 112 renal transplant patients, of whom 27 had had an episode of acute vascular rejection, while 85 had not. We found no difference in apolipoprotein E genotype distribution or in relative allele frequency in the vascular rejection group as compared with the group without vascular rejection. The apolipoprotein E genotype distribution in the transplant group was also compared with that in a group of 407 healthy Swedish individuals. The E3/E4 genotype occurred with a significantly increased frequency in the transplant group: 38.3 versus 16% in the control group (p < 0.001). The prevalence of individuals carrying the epsilon4 allele among the transplant group was also significantly higher (44%) as compared with the control group (30%; p < 0.01). This increase was entirely due to the predominant increase of E3/E4, as the E4/E4 genotype was less frequent in transplant recipients than in normal controls (3.5 vs. 10.6%; p < 0.05). The relative frequencies of epsilon2 (0.044), epsilon3 (0.716), and epsilon4 (0.238) alleles in the renal transplant group were not different from those of normal controls (0. 078, 0.718, and 0.202, respectively). With regard to the prevalence of E4/E4 in the two groups, the lack of difference in the relative frequency of the epsilon4 allele must be interpreted with caution. The results thus suggest that the E3/E4 genotype may be associated with the progression of kidney disease leading to renal insufficiency. However, the apolipoprotein E genotype does not seem to influence the risk of vascular rejection among transplant recipients.     

Mitral valve surgery and acute renal injury: port access versus median sternotomy

BACKGROUND: Many outcomes and complications of minimally invasive and conventional cardiac surgery await comparison. Patients undergoing mitral valve surgery commonly sustain renal injury. Using peak postoperative fractional change of serum creatinine as a marker of renal injury, we tested the hypothesis that mitral valve surgery with port access minithoracotomy (Port) and conventional surgery with a median sternotomy (MS) incision are associated with different degrees of acute renal injury. METHODS: We evaluated data from all isolated mitral valve operations by a single surgeon between 1990 and 2000 (MS = 90, Port = 227). We also performed a secondary analysis of mitral valve surgeries performed by both MS and Port approaches in a concurrent period from 1996 to 2002 (MS = 93, Port = 240). Univariable and multivariable tests were used to determine the association of surgical technique with peak postoperative creatinine (CrmaxPost) and peak postoperative fractional change in creatinine (%deltaCr); p less than 0.05 was considered significant. RESULTS: In our analysis that accounted for the date of surgery, we observed a highly significant independent association between surgical approach and %deltaCr, indicating a greater risk of acute renal injury in the MS group (F value 13.33; p = 0.0003). Similar findings were noted in the secondary (time-concurrent) analysis of %deltaCr (F value 12.65; p = 0.0176). CONCLUSIONS: We present retrospective evidence of reduced acute renal injury associated with the port access technique in mitral valve surgery patients. Our findings suggest that a port access minithoracotomy approach to mitral valve surgery may be preferable to conventional methods for patients with high renal risk.     

Postcardiac surgery complications: association of acute renal dysfunction and atrial fibrillation

Postoperative creatinine increase is associated with adverse outcome after cardiac surgery. Although postoperative stroke and renal dysfunction are associated after cardiac surgery, suggesting a common systemic insult, a similar assessment of atrial fibrillation and renal dysfunction has not been performed. Therefore, we tested the hypothesis that patients with new-onset atrial fibrillation complicating coronary bypass surgery have a greater postoperative creatinine increase. Data were obtained for 453 elective coronary bypass surgery patients with no history of atrial fibrillation. Multivariate regression analyses of factors associated with peak fractional change in creatinine demonstrated a two-way interaction between age and atrial fibrillation (variable estimate, -1.1; P = 0.002). Similar results were obtained in a secondary multivariate model analyzing factors associated with peak postoperative creatinine (variable estimate, -0.01; P = 0.04). We confirmed our hypothesis that patients with new-onset atrial fibrillation are more likely to have acute renal dysfunction after cardiac surgery. The association of atrial fibrillation and creatinine increase diminishes with advancing age. These data are consistent with a common pathophysiology that contributes in an age-dependent fashion to the etiology of both acute renal dysfunction and atrial fibrillation after coronary bypass surgery. IMPLICATIONS: We found an independent association between new-onset atrial fibrillation and postoperative creatinine increase that is influenced by age. The degree to which atrial fibrillation is associated with postoperative creatinine increase diminishes with advancing age. This interaction suggests that a common etiology for these two complications may be more important in younger patients.     

