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Interact CardioVasc Thorac Surg 2008;7:1054-1057. doi:10.1510/icvts.2008.187112
© 2008 European Association of Cardio-Thoracic Surgery
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Institutional report - Cardiac general

Can estimated glomerular filtration rate improve the EuroSCORE?

Jacobo Silvaa,*, Natalia Ridao-Canob, Antonio Segurac, Luis C. Marotoa, Javier Cobiellaa, Manuel Carneroa, Alberto Barrientosb and José E. Rodrígueza

a Cardiac Surgery Unit, Clínico San Carlos Hospital, C/Profesor Martín Lagos s/n, 7aplanta norte, 28040 Madrid, Spain
b Nephrology Unit of the Hospital Clínico San Carlos, Madrid, Spain
c Instituto de Ciencias de la Salud de Castilla – La Mancha, Spain

Received 30 June 2008; received in revised form 18 August 2008; accepted 20 August 2008

Corresponding author. Tel.: +34 913303691; fax: +34 913303453.

E-mail address: jsilva8252{at}yahoo.es (J. Silva).


   Abstract
Top
 Abstract
1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Several studies have shown that the glomerular filtration rate is a strong predictor of mortality following cardiac surgery. This study was designed to identify the estimated glomerular filtration rate using the MDRD-4 equation as an independent predictive variable of mortality and to determine whether the inclusion of this variable could improve the discriminating power of the EuroSCORE. Data from 2014 consecutive patients who underwent cardiac surgery over a 3-year period were analysed. Mean glomerular filtration rate was 68.4±22.7 ml/min per 1.73 m2; 704 patients (35%) showed a rate ≤60 ml/min/1.73 m2. An estimated glomerular filtration rate ≤60 ml/min/1.73 m2 was found to be an independent predictor of mortality adjusted for age, sex and EuroSCORE (P<0.001, OR 2.4, 95% CI 1.6–3.4). The discriminating power of the EuroSCORE improved when this variable was included: area under the ROC curve for EuroSCORE plus estimated glomerular filtration rate was 0.77 (0.73–0.81) compared to 0.75 (0.71–0.80) for the additive EuroSCORE (z=2.55, P<0.05) and 0.75 (0.71–0.80) for the logistic EuroSCORE (z=2.45, P<0.05). The estimated glomerular filtration rate using the MDRD-4 equation is an independent predictive factor of perioperative mortality in cardiac surgery. The inclusion of this variable could improve the discriminatory capacity of the EuroSCORE.

Key Words: Filtrate; Glomerular; Mortality; Cardiac surgery


   1. Introduction
Top
 Abstract
 1. Introduction
2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 
Most preoperative cardiac risk stratification systems include creatinine as a predictive factor of mortality [1–3]. The most widely used system in Europe, the EuroSCORE, assigns two points when the preoperative serum creatinine (Cr) concentration is ≥2.26 mg/dl [1, 2]. However, serum Cr is not a precise measure of kidney function since, besides its renal clearance, it depends on several other factors such as age, race, muscle mass and metabolic state [4–6]. The options available for assessing renal function include methods that estimate the GFR, such as Cr clearance, and equations that provide an estimated GFR (eGFR) based on anthropomorphic data and serum Cr levels [4–6]. The equations most commonly used to calculate the eGFR are the Cockcroft–Gault formula and MDRD (modification of diet in renal disease equation) [4, 5]. Hence, we find patients with a serum Cr level <2.26 mg/dl who are classed according to their GFR as having moderate or severe chronic kidney disease (CKD) but who are not, nevertheless, considered by the EuroSCORE system as patients with higher risk profile due to renal disease.

CKD defined according to the eGFR has been identified as an independent predictor of cardiovascular death, even in patients hospitalised due to cardiac insufficiency and/or acute coronary syndrome [7–9]. In these studies, an eGFR<60 ml/min/1.73 m2, the threshold generally used to define moderate CKD, was associated with a worse cardiovascular prognosis.


