European Journal of Cardiovascular Medicine

Acute kidney injury (AKI) is characterized by a fast decline in kidney function indicated by a rapid rise in blood creatinine levels and reduced urine output. [1]Approximately 30% of patients experience AKI following CABG surgery, with around 2% needing interim dialysis.[2] Postoperative acute kidney injury (AKI) is linked to higher rates of short-term and long-term illness and death.[3,4] CABG can be categorized as on-pump CABG or off-pump CABG depending on the use of cardiopulmonary bypass (CPB). CPB is widely recognized as a risk factor for AKI following CABG due to its association with inflammatory response, nonpulsatile flow, hemodilution, renal hypoperfusion, atheroembolism, and free hemoglobin. [5,6]Whether the off-pump technique can enhance the success of CABG remains a contentious topic, with numerous research comparing outcomes between on-pump and off-pump techniques. The on-pump group generally has a greater incidence of AKI compared to the off-pump group, [7,8]although there are no significant differences in terms of mortality and renal failure outcomes. [7,9,10]
The findings indicated that postoperative AKI with on-pump CABG did not lead to worse outcomes, contradicting earlier data. Age is a significant risk factor for AKI, with limited research focusing on senior patients (aged 70 years or older) who are particularly susceptible to AKI after receiving CABG.

This study aimed to investigate acute kidney injury (AKI) in older patients who underwent their first isolated coronary artery bypass grafting (CABG) using either on-pump or off-pump techniques. The study was conducted retrospectively at a single center using propensity score matching (PSM). We hypothesized that off-pump CABG could decrease the occurrence and severity of AKI in older patients and planned to observe any potential differences in long-term kidney function and survival compared to on-pump CABG

The present observational study was undertaken at a tertiary care centre on all patients undergoing CABG over an 18-month period. Adult patients aged 41 to 70, of any gender, diagnosed with triple vessel, double vessel, or single vessel illness, scheduled for on-pump CABG surgery, and classified as American Society of Anesthesiologists (ASA) II and III physical status were included. Patients having preoperative serum creatinine levels over 1.20 mg/dl in males and 0.8 mg/dl in females, aged below 40 or above 70 years, Death of a patient during or after surgery within 24 hours, not caused by decline in kidney function. Pre-existing kidney disease, prior nephrectomy, or previous renal transplantation. Pregnant women and patients who are not prepared to provide permission. After receiving ethical approval from the Institute's ethics committee, all eligible patients were enrolled based on the inclusion criteria, and written consent was obtained from each of them. Comprehensive information on socio-demographic factors, including name, age, gender, place of residence, education, occupation, socioeconomic position, etc., was collected from all participants and recorded in a questionnaire. Details of the patient's current symptoms, how long they have been experiencing the ailment, and any other existing medical issues were recorded. Subsequently, all the patients underwent a general and physical examination. Their vital signs, including pulse, blood pressure, respiration rate, and temperature, were recorded first. The ASA grade was recorded. All standard blood tests were performed initially. Serum Creatinine levels were recorded before surgery

The study included 58 participants with a mean age of 62.18 ± 8.01 years, predominantly male (76.7%). The distribution by age showed that individuals aged 51-70 years constituted the majority, with 34.5% and 40.5% respectively, while those ≤50 and ≥70 years accounted for 9.5% and 15.5% respectively. In terms of diagnosis, coronary artery disease with triple vessel disease (CAD-TVD) was the most common (51.9%), followed by CAD-TVD with left ventricular dysfunction (25%) and CAD-TVD with valvular dysfunction (5.2%). Hypertension (75.9%) and diabetes (56%) were the most prevalent medical histories, followed by obesity (6%) and cerebrovascular accidents (2.6%). Other conditions such as post percutaneous coronary intervention (PCI), osteoarthritis (OA) knee, hypothyroidism, asthma, benign prostatic hyperplasia (BPH), psoriasis, chronic kidney disease (CKD), dyslipidemia, old inferior wall myocardial infarction (IWMI), Parkinson's disease, recent myocardial infarction (MI), rheumatic heart disease (RHD), sudden cardiac death (SCD) with old coronary artery disease (CAD), smoking, and tobacco chewing were reported in smaller frequencies, each at 1.7%. Additionally, 11.2% had no reported medical history.

