Abstract

Methods: Between January 2008 and December 2014, a total of 220 patients (106 males, 114 females; mean age 50.6±14.7 years; range 14 to 79 years) who underwent aortic and mitral valve surgery were retrospectively reviewed. Baseline characteristics of the patients, comorbidities, operative variables, and postoperative outcomes were recorded. The patients were divided into two groups as those with and without acute kidney injury, as assessed by preoperative and postoperative creatinine levels using the Acute Kidney Injury Network Criteria.

Results: Of all patients, 57 developed acute kidney injury. Of these, 12 patients required hemodialysis (stage 1, n=40; stage 2, n=12; stage 3, n=5). The patients with acute kidney injury tended to be older with a higher rate of diabetes mellitus. These patients also had higher rates of postoperative sepsis, bleeding revision, atrial fibrillation, and need for intra-aortic balloon pump with longer intensive care unit and hospital stay. A higher number of patients with acute kidney injury needed packed red blood cell transfusion, compared to those without.

Conclusion: Our study results show that acute kidney injury which is diagnosed with mild postoperative creatinine changes according to the Acute Kidney Injury Network criteria is a prognostically important complication. Age, diabetes mellitus, and blood transfusion are the main risk factors of postoperative acute kidney injury. Therefore, patients should be analyzed carefully preoperatively to prevent short- and long-term results of cardiac surgery-related acute kidney injury.

There are many indicators which show kidney injury such as cystatin-C, N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, and serum creatinine (sCr); however, the latter is the most common indicator of the kidney injury.[4] Acute kidney injury may occur in a range from minimal elevation in sCr to anuria. Currently, many studies have shown that mild changes in sCr levels can be associated with high morbidity and mortality rates in the early and late postoperative period, and even after discharge from hospital with cardiac and renal recovery.[3,5] In recent years, several studies have addressed to the definition of AKI and certain criteria have been developed to define AKI and to monitor the severity of the disease, including Renal Risk, Injury, Failure, Loss of Kidney Function, End-stage Renal Disease (RIFLE) and the latest Acute Kidney Injury Network Criteria (AKIN), which focuses on mild sCr changes, have been shown to be more sensitive and specific, compared to the RIFLE.[6-8]

Although coronary artery bypass grafting (CABG) is a risk factor for AKI, cardiac valve surgery has a higher risk for postoperative AKI.[9] However, there is a limited number of studies in the literature investigating AKI in patients undergoing isolated cardiac valve surgery. In this study, we aimed to investigate the prevalence of AKI after isolated cardiac valve surgery, and to identify risk factors and one-year follow-up results.

Methods

Baseline demographic characteristics of the patients, body mass index, comorbidities, operative variables (i.e., cross-clamp time, total bypass time), preoperative ejection fraction, preoperative and postoperative hematological and biochemical profiles (i.e., sCr, hemoglobin), the amount of intra- and postoperative packed red blood cell transfusions, and postoperative outcomes were recorded.

The primary endpoints were as follows: development of AKI and one-year renal function following cardiac valve surgery. Acute kidney injury was defined by AKIN criteria,[7] as follows: stage 1: an increased postoperative sCr level of ≥1.5, but <2 times, compared to baseline; stage 2: an increased postoperative sCr level of ≥2, but <3 times, compared to baseline; and stage 3: an increased postoperative sCr level of ≥3 times, compared to baseline. The patients were, then, divided into two groups as those with AKI [AKI (+)] and without AKI [AKI (-)], based on the development of AKI within the first five days of surgery using the highest postoperative sCr levels.

Estimated glomerular filtration rate (eGFR) was also used to assess one-year follow-up of renal function and the eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) formula.[10] The e GFR was identified using postoperative fifth day, first, third, and sixth month, and first year sCr levels for survivors within this time period. The patients who were preoperatively on dialysis and patients who underwent an additional surgical intervention with mitral or aortic valve surgery such as CABG, tricuspid valve repair, left atrial ablation, combined aortic and mitral valve surgery or infective endocarditis were excluded from the study.

Postoperative complications including atrial fibrillation, intra-aortic balloon pump catheter placement, or bleeding revision, the length of stay in the intensive care unit and hospital, and in-hospital mortality were also evaluated.