   2. Materials and methods
Top
 Abstract
 1. Introduction
 2. Materials and methods
3. Results
 4. Discussion
 5. Conclusions
 References
 
2.1. Study design

We performed a retrospective study on all patients consecutively undergoing major heart surgery at our institution from January 2005 to December 2007. Major surgery was defined as all surgery involving cardiopulmonary bypass (CBP) and all myocardial revascularization procedures requiring a midline sternotomy. Patients who showed an eGFR calculated using the MDRD-4 ≤60 ml/min/1.73 m2 were compared to those whose eGFR was 60 ml/min/1.73 m2. Death was recorded when the patient died of any cause during hospitalisation or within 30 days of surgery (operative mortality).

2.2. Glomerular filtration

The eGFR was calculated using the MDRD-4 equation [4]:

eGFR (ml/min/1.73 m2)=186xCr (mg/dl)–1.154xage (years)–0.0203. Multiplied by 0.742 for women and 1.212 for black subjects.

2.3. Statistical analysis

The SPSS program (version 15.0) was used for all statistical tests. Qualitative variables were compared using the {chi}2-test or Fisher's exact test when one of the numbers in the cells was <5. Quantitative variables were compared using the Student's t-test. If the distribution was not normal, a non-parametric test was used (Mann–Whitney U-test).

To determine whether the factor eGFR ≤60 ml/min/1.73 m2 was an independent predictor of mortality, a multivariate analysis was performed by binomial linear logistic regression. In the model, we included eGFR as continuous variable and as dichotomous explicative variable according to the eGFR (> or ≤60). The additive EuroSCORE, age and sex were also included to identify confounding factors. After assessing colinearity between these variables serum Cr and logistic EuroSCORE was not included in the model because it shows high correlation with the eGFR and to avoid possible colinearity problems. The level of significance was set at 0.05 (two-sided).

The new additive EuroSCORE+eGFR score was calculated by replacing serum Cr in the equation with eGFR, assigning 0 points when this variable was >60, and 2 points when ≤60 ml/min/1.73 m2.

To compare diagnostic performance and calculate the discriminatory capacity in terms of operative mortality of the different EuroSCOREs, ROC curves were constructed for the additive EuroSCORE, the logistic EuroSCORE and the new additive EuroSCORE+eGFR. The ROC curves were then compared by the Hanley–McNeil contrast test [10], considering the existence of significant differences for a z>1.96 (P<0.05).


   3. Results
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
4. Discussion
 5. Conclusions
 References
 
3.1. Patient characteristics

Over the period January 2005–December 2007, 2014 major heart surgery procedures were undertaken at our unit. The mean age of the patients was 66.2±11.7 years; 36.4% (733) were women. The types of procedure undertaken were: coronary artery bypass grafting (CABG) in 707 (35.1%) patients; valve surgery in 785 (39%); combined valve plus CABG surgery in 143 (7.1%); aortic surgery in 205 (10.2%); and other procedures in 174 (8.6%). Mean additive and logistic EuroSCOREs were 5.96±3.2 and 8.1±9.4, respectively, and the median logistic EuroSCORE was 4.9 (IQR 2.35–9.6).

The mean Cr was 1.2±0.85 and 59 patients (2.9%) had a Cr level >2.26 mg/dl with an eGFR of 17.6±ml/min/1.73 m2; while the mean eGFR for the whole cohort was 68.4±22.3 ml/min/1.73 m2. Fig. 1 shows the non-linear relationship between the Cr and eGFR (ml/min/1.73 m2).


Figure 1
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  		Fig. 1. Relationship between creatinine (mg/dl) and glomerular filtration rate (ml/min/1.73 m2).

 
3.2. Study population characteristics according to the eGFR

Table 1 shows the characteristics of the subset of patients (704; 34.9%) whose eGFR was ≤60 ml/min/1.73 m2 vs. those with an eGFR 60 ml/min/1.73 m2 (1308 patients). When comparing the two groups, we observed higher proportions of patients with hypertension, moderate or severe left ventricular dysfunction and peripheral vascular disease in the first patient subset. Patients with an eGFR ≤60 ml/min/1.73 m2 also obtained higher logistic and additive EuroSCOREs, indicating a higher risk profile.


