Minimal Changes in Postoperative Creatinine Values and Early and Late Mortality and Cardiovascular Events After Coronary Artery Bypass Grafting
2013; Elsevier BV; Volume: 113; Issue: 1 Linguagem: Inglês
10.1016/j.amjcard.2013.09.012
ISSN1879-1913
AutoresMarcus Liotta, Daniel P. Olsson, Ulrik Sartipy, Martin J. Holzmann,
Tópico(s)Hemodynamic Monitoring and Therapy
ResumoAcute kidney injury (AKI) after coronary artery bypass grafting (CABG) is associated with adverse outcomes. This study investigated if already a minimal change of 0 to 0.3 mg/dl in postoperative serum creatinine values was associated with early death and long-term cardiovascular outcomes and death. From the SWEDEHEART registry, we included 25,686 patients who underwent elective, isolated, primary CABG in Sweden from 2000 to 2008. AKI was categorized according to increases in postoperative creatinine values: group 1, 0 to 0.3 mg/dl; group 2, 0.3 to 0.5 mg/dl; and group 3, >0.5 mg/dl. The primary outcome measure was death from any cause. During a mean follow-up of 6 years, there were 4,350 deaths (17%) and 7,095 hospitalizations (28%) for myocardial infarction, stroke, heart failure, or death (secondary outcome). The adjusted odds ratios (95% confidence interval [CI]) for early mortality in AKI groups 1 to 3 were 1.37 (0.84 to 2.21), 3.64 (2.07 to 6.38), and 15.4 (9.98 to 23.9), respectively. For long-term mortality, the corresponding hazard ratios (95% CI) were 1.07 (1.00 to 1.15), 1.33 (1.19 to 1.48), and 2.11 (1.92 to 2.32), respectively. There was a significant association between each AKI group and the composite outcome (HR 1.09, 95% CI 1.03 to 1.15; HR 1.39, 95% CI 1.27 to 1.52; and HR 1.99, 95% CI 1.84 to 2.16, respectively). In conclusion, already a minimal increase in the postoperative serum creatinine level after CABG was independently associated with long-term all-cause mortality and cardiovascular outcomes, regardless of preoperative renal function. Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) is associated with adverse outcomes. This study investigated if already a minimal change of 0 to 0.3 mg/dl in postoperative serum creatinine values was associated with early death and long-term cardiovascular outcomes and death. From the SWEDEHEART registry, we included 25,686 patients who underwent elective, isolated, primary CABG in Sweden from 2000 to 2008. AKI was categorized according to increases in postoperative creatinine values: group 1, 0 to 0.3 mg/dl; group 2, 0.3 to 0.5 mg/dl; and group 3, >0.5 mg/dl. The primary outcome measure was death from any cause. During a mean follow-up of 6 years, there were 4,350 deaths (17%) and 7,095 hospitalizations (28%) for myocardial infarction, stroke, heart failure, or death (secondary outcome). The adjusted odds ratios (95% confidence interval [CI]) for early mortality in AKI groups 1 to 3 were 1.37 (0.84 to 2.21), 3.64 (2.07 to 6.38), and 15.4 (9.98 to 23.9), respectively. For long-term mortality, the corresponding hazard ratios (95% CI) were 1.07 (1.00 to 1.15), 1.33 (1.19 to 1.48), and 2.11 (1.92 to 2.32), respectively. There was a significant association between each AKI group and the composite outcome (HR 1.09, 95% CI 1.03 to 1.15; HR 1.39, 95% CI 1.27 to 1.52; and HR 1.99, 95% CI 1.84 to 2.16, respectively). In conclusion, already a minimal increase in the postoperative serum creatinine level after CABG was independently associated with long-term all-cause mortality and cardiovascular outcomes, regardless of preoperative renal function. Acute kidney injury (AKI) affects 12% to 17% of patients who are undergoing coronary artery bypass grafting (CABG).1Rydén L. Ahnve S. Bell M. Hammar N. Ivert T. Holzmann M.J. Acute kidney injury following coronary artery bypass grafting: early mortality and postoperative complications.Scand Cardiovasc J. 2012; 46: 114-120Crossref PubMed Scopus (40) Google Scholar, 2Hobson C.E. Yavas S. Segal M.S. Schold J.D. Tribble C.G. Layon J. Bihorac A. Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery.Circulation. 