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Ann Thorac Surg 2003;75:1829-1835
© 2003 The Society of Thoracic Surgeons

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Original article: cardiovascular

Valvular heart operation is an independent risk factor for acute renal failure

^a Department of Research and Development, Liverpool, United Kingdom
^b Department of Cardiothoracic Anaesthesia, The Cardiothoracic Centre, Liverpool, United Kingdom

Accepted for publication January 16, 2003.

^* Address reprint requests to Mr Grayson, Regional Clinical Information Analyst, The Cardiothoracic Centre-Liverpool, Thomas Drive, LiverpoolL14 3PE United Kingdom.
e-mail: tony.grayson{at}ctc.nhs.uk

	Abstract

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 
BACKGROUND: Acute renal failure (ARF) after cardiac operation with cardiopulmonary bypass is associated with a high mortality rate. The purpose of this study was to determine and quantify whether valvular heart operation is an independent risk factor for developing ARF.

METHODS: We retrospectively analyzed 5,132 consecutive patients who underwent cardiac operation involving cardiopulmonary bypass between April 1997 and March 2001. Patients with significant renal impairment (preoperative serum creatinine > 200 µmol/L) were excluded. A multivariable logistic regression model was constructed to identify independent risk factors for the postoperative development of ARF.

RESULTS: In 151 (2.9%) patients ARF developed before hospital discharge. The crude incidence of ARF for isolated coronary artery bypass grafting, isolated valve(s) operation, and valve(s) with coronary artery bypass grafting operation was 1.9%, 4.4%, and 7.5%, respectively (p < 0.001). The results of the logistic regression analysis found that valve operation with or without coronary artery bypass grafting was an independent risk factor for the development of postoperative ARF (odds ratio 2.68, 95% confidence interval 1.89 to 3.79; p < 0.001). Other independent predictors of ARF were increased preoperative serum creatinine levels, urgent or emergent operation, insulin-dependent diabetes, and increased cardiopulmonary bypass time.

CONCLUSIONS: Valve operation is an independent risk factor for postoperative ARF. This risk is further increased by prolonged cardiopulmonary bypass.

	Introduction

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Although some renal dysfunction is invariably associated with cardiac operation involving cardiopulmonary bypass [1], renal reserve is usually sufficient to prevent this from becoming clinically significant. However, acute renal failure (ARF) remains a serious complication after cardiac operation performed with cardiopulmonary bypass and carries a high mortality rate. Acute renal failure has been reported to range from 1% to 30%, depending on the definition used, with a mortality rate between 7% and 38% [2–7]. When ARF requires hemodialysis, the associated mortality rate can exceed 60% [4, 8]. A greater understanding of the etiology of this condition will permit more active preventive management.

We have noted through clinical observation that patients who had valvular cardiac operation appear to be at greater risk of developing ARF. We therefore aimed to determine and quantify the independent effect of valvular operation on postoperative ARF.

	Material and methods

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Patient population and data
Data were collected prospectively on a total of 5,132 adult patients who had a cardiac operation between April 1, 1997 and March 31, 2001 at the Cardiothoracic Center-Liverpool. Patients who had coronary artery bypass grafting (CABG) with or without heart valve repair or replacement that was incidental to resection of a ventricular aneurysm, or other surgical procedures were not included. We also excluded patients with a preoperative serum creatinine level greater than 200 µmol/L, history of renal dysfunction, or who underwent operation without cardiopulmonary bypass. Data collection methods and definitions have been described in detail previously [9].

Data were collected during the patients’ admission as part of routine clinical practice. Data included patient characteristics (Table 1), . preoperative medications (Table 2), and operative characteristics (Table 3). Outcome variables collected included ARF, in-hospital mortality rate, and length of postoperative hospital stay.

In-hospital death was defined as death within the same hospital admission regardless of cause. All patients transferred from the base hospital to another hospital were followed up to confirm their status at discharge.