The distribution among participants based on ASA grading revealed that the majority were classified as ASA Grade III (84.5%), with a smaller portion falling into ASA Grade II (15.5%). Regarding coronary artery bypass grafting (CABG), the majority of surgeries had a duration between 6 to 8 hours (69.0%), followed by 8 to 10 hours (23.3%), while fewer surgeries fell within the ≤ 6 hours (5.2%) and 10 to 12 hours (2.6%) categories. Cardiopulmonary bypass (CPB) duration varied, with 39.7% falling within the 151 to 180 minutes range, and 47.4% exceeding 180 minutes. The mean CPB duration was 184.44 ± 43.24 minutes. In terms of fluid administration during surgery, the vast majority received both normal saline (NS) and Ringer's lactate (RL) solutions (96.6%), while only a small proportion received either NS alone (1.7%), RL alone (1.7%), or a combination of both

In Table 4, the serum creatinine levels were measured at different time points: pre-operation (Pre op), 24 hours post-operation (24 hrs), and 48 hours post-operation (48 hrs). The mean serum creatinine levels at these time points were as follows: pre-operation (Mean = 1, SD = 0.13, Min = 0, Max = 2), 24 hours post-operation (Mean = 1.30, SD = 0.48, Min = 1, Max = 3), and 48 hours post-operation (Mean = 1.26, SD = 0.48, Min = 0, Max = 2). These measurements provide insight into the changes in serum creatinine levels following surgery, indicating a slight increase at 24 hours post-operation followed by a slight decrease at 48 hours post-operation compared to pre-operative levels.

In Table 5, blood pressure measurements, including systolic blood pressure (SBP) and diastolic blood pressure (DBP), were recorded pre-operation (Pre op) and post-operation (Post op). The mean SBP was 127.53 mmHg (± 10.32) pre-operation and 113.47 mmHg (± 9.75) post-operation, with minimum and maximum values of 100 mmHg and 148 mmHg respectively for both pre and post-operation. For DBP, the mean was 72.53 mmHg (± 12.53) pre-operation and 58.97 mmHg (± 7.52) post-operation, with minimum and maximum values of 46 mmHg and 172 mmHg pre-operation and 44 mmHg and 90 mmHg post-operation respectively. These measurements indicate a decrease in both SBP and DBP post-operation compared to pre-operative levels.

Table 6 presents the association between the diagnosis of patients and the occurrence of acute kidney injury (AKI). Among the patients without AKI (n=33), the distribution across various diagnoses was as follows: CAD ACS-NSTEMI (3.03%), CAD-DVD (4.5%), CAD-DVD with LV dysfunction (0%), CAD-DVD with valvular dysfunction (4.5%), CAD-LM-TVD (3%), CAD-SVD+DVHD+Sev AS (0%), CAD-TVD (58.2%), CAD-TVD with valvular dysfunction (6%), and CAD-TVD with LV dysfunction (20.9%). Among those with AKI (n=25), the distribution was: CAD ACS-NSTEMI (0%), CAD-DVD (4.1%), CAD-DVD with LV dysfunction (6.1%), CAD-DVD with valvular dysfunction (4.1%), CAD-LM-TVD (0%), CAD-SVD+DVHD+Sev AS (4%), CAD-TVD (44.9%), CAD-TVD with valvular dysfunction (4.1%), and CAD-TVD with LV dysfunction (28.6%). The chi-square test for association yielded a value of 11.2 with a corresponding p-value of 0.27, suggesting no statistically significant association between the diagnosis and the occurrence of AKI among the study participants

