Is Administration of Preoperative Angiotensin-Converting Enzyme Inhibitors Important for Renal Protection after Cardiac Surgery?

Abstract

Objective: There are various reasons for renal dysfunction after cardiac surgery; however, activation of the renin–angiotensin system has an important role following cardiac surgery. We investigated the effect of preoperative angiotensin-converting enzyme (ACE) inhibitors on renal functions after cardiovascular surgery. Material–methods: Three hundred sixty-six patients awaiting elective cardiac surgery were allocated to two groups, namely the treatment group, comprising the ACE inhibitor group (n = 186), and the control group, which was without ACE inhibitor (n = 180). The renal parameters [blood urea nitrogen, creatinine, creatinine clearance, and glomerular filtration rate (GFR)] and the need for dialysis were evaluated associated with renal functions between the two groups in the postoperative period. Results: After cardiac surgery, renal dysfunction requiring dialysis developed in 11 (3.8%) patients in the control group patients. There was no required dialysis in the treatment group (p < 0.05). As an indicator of renal dysfunction, the increase in creatinine and blood urea nitrogen levels and the decrease in GFR and creatinine clearance were higher in the control group (p < 0.05). The multivariate analysis indicated that therapy with ACE inhibitors was found to decrease the incidence of postoperative renal dysfunction (odds ratio, 1.07; 95% confidence interval, 0.45–2.50; p < 0.05). The other independent predictors were age, preoperative intra-aortic blood pump, hypertension, diabetes mellitus, and a left ventricular ejection fraction below 0.40. Conclusion: Preoperative therapy with ACE inhibitors has an influence on renal functions. This study demonstrates that administration of ACE inhibitors provides better renal protection after cardiac surgery.

• renal failure
• renal dysfunction
• cardiac surgery
• cardiopulmonary bypass
• CABG

INTRODUCTION

Multiple organ dysfunction syndromes remain a common cause of death following cardiovascular surgery. Several endogenous vasoactive substances and inflammatory mediators have been suggested to induce acute organ injury and dysfunction during cardiopulmonary bypass (CPB).^1,2 Many studies have reported that CPB in patients undergoing cardiac surgery induces an increase in renal vascular resistance and a decrease in the renal blood flow and glomerular filtration rate (GFR).³ Following cardiac surgery, a major complication remains, namely renal dysfunction, which occurs in up to 30% of patients⁴ and requires dialysis. This complication is a well-known morbidity and mortality risk factor.⁵

Angiotensin II, which is one of the most potent vasoactive substances released during CPB, disrupts the perfusion and regional oxygen utilization of splanchnic organs. Angiotensin II has direct and indirect vasoconstrictive effects on the microvasculature and the macrovasculature. It augments the release and action of other endogenous vasoconstrictors such as catecholamines and endothelin and also inhibits the synthesis of vasodilators such as nitric oxide and prostacyclin from the vascular endothelium.^1,6

Angiotensin-converting enzyme (ACE) inhibitors are widely used in the treatment of hypertension and congestive heart failure. ACE inhibitors have been reported to improve organ function, to reverse structural abnormalities of the cardiovascular system, and to prolong survival in patients with chronic heart failure. ACE inhibitors abate the vasoconstrictive effects of angiotensin II and facilitate the vasodilator activity of tissue bradykinin and prostaglandins. ACE inhibitors can render better patterns of blood flow at both the macrocirculation and the microcirculation levels and can potentially protect against ischemia and reperfusion injury triggered by CPB.¹ Because ACE inhibitors decrease the glomerular perfusion pressure, they may exacerbate kidney injury during CPB-related hypoperfusion. Furthermore, ACE inhibitor therapy may cause a reversible decline in renal function in several clinical conditions associated with decreased renal perfusion, such as bilateral renal artery stenosis, severe congestive heart failure, volume depletion, or CPB. In spite of this special negative effect, ACE inhibitor therapy has been shown to confer renal protection in different clinical settings.^5,7,8

This study was carried out to evaluate the hypothesis that administration of ACE inhibitors may have a positive effect on renal function after cardiovascular surgery.