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  		Table 1 Preoperative and operative characteristics according to the estimated glomerular filtration rate (eGFR)

 
3.3. Operative mortality

Mortality 30 days after surgery or during hospitalisation was 7.2% (145 patients). Mortality for the eGFR ≤60 group was 13.1% vs. 4.1% for the eGFR 60 group (P<0.001). This higher mortality rate for the eGFR ≤60 compared to the eGFR >60 group maintained its significance in both sex groups (14.3% vs. 4% in women, P<0.001 and 11.8% vs. 4.1% in men, P<0.001).

3.4. Multivariate analysis

Tables 2 and 3 show the results of the logistic regression. The odds ratio for death corrected for age, sex and additive EuroSCORE for patients in the eGFR ≤60 group was 2.4 (95% CI 1.6–3.4) and 1.04 (95% CI 1–1.7) when eGFR was considered as continuous variable. The additive EuroSCORE was also found to be an independent predictor of death in this analysis (OR=1.3, 95% CI 1.2–1.4); each one-point increase in the EuroSCORE being associated with a 30% higher risk of death.


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  		Table 2 Multivariable analysis for operative mortality

 

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  		Table 3 Multivariable analysis for operative mortality (eGFR as continuous variable)

 
Table 4 shows the results of the logistic regression analysis when the eGFR was examined in the four groups of patients stratified by CKD grade according to the chronic kidney disease classification scheme [6]. It emerged that the grades moderate and severe CKD were independent predictors of mortality.


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  		Table 4 Multivariable analysis for operative mortality for four stages of chronic kidney disease classification

 
3.5. Power of the EuroSCORE to stratify patients by mortality risk

Fig. 2 shows the ROC curves obtained for the additive and logistic EuroSCORE and the new additive EuroSCORE+eGFR, in which Cr was replaced in the equation with the eGFR and assigned 0 points when this variable was >60 and 2 points when ≤60. The areas under the resultant curves were 0.75 (95% CI 0.70–0.80) for the additive and 0.75 (95% CI 0.71–0.80) for the logistic. In contrast, for the EuroSCORE+eGFR the area under the curve was 0.77 (95% CI 0.72–0.81). Significant differences emerged for the EuroSCORE+eGFR vs. the additive EuroSCORE (z=2.55; P<0.05) and the EuroSCORE+eGFR vs. the logistic EuroSCORE l (z=2.45, P<0.05). Hence, the substitution of Cr with eGFR increased the discriminatory capacity of the EuroSCORE.


Figure 2
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  		Fig. 2. ROC curve. Adjustment for mortality of the logistic and additive EuroSCORE and estimated glomerular filtration rate plus additive EuroSCORE. eGFR: estimated glomerular filtration rate.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
5. Conclusions
 References
 
In the present study, we assessed the impact of the eGFR on the mortality risk of patients subjected to major heart surgery. The eGFR was calculated using the MDRD-4 equation, which is based on serum Cr levels, age, sex and race. As the cut-off point, we used an eGFR ≤60 ml/min/1.73 m2 since this has been identified as the value below which mortality increases significantly in cardiology patients. Some studies have even observed that below this critical threshold mortality increases exponentially in subjects undergoing heart surgery [11–15].

Patients who underwent cardiac surgery at our centre showed a high incidence of moderate and severe CKD. Of the patients operated on, 34.9% showed an eGFR ≤60/ml/ min/1.73 m2, as well as a greater risk profile determined by higher rates of hypertension, severe ventricular dysfunction and a higher EuroSCORE. These findings are consistent with those reported by others [11–15]. It should be stressed that only 2.9% of our patients showed a serum Cr >2.26 mg/dl, which is the minimum threshold for considering renal insufficiency a risk factor in the EuroSCORE. Moreover, the Cr level is non-linearly related to the eGFR, indicating that many patients show an eGFR less than the 60 (ml/min/1.73 m2) cut-off, yet their serum Cr is under 2 mg/dl (see Fig. 1).

Given that eGFR besides Cr is determined by age and sex, we examined our data for association biases related to these two variables known to have an effect on mortality. Thus, through logistic regression we determined whether eGFR was an independent risk factor for mortality adjusted for age, sex and additive EuroSCORE. Our multivariate analysis revealed that those patients with an eGFR ≤60 ml/min/1.73 m2 were 2.4 times (OR) more likely to die than those whose eGFR was >60; both groups being adjusted for age, sex, and additive EuroSCORE. When the patients were stratified by stage of chronic kidney disease, we also observed that patients with moderate or severe CKD were 2 and 3.5 times more likely to die, respectively, adjusting for age, sex and additive EuroSCORE.