Association between Increases in Urinary Neutrophil Gelatinase-associated Lipocalin and Acute Renal Dysfunction after Adult Cardiac Surgery

Background: Acute renal dysfunction (ARD) and subsequent acute renal failure after cardiac surgery are associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of an early biomarker for acute renal injury. Recent studies showed that urinary neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2) is up-regulated early (within 1-3 h) after murine renal injury and in pediatric ARD after cardiac surgery. The authors hypothesized that postoperative urinary NGAL concentrations are increased in adult patients developing ARD after cardiac surgery compared with patients without ARD.

Methods: After institutional review board approval, 81 cardiac surgical patients were prospectively studied. Urine samples were collected immediately before incision and at various time intervals after surgery for NGAL analysis by quantitative immunoblotting. ARD was defined as peak postoperative serum creatinine increase by 50% or greater compared with preoperative serum creatinine.

Results: Sixteen of 81 patients (20%) developed postoperative ARD, and the mean urinary NGAL concentrations in patients who developed ARD were significantly higher early after surgery (after 1 h: 4,195 +/- 6,520 [mean +/- SD] vs. 1,068 +/- 2,129 ng/ml; P < 0.01) compared with patients who did not develop ARD. Mean urinary NGAL concentrations continued to increase and remained significantly higher at 3 and 18 h after cardiac surgery in patients with ARD. In contrast, urinary NGAL in patients without ARD decreased rapidly after cardiac surgery.     

A novel predictive model for poor in-hospital outcomes in patients with acute kidney injury after cardiac surgery

ObjectivePatients with cardiac surgery–associated acute kidney injury are at risk of renal replacement therapy and in-hospital death. We aimed to develop and validate a novel predictive model for poor in-hospital outcomes among patients with cardiac surgery–associated acute kidney injury.MethodsA total of 196 patients diagnosed with cardiac surgery–associated acute kidney injury were enrolled in this study as the training cohort, and 32 blood cytokines were measured. Least absolute shrinkage and selection operator regression and random forest quantile-classifier were performed to identify the key blood predictors for in-hospital composite outcomes (requiring renal replacement therapy or in-hospital death). The logistic regression model incorporating the selected predictors was validated internally using bootstrapping and externally in an independent cohort (n = 52).ResultsA change in serum creatinine (delta serum creatinine) and interleukin 16 and interleukin 8 were selected as key predictors for composite outcomes. The logistic regression model incorporating interleukin 16, interleukin 8, and delta serum creatinine yielded the optimal performance, with decent discrimination (area under the receiver operating characteristic curve: 0.947; area under the precision-recall curve: 0.809) and excellent calibration (Brier score: 0.056, Hosmer–Lemeshow test P = .651). Application of the model in the validation cohort yielded good discrimination. A nomogram was generated for clinical use, and decision curve analysis demonstrated that the new model adds more net benefit than delta serum creatinine.ConclusionsWe developed and validated a promising predictive model for in-hospital composite outcomes among patients with cardiac surgery–associated acute kidney injury and demonstrated interleukin-16 and interleukin-8 as useful predictors to improve risk stratification for poor in-hospital outcomes among those with cardiac surgery–associated acute kidney injury.     