2009; 119: 2444-2453Crossref PubMed Scopus (720) Google Scholar Even a small increase in the postoperative serum creatinine level after cardiac surgery is associated with not only early but also long-term mortality.3Lassnigg A. Schmidlin D. Mouhieddine M. Bachmann L.M. Druml W. Bauer P. Hiesmayr M. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.J Am Soc Nephrol. 2004; 15: 1597-1605Crossref PubMed Scopus (1106) Google Scholar, 4Lassnigg A. Schmid E.R. Hiesmayr M. Falk C. Druml W. Bauer P. Schmidlin D. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?.Crit Care Med. 2008; 36: 1129-1137Crossref PubMed Scopus (253) Google Scholar, 5Tolpin D. Collard C.D. Lee V.V. Virani S.S. Allison P.M. Elayda M. Pan W. Subclinical changes in serum creatinine and mortality after coronary artery bypass grafting.J Thorac Cardiovasc Surg. 2012; 143: 682-688Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar Patients who develop AKI have an increased risk of worsening renal function, new-onset heart failure, and future cardiovascular events.6James M.T. Ghali W. Tonelli M. Faris P. Knudtson M.L. Pannu N. Manns B.J. Klarenbach S.W. Hemmelgarn B.R. Acute kidney injury following coronary angiography is associated with a long-term decline in kidney function.Kidney Int. 2010; 78: 803-809Crossref PubMed Scopus (185) Google Scholar, 7James M.T. Ghali W. Knudtson M.L. Ravani P. Tonelli M. Faris P. Pannu N. Manns B.J. Klarenbach S.W. Hemmelgarn B.R. Associations between acute kidney injury and cardiovascular and renal outcomes after coronary angiography.Circulation. 2011; 123: 409-416Crossref PubMed Scopus (280) Google Scholar, 8Olsson D. Sartipy U. Braunschweig F. Holzmann M.J. Acute kidney injury following coronary artery bypass surgery and long-term risk of heart failure.Circ Heart Fail. 2013; 6: 83-90Crossref PubMed Scopus (62) Google Scholar Current definitions of AKI are plentiful and differ in their criteria and requirements for diagnosis, which leads to ambiguities in diagnostic classification.3Lassnigg A. Schmidlin D. Mouhieddine M. Bachmann L.M. Druml W. Bauer P. Hiesmayr M. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.J Am Soc Nephrol. 2004; 15: 1597-1605Crossref PubMed Scopus (1106) Google Scholar, 4Lassnigg A. Schmid E.R. Hiesmayr M. Falk C. Druml W. Bauer P. Schmidlin D. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?.Crit Care Med. 2008; 36: 1129-1137Crossref PubMed Scopus (253) Google Scholar, 5Tolpin D. Collard C.D. Lee V.V. Virani S.S. Allison P.M. Elayda M. Pan W. Subclinical changes in serum creatinine and mortality after coronary artery bypass grafting.J Thorac Cardiovasc Surg. 2012; 143: 682-688Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 9Chertow G.M. Levy E.M. Hammermeister K.E. Grover F. Daley J. Independent association between acute renal failure and mortality following cardiac surgery.Am J Med. 1998; 104: 343-348Abstract Full Text Full Text PDF PubMed Scopus (1045) Google Scholar, 10Bellomo R. Ronco C. Kellum J. Mehta R.L. Palevsky P. Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.Crit Care. 2004; 8: R204-R212Crossref PubMed Google Scholar, 11Mehta R.L. Kellum J. Shah S.V. Molitoris B. Ronco C. Warnock D.G. Levin A. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007; 11: R31Crossref PubMed Scopus (5319) Google Scholar It is possible to assess AKI using either absolute or relative changes in serum creatinine levels. It may be better to use absolute changes as advocated by the AKI Network (AKIN).3Lassnigg A. Schmidlin D. Mouhieddine M. Bachmann L.M. Druml W. Bauer P. Hiesmayr M. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.J Am Soc Nephrol. 2004; 15: 1597-1605Crossref PubMed Scopus (1106) Google Scholar, 4Lassnigg A. Schmid E.R. Hiesmayr M. Falk C. Druml W. Bauer P. Schmidlin D. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?.Crit Care Med. 2008; 36: 1129-1137Crossref PubMed Scopus (253) Google Scholar, 5Tolpin D. Collard C.D. Lee V.V. Virani S.S. Allison P.M. Elayda M. Pan W. Subclinical changes in serum creatinine and mortality after coronary artery bypass grafting.J Thorac Cardiovasc Surg. 2012; 143: 682-688Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 9Chertow G.M. Levy E.M. Hammermeister K.E. Grover F. Daley J. Independent association between acute renal failure and mortality following cardiac surgery.Am J Med. 1998; 104: 343-348Abstract Full Text Full Text PDF PubMed Scopus (1045) Google Scholar, 10Bellomo R. Ronco C. Kellum J. Mehta R.L. Palevsky P. Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.Crit Care. 2004; 8: R204-R212Crossref PubMed Google Scholar, 11Mehta R.L. Kellum J. Shah S.V. Molitoris B. Ronco C. Warnock D.G. Levin A. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007; 11: R31Crossref PubMed Scopus (5319) Google Scholar, 12Fortescue E.B. Bates D.W. Chertow G.M. Predicting acute renal failure after coronary bypass surgery: cross-validation of two risk-stratification algorithms.Kidney Int. 2000; 57: 2594-2602Crossref PubMed Scopus (150) Google Scholar, 13Rosner M.H. Okusa M.D. Acute kidney injury associated with cardiac surgery.Clin J Am Soc Nephrol. 2006; 1: 19-32Crossref PubMed Scopus (830) Google Scholar Three studies have shown that minimal absolute changes in postoperative creatinine values can predict early mortality after CABG.3Lassnigg A. Schmidlin D. Mouhieddine M. Bachmann L.M. Druml W. Bauer P. Hiesmayr M. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.J Am Soc Nephrol. 2004; 15: 1597-1605Crossref PubMed Scopus (1106) Google Scholar, 4Lassnigg A. Schmid E.R. Hiesmayr M. Falk C. Druml W. Bauer P. Schmidlin D. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?.Crit Care Med. 2008; 36: 1129-1137Crossref PubMed Scopus (253) Google Scholar, 5Tolpin D. Collard C.D. Lee V.V. Virani S.S. Allison P.M. Elayda M. Pan W. Subclinical changes in serum creatinine and mortality after coronary artery bypass grafting.J Thorac Cardiovasc Surg. 2012; 143: 682-688Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar However, these were single-center studies and did not report long-term outcomes. In a nation-wide study, we aimed to investigate if already minimal changes in serum creatinine values, below the current definitions of AKI, could predict long-term mortality and cardiovascular events after CABG. The study population was collected from the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry and has been described in detail elsewhere.14Jernberg T. Attebring M.F. Hambraeus K. Ivert T. James S. Jeppsson A. Lagerqvist B. Lindahl B. Stenestrand U. Wallentin L. The Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART).Heart. 2010; 96: 1617-1621Crossref PubMed Scopus (464) Google Scholar Data quality control showed a 96% agreement, on average, between registry data and medical records.14Jernberg T. Attebring M.F. Hambraeus K. Ivert T. James S. Jeppsson A. Lagerqvist B. Lindahl B. Stenestrand U. Wallentin L. The Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART).Heart. 2010; 96: 1617-1621Crossref PubMed Scopus (464) Google Scholar All patients who underwent a primary, isolated, CABG during January 1, 2000 to December 31, 2008 were eligible for inclusion. We excluded patients with previous cardiac surgery (n = 1,027), who underwent other than isolated CABG (n = 7,059), who had missing pre- or postoperative serum creatinine values (n = 10,582), who died on the day of surgery (n = 6), who had a myocardial infarction (MI) within 14 days before surgery (n = 4,913), who underwent an emergency procedure (n = 822), or who had a preoperative estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m2 (n = 149). The study complies with the Declaration of Helsinki and was approved by the Regional Ethical Review Board in Stockholm. The preoperative serum creatinine value was in general obtained the day before surgery. The highest postoperative serum creatinine value during the index hospitalization was selected for analysis. The preoperative creatinine value was subtracted from the postoperative value, and patients were categorized into different groups of AKI. The reference group was defined as a Δcrea of ≤0 mg/dl (0 μmol/L), group 1 as Δcrea of 0 to <0.3 mg/dl (0 to 0.5 mg/dl (>44 μmol/L).3Lassnigg A. Schmidlin D. Mouhieddine M. Bachmann L.M. Druml W. Bauer P. Hiesmayr M. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.J Am Soc Nephrol. 