MATERIALS AND METHODS

Patient Characteristics

We analyzed 366 patients who had undergone cardiac surgery at our institution between February 2012 and December 2012. The patients were divided into two groups. Those who had been treated with ACE inhibitors constituted the treatment group (n = 186). The patients generally received ≥2 weeks of treatment with ACE inhibitors at the standard dosage schedule before the date of surgery. Ramipril (Delix, Aventis Pharma, Scoppito, Italy) was administered orally at a dose of 5 mg per day. The effect of ACE inhibitors on GFR reduction is generally achieved after 2 weeks of oral treatment (expected to provide more than 90% inhibition of the converting enzyme).⁹ These patients were compared with the remaining patients who had not received the ongoing ACE inhibitor therapy preoperatively (control group; n = 180). The patients were given the usual cardiac treatment, consisting of β-blockers, diuretics, or antiarrhythmics. This treatment was maintained until the day before surgery.

Surgical Techniques

General anesthesia was induced and maintained with midazolam and fentanyl. Pancuronium was used to facilitate endotracheal intubation. Following tracheal intubation, ventilation was controlled to ensure normal blood gases, using an inspired oxygen concentration of 50% before CPB and 100% after CPB. In all the patients, a peripheral vein was cannulated before anesthesia and then the radial artery was accessed after induction of anesthesia for continuous monitoring of the central venous pressure. After cannulation of the aorta and the right atrium (bicaval cannulation for valve surgery), CPB was instituted with a membrane oxygenator primed with 1.5 L of crystalloid solution and the body temperature was cooled down to 28–32°C. Following aortic clamping, a cardioplegic solution was infused into the root of the aorta. A pulsatile pump flow rate was maintained at 1.6–2.2 L/min. After completion of the surgical procedure (coronary, valve, septal defect operations) and systemic rewarming, the patients were weaned from the CPB when a rectal temperature of at least 36°C had been reached. In the intensive care unit (ICU), repeated boluses of morphine were administered to keep the patient pain-free. Weaning from the ventilator was begun during the wakening from anesthesia and when stable hemodynamic variables and normothermia had been maintained for at least 1 h.

Data and Study Design

The data were prospectively collected and recorded by clinical cardiac surgeons. Renal dysfunction after cardiac surgery was defined as shown below:

1.	Postoperative renal failure requiring dialysis before discharge or death
2.	Decreases of 50% or higher in the GFR and creatinine clearance of 80mL/dk/1.73 m2 without requiring dialysis
3.	Blood urea nitrogen levels of >50 mg/dL and creatinine levels of >1.4 mg/dL without requiring dialysis.

The preoperative data included age, gender, history of diabetes mellitus, arterial vascular disease, hypertension (history of hypertension requiring medical therapy), history of MI, and smoking. The hemodynamic variables were measured or calculated before induction of anesthesia (Table 1). The surgical procedures performed were classified as coronary artery bypass graft (CABG) isolated or combined with valve surgery, isolated valve repair or replacement surgery, adult congenital procedures, and aortic surgery. The data on operative events included the duration of operation, total CPB, and cross clamping times. The infusions of the inotrope vasopressors and nitrodilators after completion of surgery and installing of an intra-aortic balloon pump (IABP) in the ICU were recorded. The biochemical, hematological, and microbiological laboratory data from the ICU and the duration of hospital stay were obtained from the medical records.

Table 1. Preoperative patient characteristics among groups.

