Effects of Chronic Kidney Disease on 5-Year Follow-Up Clinical Outcomes After Off-pump Coronary Artery Bypass Grafting-A Retrospective Study

Backgroud To investigate the effect of chronic kidney disease (CKD) on mid- and long-term clinical outcomes after off-pump coronary artery bypass grafting (CABG). Methods This was a retrospective analysis of data of1141 discharged patients from January 2010 to June 2018 after undergoing off-pump CABG. Follow-up endpoints included stroke, myocardial infarction, heart failure, revascularization, and all-cause death.Patients with preoperative estimated glomerular ltration rate calculated, using the Chronic Kidney Disease Epidemiology equation of ≥ 60 mL/min/1.73 m 2 and < 60 mL/min/1.73m 2 , were assigned tonormal Group (1, 910 cases) and CKD group (231 cases), respectively. The effects of CKD on selected endpoint events were compared and analyzed. long-term survival rate.


Abstract Backgroud
To investigate the effect of chronic kidney disease (CKD) on mid-and long-term clinical outcomes after off-pump coronary artery bypass grafting (CABG).

Methods
This was a retrospective analysis of data of1141 discharged patients from January 2010 to June 2018 after undergoing off-pump CABG. Follow-up endpoints included stroke, myocardial infarction, heart failure, revascularization, and all-cause death.Patients with preoperative estimated glomerular ltration rate calculated, using the Chronic Kidney Disease Epidemiology equation of≥ 60 mL/min/1.73 m 2 and < 60 mL/min/1.73m 2 , were assigned tonormal Group (1, 910 cases) and CKD group (231 cases), respectively. The effects of CKD on selected endpoint events were compared and analyzed.

Results
There was a higher proportion of women, more preoperative complications, and a higher incidence of early postoperative complications in patients with CKD than inthose with normal renal function.After 1-9 years of follow-up (mean5.0±2.2 years), the incidences of stroke, myocardial infarction, and all-cause mortality were signi cantly higher in the CKD than in the normal renal function group, whereas incidences of revascularization and heart failure were not.Logistic regression analysis showed that preoperative CKD was a risk factor for stroke, myocardial infarction, and all-cause death during follow-up. After correctingfor common confounding factors, such as sex, age, and left ventricular ejection fraction, preoperative CKD was a risk factor for myocardial infarction and all-cause death.

Conclusions
In patientsundergoing off-pump CABG, preoperative CKD is associated with increases in the incidences of myocardial infarction and all-cause mortality 5-year postoperation..

Background
Chronic kidney disease (CKD) is a major risk factor for coronary artery disease (CAD) [1], andtherisk of death, cardiovascular events, and hospitalization increasewith decreasingestimated glomerular ltration rate (EGFR) [2].Coronary artery bypass grafting(CABG) and percutaneous coronary intervention (PCI) are effective treatments for severe coronary heart disease. A meta-analysis found that CABG is associated withsigni cantly lowerlong-term mortality in patients with CKD and end-stage renal diseasethan is PCI [3].
Whether off-pump or on-pump CABG is preferable for patients with coronary heart disease with CKDis controversial. Current studies have shown that off-pumpCABG may be superior, possibly because offpump obviates the need forcardiopulmonary bypass and protectsrenal function in the perioperative period. It is alsoassociated with fewer complications,including allogeneic blood transfusion, postoperative thoracotomy hemostasis, acute kidney injury, and respiratory system dysfunction [4].In particular, off-pump CABG signi cantly reduces operative mortality and risk of postoperative dialysis in patients with moderate or severe renal insu ciency [5]. Off-pump CABG is currently preferred in mainland China, accounting for approximately 95% of total CABG procedures in our department.Management of such patients is very complicated, and the impact of the comorbidity of CKD on mid-and long-term clinical outcomes of off-pump CABG hasrarelybeen studied. We therefore conducted a retrospective study

