Impact of Chronic Kidney Disease on Clinical Outcomes during Hospitalization and Five-Year Follow-Up after Coronary Artery Bypass Grafting

Background Chronic kidney disease (CKD) is often associated with multiple comorbidities including diabetes mellitus, and each has its own complications and impact after cardiac surgery including coronary revascularization. The objective of this work was to study the impact of CKD on clinical outcomes after coronary artery bypass grafting (CABG) and to compare outcomes in patients with different grades of renal functions. We retrospectively reviewed all patients who underwent CABG from January 2016 to August 2020 at our tertiary care hospital using electronic medical records. Results The study included 410 patients with a median age of 60 years, and 28.6% of them had CKD and hospital mortality of 2.7%. About 71.4% of the patients had GFR > 60 mL/min per 1.73 m2, 18.1% had early CKD (GFR 30–60), 2.7% had late CKD (GFR < 30), and 7.8% of them had end-stage renal disease (ESRD) requiring dialysis. The CKD group had significantly more frequent hospital mortality (p = 0.04), acute cerebrovascular stroke (p = 0.03), acute kidney injury (AKI) (p < 0.001), longer ICU stay (p = 0.002), post-ICU stay (p = 0.001), and sternotomy wound debridement (p = 0.03) compared to the non-CKD group. The frequencies of new need for dialysis were 2.4% vs. 14.9% vs. 45.5% (p < 0.001) in the patients with GFR > 60 mL/min per 1.73 m2, early CKD, and late CKD, respectively. Acute cerebral stroke (OR: 10.29, 95% CI: 1.82–58.08, and p = 0.008), new need for dialysis (OR: 25.617, 95% CI: 13.78–85.47, and p < 0.001), and emergency surgery (OR: 3.1, 95% CI: 1.82–12.37, and p = 0.036) were the independent predictors of hospital mortality after CABG. The patients with CKD had an increased risk of strokes (HR: 2.14, 95% CI: 1.20–3.81, and p = 0.01) but insignificant mortality increase (HR: 1.44, 95% CI: 0.42–4.92, and p = 0.56) during follow-up. Conclusion The patients with CKD, especially the late grade, had worse postoperative early and late outcomes compared to non-CKD patients after CABG. Patients with dialysis-independent CKD had increased risks of needing dialysis, hospital mortality, and permanent dialysis after CABG.

Background.Chronic kidney disease (CKD) is often associated with multiple comorbidities including diabetes mellitus, and each has its own complications and impact after cardiac surgery including coronary revascularization.Te objective of this work was to study the impact of CKD on clinical outcomes after coronary artery bypass grafting (CABG) and to compare outcomes in patients with diferent grades of renal functions.We retrospectively reviewed all patients who underwent CABG from January 2016 to August 2020 at our tertiary care hospital using electronic medical records.Results.Te study included 410 patients with a median age of 60 years, and 28.6% of them had CKD and hospital mortality of 2.7%.About 71.4% of the patients had GFR > 60 mL/min per 1.73 m 2 , 18.1% had early CKD (GFR 30-60), 2.7% had late CKD (GFR < 30), and 7.8% of them had end-stage renal disease (ESRD) requiring dialysis.Te CKD group had signifcantly more frequent hospital mortality (p = 0.04), acute cerebrovascular stroke (p = 0.03), acute kidney injury (AKI) (p < 0.001), longer ICU stay (p = 0.002), post-ICU stay (p = 0.001), and sternotomy wound debridement (p = 0.03) compared to the non-CKD group.Te frequencies of new need for dialysis were 2.4% vs. 14.9% vs. 45.5% (p < 0.001) in the patients with GFR > 60 mL/min per 1.73 m 2 , early CKD, and late CKD, respectively.Acute cerebral stroke (OR: 10.29, 95% CI: 1.82-58.08,and p = 0.008), new need for dialysis (OR: 25.617, 95% CI: 13.78-85.47,and p < 0.001), and emergency surgery (OR: 3.1, 95% CI: 1.82-12.37,and p = 0.036) were the independent predictors of hospital mortality after CABG.Te patients with CKD had an increased risk of strokes (HR: 2.14, 95% CI: 1.20-3.81,and p = 0.01) but insignifcant mortality increase (HR: 1.44, 95% CI: 0.42-4.92,and p = 0.56) during follow-up.Conclusion.Te patients with CKD, especially the late grade, had worse postoperative early and late outcomes compared to non-CKD patients after CABG.Patients with dialysis-independent CKD had increased risks of needing dialysis, hospital mortality, and permanent dialysis after CABG.