Variables	Treatment group (n = 186)	Control group (n = 180)	p-Value
Median age	59 ± 5.1	60 ± 5.5	0.870
Sex			0.910
Male	92 (49.4%)	89 (49.5%)
Female	94 (50.6%)	91 (50.5%)
Median weight (kg)	72 ± 3.1	69 ± 2.1	0.670
Diabetes mellitus	95 (51%)	42 (23.3%)	<0.05
COPD	77 (41.4%)	69 (38.3%)	0.338
Smoking	121 (65%)	118 (65.5%)	0.289
Hematocrit	44 ± 4	45 ± 5	0.777
Hypertension	138 (74.2%)	62 (34.4%)	<0.05
Preoperative IABP	21 (11.3%)	26 (14.4%)	0.144
Preoperative median GFR	156 ± 32	148 ± 34	0.766
PAD	41 (22%)	45 (25%)	0.190
History of MI	84 (45.1%)	81 (45%)	0.250
LVEF 0.40	45 (24.2%)	50 (27.7%)	0.870
BUN levels (mg/dL)	20 ± 7	21 ± 12	0.399
Creatinine levels (mg/dL)	1.1 ± 0.5	1.0 ± 0.6	0.557
CCL (mL/min)	52 ± 12	50 ± 14	0.902
Use of β-blockers	112 (60.2%)	55 (30.5%)	<0.05
Use of diuretics	49 (26.3%)	44 (24.4%)	0.221
Use of antiarrhythmic	21 (11.3%)	25 (13.9%)	0.233
Mean pulse rate (beats/min)	77 ± 14	80 ± 12	0.578
Mean BP (mm Hg)	97 ± 17	94 ± 18	0.103
Mean CVP (mm Hg)	10 ± 4	11 ± 5	0.911
Mean PAP (mm Hg)	20 ± 10	22 ± 11	0.907
Mean CI (L/min/m^2)	2.4 ± 0.6	2.3 ± 0.6	0.101

Notes: p-Values of <0.05 were considered significant. COPD, chronic obstructive pulmonary disease; GFR, glomerular filtration rate; IABP, intra-aortic balloon pump; LVEF, left ventricular ejection fraction; CI, cardiac index; PAP, pulmonary artery pressure; CVP, central venous pressure; BP, blood pressure; PAD, peripheral arterial disease; MI, myocardial infarction.

Catecholamines, loop diuretics, antiarrhythmics (xylocaine and amiodarone), and standard doses of intravenous glyceryl trinitrate were permitted throughout the study, in addition to digitalis glycosides. Other vasodilators, PDEIII inhibitors, potassium-sparing diuretics, β-blockers, calcium antagonists, and all the long-acting nitrates were discontinued 24 h before inclusion in the study. The investigation was approved by the institutional ethics committee, and informed consent was obtained either from the patients or from the patient’s closest relatives. The exclusion criteria included emergency and redo operations, renal artery stenosis, hypertrophic cardiomyopathy, prior CABG, use of non-steroidal anti-inflammatory drugs, severe anemia, active infection, severe hepatic disorder, or patients with earlier renal dysfunction (serum creatinine levels of >1.44 mg/dL and creatinine clearance levels of <80 mL/dk/1.73 m²).

Routine clinical monitoring included a central venous catheter and a femoral or radial artery catheter. Systemic arterial pressures and central venous pressure were constantly measured with disposable transducers. Cardiac output was continuously measured: a high level of accuracy and precision has previously been demonstrated between the continuous cardiac output measurements and the intermittent manual bolus thermodilution technique.¹⁰ The serum creatinine, creatinine clearance, blood urea nitrogen, and GFR levels were measured at the baseline and at the 6th, 12th, 24th, 48th, and 72nd h after cardiac surgery. The clearances during these time intervals were calculated according to the standard formulae.

Operative mortality was defined as all the deaths that had occurred during the hospital stay or after discharge from the hospital, but within 30 days postoperatively.

Statistical Analysis

The qualitative data were presented in numbers and percentages, and the measurement data were given in arithmetic mean ± standard deviation (SD) for all the continuous variables. The Mann–Whitney test was used for the continuous variables; the Wilcoxon’s signed rank test was used for comparing the pre- and postoperative variables within the same group. The categorical variables were expressed as actual numbers and percentages and compared using χ² or the Fisher’s exact test. A logistic regression analysis was performed with the administered ACE inhibitors as the dependent variables and the preoperative factors as independent variables. First, the univariate logistic regression analysis was applied to determine the significant predictors of renal dysfunction after cardiac surgery. The effect of therapy with ACE inhibitors was examined using the multiple logistic regression analysis. Factors determined to have a p-value of <0.05 in the univariate analysis were considered as candidates for multivariable analysis, which was performed in a gradual style to determine the independent predictors of renal dysfunction. The results of the logistic regression analysis were presented as Odds ratios (OR) and 95% confidence intervals (CI). Statistically significant differences were noted for each analysis, with statistical significance based on a p-value of <0.05. The statistical analyses were performed using the SPSS 11 software (SPSS, Chicago, IL).