Table 7 illustrates the association between the stage of acute kidney injury (AKI) and the diagnosis of patients. Among those without AKI (n=33), the distribution across various diagnoses was: CAD ACS-NSTEMI (3%), CAD-DVD (3%), CAD-DVD with LV dysfunction (0%), CAD-DVD with valvular dysfunction (4.5%), CAD-LM-TVD (3%), CAD-SVD+DVHD+Sev AS (0%), CAD-TVD (59.7%), CAD-TVD with valvular dysfunction (6%), and CAD-TVD with LV dysfunction (20.8%). Among those with Stage I AKI (n=22), the distribution was: CAD ACS-NSTEMI (0%), CAD-DVD (4.7%), CAD-DVD with LV dysfunction (4.7%), CAD-DVD with valvular dysfunction (4.7%), CAD-LM-TVD (0%), CAD-SVD+DVHD+Sev AS (4.7%), CAD-TVD (46.4%), CAD-TVD with valvular dysfunction (4.7%), and CAD-TVD with LV dysfunction (30.2%). Among those with Stage II AKI (n=3), the distribution was: CAD ACS-NSTEMI (0%), CAD-DVD (0%), CAD-DVD with LV dysfunction (33.3%), CAD-DVD with valvular dysfunction (0%), CAD-LM-TVD (0%), CAD-SVD+DVHD+Sev AS (0%), CAD-TVD (66.6%), CAD-TVD with valvular dysfunction (0%), and CAD-TVD with LV dysfunction (0%). The chi-square test for association yielded a value of 4.8 with a corresponding p-value of 0.51, indicating no statistically significant association between the stage of AKI and the diagnosis among the study participants.

The kidneys, which are part of the renal system, are particularly responsive to intravenous fluids and volume levels. Inadequate arterial flow or venous congestion can quickly impact the kidneys' ability to discharge waste from the body.[11]Fluid management is a crucial aspect of caring for patients having cardiac surgery, ensuring proper preload and cardiac output during the pre-operative, intraoperative, and post-operative periods.[12] Recent studies have shown that excessive use of normal saline might cause acute kidney injury, yet it is commonly recommended along with Ringer lactate as a fluid for this purpose.[13,12] Both fluids are chloride-rich. The study titled "The Incidence of Acute Kidney Injury in On-Pump CABG Surgery Cases Managed Intraoperatively with Chloride Liberal Fluids" aimed to determine the occurrence of acute kidney injury in post-coronary artery bypass graft surgery cases treated intraoperatively with chloride liberal fluids. Acute Kidney Injury (AKI) refers to a quick decline in renal function marked by a decrease in glomerular filtration rate.[14] The AKIN criteria were utilised in our study to diagnose and classify acute kidney injury. It is defined by a sudden rise in the concentration of serum creatinine levels.[15] The serum creatinine levels rose from 1±0.13 mg/dL before the surgery to 1.26±0.48 mg/dL 48 hours post-operation. The incidence of acute renal damage in patients who received chloride generous fluid during CABG surgery was 42.2% according to AKIN criteria. 37.1% of the patients had stage I Acute Kidney Injury (AKI) and 5.2% had stage II AKI. The study results we obtained were corroborated by Gross JL et al (2015), who reported that around 50% of patients experienced some level of post-operative acute renal injury after heart surgery using CPB.[16] Our study results were consistent with the findings of Weng R et al (2020).[17] The occurrence of acute kidney injury (AKI) in elderly patients who underwent either on-pump or off-pump coronary artery bypass grafting (CABG) was 40.3%, with most of them classified as stage I.[17]
The blood creatinine level increased from 0.94±0.34 mg/dL before the surgery to 1.07±0.47 mg/dL after the surgery.[18] The discrepancy in AKI incidence between the current study and the reference study may be due to the unspecified type of fluid used in the reference study. Bhaskaran A et al (2018) reported that 9.2% of subjects undergoing off-pump CABG and receiving perioperative chloride generous fluid experienced AKI. All of them had stage I acute kidney injury according to the AKIN criteria.[13] The variation in AKI incidence may be due to differences in the type of operation performed.[19]
The mean age of those receiving cardiac operations in India is 60 years. Non-communicable illnesses are on the rise in India due to the combination of longer life expectancy and changes in lifestyle.[20] Older age and being female are significant risk factors for developing AKI after cardiac operations.[19] The majority of patients undergoing on-pump CABG in the current study were older (>60 years old) and over 75% of the cases were male. No statistically significant connection was seen between AKI or stage and age or gender. The average age of patients with AKI was 63.31±8.12 years, while for those without AKI it was 61.36±7.89 years.