Background
Coronary artery bypass grafting (CABG) is surgical coronary revascularization in patients with advanced coronary artery disease who are unsuitable for or after unsuccessful trials of percutaneous coronary interventions (PCI) [1].Chronic kidney disease (CKD) is often associated with multiple comorbidities including diabetes mellitus, and each has its impact after cardiac surgeries and revascularization.Tere is a proven association between CKD and a high prevalence of cardiovascular disorders.Moreover, patients with end-stage renal disease (ESRD) have a 10-30-fold increased mortality compared with general people [2].Chronic renal failure was linked to cardiovascular mortality due to myocardial dysfunction, systemic hypertension, chronic anemia, dyslipidemia, hyperhomocysteinemia and hyperfbrinogenemia, nitric oxide/endothelin imbalance, oxidative stress, and chronic infammation [2][3][4][5].Many studies proved the association between ESRD and diferent worse outcomes after CABG [6][7][8].We conducted this study to identify the impact of CKD on outcomes after CABG and to compare the outcomes in patients with diferent grades of renal functions.

Study Design and Data Collection.
We conducted this retrospective study including all adult patients who underwent CABG between 2016 and 2020 in our tertiary care hospital.We collected the variables studied from electronic hospital records.Te study was approved by the Ethical Committee of King Faisal Specialist Hospital and Research Center and waived from specifc consent as there were no personally identifable data or photos.Te study reference number is 2211015, and the publication number is 22350215021.Te data collected included demographic and perioperative variables.Te primary outcome was hospital mortality, while the secondary outcomes included cerebrovascular stroke, new need for dialysis, sternotomy wound debridement, and length of hospitalization.Te studied variables included patients' characteristics, risk factors of cardiovascular and cerebrovascular diseases, prior revascularization, left ventricular ejection fraction, perioperative mechanical circulatory support, and laboratory workup including blood lactate, troponin, and glycated hemoglobin (HbA1c).Te operative data collected included cardiopulmonary and aortic cross-clamping times, urgency and the approach of surgery, surgical bleeding, and need for exploration.Te postoperative data collected included acute kidney injury (AKI), new need for dialysis, acute cerebrovascular stroke, mortality, length of stay, gastrointestinal bleeding, arrhythmias, sternotomy wound infection, and need for debridement.Follow-up data included mortality and acute cerebrovascular stroke.
According to the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines, CKD was defned as a glomerular fltration rate (GFR) less than 60 mL/ min/1.73m 2 for ≥3 months irrespective of etiology [9,10].According to the degree of kidney injury, there were 5 stages of CKD.Because of imprecision to accurately estimate GFR at higher ranges, it is difcult to distinguish between stages 1 and 2. Clinically, CKD was classifed according to severity into early CKD, late CKD, and ESRD [9] (Table 1).AKI was defned as an acute reduction of renal functions as monitored by urine output or GFR according to the risk, injury, failure, loss, and end-stage renal disease (RIFLE) criteria [11].

Statistical Analysis.
Data were summarized using the median with an interquartile range in quantitative data and frequency (count) with relative frequency (percentage) for categorical data.Te nonparametric Kruskal-Wallis and Mann-Whitney tests were used for quantitative variable comparison.Te Chi-square (c2) test was performed to compare the categorical variables.Two-sided p values were considered statistically signifcant if < 0.05.Multivariate logistic regression was performed to get the predictors of hospital mortality and acute cerebrovascular stroke.We obtained the Kaplan-Meier survival curves using the logrank test.Te Hosmer-Lemeshow test was used to detect the goodness of ft of the regression models.Variance infation testing was performed to detect multicollinearity of the regression models.Te Statistical Package for Social Sciences (SPSS) version 26 (IBM Corp., Armonk, NY, USA) was used in our study analysis.

Baseline Clinical Variables of the Studied Patients.
Four hundred and ten adult patients with a median age of 60 (55-68) years were enrolled in our study and divided into 2 groups according to presence of CKD.A total of 117 (28.6%) patients had CKD, while 293 (71.4%) patients did not have CKD before CABG (Table 2).

Laboratory Variables of the Studied Patients.
Preoperatively, the studied patients with CKD had signifcantly lower median levels of hemoglobin (p < 0.001), albumin (p < 0.001), and bilirubin (p < 0.001) but a higher median HBA1c level (p � 0.003) compared to the patients without CKD, respectively.Postoperatively, the patients with CKD had signifcantly higher blood lactate (p � 0.006) and troponin levels (p < 0.001) compared to the non-CKD group, respectively (Table 2).