Statistical methods
Because of the nonnormality of continuous variables they are reported as median with 25th and 75th percentiles. Categorical variables are reported as a percentage with 95% confidence intervals (CI). Comparisons were made with Wilcoxon rank-sum test and ² test as appropriate. Standard statistical tests were used to calculate odds ratios (OR) and 95% CI. A multivariable logistic regression analysis was undertaken to identify independent risk factors for ARF [10, 11]. All variables in Tables 1, 2, and 3 were included as potential risk factors in the logistic regression model, including interactions between variables such as type of procedure and duration of cardiopulmonary bypass. The C statistic (equivalent to the area under the receiver operating characteristic curve) and the Hosmer-Lemeshow goodness-of-fit statistic were calculated to assess the performance and calibration of the model, respectively [11, 12]. In all cases a p value less than 0.05 was considered significant. All statistical analyses were performed retrospectively with SAS for Windows version 8 (SAS Institute, Cary, NC).

	Results

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Overall, of the 5,132 patients in the study, ARF developed in 151 patients (2.9% [95% CI 2.5% to 3.4%]) after cardiac operation and before discharge from the hospital. One hundred five (2.0% [95% CI 1.7% to 2.5%]) patients with ARF did not require dialysis, compared with 46 (0.9% [95% CI 0.7 to 1.2]) patients who had ARF that required dialysis. The patients classified as having ARF with a postoperative serum creatinine level greater than 200 µmol/L without requiring dialysis had an average preoperative serum creatinine of 108 µmol/L (minimum 73 µmol/L and maximum 127 µmol/L).

Three thousand seven hundred forty-two patients (72.9% [95% CI 71.7% to 74.1%]) had isolated CABG, compared with 855 (16.7% [95% CI 15.6% to 17.7%]) with isolated valve procedures and 535 (10.4% [95% CI 9.6% to 11.3%]) with combined CABG and valve procedures.

Table 1 shows patient characteristics and the association with ARF. In the univariate analysis, the preoperative characteristics that were significantly associated with the development of ARF included advanced age, greater severity of angina and dyspnea, insulin-dependent diabetes, higher serum creatinine level, congestive cardiac failure, respiratory disease, peripheral vascular disease, previous cardiac operation, decreased left ventricular ejection fraction, and priority of operation. Preoperative digoxin, diuretics, and angiotensin-converting enzyme inhibitors were also significantly associated with postoperative ARF (Table 2).

In the univariate analysis, valve operation with or without CABG increased the odds of postoperative ARF (Table 3). The associated risk between valve operation and ARF increased with the number of valves (single valve 5.5%, double valve 7.6%), although this failed to reach statistical significance (p = 0.50). No association could be found in relation to whether the type of valve operation (ie, repair or replacement valve operation) influenced the development of ARF. However, there was a trend to suggest that a single mitral valve operation had a higher incidence of ARF than single aortic valve operation (7.6% versus 5%, p = 0.13).

Patients with prolonged cardiopulmonary bypass and aortic cross-clamp times also had increased odds of ARF (Table 3). Cardiopulmonary bypass times were significantly longer (p < 0.001) in combined CABG and valve procedures (median 146 minutes [25th and 75th percentiles 122 to 171 minutes]) than in isolated valve operation (median 103 minutes [25th and 75th percentiles 80 to 121 minutes]) or isolated CABG (median 105 minutes [25th and 75th percentiles 87 to 126 minutes]). Overall, valve operation with or without CABG on average lasted 114 minutes (25th and 75th percentiles 89 to 147 minutes) compared with 105 minutes (25th and 75th percentiles 87 to 126 minutes) for isolated CABG (p < 0.001).

The results of the logistic regression analysis found that valve operation with or without CABG was an independent risk factor for the development of postoperative ARF (OR 2.68, 95% CI 1.89 to 3.79; p < 0.001). Other independent predictors of ARF were higher preoperative creatinine level, urgent or emergent operation, insulin-dependent diabetes, and longer cardiopulmonary bypass time. These variables are summarized in Table 4, with their regression coefficient, adjusted odds ratios, and p values.

Table 4 shows an example of the calculation of predicted risk for an individual patient. Using the logistic regression equation, Figures 1 and 2 show the increased risk of ARF, with associated 95% confidence intervals, stratified by procedure as preoperative serum creatinine and cardiopulmonary bypass time increase.