RESULTS

A total of 186 patients (50.8%) received ACE inhibitor therapy preoperatively and 180 patients (49.2%) did not. The age, gender distribution, weight, arterial vascular disease, smoking, history of myocardial infarction, and the preoperative GFR were found to be similar between groups. Table 1 depicts the demographic preoperative characteristics. ACE inhibitor (Ramipril 5 mg tablet) was administered orally at a dose of 5 mg per day before surgery for at least 2 weeks. There were no significant differences with regard to the preoperative characteristics, excluding the number of patients with hypertension and diabetes mellitus and regarding the use of β-blockers between the groups (Table 1). Patients receiving ACE inhibitors preoperatively were more likely to have hypertension and to have received preoperative β-blockers. Furthermore, patients who had received preoperative ACE inhibitor therapy had a higher rate of diabetes mellitus than the other group. Moreover, the preoperative hematocrit and the serum creatinine, creatinine clearance, and blood urea nitrogen levels were similar in the two groups. There was no statistical significance in terms of preoperative drug medications and systemic hemodynamic variables (p > 0.05).

The surgical procedures, the cross clamping time, the distal anastomoses numbers, the extubation durations, and the use of cardiac drugs were determined to be similar in both groups (p > 0.05) (Table 2). Thirty-two patients in the control group had required a new insertion of an IABP, whereas this was required for seven patients in the treatment group (p < 0.05). There was no difference in the number of bypassed vessels, in the type of arterial conduits, or the sites of surgical anastomoses between the groups. There was no difference between the groups with regard to the use of IMA. The operation and the CPB times were less in the treatment group than in the control group (p < 0.05). The operative and the postoperative outcomes after cardiovascular surgery in the groups have been summarized in Table 2. There was an important difference between the groups in terms of durations of ICU and hospital stay. In the treatment group, the ICU and the hospital stay were shorter compared with group II, and this result was statistically significant (p < 0.05) (Table 2). The increase in postoperative creatinine and blood urea nitrogen levels compared to the preoperative value was markedly higher in Group II (p < 0.05). The decreases in the GFR and the creatinine clearance levels were higher in the control group as opposed to the treatment group (p < 0.05). Twenty-four patients in the control group had required dialysis, whereas only two patients in the treatment group had required dialysis (p < 0.05). Consequently, it was deduced that renal dysfunction was higher in the control group than in the treatment group after cardiac surgery.

Table 2. Operative and postoperative data.

Data	Treatment group (n = 186)	Control group (n = 180)	p-Value
Only CABG	131 (70.4%)	129 (71.6%)	0.721
Only MVR	21 (11.3%)	16 (8.8%)	0.911
Only AVR	16 (8.6%)	13 (7.2%)	0.855
CABG + MVR	5 (2.7%)	7 (3.8%)	0.110
CABG + AVR	7 (3.7%)	6 (3.3%)	0.402
Aortic surgery	3 (1.6%)	5 (2.7%)	0.632
ASD	3 (1.6%)	4 (2.2%)	0.479
CC time (min)	58 ± 14	56 ± 12	0.303
CPB time (min)	35 ± 13	73 ± 13	<0.05
Operating time (h)	3.2 ± 1.8	5.3 ± 1.7	<0.05
Distal anastomoses	3 ± 1.2	3.1 ± 1.1	0.621
Postoperative IABP	7 (3.7%)	32 (17.7%)	<0.05
IMA usage	184 (99%)	179 (99.4%)	0.933
Use of inotropes	101 (54.3%)	111 (61.6%)	0.318
Use of trinitrates	16 (8.6%)	14 (7.7%)	0.402
Use of nipruss	6 (3.2%)	7 (3.8%)	0.430
Extubation time (h)	4.1 ± 2.1	3.1 ± 2.3	0.701
Postoperative BUN levels (mg/dL)	18 ± 11	41 ± 12	<0.05
Postoperative creatinine levels (mg/dL)	1.1 ± 0.8	2.1 ±1.4	<0.05
Postoperative CCL (mL/min)	41 ± 19	21 ± 14	<0.05
Postoperative median GFR	136 ± 22	88 ± 24	<0.05
Requiring dialysis	2 (1.1%)	24 (13.3%)	<0.05
ICU stay	3 ± 5	8 ± 4	<0.05
Hospital stay	7 ± 4	15 ± 3	<0.05
Operative mortality	6 (3.2%)	8 (4.4%)	0.127