Operative Details and Outcomes of the Studied Patients.
Te operative details and use of mechanical circulatory support were statistically insignifcant among the studied patients with diferent grades of GFR.Te frequencies of new need for dialysis were 2.4% vs. 14.9% vs. 45.5% (p < 0.001) in the patients with GFR > 60 mL/min per 1.73 m 2 , early CKD, and late CKD, respectively.Te CKD group had signifcantly more frequent acute ischemic cerebrovascular stroke (p � 0.03), higher hospital mortality (p � 0.04), longer ICU (p � 0.002), and post-ICU stay (p � 0.001) than the non-CKD group (Tables 4 and 5).
Kaplan-Meier curves revealed that the CKD group had an increased risk of cerebrovascular strokes (HR: 2.      6 and 7).

Discussion
Our study showed that the presence of CKD before CABG was associated with increased hospital mortality, multiple morbidities, and prolonged hospitalization.Te overall mortality in this cohort was 2.7%, and it ranged from 2.1% in patients with GFR >60 mL/min/1.73m 2 to 9.1% in patients with late CKD.Our mortality report was similar to Cooper et al.'s study [12] that reported a hospital mortality of 2.5%, and it was 9.3% in patients with late CKD and 9% in hemodialysis dependents before CABG.Reddan et al. [13] studied the relation between GFR and hospital mortality after revascularization and documented that each GFR decline of 10 ml/min/1.73m 2 was associated with a 14% increased risk of mortality, but at GFR >85 mL/min/1.73m 2 , the relation was attenuated.Te subgroup analysis revealed a lower mortality in preoperative dialysis-dependent patients compared to the late group which may be related to the small group size.Moreover, in our cohort, 5% of the late CKD group required dialysis during hospitalization, and the new need for dialysis was a predictor of hospital mortality.Liu et al. [6] reported that preoperative hemodialysis had a three-fold increase in hospital mortality after CABG.Yamauchi et al. [7] reported signifcantly higher operative and 30-day mortality in hemodialysis compared to nonhemodialysis patients after CABG.Safaie et al. [8] reported a hospital mortality of 10.5% in CKD patients who underwent CABG, and there was an insignifcant diference between dialysis-dependent and nondialysis-dependent patients.
Acute cerebrovascular stroke occurred in 7.3% of the patients after CABG in our study.Compared to the non-CKD group, the patients with CKD, especially those with late CKD, had an increased risk of acute stroke during hospitalization and the 5-year follow-up.Moreover, preoperative CKD was a predictor of acute postoperative stroke in the logistic regression analysis.Cooper et al. [12] reported that late CKD and dialysis dependence were associated with postoperative stroke.Liu et al. [6] reported that patients with preoperative hemodialysis dependence were 2.1 times more likely to have postoperative stroke.Preoperative CKD carried an increased risk of acute cerebrovascular stroke during the follow-up after CABG [5,14].Regarding other postoperative morbidities, the study results revealed a higher frequency of sternotomy wound debridement in the CKD group compared to the non-CKD group.Tere was a statistically insignifcant diference between both groups regarding mediastinal exploration for bleeding.Te CKD group had longer hospitalizations with more days of vasopressor and IABP support compared to the non-CKD group.Tese fndings were similar to those of Cooper et al.'s report [12] which revealed prolonged hospitalization, deep sternal wound infection, and exploration for bleeding, especially in late CKD and dialysis-dependent patients.Liu et al. [6] reported that preoperative hemodialysis dependence carried a higher risk of mediastinitis but an insignifcant diference for exploration because of bleeding compared to nondialysis dependence.CKD was linked to postcardiotomy 30-day and 1-year mortality [15,16].However, Powell et al. [17] conducted a small study and reported that dialysis dependence was associated with prolonged hospitalization without an increase in perioperative mortality and morbidities.Kan and Yang [18] reported that uremia was associated with bleeding tendency, prolonged ICU stay, and late mortality after CABG.
Te patients with CKD have abnormal hemostatic profles with abnormal risks of bleeding and thrombotic events.Ocak et al. [19] studied 10,347 patients and reported that patients with GFR <45 mL/min per 1.73 m 2 and albuminuria had a 3.5-fold increased risk of bleeding.Platelet dysfunction was described in patients with advanced renal impairment as uremic thrombocytopathy and was related to decreased thromboxane A2 formation and von Willebrand factor (vWF) defect [20].Renal impairment has been included in multiple bleeding risk scores such as ATRIA and HAS-BLED scores [21,22].Te abnormal hemostatic profles of CKD with added efects of cardiopulmonary bypass may lead to increased postoperative bleeding and thromboembolic complications.Cardiopulmonary bypass circulation leads to acute phase reaction and systemic infammatory response with platelet activation and consumption and possible thromboembolic events [23].Te enrolled patients in this study underwent on-pump CABG, and there were insignifcant diferences regarding cardiopulmonary bypass and aortic clamping times in the CKD and non-CKD groups.It is still controversial to select onpump or of-pump during CABG for better postoperative outcomes.Lamy et al. [24] reported the advantages of ofpump CABG regarding lower rates of AKI and respiratory and bleeding complications but similar rates of 30-day mortality, cerebrovascular stroke, myocardial infarction, and new need for dialysis compared to on-pump CABG.Li et al. [25] reported higher 30-day mortality and worse outcomes including new need for dialysis in the CKD group after of-pump CABG compared to the non-CKD group.Ueki et al. [26] reported that of-pump CABG signifcantly decreased the postoperative mortality in patients with CKD and decreased the need for dialysis in patients with late CKD.
In our study, deep sternal wound infection that required debridement was signifcantly more frequent in the CKD group compared to the non-CKD group.Our fndings were consistent with Cooper et al.'s report [12].Ishigami et al. [27] studied 9,697 patients with a 13.6-year median follow-up and reported increased hazard ratios (HRs) of infectionrelated hospitalizations and death with the decline of GFR.CKD is associated with a chronic low-grade infammatory state with increased proinfammatory cytokines, resulting in increased cardiovascular risks, infections, and malignancy [28,29].
CKD is associated with increased cardiovascular and cerebrovascular insults due to accelerated atherosclerosis, chronic infammation, vascular calcifcation, electrolytes abnormalities, and anemia in addition to associated comorbidities including diabetes mellitus, dyslipidemia, and hypertension.Vascular calcifcation afects both the intima and media of arteries causing stifness which increase the systolic and decrease diastolic blood pressure, resulting in decreased coronary perfusion, increased left ventricular afterload, and increased cardiovascular mortality [5,29].Calcifcation of the vascular media is the characteristic of CKD patients, described as Monckebergʼs sclerosis, and results from hyperphosphatemia [30].Impaired renal phosphate secretion results in hyperphosphatemia and increased cardiovascular mortality [5].CKD is associated with anemia due to decreased erythropoietin secretion and results in decreased oxygen supply, increasing cardiovascular risks [31].
Another challenging point in management of patients with CKD is postoperative analgesia.Postoperative sternotomy pain requires strong analgesia to control the sympathetic stimulation and cardiovascular side efects.However, impaired pharmacokinetics of opiates in the presence of CKD can result in side efects including prolonged sedation, seizures, delirium, nausea, vomiting, and respiratory complications [32].Appropriate postcardiac surgery analgesia is critical, especially in CKD, to achieve a balance of pain control with patient satisfaction and avoid drug accumulation with side efects [33,34].
Finally, with the advances of medical care, the patients presented to CABG have advanced age and multiple comorbidities including CKD and dialysis dependence.Meticulous perioperative management including hemodynamics optimization, appropriate fuid and electrolyte management, and appropriate analgesia should be addressed to high-risk patients with CKD to minimize perioperative morbidities and mortality.

