| BackgroundAcute kidney injury (AKI) is a clinical syndrome of nitrogenous waste detained and (or) urine output decreased that renal function caused by all factors declined rapidly in a short period of time. Currently, hospital-acquired acute kidney injury is one of the hot and difficult topics. Acute kidney injury is a challenge and common complication of cardiac surgery in hospitalized patients. Depending on the study population and different AKI diagnostic criteria, the incidence of AKI after cardiac surgery is3%-30%, and the incidence of renal replacement therapy after cardiac surgery is1%-5%.With the development of medicine, increasing attention has been focused on the rising prevalence of elderly patients in the intensive care unit. This interest in the elderly is warranted by the fact that this segment of the population is rapidly growing. Some studies indicate that the elderly (age>65years) is expected to double worldwide by the year2025. In the United States, it has been predicted that by the year2030, there will be71million elderly Americans accounted for20%of the total population. Similar growth in the geriatric population is not limited to the fully developed nations. Currently, the population older than the age of60is predicted to increase from143million to374million by the year2040in China. Comorbidities, such as chronic heart failure, renal vascular disease, are common among older patients and the therapy of comorbidities may accelerate kidney injury. In addition, with the increasing age, kidney structure and function is marked by changes similar to those seen with chronic kidney disease which is an independent risk factor of acute kidney injury. Thus, advance older is an independent risk factor of acute kidney injury after cardiac surgery. Compared with the young, the prognosis of the elderly patients with acute kidney injury may be worse. A study enrolled1056patients with cardiac surgery showed that every increase of10-year-old, the risk of postoperative acute kidney injury increased by1.35times, and the risk of hospital mortality increased by1.32times. Acute kidney injury is an important challenge and heavy burden for society. Epidemic studies report that the hospital stay, mortality, and costs of acute kidney injury patients are higher than the non acute kidney injury patients. Even the recovery of acute kidney injury is associated with chronic kidney disease, end stage of renal disease, and cardiac disease.Although a great progress was made in the technical and theoretical of the therapy of acute kidney injury, the mortality of patients with acute kidney injury is not improved during the past two decades. In the absence of proven interventions, a reasonable strategy would be to identify risk factors for acute kidney injury in this setting. These risk factors might serve as therapeutic targets for preventing acute kidney injury and improving prognosis. The primary purpose of most of previous studies of acute kidney injury after cardiac surgery in adults was prognosis and risk stratification. The risk factors of acute kidney injury after cardiac surgery with cardiopulmonary bypass in elderly Chinese patients are unknown. Further more, the pathophysiology of AKI suggests that early intervention may improve the prognosis. The ability to identify patients who are at a greater risk of developing acute kidney injury would be extremely valuable for management planning and to guide future research. A score comprising perioperative factors that can be measured routinely could be used to accurately ascertain the outcome.Several scores for predicating AKI after cardiac surgery in adults have been reported, but some authors have suggested that the pathogenesis of AKI in elderly and young patients are different. Hence, the scores used previously may be not suitable for elderly individuals undergoing cardiac surgery. Little is known about the risk profile of elderly patients undergoing cardiac surgery. So we embarked on a study to explore risk factors of acute kidney injury and establish a score to predict AKI after cardiac surgery in elderly patients in China.Part I Acute kidney injury after cardiac surgery in elderly patients:focus on risk factorsObjectiveAcute kidney injury (AKI) is a common complication after cardiac surgery, especially in elderly patients, and related with poor prognosis. Although much advances in therapies of AKI have been obtained, the prognosis of patients did not improved. In the absence of proven interventions, a reasonable strategy would be to identify risk factors for AKI. The objective of the present study was to explore risk factors of acute kidney injury after cardiac surgery with cardiopulmonary bypass in elderly patients.MethodsWe analyzed retrospectively data from consecutive elderly patients (age≥60years old) who underwent cardiac surgery with cardiopulmonary bypass in the Guangdong general hospital between January1,2007and December31,2009. Patients who met any of the following a priori criteria were excluded:end-stage renal disease (estimated glomerular filtration rate (eGFR) based on the modified Modification of Diet in Renal Disease (MDRD) study equation<15mL/min), preoperative renal replacement therapy, other infrequent cardiac procedures (e.g., heart transplantation, insertion of a ventricular assist device), off-pump coronary artery bypass grafting, AKI before cardiac surgery, died during surgery or in the first24h after surgery, and missing clinical data. To facilitate the clinical practice use, we consider the following predictors based on literature review. Preoperative variables included age, gender, hypertension, diabetes mellitus, cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, previous cardiac surgery, current use (within2weeks before surgery) of tobacco, acute myocardial infarction (within30days before surgery), left ventricular ejection fraction,basic eGFR based on the modified MDRD Study Equation using the lowest creatinine value obtained3months before hospital admission or the lowest serum level of creatinine before surgery during hospital admission if pre-admission data