Notes: p-Values of <0.05 were considered significant. CABG, coronary artery bypass grafting; MVR, mitral valve replacement; AVR, aortic valve replacement; ASD, atrial septal defect; CC, cross clamping; CPB, cardiopulmonary bypass; IMA, internal mammaria artery; BP, blood pressure; CVP, central venous pressure; PAP, pulmonary arterial pressure; CI, cardiac index; IABP, intra-aortic balloon pump; GFR, glomerular filtration rate; CCL, creatinine clearance; ICU, intensive care unit.

The unadjusted univariate analysis demonstrated that the risk factors related with renal dysfunction were age, preoperative ACE inhibitor treatment, preoperative left ventricular ejection fraction (LVEF) of <40, diabetes mellitus, hypertension, and preoperative use of IABP (Table 3). The independent risk factors for renal dysfunction were specified with the multivariate analysis for preoperative ACE inhibitor treatment. After adjustment for the propensity score and the covariates, preoperative ACE inhibitors were found to have a protective effect on the incidence of renal dysfunction after cardiac surgery (OR: 1.07; CI: 0.45–2.50; p < 0.05). The other independent predictors were age, preoperative use of IABP, hypertension, diabetes mellitus, and a LVEF of lower than 0.40. These have been presented in Table 4.

Table 3. Univariate logistic regression analysis (independent predictors for risk factors associated with renal dysfunction).

	Odds ratio	95% CI	p-Value
Median age	0.71	0.55–1.16	<0.05
Sex	4.66	2.01–9.62	0.521
Male
Female
Median weight (kg)	0.8	0.66–1.19	0.075
COPD	2.90	2.05–3.15	0.114
Smoking	2.5	1.26–5.18	0.870
PAD	1.19	1.01–1.33	0.521
History of MI	0.41	0.35–0.06	0.075
Hematocrit	3.79	2.41–6.88	0.101
Preoperative ACE inhibitors	0.71	0.55–1.16	<0.05
Preoperative LVEF <40	4.66	2.01–9.62	<0.05
Diabetes mellitus	2.90	2.05–3.15	<0.05
Hypertension	2.5	1.26–5.18	<0.05
Use of β-blockers	2.90	2.05–3.15	0.870
Use of diuretics	2.5	1.26–5.18	0.521
Use of antiarrhythmic	1.45	1.01–1.93	0.075
Mean BP (mm Hg)	1.45	0.17–12.14	0.075
Mean CVP (mm Hg)	0.86	0.61–1.30	0.114
Mean PAP (mm Hg)	0.77	0.81–2.80	0.870
Mean pulse rate (beats/min)	3.3	2.7–4.2	0.521
Mean CI (L/min/m^2)	2.7	2.3–3.1	0.521
Preoperative IABP	6.8	5.66–11.19	<0.05

Notes: p-Values of <0.05 were considered significant. ACE, angiotensin converting enzyme; CPB, cardiopulmonary bypass; CCL, creatinine clearance; ICU, intensive care unit; GFR, glomerular filtration rate; COPD, chronic obstructive pulmonary disease; PAD, peripheral arterial disease; IABP, intra-aortic balloon pump; LVEF, left ventricular ejection fraction; CI, cardiac index; PAP, pulmonary artery pressure; CVP, central venous pressure; BP, blood pressure.

Table 4. Multivariate logistic regression analysis for risk factors associated with renal dysfunction to receive angiotensin-converting enzyme inhibitor treatment preoperatively.

	Odds ratio	95% CI	p-Value
Age	0.76	0.58–1.19	<0.05
Preoperative ACE inhibitors	1.07	0.45–2.50	<0.05
Preoperative LVEF 40	0.96	0.41–2.25	<0.05
Diabetes mellitus	1.45	0.17–12.1	<0.05
Hypertension	0.86	0.61–1.30	<0.05
Preoperative IABP	7.33	6.80–10.5	<0.05

Note: p-Values of <0.05 were considered significant.

Table 5. The clinical results after cardiac surgery.