The results of our ROC curve indicate that it is possible to improve the ability of the EuroSCORE to predict mortality in a certain number of patients with obvious renal disease defined by their eGFR who would otherwise not score as such, given their serum Cr levels were below 2.26 mg/dl. Further multicentre studies are required in which a new regression model is constructed, including a larger number of patients, to assess the incorporation of eGFR in the EuroSCORE.

Several studies have examined the effect of eGFR on mortality following coronary surgery [11–15]. In a prospective study by Hillis et al. [11] performed on 2067 patients undergoing CABG, the eGFR calculated using the MDRD equation was found to be an independent predictor of in-hospital and early follow-up death. Cooper et al. [12] analysed 483,914 CABG patients. Calculating the eGFR using the MDRD formula, these authors determined it to be an independent predictor of in-hospital morbidity and mortality. Of note was the exponential increase in mortality observed when the eGFR fell below the 60 ml/min/1.73 m2 threshold. Noyez et al. [13], in a study conducted on 627 coronary patients, calculated GFR according to the Cockcroft–Gault formula and correlated this factor with the development of postoperative complications, including worsening kidney function. More recently, Kangasniemi et al. [14] and Howell et al. [15] identified the eGFR as a predictor of long-term survival following cardiac surgery.


   5. Conclusions
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
References
 
The eGFR as calculated by the MDRD-4 equation is an independent predictor of in-hospital mortality in patients undergoing cardiac surgery. The eGFR also seems to be capable of increasing the discriminatory power of the additive EuroSCORE to predict mortality. Further multicentre studies are required to assess the incorporation of eGFR in the EuroSCORE.


   References
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 5. Conclusions
 References
 

  1. Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salomon R. The EuroSCORE study group. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999;16:9–13.[Abstract/Free Full Text]
  2. Roques F, Nashef SA, Michel P, Pinna Pintor P, David M, Baudet E. The EuroSCORE study group. Does EuroeSCORE work in individual European countries. Eur J Cardiothorac Surg 2000;18:27–30.[Abstract/Free Full Text]
  3. Parsonnet V, Dean D, Bernstein AD. A method of uniform stratification of risk for evaluating the results of surgery in acquired adult heart disease. Circulation 1989;79(6 Suppl 2):13.
  4. Levey AS, Bosch JP, Lewis JB, Greene T, Rodgers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med 1999;130:461–470.[Abstract/Free Full Text]
  5. Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function-measured and estimated glomerular filtration rate. N Engl J Med 2006;354:2473–2483.[Free Full Text]
  6. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39(Suppl_1):S1–S266.[CrossRef][Medline]
  7. Go A, Chertow G, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events and hospitalization. N Engl J Med 2004;351:1296–1305.[Abstract/Free Full Text]
  8. Muntner P, He J, Hamm L, Loria C, Whelton PK. Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States. J Am Soc Nephrol 2002;13:745–753.[Abstract/Free Full Text]
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  10. Hanley JA, McNeil BJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 1983;148:839–843.[Abstract/Free Full Text]
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  13. Noyez L, Plesiewicz I, Verheugt WA. Estimated creatinine clearance instead of plasma creatinine level as prognostic test for postoperative renal function in patients undergoing coronary artery bypass surgery. Eur J Cardiothorac Surg 2006;29:461–465.[Abstract/Free Full Text]
  14. Kangasniemi OP, Asin Mahar MA, Rasinaho E, Satomaa A, Tiozzo V, Lepojärvi M, Fausto Biancari F. Impact of estimated glomerular filtration rate on the 15-year outcome after coronary bypass surgery. Eur J Cardiothorac Surg 2008;33:198–202.[Abstract/Free Full Text]
  15. Howell NJ, Keogh BE, Bonser RS, Graham TR, Mascaro J, Rooney SJ, Wilson IC, Pagano D. Mild renal dysfunction predicts in-hospital mortality and post-discharge survival following cardiac surgery. Eur J Cardiothorac Surg 2008;34:390–395.[Abstract/Free Full Text]




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