Weinberg L et al (2018) found a significant association between age and post-operative AKI in patients following cardiac surgery while using chloride-liberal fluid.[21] The current study's results were corroborated by Wang R et al's (2020) findings, which showed a greater prevalence of AKI in older patients receiving on or off-pump CABG in the study group.[17] The current study's results align with those of Kumada Y et al (2017), showing that most patients were elderly (>75 years old) and that being female did not have a significant association with AKI.[18] The study involved all patients with coronary artery disease who had either triple vessel disease or double vessel disease, with or without ventricular or valvular dysfunctions. Hypertension is the most prevalent comorbidity and is recognised as a significant risk factor for coronary artery disease.[20] In the current investigation, the diagnosis and concomitant illnesses were not shown to be correlated with AKI or its staging (p>0.05). Kumada Y et al (2017) found no significant link between AKI and concomitant diseases, save for diabetes.[18] Lim JY et colleagues (2018) found no significant link between AKI and hypertension or CVA.[12]The current study's findings eliminate the probability of diabetic or hypertensive nephropathy.[22]The American Society of Anesthesiologist categorization was utilised to evaluate the patient's medical co-morbidities and anticipate the perioperative risks.[32] We included patients with ASA grades II and III, with the majority falling under ASA grade III, indicating significant concomitant problems. AKI was not correlated with ASA grade of patients in our study (p>0.05). Our study results aligned with Weinberg L et al's (2018) findings, indicating that patients with higher ASA scores, representing systemic comorbidities, were at a significantly increased risk of AKI (p<0.05).[21] Coronary artery bypass grafting (CABG) can be performed using either off-pump or on-pump techniques. During coronary artery bypass grafting (CABG) surgery, using a heart-lung machine (CPB) is the preferred method. Literature suggests CPB is a significant factor linked to AKI.[24,25] Additional intraoperative parameters linked to AKI include the length of CPB and the requirement for a return to CPB.[19] All patients in our study underwent coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). The length of cardiopulmonary bypass (CPB) and coronary artery bypass grafting (CABG) did not show a correlation with acute kidney injury (AKI) in our research. Salis L et al (2008) determined that the duration of cardiopulmonary bypass (CPB) is a standalone factor linked to the onset of acute kidney injury (AKI).[26] The duration of extracorporeal support is suggested to be directly related to the risk of coagulopathy, gut hypoperfusion, transfusion support, and consequently, the risk of acute kidney injury (AKI).[27] The duration of coronary artery bypass grafting (CABG) is not specified as a risk factor for acute kidney injury (AKI), but the duration of cardiopulmonary bypass (CPB) is an independent risk factor linked to AKI. Gross JL et al (2015) found that using a CPB pump results in higher levels of systemic inflammatory mediators, which are further heightened with longer CB operation duration. Oxidative and inflammatory processes occurring during cardiopulmonary bypass may be exacerbated by extracorporeal circuit hemolysis, resulting in hem-induced oxidant damage to the renal system.[16] The results of our investigation were consistent with the findings of Fischer UM et al (2002) [28]and Tuttle KR et al (2003),[29] indicating that AKI was not linked to the duration of CPB (p>0.05). Our study utilised chloride-rich drinks in patients undergoing on-pump coronary artery bypass surgery. Ringer lactate and normal saline, both chloride generous fluids, were given in over 95% of cases regardless of the presence or absence of AKI. We examined the relationship between acute kidney injury (AKI) and the volume of normal saline (NS) and Ringer's lactate (RL) individually. Our study did not reveal a statistically significant link between acute kidney injury (AKI) and the type or volume of fluids administered (p>0.05). IV fluids have a substantial impact on the prognosis of critically ill patients.[30] Fluids rich in chloride can impact the renal blood vessels by inducing hyperchloremic metabolic acidosis, resulting in renal vasoconstriction and a decrease in glomerular filtration rate (GFR).[31-33]
The results of our investigation were corroborated by Younus NM et al (2005), who observed a notably increased risk of AKI in patients treated with liberal chloride treatment.[34]Toyonaga Y et al (2016) found that the AKI group had significantly lower base excess-chloride (BE-Cl) and strong ion difference (SID), as well as higher chloride levels compared to the non-AKI group (P < 0.05). They proposed that the amount of chloride ions administered during surgery could be a significant indicator of postoperative AKI (P < 0.01).[35]Bhaskaran K et al (2018) found a greater incidence of acute kidney injury (AKI) in patients treated with chloride liberal fluids (9.2%) compared to those treated with chloride limited fluids (4.6%) due to hyperchloremic metabolic acidosis associated with the former.[13] Weinberg L et al (2018) found that a 100 ml increase in mean daily fluid balance was substantially linked with a 5% decrease in the hazard of AKI (aHR- 0.951). The authors found that for every 5% rise in the amount of chloride-liberal fluid used, the risk of AKI increased by 8% (aHR 1.079, 95% CI 1.032 to 1.128, P=0.001).Most patients needed PRBC and cryoprecipitate, but only a small number required FFP and SDP.[21] The current investigation found no significant correlation between AKI and the blood products utilised (p>0.05). O’Neal JB et al (2016) found that receiving red blood cell transfusions, particularly during cardiopulmonary bypass, was a major factor linked to acute kidney injury.[19] Karkouti K et al (2011) found that the risk of acute kidney injury (AKI) dramatically rose with a higher proportion of packed red blood cell (PRBC) transfusions, particularly in anaemic patients. The risk rose from 1.8% to 6.6% in anaemic cases without and with transfusion, and from 1.7% to 3.2% in non-anemic patients. Gomez H et al (2014) found that blood and blood products are important factors linked to AKI in CABG patients. This is due to their impact on renal perfusion, oxidative damage