View larger version (21K): [in this window] [in a new window]   Fig 1. Risk of acute renal failure (ARF) stratified by procedure as preoperative serum creatinine increases. The solid lines represent the predicted risk of acute renal failure and the dashed lines represent the associated 95% confidence intervals. (CABG = coronary artery bypass grafting.)

View larger version (22K): [in this window] [in a new window]   Fig 2. Risk of acute renal failure (ARF) stratified by procedure as cardiopulmonary bypass time increases. The solid lines represent the predicted risk of acute renal failure and the dashed lines represent the associated 95% confidence intervals. (CABG = coronary artery bypass grafting.)

The incidence of in-hospital death after valve operation with or without CABG for patients with ARF was 46.2% (95% CI 34.9% to 57.7%) compared with 3.4% (95% CI 2.5% to 4.6%) for patients without ARF (p < 0.001). The median postoperative length of stay in survivors after valve operation with or without CABG for patents with ARF was 20 days (25th and 75th percentiles 15 to 44 days) compared with 9 days (25th and 75th percentiles 7 to 11 days) for patients without ARF (p < 0.001).

	Comment

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Acute renal failure after cardiac operation, necessitating dialysis, has a profound effect on survival. Chertow and colleagues [4] reported a mortality rate of 63.7% in patients with ARF requiring dialysis compared with a mortality rate of 4.3% in those without ARF.

Several investigators have attempted to determine which factors predict development of ARF, with the expectation that by modifying the factors identified the incidence of ARF will decrease. Several studies have lacked a large enough sample size to reach firm conclusions [6, 13–15]. Notable exceptions are the studies by Chertow and colleagues [4], Conlon and associates [2], Mangano and colleagues [3], Andersson and associates [5], and Frost and coworkers [8].

In the multivariable logistic regression analysis we confirmed that valvular heart operation with or without CABG confers a 2.68-fold higher risk of ARF than isolated CABG, independent of other risk factors. This finding was adjusted for preoperative serum creatinine, nonelective operation, insulin-dependent diabetes, and most importantly independent of duration of cardioplumonary bypass.

The finding that valve operation is a risk factor for ARF is not surprising, as we would expect that most complications are higher in valve operation compared with isolated CABG. This study, however, quantifies by how much more the risk of ARF is increased, with a prediction equation which may be useful to clinicians in assessing the risk of a patient developing this severe complication.

Chertow and colleagues, in a landmark study involving 42,773 predominately white men who had cardiac operation at 43 Department of Veterans Affairs medical centers, also showed that valve operation was an independent predictor for ARF. Other independent risk factors for the development of ARF included preoperative renal dysfunction, intraaortic balloon pump support, previous heart operation, preoperative heart failure, peripheral vascular disease, and chronic obstructive airway disease. Their study had relatively few women, and the authors also acknowledged that extremes of age and patients with severe diabetes mellitus were both underrepresented in the cohort studied [4].

As with other reports [2, 3, 5, 8], higher preoperative serum creatinine level was an independent risk factor for ARF in our study. Frost and colleagues [8], in a study involving 1,988 patients, found that preoperative serum creatinine greater than 110 µmol/L significantly increased the risk of developing postoperative ARF. In our own experience, preoperative serum creatinine more than 100 µmol/L significantly increased the risk of ARF (Fig 1).

Our experience agrees with the work done at the Duke University Medical Center in Durham North Carolina, in which diabetes was identified as a risk factor for ARF [2, 16]. This finding is also supported by Mangano and colleagues [3]. However, these studies did not look at which type of diabetes influenced ARF. We identified insulin-dependent diabetes as an independent predictor, but not diet or oral-medication controlled diabetes.

As with other reports [2, 3, 17, 18], our study identified prolonged cardiopulmonary bypass duration as a significant risk factor for postoperative ARF. Conlon and associates [2], in their study involving 2,848 patients who underwent cardiac operation, observed a linear relationship between duration on bypass and ARF. They concluded that shortening the time on bypass might help reduce the risk of ARF, but they did not suggest how this might be achieved, nor did they propose a mechanism to explain the phenomenon.