2004; 15: 1597-1605Crossref PubMed Scopus (1106) Google Scholar, 4Lassnigg A. Schmid E.R. Hiesmayr M. Falk C. Druml W. Bauer P. Schmidlin D. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?.Crit Care Med. 2008; 36: 1129-1137Crossref PubMed Scopus (253) Google Scholar Group 2 agrees with the definition of AKIN group 1, in which the absolute criterion of a postoperative increase in serum creatinine level of 0.3 mg/dl (26 μmol/L) is required.11Mehta R.L. Kellum J. Shah S.V. Molitoris B. Ronco C. Warnock D.G. Levin A. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007; 11: R31Crossref PubMed Scopus (5319) Google Scholar We used the simplified Modification of Diet in Renal Disease study equation for eGFRs: 186 × (serum creatinine)−1.154 × (age)−0.203 × (0.742 if female). The primary study outcome was long-term all-cause mortality. We had 2 secondary outcomes: all-cause mortality within 30 days of surgery and a composite end point of MI, heart failure, stroke, or long-term all-cause mortality. Survival status was ascertained in February 2011 using the Swedish personal identity number and the Total Population Register (Statistics Sweden). Follow-up regarding rehospitalization for MI, heart failure, or stroke ended on December 31, 2008, and the data were obtained from the National Inpatient Registry (Swedish National Board of Health and Welfare).15Ludvigsson J.F. Andersson E. Ekbom A. Feychting M. Kim J.L. Reuterwall C. Heurgren M. Olausson P.O. External review and validation of the Swedish national inpatient register.BMC Public Health. 2011; 11: 450Crossref PubMed Scopus (3189) Google Scholar The Kaplan-Meier estimated survival was graphed over 8 years for each AKI group. Unadjusted and multivariate-adjusted Cox regression models were used to study the association between AKI diagnosis and long-term death and the composite end point of MI, heart failure, stroke, or death. Logistic regressions were used to calculate odds ratios for 30-day mortality. All baseline characteristics were considered for inclusion in the model. Primary and secondary interactions among variables were also checked. Finally, age, chronic obstructive pulmonary disease, diabetes mellitus, eGFR, left ventricular ejection fraction (LVEF), previous MI, peripheral vascular disease, gender, and previous stroke were included in the multivariate model. LVEF was used as a 3-stage categorical variable indicating normal, moderate, or poor function: ejection fraction ≥50%, 30% to 50%, and <30%, respectively. Age and eGFR were analyzed as continuous variables. The remaining variables were used as dichotomous indicators. Multiple imputations by chained equations model was used to handle missing data. The frequency of missing data was 8.3% for LVEF, 29% for diabetes, and 8.0% for peripheral vascular disease. A complete-case analysis was also performed, where only patients with complete information on all confounders were included. Statistical analyses were performed using Stata, version 12.1 (StataCorp LP, College Station, Texas). In Table 1, the study population is presented in relation to AKI group. In total, 25,665 patients with a mean age of 67 years were included. The mean follow-up was 6 years. Patients with AKI had a greater prevalence of heart failure and a reduced eGFR. They were also more likely to be older or having had previous MI, stroke, or reduced LVEF. More than 1/2 of the study population qualified for AKI groups 1 to 3, with 40% of patients in AKI group 1.Table 1Patient characteristics in relation to acute kidney injury (AKI) groupsVariableAll Patients, n = 25,665 (%)No AKI, n = 12,066 (%)AKI Groups1, n = 10,322 (%)2, n = 1,631 (%)3, n = 1,646 (%)Age (yrs), mean ± SD67 ± 9.266 ± 9.267 ± 9.170 ± 8.971 ± 8.9Women2123202021eGFR (ml/min/1.73 m2), mean ± SD77 ± 2175 ± 1982 ± 2172 ± 2363 ± 26Preoperative serum creatinine level (μmol/L), mean ± SD92 ± 2793 ± 2387 ± 2299 ± 33117 ± 50Diabetes mellitus2421232836Hypertension5854586472Hyperlipidemia6160606065Peripheral vascular disease9.48.48.91316Current smokers1819171417Chronic obstructive pulmonary disease6.26.45.66.98.4Previous