Statistical analysis
Statistical analysis was performed using IBM SPSS version 22.0 software (IBM Corp., Armonk, NY, USA). Descriptive data were expressed in mean and standard deviation, median, frequency, and percentage. The Kolmogorov-Smirnov test was used to analyze the distribution of the variables. Baseline, operative, and postoperative characteristics and outcomes were compared between AKI (+) and AKI (-) patients using the Mann-Whitney U and chi-square tests. The Wilcoxon tests and Mann-Whitney U test were used to compare the difference between pre and post measurements of creatinine and eGFR levels, intraoperative and postoperative red packed cell transfusion amounts, and preoperative and postoperative hemoglobin levels between the groups. Chi-square test or Fisher’s test was used for analyzing of the qualitative data. A p value of <0.05 was considered statistically significant.

Results

Table 1: Baseline characteristics of the patients

Of 220 patients, 57 (26%) developed AKI, of which 12 (21%) required renal replacement therapy. Forty patients (18%) had stage 1 AKI, 12 (5%) had stage 2 AKI, and five (2%) had stage 3 AKI. There were no significant differences in the prevalence of AKI between patients who had aortic valve replacement and mitral valve replacement. However, the patients with AKI tended to be older than those without AKI (57.9±12.9 years vs 48.1±14.5 years; p=0.000). There was no significant difference in the gender, preoperative ejection fraction values, body mass index, cross-clamp time, total bypass time, preand postoperative lowest hemoglobin levels, and body temperature during cardiopulmonary bypass between the groups (p>0.05). However, the patients with AKI had a higher rate of diabetes mellitus (p=0.042), although AKI was not found to be associated with other preoperative risk factors such as peripheral and cerebrovascular disease, chronic pulmonary disease, and prior history of cardiac catheterization (Table 2).

Table 2: Patient’s operative characteristics and postoperative outcomes

There were no significant differences in preoperative creatinine levels between the two groups. In AKI (+) patients, postoperative creatinine levels were significantly higher, compared to AKI (-) patients. In AKI (-) patients, postoperative creatinine levels were significantly higher, compared to baseline levels; however, there was no significant difference at one, three, and six months, and one year, compared to baseline levels. On the other hand, in AKI (+) patients, sCr levels increased at one, three, and six months, and one year, compared to baseline levels (Table 3).

Tablo 3: The comparison of the creatinine and estimated glomerular filtration rate levels between acute kidney injury (-) and acute kidney injury (+) patients

In addition, in AKI (+) group, eGFR values decreased at one, three, and six months, and one year, compared to baseline levels (p<0.05). In AKI (-) patients, postoperative eGFR values decreased, compared to baseline eGFR; however, there was no significant difference at one, three, and six months, and one year, compared to baseline values (Table 3). One-year eGFR follow-up results of the patients are shown in Figure 1.

Figure 1: One year estimated glomerular filtration rate (eGFR) follow-up results between acute kidney injury (-) and acute kidney injury (+) patients.

The patients with AKI also had more complicated postoperative course. They had higher postoperative sepsis rates, bleeding revision, postoperative atrial fibrillation, need for intra-aortic balloon pump, and renal replacement therapy. These patients had also longer intensive care unit stay compared to those without (4.6±4.1 days vs 3.0±1.8 days; p=0.004); however, there was no significant difference in the in-hospital stay length between the groups. In addition, AKI (+) group also had higher in-hospital mortality rates (p=0.000). Considering the intra- and postoperative blood transfusion rates, the amount of transfused packed red blood cells was higher in AKI (-) group, than AKI (+) group (0.7±1.2 in AKI (-) vs 2.3±1.7 in AKI (+) group; p=0.000, for total transfusion values) (Table 4).

Tablo 4: The comparison of the preoperative/postoperative hemoglobin levels and number of intraoperative/ postoperative transfused packed red blood cell

Discussion

Acute kidney injury risk after cardiac surgery is also higher due to high inflammatory potential during cardiac surgery.[3] However, it varies among surgical interventions in cardiac surgery. Several studies have shown that cardiac valve surgery has a higher AKI risk than CABG and aortic surgery.[3,12] Some authors have claimed that this high risk may be explained with high congestive heart failure risk during pre- and postoperative period due to valve disease.[3,9] In our study, we only analyzed AKI risk after aortic and mitral valve replacement and we excluded combined CABG and valve surgery, combined valve surgery, aortic surgery, and left atrial ablation due to extrainflammatory capacity of these interventions in the pre- and postoperative period. Therefore, we had a homogeneous pre- and postoperative risk potential.

