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ARTIGO ORIGINAL

Lesão renal aguda baseada nos critérios KDIGO (Kidney Disease: Improving Global Outcomes) em pacientes com creatinina sérica elevada submetidos à cirurgia cardíaca

Mauricio Nassau MachadoI; Marcelo Arruda NakazoneII; Lilia Nigro MaiaI

DOI: 10.5935/1678-9741.20140049

ABREVIAÇÕES E ACRÔNIMOS

ADQI: Acute Dialysis Quality Initiative

AKI: Acute Kidney Injury

AKIN: Acute Kidney Injury Network

CABG: Coronary Artery Bypass Grafting

CPB: Cardiopulmonary Bypass

CVS: Cardiac Valve Surgery

eGFR: Estimated Glomerular Filtration Rate

HR: Hazard Ratio

KDIGO: Kidney Disease Improving Global Outcomes

OR: Odds Ratio

RIFLE: Risk, Injury, Failure, Loss and End-stage Kidney Disease

SCr: Serum creatinine

INTRODUCTION

As the population ages, more patients with renal dysfunction are being referred for cardiac surgery[1]. Elevated serum creatinine (SCr) preoperatively is considered an independent risk factor for morbidity and mortality after cardiac surgery[2,3], with the overall risk of death for patients with creatinine > 1.5 mg/dL ranging from 5% to 30%. Postoperatively, small changes in SCr, however small they may be, are also associated with a significant reduction in survival[4,5]. Elevated SCr may be associated with increased morbidity and mortality even when its change does not meet the criteria for acute kidney injury (AKI)[6].

Several consensus definitions have been developed to provide uniform criteria for AKI diagnosis. In 2004, the "Acute Dialysis Quality Initiative (ADQI)" group proposed consensus guidelines and evidence-based treatment and prevention of AKI, which were later called the RIFLE criteria (Risk, Injury, Failure, Loss and End-stage Kidney Disease)[7]. The modification of these criteria was subsequently proposed by the "Acute Kidney Injury Network" (AKIN, which included the ADQI group)[8-10]. More recently, the AKI study group "Kidney Disease: Improving Global Outcomes (KDIGO)" proposed a modified definition, combining the differences between the RIFLE and AKIN definitions[11] (Table 1).

 

The aim of this study was to apply the criteria for AKI based on the KDIGO classification in a population of patients with preoperative SCr above normal limits after cardiac surgery [coronary artery bypass grafting (CABG) or cardiac valve surgery (CVS)] and to evaluate acute worsening of renal function as a predictor of risk of 30-day mortality.

 

METHODS

Patient selection

This was a single-center study. We carried out a retrospective evaluation in patients from the Cardiac Surgery Intensive Care Unit at a Brazilian Medical School Center. Demographics, type of surgery, laboratory data and information of pre, peri and postoperative periods were obtained from a prospectively collected database of 2,878 patients who were older than 18 years and had undergone isolated CABG (1,786) or CVS (1,092) from January 2003 to June 2013. We excluded 51 patients with incomplete data, 23 dialysis patients and 1,886 patients with preoperative SCr within normal limits (Men - SCr < 1.30 mg/dL / Women - SCr < 1.00 mg/dL). After applying the exclusion criteria, 918 patients were analyzed [549 (60%) underwent CABG and 369 (40%) underwent CVS] (Figure 1).


 

This study was approved by the local Research Ethics (CAAE: 5974/2008). Because of its observational nature, informed consent was waived. This research fully adheres to Resolution 466/2012 of the National Health Council (CNS).

Serum Creatinine Measurement

The Jaffe colorimetric method (ADVIATM 1650, Bayer, Germany) was used to measure SCr concentration. The reference value for adults is 0.6 to 1.3 mg/dL for men and 0.6 to 1.0 mg/dL for women.

Stages of AKI based on KDIGO Classification[11]

Stage 1: Increase in SCr > 0.3 mg/dL (in 48 hours) or 1.5 to 1.9 multiplied by baseline (in 7 days);

Stage 2: 2.0 to 2.9 multiplied by baseline SCr;

Stage 3: 3.0 or more multiplied by baseline; increase in SCr > 4.0 mg/dL; or beginning of renal replacement therapy regardless of a previous KDIGO stage.