MI3635364048Previous stroke5.04.34.87.69.1Previous congestive heart failure4.13.43.66.310Left ventricular function ≥50%7173726558 30%–50%2524242935 <30%3.83.33.55.37.6Internal thoracic artery use9494949494CABG without cardiopulmonary bypass5.85.55.86.77.5Waiting time <7 days2322232527AKI groups were defined according to absolute increases in postoperative serum creatinine values: no AKI, <0 mg/dl ( 0.5 mg/dl (>44 μmol/L). Open table in a new tab AKI groups were defined according to absolute increases in postoperative serum creatinine values: no AKI, <0 mg/dl ( 0.5 mg/dl (>44 μmol/L). Kaplan-Meier survival data are presented in Figure 1. The plot describes survival for the reference group and each AKI groups separately. Survival rate decreased with increasing severity of AKI. Already within a few months of surgery, the survival rate for patients in AKI groups 2 and 3 were considerably lower compared with patients with no AKI. The increased mortality in AKI groups 2 and 3 were consistent throughout the study period and even seemed to increase over time. In total, 268 deaths (1.0%) occurred within 30 days. In AKI groups 1, 2 and 3, 54 (0.52%), 29 (1.8%), and 138 (8.4%) patients died, respectively. In contrast, only 47 patients (0.39%) died in the group with no AKI. In Figure 2, early mortality is shown in relation to the change in the postoperative serum creatinine values. The lowest mortality was found in patients with no change or a decrease in postoperative serum creatinine level. With increasing serum creatinine values, there was a graded increase in mortality from 0.2 mg/dl (18 μmol/L), which became steep >0.6 mg/dl (53 μmol/L). During a mean follow-up of 6 years, there were in total 4,350 deaths (17%) and 7,095 hospitalizations (28%) for MI, stroke, heart failure, or death combined. In AKI groups 1, 2, and 3, there were 1,613 (16%), 400 (25%), and 660 (40%) deaths, respectively, during follow-up compared with 1,677 (14%) among patients without AKI. The unadjusted analysis showed an increase in the relative risk of death with each AKI group for long-term mortality as well as 30-day mortality and the composite end point (Table 2). The 30-day mortality in AKI group 2 was increased by almost fourfold and in AKI group 3, by 15-fold. For long-term mortality, there was already a significantly increased risk of death by 7% in AKI group 1. After adjustment for confounders, the hazard ratios of the composite end point were increased in each group of AKI (Table 2).Table 2Relative risks with 95% confidence intervals (CIs) in relation to acute kidney injury (AKI) groups 1 to 3∗AKI groups were defined in relation to the differences in pre- to postoperative serum creatinine values: group 1, 0 to 0.3 mg/dl (0 to 26 μmol/L); group 2, 0.3 to 0.5 mg/dl (26 to 44 μmol/L); group 3, >0.5 mg/dl (>44 μmol/L); and no kidney injury, <0 mg/dl ( 0.5 mg/dl (>44 μmol/L); and no kidney injury, <0 mg/dl ( 0.5 mg/dl (>44 μmol/L); and no kidney injury, <0 mg/dl ( 0.5 mg/dl (>44 μmol/L); and no kidney injury, <0 mg/dl (<0 μmol/L).† Multivariate adjustments were made for age, chronic obstructive pulmonary disease, heart failure, diabetes mellitus, eGFR, left ventricular function, MI, peripheral vascular disease, and stroke, all before surgery.‡ The composite end point includes heart failure, stroke, MI, or death. Open table in a new tab ♂ = male; ♀ = female. We found that even small increases in the postoperative serum creatinine values of 0.5 mg/dl. A similar pattern for early mortality related to absolute changes in postoperative creatinine value was found in the study by Tolpin et al. Our AKI group 3 definition agrees with the "large increases" category in the study by Lassnigg et al,4Lassnigg A. Schmid E.R. Hiesmayr M. Falk C. Druml W. Bauer P. Schmidlin D. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?.Crit Care Med. 2008; 36: 1129-1137Crossref PubMed Scopus (253) Google Scholar who reported a relative risk of >8 for early mortality in this category. Accordingly, the results presented herein showed a relative risk of >15 in the corresponding group of AKI. The long-term risk of heart failure, stroke, MI, and all-cause mortality combined was significantly increased for all AKI groups. The view that AKI is also related to long-term cardiovascular disease and death was strengthened.1Rydén L. Ahnve S. Bell M. Hammar N. Ivert T. Holzmann M.J. Acute kidney injury following coronary artery bypass grafting: early mortality and postoperative complications.Scand Cardiovasc J. 2012; 46: 114-120Crossref PubMed Scopus (40) Google Scholar, 3Lassnigg A. Schmidlin D. Mouhieddine M. Bachmann L.M. Druml W. Bauer P. Hiesmayr M. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.J Am Soc Nephrol. 2004; 15: 1597-1605Crossref PubMed Scopus (1106) Google Scholar, 4Lassnigg A. Schmid E.R. Hiesmayr M. Falk C. Druml W. Bauer P. Schmidlin D. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?.Crit Care Med. 2008; 36: 1129-1137Crossref PubMed Scopus (253) Google Scholar, 5Tolpin D. Collard C.D. Lee V.V. Virani S.S. Allison P.M. Elayda M. Pan W. Subclinical changes in serum creatinine and mortality after coronary artery bypass grafting.J Thorac Cardiovasc Surg. 2012; 143: 682-688Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 6James M.T. Ghali W. Tonelli M. Faris P. Knudtson M.L. Pannu N. Manns B.J. Klarenbach S.W. Hemmelgarn B.R. Acute kidney injury following coronary angiography is associated with a long-term decline in kidney function.Kidney Int. 2010; 78: 803-809Crossref PubMed Scopus (185) Google Scholar, 7James M.T. Ghali W. Knudtson M.L. Ravani P. Tonelli M. Faris P. Pannu N. Manns B.J. Klarenbach S.W. Hemmelgarn B.R. Associations between acute kidney injury and cardiovascular and renal outcomes after coronary angiography.Circulation. 2011; 123: 409-416Crossref PubMed Scopus (280) Google Scholar, 8Olsson D. Sartipy U. Braunschweig F. Holzmann M.J. Acute kidney injury following coronary artery bypass surgery and long-term risk of heart failure.Circ Heart Fail. 2013; 6: 83-90Crossref PubMed Scopus (62) Google Scholar Because there was no significant increase in the risk of early death in AKI group 1, it may not be meaningful to include such small increases of creatinine value in the classification of AKI. Nevertheless, the group included many patients who died. Therefore, the question is raised if the group can be further refined to increase specificity. This could perhaps be achieved using biomarkers to detect renal injury. Tubular kidney damage can occur without subsequent dysfunction, so-called subclinical AKI.17Ronco C. Kellum J. Haase M. Subclinical AKI is still AKI.Crit Care. 2012; 16: 313Crossref PubMed Scopus (49) Google Scholar Tubular damage without functional loss is associated with worse renal and overall outcomes.18Ricci Z. Cruz D.N. Ronco C. Classification and staging of acute kidney injury: beyond the RIFLE and AKIN criteria.Nat Rev Nephrol. 2011; 7: 201-208Crossref PubMed Scopus (176) Google Scholar This has challenged the traditional view that a functional loss of filtration with ensuing measurable changes in blood values are required to be clinically relevant. Biomarkers such as neutrophil gelatinase–associated lipocalin, kidney injury molecule 1, and interleukin 18 may improve diagnosis of subclinical AKI by providing urine tests that can detect tubular injury at an early stage.18Ricci Z. Cruz D.N. Ronco C. Classification and staging of acute kidney injury: beyond the RIFLE and AKIN criteria.Nat Rev Nephrol. 2011; 7: 201-208Crossref PubMed Scopus (176) Google Scholar, 19Nickolas T.L. O'Rourke M.J. Yang J. Sise M.E. Canetta P.A. Barasch N. Buchen C. Khan F. Mori K. Giglio J. Devarajan P. Barasch J. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury.Ann Intern Med. 2008; 148: 810-819Crossref PubMed Scopus (585) Google Scholar Ronco et al17Ronco C. Kellum J. Haase M. Subclinical AKI is still AKI.Crit Care. 2012; 16: 313Crossref PubMed Scopus (49) Google Scholar suggested that AKIN and RIFLE should be extended with a group 0 condition, always involving biomarker testing. Perhaps, our results in AKI group 1 would have been different if we could have included biomarker testing to distinguish patients at risk of adverse early outcome. New biomarkers such as neutrophil gelatinase–associated lipocalin are being introduced to improve diagnosis of AKI.20McIlroy D.R. Wagener G. Lee H.T. Neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery: the effect of baseline renal function on diagnostic performance.Clin J Am Soc Nephrol. 