	Treatment group (n = 186)	Control group (n = 180)	p-Value
Cardiac dysfunction	11 (5.9%)	16 (8.8%)	NS
Cardiac arrhythmia	32 (17.2%)	45 (25%)	NS
Pulmonary dysfunction	41 (22%)	50 (27.7%)	NS
GI dysfunction	5 (2.7%)	4 (2.2%)	NS
Hepatic dysfunction	4 (2.2%)	3 (1.6%)	NS
Neurological dysfunction	9 (4.8%)	12 (6.6%)	NS
Multiple organ dysfunction	2 (1.1%)	4 (2.2%)	NS
Nosocomial infection	32 (17.2%)	27 (15%)	NS
Urinary tract infection	9 (4.8%)	8 (4.4%)	NS
Mediastinal infection	3 (1.6%)	3 (1.6%)	NS
Pneumonia	14 (7.5%)	16 (5%)	NS
Time to extubation (h)	2.7 ± 1.3	2.9 ± 1.8	NS
Surgical revision for bleeding	11 (5.9%)	10 (5.5%)	NS
Postoperative bleeding >1000 mL	11 (5.9%)	12 (6.6%)	NS
Death	3.6 ± 9.0	3.5 ± 10.2	NS

There was no significance with regards to the systemic dysfunctions, infection, and the amount of blood and death between the groups. Overall, the operative mortality rate was 3.8% (14 of 366). The operative mortality was 3.2% in patients who had received preoperative ACE inhibitor therapy and 4.4% in patients who did not (p > 0.05) (Table 5).

DISCUSSION

Renin angiotensin system blockade with an ACE inhibitor may improve renal function in patients without pre-existing cardiac or renal failure, who are undergoing cardiac surgery with CPB-support.^3,5,11 In general, ACE inhibitors increase the renal blood flow and decrease the renal vascular resistance^11,12; hence, treatment with ACE inhibitors has a positive effect on renal functions after cardiac surgery.

Renal dysfunction after cardiac surgery with CPB-support is an indomitable problem. Despite the new anesthesia techniques, surgical techniques, and myocardial protection techniques, the postoperative adverse events related to postoperative renal dysfunction have not been completely eliminated. The theoretical benefits have been based on several features attributed to treatment with ACE inhibitors.^1,13 ACE inhibitors have been stated to restore the vascular endothelial integrity, which is essential for adequate microvascular blood flow and preservation of organ function.

ACE inhibitor treatment may cause a reversible deterioration in renal function in situations such as renal artery stenosis, heart failure, hypertrophic cardiomyopathy, use of non-steroidal anti-inflammatory drugs, or lack of volume, and it may extensively impair the renal blood flow during CPB.^5,14 Patients with these conditions were excluded from our study. This study shows that preoperative ACE inhibitors are associated with a significantly lower risk of postoperative renal dysfunction compared to those with no preoperative ACE inhibition treatment. In our study, ramipril notably decreased the creatinine and the blood urea nitrogen levels in the treatment group. Besides, the postoperative creatinine clearance and GFR were consistently higher in the control group than in the treatment group. Furthermore, the need for dialysis was higher in the control group. Contrary to our findings, some authors have failed to detect any improvement in renal function associated with preoperative ACE inhibitor treatment.^1,15 The reason for this contrast may be the differences in the surgical patient populations and differences in defining renal impairment in their studies. Moreover, our results have been supported by some authors. They found that administration of intravenous ACE inhibitor improved the renal perfusion by counteracting the renin angiotensin system activity and that ACE inhibitors increased the cardiac output in patients with left ventricular dysfunction, thus, improving the renal perfusion.^3,16 The decrease in the rate of renal dysfunction that we observed in patients receiving preoperative ACE inhibitors may, therefore, be related to the protective effect of ACE inhibition on renal perfusion intra-operatively. Furthermore, preoperative ACE inhibitor therapy in the surgical population may be associated with a higher preoperative renal function reserve, making these patients less susceptible to renal injury during further CPB.

Preoperative long-term treatment with ACE inhibitors may cause hypotension intra-operatively and postoperatively.¹⁷ We did not encounter any side effect in patients who were receiving ACE inhibitors, including hypotension on induction of anesthesia or an increase in extra and long-term vasoconstrictor need after CPB.