Conclusion
Te patients with CKD, especially the late grade, had worse postoperative early and late outcomes compared to non-CKD patients after CABG.Patients with dialysisindependent CKD had increased risks of needing dialysis hospital mortality and permanent dialysis after CABG.

Limitations
Tis work was a single-center retrospective study with a relatively small sample size.It missed perioperative blood sugar control and the amount of postoperative bleeding and Critical Care Research and Practice blood transfusions.We used preoperative glycated hemoglobin as a marker of blood sugar control in the studied patients.We could not get data on blood glucose variability and control during hospitalization.We studied the impact of renal impairment on outcome, but the study missed some key details about dialysis modalities and efciency and the laboratory fnding of parathormone and electrolytes.Te enrolled patients in this study underwent on-pump CABG as this is the standard approach in our hospital, and we do not know the validity of our result for of-pump CABG.We studied the surgical wound infection without other infections during hospitalization.

Table 2 :
Demographic and clinical variables of the patients studied.
Critical Care Research and Practice

Table 3 :
Demographic and clinical variables of the patients according to GFR.

Table 4 :
Operative details and outcomes of the studied patients.
logistic regression analysis.Te regression model had a goodness of ft by the Hosmer-Lemeshow test (Pearson chi 2 � 57.61, p value � 1), and the mean variance infation factor was 1.19 (Tables

Table 5 :
Operative details and outcomes of the studied patients according to GFR.

Table 6 :
Univariate analysis according to hospital mortality.

Table 7 :
Logistic multivariate regression to obtain the predictors of postoperative stroke and hospital mortality.