Because of the susceptibility of the brain to clinically evident embolic damage, much attention has been focused on this organ. The kidney is also susceptible to embolic damage. Deal and colleagues [19] have shown that embolic load to an organ is proportional to the cardiac output that organ receives. Subsequently they [20] showed that cardiotomy suction during cardiopulmonary bypass can also produce embolic injury in a dog model. It seems likely that the increased cardiotomy suction and other embolic loads that are known to be associated with valve operation could, at least in part, explain the independent predictive power of valve operation for the development of ARF. This mechanism would also provide an explanation for the predictive effect of prolonged cardiopulmonary bypass (with its associated increased cardiotomy suction).

Although our sample size was relatively large, there are some limitations that might affect the findings drawn from our observational study of patients who underwent cardiac operation. Using a threshold definition of more than 200 µmol/L of postoperative serum creatinine for ARF may imply that some patients had a trivial baseline increase in serum creatinine resulting in a classification of ARF. However, all our patients classified as ARF, without requiring dialysis, had a baseline serum creatinine increase of 73 µmol/L. This is comparable with the findings of Mangano and colleagues [3], who regarded anyone with a serum creatinine increase of 62 µmol/L or more over baseline as having clinically significant ARF. Increased age was a univariate risk factor for ARF; however, our study did not show increased age as an independent predictor for ARF after cardiopulmonary bypass, as other studies have suggested [2, 3, 5, 16]. This could result from possible selection bias, with older patients not being offered cardiac operation. Aprotinin containing preservative also contributes to ARF, whereas preservative-free aprotinin is not associated with ARF [21, 22]. The use of aprotinin in this series was less than 1% and was entirely preservative free.

Multivariable analysis is not a substitute for a well-designed randomized control trial. The retrospective nature of the study cannot account for the unknown variables affecting the outcome that are not measured in this study. Conversely, retrospective comparisons with multivariable analysis are more versatile and more widely applicable than randomized control trials.

In conclusion, we have shown that valve operation, with or without CABG, carries a higher risk of acute renal failure than isolated CABG. Other risk factors included higher preoperative serum creatinine level, urgent or emergent operation, insulin-dependent diabetes, and longer cardiopulmonary bypass time. Furthermore, we have quantified this risk with a prediction equation, which might prove useful in assessing the probability of a patient developing this severe complication.

	Acknowledgments

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We would like to acknowledge the cooperation given to us by all the Consultant Cardiac Surgeons at the Cardiothoracic Centre-Liverpool: Mr John A. C. Chalmers, Mr Walid C. Dihmis, Mr M. John Drakeley, Mr Brian M. Fabri, Miss Elaine M. Griffiths, Mr Neeraj K. Mediratta, Mr Richard D. Page, Mr D. Mark Pullan, Mr Abbas Rashid, and Mr W. Ian Weir. We also would like to thank Janet Deane, who maintains the quality and ensures completeness of data collected in our Cardiac Surgery Registry.

	References

Top Abstract Introduction Material and methods Results Comment Acknowledgments References

 