Data Analysis

The criteria for AKI were applied in 918 patients in the first seven postoperative days. Due to lack of data on urinary output, only SCr was used to determine the categories of AKI. According to the changes in SCr, the patients were classified as no AKI (KDIGO 0) and AKI stages 1, 2 or 3, based on the KDIGO criteria. Glomerular filtration rate (eGFR) was estimated by the Cockcroft-Gault[12] equation. The risk of postoperative death was assessed by EuroSCORE[13,14], in the absence of a specific tool for our population.

Statistical Analysis

Variables are presented as absolute numbers and percentages or median and interquartile ranges (25th and 75th percentile) when applicable. Continuous variables were compared using the nonparametric Mann-Whitney or Kruskal-Wallis tests, and the chi-square or Fisher's exact test was used to compare categorical variables.

Univariate and multivariate Cox proportional hazards models (stepwise) were used to determine the association between AKI and 30-day mortality. The model was adjusted for age (years), gender (reference - female gender), type of surgery (reference - CVS), body mass index (kg/m2), diabetes mellitus (reference - non-diabetic), left ventricular function (reference - preserved left ventricular ejection fraction), cardiopulmonary bypass (CPB) times (min) and AKI (reference - KDIGO 0). The adjusted Hazard Ratio (HR) and 95% confidence intervals (95% CI) were calculated for the predictors. Cumulative survival graphics were built to demonstrate the AKI impact as a predictor of 30-day mortality. P values<0.05 were considered statistically significant (two-tailed). The data were analyzed using the IBM SPSS Statistical Package v.20 (IBM Corporation, Armonk, NY).

 

RESULTS

Baseline characteristics of the patients are shown in Table 2. Median age was 61 years and 52% of the patients were male. Twenty-seven percent of the patients had preoperative eGFR above 60 mL/min. SCr measured in the immediate postoperative period was slightly lower than the preoperative SCr suggesting hemodilution during surgery (Table 3).

 

 

Of the 918 patients studied, 391 (43%) developed AKI: 318 (35%) stage 1, 27 (2.9%) stage 2 and 46 (5.0%) stage 3 (Table 3). Fewer patients in stage 2 may be because the indication for dialysis automatically classifies the patient in stage 3. Any degree of AKI was associated with a significant increase in overall mortality at 30 days compared with patients with no AKI (Table 4). In univariate analysis, the hazard ratio for death at 30 days was 5.4 for patients with KDIGO stage 1, 16.8 for patients with KDIGO stage 2 and 27.2 for patients with KDIGO stage 3 (P<0.001 for all).

 

Patients with AKI had higher EuroSCORE scores, but there was no difference in the percentage of patients at low, intermediate and high risk among the groups (Table 5). The 30-day mortality rate increased progressively in all KDIGO stages (Table 4). Time on CPB and intensive care length of stay also increased (Table 5). The proportion of patients who required mechanical ventilation for more than 24 hours after surgery increased from 6.3% for patients with KDIGO 0 to 67% among those with KDIGO 3 (Table 5). Of the patients with KDIGO 3, 76% required dialysis with a 30-day mortality rate of 66%. However, patients treated with dialysis were more severely ill, as demonstrated by the EuroSCORE calculated preoperatively [4 (2-6) vs. 8 (5-10)], P<0.001.

 

Cox regression analysis

In a multivariate analysis, age (years), CPB time (minutes) and AKI (KDIGO 1-3) were independent predictors of 30-day mortality, with KDIGO stage 3 being the strongest predictor. Male gender had a reduced risk of death at 30 days (Table 6, Figure 2). Subgroup analysis (CABG and CVS) demonstrated similar results, except for reduced risk of death among male patients who underwent CABG (data not shown).