The other independent effective factors for renal dysfunction identified in the present analysis were consistent with the other reports.^5,18–23 We found that postoperative renal dysfunction was strongly related to age, preoperative LVEF of <40, diabetes mellitus, hypertension, and preoperative IABP. Our results confirmed that the variables related to perioperative hemodynamic instability, such as impaired LVEF and the preoperative use of an IABP, were related to postoperative renal dysfunction.^5,18,20–23 Such conditions are highly predictive of low cardiac output syndrome, which is one of the most important determinants of postoperative renal dysfunction. We determined that diabetes was an independent determinant of renal dysfunction. Differences have been determined in many studies associated with the effect of diabetes on renal dysfunction. As in our study, some studies have shown an increased risk of renal dysfunction among patients with diabetes mellitus,²⁴ but others have failed to demonstrate this.⁵ These differences may be due to the prevalence of diabetic patients among the populations of interest and the predominant type of diabetes.

Moreover, in our study, hypertension was identified as an independent factor in terms of renal dysfunction. This result has been shown in many studies. Together with diabetes mellitus, arterial hypertension is the most important cause of renal failure and of dialysis in the world. Hypertension is also a well-known consequence of chronic renal disease and, at the same time, one of the main factors causing diabetic or non-diabetic progression of chronic renal failure.^25,26 Beside the improvement in blood glucose control, the most important factor preventing the progression of renal damage in diabetes mellitus is tight BP control. One of the most important factors in the progression of chronic renal failure is activation of the RAS. Its effect is not only elevated blood pressure, but also promotion of cell proliferation, inflammation, and matrix accumulation. RAS over-activity is a hallmark of diabetes, which contributes to target organ damage. ACE inhibitors have demonstrated their efficacy in slowing the progression of renal failure in diabetic nephropathy. The treatment guidelines recommend ACE inhibitors for reducing the cardio–renal risk in patients with hypertension plus diabetes. However, these agents only partially prevent cardiovascular and renal morbidity/mortality.

In some studies, ACE inhibitors were seen to have no effects on any of the measures of the clinical outcome, such as the incidence of individual or multiple organ dysfunction, prolonged mechanical ventilation, ICU stay, or mortality after cardiovascular surgery.¹ The postoperative IABG rates were found to be lower, and the ICU and hospital stay were found to be shorter in the treatment group than in the control group in our study.

Treatment with ACE inhibitors has been proposed to facilitate the regression of hypertrophic changes and remodeling of the vascular smooth muscle and cardiac myocytes. The structural modification of end organs has explained the decreased adrenergic responsiveness of the cardiovascular system after treatment with ACE inhibitors.^27,28 In contrast, the current study found no difference in the hemodynamic variables or the cardiovascular support with inotropes and vasopressors after surgery associated with preoperative therapy with ACE inhibitors. Although there was no difference between the two groups with regard to the EF, there was a difference regarding the IABP rates and CPB times between the groups. Furthermore, the ICU and hospital stay were shorter in the treatment group.

The present study has some limitations. First, this study was non-randomized. For this reason, our results may have been affected by deviations in the treatment. In spite of the use of specific statistical evaluations permitting a relatively precise risk and outcome assessment and comparison, being a retrospective study among a small number of patients has made the validity of the clinical results limited. Further studies are needed, particularly to follow-up these patients to find the benefit of treatment with preoperative ACE inhibitors. Although a larger population of patients would be mandatory to guarantee more statistically significant results, we believe that our study can already show interesting results associated with preoperative ACE inhibitors. Furthermore, our analysis has many different surgical types associated with cardiac surgery operations on CPB; therefore, our results may be adversely affected by a number of different systemic changes and pathological situations during and after the cardiac surgery.

In conclusion, our results have demonstrated that preoperative ACE inhibitors are associated with a significant improvement in renal outcomes after cardiac surgery. The optimal management of preoperative ACE inhibitor treatment before cardiac surgery may be helpful in prevention of renal dysfunction. Preoperative therapy with ACE inhibitors positively affects the renal functions, and it can affect the clinical sequelae of CPB and cardiac surgical procedures.