1. Ip-Yam P.C., Murphy S., Baines M., Fox M.A., Desmond M.J., Innes P.A. Renal function and proteinuria after cardiopulmonary bypass: the effects of temperature and mannitol. Anesth Analg 1994;78:842-847.[Abstract/Free Full Text]
2. Conlon P.J., Stafford-Smith M., White W.D., et al. Acute renal failure following cardiac surgery. Nephrol Dial Transplant 1999;14:1158-1162.[Abstract/Free Full Text]
3. Mangano C.M., Diamondstone L.S., Ramsay J.G., Aggarwal A., Herskowitz A., Mangano D.T. Renal dysfunction after myocardial revascularisation: risk factors, adverse outcomes, and hospital resource utilization. Ann Intern Med 1998;128:194-203.[Abstract/Free Full Text]
4. Chertow G.M., Lazarus J.M., Christiansen C.L., et al. Pre-operative renal risk stratification. Circulation 1997;95:878-884.[Abstract/Free Full Text]
5. Andersson L.G., Ekroth R., Bratteby L.E., Hallhagen S., Wesslen O. Acute renal failure after coronary surgery—a study of incidence and risk factors in 2009 consecutive patients. J Thorac Cardiovasc Surg 1993;41:237-241.
6. Corwin H.L., Sprague S.M., DeLaria G.A., Norusis M.J. Acute renal failure associated with cardiac operations: a case-control study. J Thorac Cardiovasc Surg 1989;98:1107-1112.[Abstract]
7. Mangos G.J., Brown M.A., Chan W.Y., Horton D., Trew P., Whitworth J.A. Acute renal failure following cardiac surgery: incidence, outcomes and risk factors. Aust NZ J Med 1995;25:284-289.[Medline]
8. Frost L., Pedersen R.S., Lund O., Hansen O.K., Hansen H.E. Prognosis and risk factors in acute, dialysis-requiring renal failure after open-heart surgery. Scand J Thorac Cardiovasc Surg 1991;25:161-166.[Medline]
9. Wynne-Jones K., Jackson M., Grotte G., Bridgewater B., north west regional cardiac surgery audit steering group. Limitations of the Parsonnet score for measuring risk stratified mortality in the north west of England. Heart 2000;84:71-78.[Abstract/Free Full Text]
10. Allison P.D. Logistic regression using the SAS system: theory and application. Cary, NC: SAS Institute Inc, 1999.
11. Hosmer D., Lemeshow S. Applied logistic regression. New York: John Wiley & Sons Inc, 1989.
12. Hanley J.A., McNeil B.J. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982;143:29-36.[Abstract/Free Full Text]
13. Abel R.M., Buckley M.J., Austen W.G., Barnett G.O., Beck C.H., Fischer J.E. Etiology, incidence, and prognosis of renal failure following cardiac operations: results of a prospective analysis of 500 consecutive patients. J Thorac Cardiovasc Surg 1976;71:323-333.[Abstract]
14. Suen W.S., Mok C.K., Chiu S.W., et al. Risk factors for development of acute renal failure requiring dialysis in patients undergoing cardiac surgery. Angiology 1998;49:789-800.
15. Hilberman M., Myers B.D., Carrie B.J., Derby G., Jamison R.L., Stinson E.B. Acute renal failure following cardiac surgery. J Thorac Cardiovasc Surg 1979;77:880-888.[Abstract]
16. Gamoso M.G., Phillips-Bute B., Landolfo K.P., Newman M.F., Stafford-Smith M. Off-pump versus on-pump coronary artery bypass surgery and post-operative renal dysfunction. Anesth Analg 2000;91:1080-1084.[Abstract/Free Full Text]
17. Heikkinen L., Harjula A., Merikallio E. Acute renal failure related to open-heart surgery. Ann Chir Gynaecol 1985;74:203-209.[Medline]
18. Llopart T., Lombardi R., Forselledo M., Andrade R. Acute renal failure in open heart surgery. Renal Failure 1997;19:319-323.[Medline]
19. Deal D.D., Jones T.J., Hammon J.W., Vernon J.C., Wall M.H., Stump D.A. Hypothermic cardiopulmonary bypass in dogs does not protect the kidney from embolization. Anesth Analg 2000;90:S40.
20. Deal D.D., Jones T.J., Vernon J.C., Zboyovski J.M., Stump D.A. Real time OPS imaging of embolic injury of the renal micro-circulation during cardiopulmonary bypass. Anesth Analg 2001;92:S23.
21. Lemmer J.H., Jr, Stanford W., Bonney S.L., et al. Aprotinin for coronary artery bypass grafting: effect on postoperative renal function. Ann Thorac Surg 1995;59:132-136.[Abstract/Free Full Text]
22. Lemmer J.H., Jr, Dilling E.W., Morton J.R., et al. Aprotinin for primary coronary artery bypass grafting: a multicentre trial of three dose regimens. Ann Thorac Surg 1996;62:1659-1667.[Abstract/Free Full Text]

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