Methods
Inclusion criteria were as follows: consecutive, rst-time patients undergoing off-pump CABGdischarged from our hospital from January 2010 to June 2018.Exclusion criteria were as follows: acute renal insu ciency, preoperative end-stage renal disease dependent ondialysis, intraoperative transfer to onpump, death within 30 days after surgery, incomplete data, and refusal to attend for follow-up.The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR [6].Patients with eGFR CKD−EPI > 60 mL/min/1.73 m 2 were classi ed as having normal renal functionand those with < 60 mL/min/1.73 m 2 as havingCKD.Baseline and operative data during hospitalization andpostoperative outpatient or telephone follow-up data were collected for statistical analysis.Clinical outcomes included stroke, myocardial infarction, heart failure, revascularization, and allcause death. SPSS21.0 software(IBM Corp., Armonk, NY, USA) was used for analysis;the χ 2 or Fisher's exact test for analyzing count data between two groups and agroup t-test for measurement data.The effect of preoperative CKD on all clinical outcome events during follow-up was analyzed by logistic regression.Odds ratios (ORs) and 95% con dence intervals were calculated byunivariateanalysis and corrected for common confounding factors, such as sex, age, and left ventricular ejection fraction (LVEF).P < 0.05 was consideredto denote a signi cant difference (two-sided test).

Results
A total of 1141 patients were included in the study: 910 in the normal Group and 231 in the CKD group.Comparisons of baseline and operative data during hospitalization are shown in Table 1.There was a higher proportion of women, older mean age, and higher incidence of preoperative and postoperative complications in the CKD group than in the normal renal function group.
All patients underwentoutpatient or telephone follow-up for 1-9 years (mean 5.0 ±2.2 years). The incidences of stroke, myocardial infarction, and all-cause mortality were signi cantly higher in the CKD than the normal renal function group, whereas the incidences of revascularization and heart failure were not. Clinical endpoints according to study group areshown in Table 2.
Results of logistic regression analysis on the effect of preoperative CKD on clinical outcome events areshown in Table 3.Preoperative CKD was found to be a risk factor for stroke, myocardial infarction, and all-cause mortality. After correctionfor common confounding factors, such as sex, age, and LVEF, preoperative CKD was identi ed asa risk factor for myocardial infarction and all-cause mortality.