were not known, levels of uric acid, plasma albumin, serum potassium, serum sodium, serum platelet count, anemia (a baseline hemoglobin value<13mg/dL for men and<12mg/dL for women), proteinuria defined as urine protein dipstick results of1+or greater (approximately30mg per100ml or greater) in the absence of a possible urinary tract infection, use of an intra-aortic balloon pump within2weeks before surgery, exposure to medicine during2weeks before surgery(angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, digoxin, diuretics, statin therapy), and current exposure to contrast media (exposure to contrast media during the7days before surgery). Intraoperative variables were also considered:cardiopulmonary bypass time, aortic cross-clamping time, procedure type, urgency of surgery, and intra-aortic balloon pump use. Early postoperative (first24h after surgery) variables included central venous pressure (mean value of central venous pressure after surgery), surgical re-exploration, prolonged mechanical ventilation (total duration of ventilator-assisted respiration during postoperative hospitalization of≥24h), use of medicine (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, digoxin, diuretics, statin therapy), requirement of intra-aortic balloon pump. All early postoperative variables were collected before AKI was diagnosed.The primary outcome was AKI according to the serum creatinine criteria of the RIFLE (renal Risk, Injury, Failure, Loss of renal function and End-stage renal disease) classification as an increase in serum creatinine>50%from baseline to peak value within the first seven postoperative days. The baseline serum creatinine was defined as the latest serum creatinine before cardiac surgery. Univariate analysis was carried out for patients’ demographics data and multivariate analysis by logistic regression was used to obtain the independent risk factors for AKI.ResultsA total of457elderly patients with cardiac surgery were finally enrolled in the study. patients’ mean age was65years (standard deviation:4), with a prevalence of males(55.4%). Mean baseline serum creatinine was (95.62±27.23) μmol/L, mean baseline eGFR was (54.40±16.57) ml/min,67.8%patients had preexisting chronic renal disease which eGFR<60ml/min. AKI occurred in313(68.5%) participants and9(2.0%) patients died during hospitalization. Compared with patients without postoperative AKI, the media length of intensive care unit was longer in patients with postoperative AKI,4.0(2.0-7.5) days versus2.0(1.0-3.0) days, respectively. Significant risk factors for development of AKI at univariate analysis were the following:male, age above65years, basic eGFR <60ml/min, hypertension, left ventricular ejection fraction <0.4, use of an intra-aortic balloon pump within2weeks before surgery, exposure to medicine during2weeks before surgery(angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statin therapy), use of intra-aortic balloon pump within2weeks before surgery, preoperative uric acid>450μmol/L, surgery type, intraoperative use of intra-aortic balloon pump, the cardiopulmonary bypass time>120min, aortic clamping time>70min, central venous pressure above14mmH2O, perioperative transfusion red blood cells>1000ml, early postoperative use of medicine (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, digoxin, diuretics), postoperative use of intra-aortic balloon pump and prolonged mechanical ventilation.After multivariate analysis by logistic regression, we found some independent risk factors for AKI. In logistic regression model, male (odds ratio [OR]1.894,95%confidence interval [CI]1.136-3.157), age above65years (OR2.391,95%CI1.381-4.142), hypertension (OR2.286,95%CI1.249-4.184), basic eGFR less than60ml/min (OR1.933,95%CI1.111-3.362), preoperative uric acid>450μmol/L (OR2.938,95%CI1.633-5.285), use of angiotensin converting enzyme inhibitors/angiotensin receptor inhibitors before cardiac surgery (OR2.196,95%CI1.283-3.759), use of angiotensin converting enzyme inhibitors/angiotensin receptor inhibitors after surgery (OR0.329,95%CI0.156-0.691), use of diuretics (OR0.149,95%CI0.068-0.326), time of cardiopulmonary bypass above120min (OR5.228,95%CI3.023-9.041) and prolonged mechanical ventilation (OR2.921,95%CI1.527-5.586) were independent factors of AKI after cardiac surgery with cardiopulmonary bypass.ConclusionAKI remains a common complication after cardiac surgery in elderly patients, and associated with poor prognosis. Aside from several traditional risk factors, such as hypertension, we found preoperative uric acid above450μmol/L was a novel risk factor of AKI after cardiac surgery with cardiopulmonary bypass in Chinese elderly patients. Part Ⅱ A new clinical score to predict acute kidney injury after cardiac surgery in elderly patients in ChinaObjectiveAcute kidney injury (AKI) remains a common complication after cardiac surgery. Epidemiologic evidences have suggested that AKI, even a reversible AKI is an independent risk factor for chronic kidney disease, end-stage renal disease, death, and other important non-renal outcomes. Patients aged>60years undergoing cardiac surgery can experience a greater frequency of this complication in China. The pathophysiology of AKI suggests that early intervention may improve the prognosis. The ability to identify patients who are at a greater risk of developing AKI would be extremely valuable for management planning and to guide future research. A score comprising perioperative factors that can be measured routinely could be used to accurately ascertain the outcome. Several scores for predicating AKI after cardiac surgery in adults have been reported, but some authors have suggested that the pathogenesis of AKI in elderly and young patients are different. Hence, the scores used previously may be not suitable for elderly individuals undergoing cardiac surgery. Little is known about the risk profile of elderly patients undergoing cardiac surgery, so we embarked on a study to establish a score to predict AKI after cardiac surgery in elderly patients in China.MethodsThe study comprised two parts. In part1, the data collected