Renal function after cardiac surgery: adverse effect of furosemide

Renal failure is a frequent event after cardiopulmonary by-pass. Hemodynamic alterations that occur during surgery, as well as factors depending on the host, are the main risk factors for renal dysfunction. To evaluate the frequency and risk factors for renal dysfunction in this setting, a cohort of fifty patients with preoperative serum creatinine under 1.5 mg/dL, submitted to cardiac surgery with cardiopulmonary by-pass was analyzed. Variables related to preoperative patient condition, intraoperative and postoperative periods were recorded. Renal function was assessed by clearances of creatinine, urea and free water, also by fractional excretion of sodium (FENa), at baseline, at anesthetic induction and during postoperative period. Patients were arbitrarily divided in two groups, according to the serum creatinine (S(Cr)) value at the end of the postoperative period: Group 1: S(Cr) < 2 mg/dL (n = 44 patients (88.5%)) and Group II: S(Cr) > 2 mg/dL (n = 6 patients (11.5%)). A decrease of renal function was observed in all patients: creatinemia raised from 1.04 +/- 0.2 to 1.55 +/- 0.4 mg/dL (33%), associated with a rise in FENa. Differences between group I and group II using univariate analysis were: baseline serum creatinine (1.01 +/- 0.23 mg/dL vs. 1.26 +/- 0.19 mg/dL, p = 0.03), FENa (0.99 +/- 0.8 vs. 2.2 +/- 2.1, p = 0.04), furosemide dose during surgery normalized to body surface area (93.2 +/- 23 mg/1.73 m2 BSA vs. 135 +/- 38 mg/1.73 m2 BSA, p < 0.001), and hemodilution index (17.3 +/- 4.3% vs. 22.8 +/- 3.2%, p < 0.01). In the multiple regression model, baseline creatinemia and furosemide dose were associated to renal dysfunction.     

The association of epsilon-aminocaproic acid with postoperative decrease in creatinine clearance in 1502 coronary bypass patients

Renal dysfunction is a common serious complication after cardiac surgery. Reports of proteinuria and hyperkalemia after cardiac surgery with epsilon-aminocaproic acid (EACA) have therefore raised concerns for renal safety. Since EACA renders these markers unreliable, we used perioperative change in creatinine clearance (DCrCl) to test the hypothesis that EACA is associated with greater reductions in creatinine clearance after heart surgery, particularly for patients with renal disease. We evaluated data from all elective primary coronary bypass patients during EACA introduction at our institution (July 1, 1991-December 31, 1992; 10 g iv bolus pre-cardiopulmonary bypass, then 1 g/h for 5 h). DCrCl was calculated using preoperative (CrPre) and postoperative peak serum creatinine values, using the Cockroft-Gault equation. Patients with CrPre > or = 133 micromol/L were also separately analyzed. Evaluated patients (n = 1502, +/-EACA; 581/905, 16 exclusions) included 233 with CrPre > or = 133 micromol/L (+/-EACA; 98/135). Multivariate analyses confirmed several known risk factors, but no association between DCrCl and EACA in all patients (P: = 0.66), and the subgroup with CrPre > or = 133 micromol/L (P: = 0.42). Implications: In a large population of primary Coronary Artery Bypass Graft including a subset with preoperative renal dysfunction, there were no postoperative reductions in creatinine clearance attributable to epsilon-aminocaproic (EACA) administration. This retrospective study suggests that moderate epsilon-aminocaproic acid dosing during cardiac surgery is safe for the kidney; however, this inference is based on a single marker of renal dysfunction and requires prospective confirmation using a variety of tests of renal function.     

Report of a substudy on warm versus cold cardiopulmonary bypass: changes in creatinine clearance.

BACKGROUND: Renal dysfunction remains a major complication of cardiac operations. There is concern regarding the possibility of increased renal injury during warm cardiopulmonary bypass (CPB). Therefore, we tested the hypothesis that warm CPB is associated with a greater reduction in creatinine clearance after cardiac surgery than hypothermic CPB. METHODS: We randomly assigned 300 patients who had elective coronary artery bypass grafting to warm (35.5 to 36.5 degrees C) or cold (28 degrees C to 30 degrees C) CPB. Preoperative and peak postoperative serum creatinine values were recorded. Creatinine clearance was estimated using the Cockroft Gault equation. Univariate and multivariable analyses were performed to test the association of CPB temperature and perioperative change in creatinine clearance. RESULTS: Demographic variables were similar between groups. Multivariable analysis did not confirm an association between temperature and change in creatinine clearance (p = 0.87). CONCLUSIONS: We did not confirm an association between warm CPB and increased renal dysfunction after cardiac operations compared with hypothermic CPB.     

Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery

BACKGROUND: Acute renal dysfunction (ARD) and subsequent acute renal failure after cardiac surgery are associated with high mortality and morbidity. Early therapeutic or preventive intervention is hampered by the lack of an early biomarker for acute renal injury. Recent studies showed that urinary neutrophil gelatinase-associated lipocalin (NGAL or lipocalin 2) is up-regulated early (within 1-3 h) after murine renal injury and in pediatric ARD after cardiac surgery. The authors hypothesized that postoperative urinary NGAL concentrations are increased in adult patients developing ARD after cardiac surgery compared with patients without ARD. METHODS: After institutional review board approval, 81 cardiac surgical patients were prospectively studied. Urine samples were collected immediately before incision and at various time intervals after surgery for NGAL analysis by quantitative immunoblotting. ARD was defined as peak postoperative serum creatinine increase by 50% or greater compared with preoperative serum creatinine. RESULTS: Sixteen of 81 patients (20%) developed postoperative ARD, and the mean urinary NGAL concentrations in patients who developed ARD were significantly higher early after surgery (after 1 h: 4,195 +/- 6,520 [mean +/- SD] vs. 1,068 +/- 2,129 ng/ml; P < 0.01) compared with patients who did not develop ARD. Mean urinary NGAL concentrations continued to increase and remained significantly higher at 3 and 18 h after cardiac surgery in patients with ARD. In contrast, urinary NGAL in patients without ARD decreased rapidly after cardiac surgery. CONCLUSIONS: Patients developing postoperative ARD had significantly higher urinary NGAL concentrations early after cardiac surgery. Urinary NGAL may therefore be a useful early biomarker of ARD after cardiac surgery. These findings may facilitate the early detection of acute renal injury and potentially prevent progression to acute renal failure.     

Mannitol, furosemide, and dopamine infusion in postoperative renal failure complicating cardiac surgery

BACKGROUND: Acute renal failure occurring in the postoperative period, requiring dialysis after cardiac surgery is an important risk factor for an early mortality, and the overall mortality of this complication is as high as 40% to 60%. Dialysis in the early postoperative period is often complicated by acute hemodynamic, metabolic, and hematologic effects that adversely affect cardiopulmonary function in patients stabilizing from recent surgery. The purpose of this study was to avoid the need for dialysis by infusion of the solution of mannitol, furosemide, and dopamine in the early postoperative period in oliguric renal failure. METHODS: One hundred patients with postoperative oliguric or anuric renal failure despite adequate postoperative cardiac output and hemodynamic function were randomized. Forty patients (group A) were given intermittent doses of diuretics (furosemide, bumetadine, and ethracrynic acid) and fluids. Sixty patients (group B) were given continuous infusion of the solution of mannitol, furosemide, and dopamine; the infusion was started within 6 hours (mean 3.5 hours) in subgroup B1 (n = 30), and later than 6 hours (mean 7.5 hours) in subgroup B2 (n = 30) after the onset of renal failure. RESULTS: Diuresis occurred in 93.3% of group B (n = 56) versus 10% in group A (n = 4; patients with preop normal renal function). Ninety percent of group A (n = 36) required dialysis versus only 6.7% of group B (n = 4; patients with preexisting renal disease of subgroup B2). Renal function returned to preoperative normal (serum creatinine 0.9 +/- 0.05, p < 0.0001) or baseline value (serum creatinine 2.5 +/- 0.01, p < 0.0001) after first postoperative week in subgroup B1 and third postoperative week in subgroup B2. CONCLUSIONS: Infusion of solution of mannitol, furosemide, and dopamine promoted diuresis in patients with acute postoperative renal failure with adequate postoperative cardiac output and had decreased the need for dialysis in the majority of patients. Early administration of this solution in acute renal failure caused early restoration of renal function to normal or baseline status. It remains to be determined whether routine administration of this solution in the early postoperative period for oliguric renal failure influences the long-term mortality and morbidity in those patients who do require dialysis.