repetitive cycles of ischemia and reperfusion, and elevated inflammation.[36] In their investigation, Kumada Y et colleagues (2017) found no significant correlation between anaemia and AKI.[18] It is crucial to manage blood pressure before, during, and after surgery to prevent AKI.[37] The average systolic blood pressure before surgery was 127.53±10.32 mmHg, while after surgery it was 113.47 ± 9.75 mmHg. The average diastolic blood pressure was 72.53±12.53 mmHg before the procedure and 58.97 ±7.52 mmHg after the treatment. No significant difference was seen in the average systolic blood pressure (SBP) and diastolic blood pressure (DBP) between individuals with acute kidney injury (AKI) and those without AKI (p>0.05). While systolic blood pressure (SBP) or diastolic blood pressure (DBP) have not been linked to acute kidney injury (AKI), Wong BT et al (2015) identified mean perfusion pressure as a significant factor related with AKI.[38] In 2016, Saito and colleagues found a notable link between diastolic arterial pressure, mean perfusion pressure, diastolic perfusion pressure, and AKI through changes in central venous pressure.[39]
The majority of instances in our study had a positive outcome. Among the 33 instances without acute kidney injury (AKI), 1.5% resulted in mortality and the remaining 1.5% required nitroglycerin (NTG) injection. In 2% of the 25 instances with AKI, mortality occurred. In approximately 2% of cases, intraoperative arrest was necessary, leading to reopening in 2% of cases. No significant correlation was seen between the result and AKI (p>0.05). The results of our study were consistent with those of Kirmani B et al (2016),[40] Zakkar M et al (2018),[41] Filardo G et al (2018),[42] and Shroyer AL et al (2017), [43]who all reported a higher incidence of peri-operative AKI in on-pump CABG cases compared to off-pump CABG. However, no significant difference in mortality was observed.

The study data suggest that the occurrence of peri-operative AKI is elevated in patients who have on-pump CABG and receive chloride-rich fluids like normal saline and/or ringer lactate. Chloride generous fluids used in on-pump CABG was an independent predictor of AKI. Other parameters like age, gender, comorbidities, fluid volume, CPB & CABG duration, blood transfusions, and blood pressure were not linked to AKI. Although the occurrence of AKI was more frequent in our research participants, it was not linked to negative outcomes or mortality.

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