retrospectively from consecutive elderly patients (age≥60years) who underwent cardiac surgery using cardiopulmonary bypass in Guangdong Cardiovascular Institute between January2005and July2010was used to develop and internally validate a risk-prediction score. In part2, the data collected in elderly patients who underwent cardiac surgery between July2011and January2012was used to create a validation score. Patients who met any of the following a priori criteria were excluded:end-stage renal disease (estimated glomerular filtration rate (eGFR) based on the modified Modification of Diet in Renal Disease (MDRD) study equation<15mL/min), preoperative renal replacement therapy, other infrequent cardiac procedures (e.g., heart transplantation, insertion of a ventricular assist device), off-pump coronary artery bypass grafting, AKI before cardiac surgery, died during surgery or in the first24h after surgery, and missing clinical data. To develop a score for predicting AKI after cardiac surgery, potential predictor variables were selected based on clinical availability and literature review. Preoperative variables included demographic characteristics (age, gender), co-morbidities (hypertension, diabetes mellitus, cerebrovascular disease, peripheral vascular disease, chronic obstructive pulmonary disease, previous cardiac surgery), current use (within2weeks before surgery) of tobacco, acute myocardial infarction (within30days before surgery), New York Heart Association (NYHA) function stage, basic eGFR based on the modified MDRD Study Equation using the lowest creatinine value obtained3months before hospital admission or the lowest serum level of creatinine before surgery during hospital admission if pre-admission data were not known, levels of uric acid, plasma albumin, serum potassium, serum sodium, serum platelet count, anemia (a baseline hemoglobin value<13mg/dL for men and<12mg/dL for women), proteinuria defined as urine protein dipstick results of1+or greater (approximately30mg per100ml or greater) in the absence of a possible urinary tract infection, use of an intra-aortic balloon pump within2weeks before surgery, exposure to angiotensin-converting enzyme inhibitors/angiotensin receptor blockers during2weeks before surgery, and current exposure to contrast media (exposure to contrast media during the7days before surgery). Intraoperative variables were also considered:cardiopulmonary bypass time, aortic cross-clamping time, procedure type, urgency of surgery, hemorrhage and intra-aortic balloon pump use. Early postoperative (first24h after surgery) variables included central venous pressure (mean value of central venous pressure after surgery), surgical re-exploration, prolonged mechanical ventilation (total duration of ventilator-assisted respiration during postoperative hospitalization of≥24h), use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, requirement of intra-aortic balloon pump. All early postoperative variables were collected before AKI was diagnosed. The primary outcome was AKI according to the RIFLE (renal risk, injury, failure, loss of renal function and end-stage renal disease) criteria as an increase in serum creatinine>50%from baseline to peak value within the first7postoperative days. The baseline serum level of creatinine was defined as the latest serum creatinine level before cardiac surgery (usually within1week before surgery or on the day of surgery). All patients were followed up until hospital discharge. The length of stay in the intensive care unit (ICU) and hospital was also recorded. The association of potential risk factors with AKI was tested by logistic regression analyses, and a score created.Results682participants (about four-fifths of the total number of patients) were selected randomly to develop the new score:166patients served as a dataset for validation of the score (internal validation group) and127patients were used to prospective validation (external validation group). Of the848patients in a retrospectively collected dataset,524(61.7%) patients fulfilled the AKI criteria, and71(55.9%) patients underwent AKI in the external validation group. Compared with patients who did not have AKI, those who had AKI tended to have a higher in-hospital mortality. Median values of stay in ICU and hospital were2days and4days longer, respectively, in AKI patients compared with non-AKI patients. After multivariate analyses, nine risk factors were included in the final model. A risk-prediction score was established based on the regression coefficients of each significant factor in the logistic regression model. Nine variables were included in the score, and each was assigned a number of points proportional to its regression coefficients:male (4points), hypertension (4points), basic eGFR<60mL/min/1.73m2(3points), NYHA class Ⅲ or Ⅳ(3points), exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers during2weeks before surgery (2points), cardiopulmonary bypass time>113min (5points), intraoperative hemorrhage>200mL (4points), duration of postoperative ventilator-assisted respiration>24h (7points), and previous cardiac surgery (6points). The scoring system ranged from0points to38points. The area under the receiver operating characteristic curve used to judge discrimination of the score was0.807(95%confidence interval,(CI),0.7774-0.840), and that in the internal and external validation groups were0.801(95%CI,0.735-0.868),0.751(95%CI,0.666-0.835), respectively. The risk score also had good calibration ability based on the Hosmer-Lemeshow test because it did not show differences between observed and predicted risk among all risk categories in the development and validation set (P=0.152,0.189,0.953, respectively).ConclusionWe developed an score to predict AKI after cardiac surgery in elderly patients in China according to RIFLE criteria. The new risk-prediction score was validated in an independent group of patients. This score may improve the risk assessment for AKI and early institution of therapeutic interventions to attenuate the impact of AKI on the prognosis. |
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