 

 

DISCUSSION

In our study, AKI after CABG or CVS was found to be common and associated with high rates of prolonged intensive care length of stay, morbidity and mortality. This study also demonstrated the importance of KDIGO AKI criteria as a powerful predictor of 30-day mortality in patients with preoperative SCr above normal limits. We found a higher risk of death in those with poor renal function as well as those who required dialysis; however, even slight increases in SCr postoperatively (KDIGO stage 1) were associated with a significant increase in mortality.

The reasons why small changes in SCr correlated with increased hospital mortality are not entirely clear. Possible explanations include the adverse effects of decreased renal function, such as volume overload, anemia, uremia, acidosis, electrolyte disturbances, and increased risk of infections[11,15]. Visual analysis of the survival curves graph of our study showed a continuous decrease of survival in patients who developed AKI, with a higher risk of death within the first week postoperatively (Figure 2).

Preoperative renal dysfunction is known as a postoperative risk predictor; however, in tools such as EuroSCORE[13,14], InsCor[16], and Parsonnet[17], preoperative renal dysfunction is considered a risk factor only in cases of advanced kidney disease (SCr>2.00 or 2.26 mg/dL) or in patients on dialysis. In its update published in 2012, called EuroSCORE II[3], assessment of renal function was included by calculating the eGFR, with values below 85 mL/min being a risk factor.

Estimates of preoperative renal function based on eGFR show that over 75% of patients undergoing CABG have an eGFR below 90 mL/min[18], highlighting the importance and high prevalence of renal dysfunction in patients undergoing heart surgery. Furthermore, these patients are older and have more comorbidities, such as cerebrovascular disease, peripheral artery disease, chronic obstructive pulmonary disease and diabetes mellitus[18].

Several studies have shown that slight changes in renal function have a significant impact on short and long term outcomes in patients undergoing cardiac surgery[5,19-23]. Other studies suggest that intraoperative factors such as CPB times are important contributors to postoperative renal dysfunction[24-26], as observed in our study (OR 1.01 - 95% CI 1.01 to 1.02, P value<0.001 - data not shown), but others have not demonstrated this direct relationship[27,28]. The use of off-pump CABG was also tested in preoperative renal dysfunction with contradictory results[18,29,30].

Many publications have reported preoperative renal dysfunction as a risk predictor for morbidity and postoperative mortality. Kumar et al.[31] identified class III obesity (BMI > 40 kg/m2) as an independent predictor of AKI after on-pump CABG, and Brown et al.[32] found high rates of readmission within 30 days after cardiac surgery in patients who developed AKI. Zakeri et al.[22] evaluated patients with mild to moderate impaired renal function (SCr < 2.26 mg/dL) who underwent CABG. Operative mortality was higher in this group of patients as well as the need for dialysis and occurrence of stroke postoperatively. Both the measurement of SCr as well as eGFR (< 60 mL/min) were independent predictors of hospital mortality and in a 3-year follow-up. Cooper et al.[33] evaluated more than 483,000 patients using the American Society of Thoracic Surgeons database. Seventy-eight percent of patients had some degree of preoperative (CrCl < 90 mL/min) renal dysfunction. Mortality was inversely proportional to the renal function. In an adjusted model, the eGFR was one of the strongest predictors of morbidity and hospital mortality.

Study limitations

Our study has several limitations. First, these data originated from a single center. Although data were collected prospectively, the analysis was performed retrospectively. There was no determination of cause of death, which did not allow us to differentiate between cardiovascular death and death from all causes. Several known and unknown confounding variables could theoretically have influenced the observed mortality rates. Despite the use of multivariate models for control and adjustment of some of these variables, the possibility of the presence of other unknown confounders cannot be ruled out.

 

CONCLUSION

The development of AKI, based on KDIGO criteria, correlated with increased morbidity and was a robust predictor of 30-day mortality in patients with preoperative baseline SCr above normal limits undergoing coronary artery bypass grafting or cardiac valve surgery.

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No financial support.

Authors' roles & responsibilities

MNM: Design of the project; data collection; statistical analysis; discussion of results; manuscript writing

MAN: Discussion of results; manuscript writing, article review

LNM: Discussion of results; manuscript writing, article review

Article receive on segunda-feira, 11 de novembro de 2013

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