Discussion
Patients with CKD have a signi cantly increased risk of coronary heart disease, not only because oftraditionally recognized CAD risk factors such as diabetes and hypertension, but also because of other non-traditionally recognized cardiovascular disease risk factors associated with uremia, including in ammation, oxidative stress, and abnormal calcium-phosphorus metabolism [1].Lipid metabolism disorders, mainly hypertriglyceridemia, are risk factors for coronary heart diseasein patients with CKD.This accounts for a prevalence of coronary heart disease of approximately 12% in patients with Stage 3 or greater CKD, compared with only 5% in those with normal renal function [7].CKD is often accompanied by disorders of mineral bone metabolism, hypocalcemia,hyperphosphatemia, and secondary hyperparathyroidism, all of which canaccelerate systemic atherosclerosis and vascular calci cation [8].In ammatory responses, oxidative stress, impaired endothelial cell function, coronary artery calci cation, hyperhomocysteinemia, immunosuppression, and other mechanismscan contribute to signi cant acceleration of atherosclerosis, leading to a poor prognosis in this patient group.Complicationsof coronary heart disease, such as myocardial infarction and heart failure, are the main causes of death [9].Particularly in dialysis-dependent patients withadvanced CKD, the death rate is as high as 40%-50% [10].A 2012 epidemiological survey reported anincidence of CKD in mainland China of10.8% and estimated that there were 119.5 million patients withCKD in that country [11].Increasing numbers of thesepatients will require CABG in the future. There is an urgent need to improvepostoperative long-term survival rate.
In patients with severe coronary heart disease and non-dialysis-requiring CKD, CABG achieves signi cantly lowermortality, re-infarction, and revascularization rates than do PCI and drug therapy [12,13].In one study 2108 patients with CKD who underwentPCI usingdrug-eluting stents, (n=1165) orCABG (n=943) were prospectively analyzed in a nonrandomized study with anaverage follow-up of 41.4 months.Although no signi cant differences in all-cause death, stroke, and myocardial infarction were observed between the two groups, the revascularization rate was signi cantly higher in the PCI group [14].A meta-analysis of 29,246 patients enrolled in 11 studies showed that CABG achievedlower long-term all-cause mortality, cardiac mortality, andincidences of myocardial infarction and revascularization, and fewer major adverse cardiacand cerebrovascular events (MACCE) than did drug-eluting stents forrevascularization in patients with multivesselcoronary heart disease and CKD. However, mortality and risk of cerebrovascular eventshaverecentlyincreased [15].Although CABG can signi cantly improve the survival rate, it also increases the incidence of postoperativerenal failure, especially in high-risk patients [16].
Off-pump CABG reportedly has a protective effect on renal function in the perioperative period because of it does not entailcardiopulmonary bypass; it also reduces the incidences of complications, such as allogeneic blood transfusion, post-operative thoracotomy hemostasis, acute kidney injury, and respiratory system dysfunction [4].However, in the CORONARY study, no signi cant difference was observedbetweenon-pump and off-pump CABGin effectson renal function at the 1 year follow-up, and offpump had no demonstrable long-term renal protective effect [17]. In the present study, there was a higher proportion of women, older mean age, and higher incidences of preoperative and postoperative complications in theCKD thanin the normal group.The follow-up period ranged from 1 to 9 years, with an average of 5.0±2.2 years.The incidences of stroke, myocardial infarction, and all-cause mortality were signi cantly higher in the CKD than in the normal renal function group; however, those of revascularization and heart failure were not.Logistic regression analysis showed that preoperative CKD was a risk factor for stroke, myocardial infarction, and all-cause mortality. After correctingfor common confounding factors such as sex, age, and LVEF, preoperative CKD was identi ed as a risk factor for myocardial infarction and all-cause mortality in the off-pump CABG over a mid-to long-term follow-up.
CKD and end-stage renal disease not only increase the risk of CAD, but also change its clinical manifestations and main symptoms.Management of patients with CAD and CKD is complexbecause of the possibility of complications and adverse effects during interventions [1].Protection of renal function and improvement in postoperative survival are criticalfor discharged patients with CKD not undergoing dialysiswho have undergone CABG.There is a need for cooperation among cardiac surgeons, cardiologists, nephrologists, and endocrinologists to enhance postoperative management and constructcomprehensive strategies, to improve prognosis and reduce complications and mortalityin highrisk patients.
First, the identi cation of high-risk patients facilitates rational allocation of medical resources, targeted prevention, and management.As renal function worsens,the length of hospital stay and medical costsand the number of complications increase.Decreasesin creatinine clearance to80, 60, and 20 mL/min reportedly lead to cost increases of 10%, 20%, and 30%, respectively.Additionally, the incidence of need for dialysis and mortality increase postoperatively [18].Grouping of CKD severity on the basis ofeGFR calculated by the CKD-EPI equation effectively predictspostoperative complications and mortality in both the short-and long-term [23]. eGFR CKD-EPI <30 mL/min/1.73 m 2 , <41 mL/min/1.73 m 2 , <27 mL/min/1.73 m 2 , and <29 mL/min/1.73 m 2 are predictors of early mortality, stroke, prolonged length of hospital stay, and postoperative dialysis substitution, respectively.Additionally, eGFR CKD-EPI <26mL/min/1.73 m 2 , <25mL/min/1.73 m 2 , <35mL/min/1.73 m 2 ,and <29mL/min/1.73 m 2 are predictors of all-cause death, cardiovascular death, myocardial infarction, and heart failure,respectively, during follow-up (average follow-up time 66 months) [19].Therefore, the management of high-risk patients needs to be further strengthened.
Second, active treatment ofcomorbidities such as hypertension, diabetes, and anemia is vital.Hypertension and diabetes are the two commonestcomorbidities in patients with CKD.Recommendations for treatment of diabetic nephropathy include control of HB1Ac<7%, blood pressure <140/90 mmHg, and treatment with renin-angiotensin system blockers [20].Patients with CKD have a high incidence of hypertension that may lead to or originate from CKD.Hypertension aggravates CKD, resulting in uncontrollable hypertension [21].The 2017 American College of Cardiology/American Heart Association Hypertension Guidelines set a BP target of <130/80 mm Hg for patients with CKD and other strongcardiovascular risk factors toreduce mortality in patients with CKD. However, fewdata are available for patients with diabetes or Stage 4-5 CKD [22].Anemia, another common manifestation of renal insu ciency, causes decreased erythropoietin secretion and renal anemia.Anemia predicts the risk of cardiovascular events and death in patients with coronary heart disease [23].
Third, measures for secondary prevention of coronary heart disease should be actively continued postoperatively, including oral antiplatelet drugs, statin treatment, and good living habits.

Conclusions
Patients withCKD undergoing CABG are older preoperatively, have more complications, and moreearly postoperative complications than those with normal renal function.5-year follow-up after CABGrevealed associations between preoperative CKD and higher incidences of MI and all-cause mortality (after correcting forcommon confounding factors such as sex, age, and LVEF).Among patients with CKD undergoing off-pump CABG, it is necessary to identify high-risk patients and strengthen comprehensive management to reduce complications and improve long-term survival.   Table 3. Logistic regression analysis of the effect of CKD on clinical outcome events (before and after adjusted)