The studies which investigated AKI risk after CABG showed an AKI incidence of 10 to 14%.[13-15] Several studies investigated AKI after all types of cardiac surgery interventions, such as CABG, valve surgery, and combined surgery reported an AKI incidence ranging from 30 to 43%.[16,17] Mao et al.[18] investigated 209 patients who underwent aortic, mitral, tricuspid, and combined valve operations. The authors reported the AKI risk to be 46%. In another study, Najjar et al.[19] investigated a total of 2,169 patients who underwent aortic valve replacement. In their study population, AKI occurred in 8.5% of patients (stage 1: 67%; stage 2: 23%; stage 3: 10%). In our study, we found an AKI incidence of 26% (stage 1: 70%; stage 2: 21%; and stage 3: 9% of the AKI (+) patients). These results show that isolated CABG has the lowest AKI risk. If the rate of combined cardiac surgery increases, AKI risk may also increase. Isolated valve surgery has the lower AKI risk, compared to combined valve intervention.

Furthermore, AKI risk is closely associated with preoperative risk factors.[4] Preoperative comorbidities and intraoperative factors are of utmost importance and they may be modifiable factors for developing AKI.[5] Karkouti et al.[16] described major risk factors of AKI as follows: intraoperative mean arterial pressure, pre- and intraoperative anemia, need for intraoperative red blood cell transfusion, and pre- and intraoperative proinflammatory activity due to other organic diseases. Considering the comorbidities, there is a number of studies showing that diabetes mellitus, chronic obstructive pulmonary disease, high body mass index, congestive heart failure, and cardiopulmonary bypass time are important factors for AKI development.[16,19] In our study, we found a higher rate of diabetes mellitus in AKI (+) group with an older age. Other preoperative comorbidities were not related with AKI in our study. We also observed no significant difference in preoperative hemoglobin levels between the groups; however, intra- and postoperative amount of packed red blood cell transfusion were higher in AKI (+) patients, compared to AKI (-) patients. These results are also consistent with the literature data.[16,17,19]

Furthermore, cardiac surgery and cardiopulmonary bypass are significant factors which increase inflammatory activity due to artificial surface and ischemia reperfusion injury.[20] In patients with other active organic problems in addition to this inflammatory activity, such as AKI, lung injury, or sepsis and in patients with a high blood transfusion rate, prolonged ventilation time, and re-exploration in the postoperative period, postoperative morbidity and mortality increase.[20,21] There are several studies showing that postoperative AKI is associated with worse postoperative early and late outcomes.[3] Patients with AKI in the postoperative period have a higher infection and sepsis rate with longer intensive care unit stay and higher mortality rate, while they need more intra-aortic balloon pump and inotropic support.[19,22-25] Consistent with the previous findings, we found higher sepsis and postoperative atrial fibrillation rates in AKI (+) patients. Our patients with AKI also needed more intra-aortic balloon pump and renal replacement therapy during the postoperative course. They had also longer intensive care unit stay and higher in-hospital mortality rates. However, length of in-hospital stay did not significantly differ between the groups. In addition, a higher number of patients with AKI underwent postoperative bleeding revision.

Acute kidney injury occurs even with mild changes in the postoperative sCr and sCr normalizes in the short-term follow-up.[11] Despite early normalization of sCr, some studies have shown that renal blood flow and clearance function can remain impaired.[3] This can explain high morbidity and mortality rates in the longterm follow-up and may be the reason of developing chronic kidney disease.[3,16] Thakar et al.[26] investigated the effects of renal dysfunction on mortality in patients with renal dysfunction after cardiac surgery, but not requiring dialysis during the postoperative period. The authors reported equal to or more than 30% decline in the postoperative GFR values, compared to baseline. This decline in the GFR was found to be associated with a six-time higher mortality risk during long-term followup. In our study, we retrospectively analyzed survivors for one year. We found a decline in the eGFR values both in the AKI (-) and AKI (+) groups in the postoperative period. Nevertheless, this decline was not so prominent to cause AKI in -as the name implies- AKI (-) group. No significant changes were observed at the one, three, and six months, and one year, compared to baseline values. In AKI (+) group, eGFR values were always significantly lower, compared to previous time points, suggesting that postoperative AKI is a progressive disorder.

In conclusion, isolated cardiac valve surgery has higher acute kidney injury risk than isolated coronary artery bypass grafting; however, it did not significantly differ, compared to combined cardiac surgical interventions. Diabetes mellitus is a significant preoperative risk factor for isolated cardiac valve replacement. Age, diabetes mellitus, and blood transfusion are the main risk factors of postoperative acute kidney injury. Therefore, patients should be analyzed carefully preoperatively to prevent short- and long-term results of cardiac surgery-related acute kidney injury. Finally, it must be kept in mind by surgeons that even mild changes in serum creatinine levels may indicate acute kidney injury in the postoperative period and its effect may be progressive or even irreversible.

Declaration of conflicting interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding
The authors received no financial support for the research and/or authorship of this article.

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