2010; 5: 211-219Crossref PubMed Scopus (169) Google Scholar, 21Haase M. Bellomo R. Devarajan P. Schlattmann P. Haase-Fielitz A. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis.Am J Kidney Dis. 2009; 54: 1012-1024Abstract Full Text Full Text PDF PubMed Scopus (1024) Google Scholar The additional overhead of biomarker testing may prove too costly or impractical for testing of all patients undergoing CABG. Perhaps, group 1 of our study provides a realistic compromise where subclinical AKI is more likely, and additional testing could help improve specificity. A decrease in serum creatinine levels occurred postoperatively in almost 1/2 of the patients, which may be related to hemodilution or volume therapy.3Lassnigg A. Schmidlin D. Mouhieddine M. Bachmann L.M. Druml W. Bauer P. Hiesmayr M. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study.J Am Soc Nephrol. 2004; 15: 1597-1605Crossref PubMed Scopus (1106) Google Scholar Patients are treated with ample amounts of fluid during and after surgery and are expected to gain weight by the CABG procedure. Interestingly, this negative change in serum creatinine level was associated with the lowest early and long-term mortalities. These early events are possible signals for a global injury and are indicative of the increased risk of postoperative complications. Further studies are needed to characterize the pre-, peri-, and postoperative care of the patients with the lowest risk of adverse outcome. Our data showed that the association between AKI and risk for early death was stronger for women than men. In general, women have lower serum creatinine levels than men. Thus, an absolute increase in serum creatinine values of 0.3 mg/dl (26 μmol/L) is a larger relative increase for women than men. This indicates that the threshold for the elevation of serum creatinine level that is required for the diagnosis of AKI maybe should differ between men and women. The core strength of this study was the number of patients included and the length of follow-up, which provided a large number of events. Also, the detail and validity of the registers used in this study enabled adjustment for confounding factors.14Jernberg T. Attebring M.F. Hambraeus K. Ivert T. James S. Jeppsson A. Lagerqvist B. Lindahl B. Stenestrand U. Wallentin L. The Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (SWEDEHEART).Heart. 2010; 96: 1617-1621Crossref PubMed Scopus (464) Google Scholar, 15Ludvigsson J.F. Andersson E. Ekbom A. Feychting M. Kim J.L. Reuterwall C. Heurgren M. Olausson P.O. External review and validation of the Swedish national inpatient register.BMC Public Health. 2011; 11: 450Crossref PubMed Scopus (3189) Google Scholar Furthermore, follow-up was complete for all outcomes. Because register data were collected for every medical center that performs CABG in Sweden, the external validity was well established, and our findings can probably be extended to other centers. A number of limitations were identified. Although the study design adjusted for multiple confounders, residual confounding cannot be ruled out. Medication use that could be harmful to the kidney such as angiotensin-converting enzyme inhibitors, diuretics, and nonsteroidal anti-inflammatory drugs and, thus, related to AKI was unknown to us. Additionally, data were unavailable for inotropic drug use during surgery. The amount of fluid given, operation time, and cardiopulmonary bypass time, all factors that can affect serum creatinine level postoperatively, were also unknown. Finally, because the study had a retrospective cohort design, causal inferences could not be made. The authors are thankful to the steering committee of the SWEDEHEART registry for providing us with data to this study. The authors have no conflicts of interest to disclose.
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