Cardiac surgery-associated acute kidney injury: The core of etiology, treatment, and prognosis

Dimitrios C Karathanasis; Christos-Rafail D Karathanasis; Androula C Karaolia

doi:10.4103/jcpc.jcpc_5_22

REVIEW ARTICLE

Year : 2022 | Volume : 11 | Issue : 3 | Page : 74-78

Cardiac surgery-associated acute kidney injury: The core of etiology, treatment, and prognosis

Dimitrios C Karathanasis¹, Christos-Rafail D Karathanasis², Androula C Karaolia³
¹ Department of Nephrology, Synchroni Polykliniki, Larissa, Greece
² School of Medicine European University Cyprus, Nicosia, Cyprus
³ Department of Neurosurgery, University of Thessaly, Larissa, Greece

Date of Submission	17-Jan-2022
Date of Decision	06-Jun-2022
Date of Acceptance	16-Jun-2022
Date of Web Publication	21-Nov-2022

Correspondence Address:
MD, MSc, PhD Dimitrios C Karathanasis
Synchroni Polykliniki, 6^th Klm Larisas-Farsalon, Larisa 41500
Greece

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jcpc.jcpc_5_22

Abstract

Cardiac surgery-associated acute kidney injury (CS-AKI) is a very serious and common complication after heart surgery. Standard knowledge of the etiology, treatment, and prognosis is a prerequisite for effective therapy. The etiology includes a set of predisposing pre-, intra-, and postoperative factors with varying incidence and severity. Although not specified yet, the treatment involves standard and modern modalities based on medication, nutrition, and dialysis as well as on alleviative measures. CS-AKI enhances the incidence of infections and hospitalization leading to increased morbidity and overall mortality. Early diagnosis and treatment reduce the risk of transition to a more severe stage of AKI or chronic kidney disease.

Keywords: Acute kidney injury, cardiac surgery, etiology, prognosis, treatment

How to cite this article:
Karathanasis DC, Karathanasis CRD, Karaolia AC. Cardiac surgery-associated acute kidney injury: The core of etiology, treatment, and prognosis. J Clin Prev Cardiol 2022;11:74-8

How to cite this URL:
Karathanasis DC, Karathanasis CRD, Karaolia AC. Cardiac surgery-associated acute kidney injury: The core of etiology, treatment, and prognosis. J Clin Prev Cardiol [serial online] 2022 [cited 2023 Jun 9];11:74-8. Available from: https://www.jcpconline.org/text.asp?2022/11/3/74/361694

Introduction

Acute kidney injury (AKI) after heart surgery or cardiac surgery-associated AKI (CS-AKI) is a very common complication with an incidence according to the literature ranging from 6.9% to 43% in studies that vary in the number of patients and type of surgery.^[1] The definition of CS-AKI is identical to the widely accepted definition of AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO). According to KDIGO, AKI is defined as an increase in serum creatinine (SC) by ≥ 0.3 mg/dL within 48 h or an increase in SC to ≥ 1.5 times baseline within 7 days or urine volume < 0.5 ml/kg/h for 6 h. Despite the obvious limitations of SC either before or after heart surgery such as older age, use of diuretics or contrast media (CM), and intraoperative fluid administration, SC remains the “gold standard” for the definition of AKI.^[2],[3],[4] The case of CS-AKI has been extensively studied firstly since the onset of AKI is well known and predetermined and secondly because it has a negative effect on morbidity, mortality, and health-care costs.

Etiology

The increased incidence of CS-AKI was associated with a variety of predisposing factors that could be divided into three types depending on the time of their effect.

Preoperative

Age: Older patients are more likely to develop AKI.^[5] As age increases, glomerular filtration and strength of the hemodynamic mechanisms of the kidney against injury are both being decreased. In addition, elderly patients are more likely to receive diuretics or intravenous CM^[6]
Sex: Females are more likely to develop AKI, probably due to the already reduced glomerular filtration rate compared to men^[7],[8]
Genetic predisposition: Although genetic factors have been proposed, their etiologic contribution has not been sufficiently approved^[9],[10]
Bodyweight: Body mass index (BMI) >40 is associated with a higher probability of developing AKI compared to BMI <30^[6]
Preoperative renal function^[11]
Heart failure: Pre-existing heart failure, especially Type IV according to the New York Heart Association, has been directly associated with the development of AKI postoperatively^[8],[12]
Chronic obstructive pulmonary disease^{[8],[12],[13]}
Diabetes mellitus: Diabetes promotes the manifestation of AKI possibly on the ground of preexisting renal parenchymal lesions.^{[8],[12],[13]} Glycosylated hemoglobin (HbA1c) above 6.7% in diabetic patients was associated with AKI.^[14] The same correlation was found for nondiabetic patients with HbA1c above 6%^[15] or serum glucose over 140 mg/dL.^[16] It seems that preoperative hyperglycemia promotes oxidative stress, increases renal ischemia, especially in the medulla, and finally causes hypovolemia through osmotic diuresis.^[17] According to the KDIGO guidelines, preoperative hyperglycemia should be corrected to the range of 110–149 mg/dL^[2]
Anemia: Anemia increases the likelihood of AKI by reducing the supply of oxygen, especially to the sensitive renal medulla where oxygenation is marginal.^[11],[18] In particular, HbA1c >9 g/dL has been directly correlated with AKI^[19]
Hyperuricemia: Increased serum uric acid, especially above 6.5 mg/dL, has been directly linked to CS-AKI.^[20],[21] It seems to have a higher predictive value than well-known biomarkers such as neutrophil gelatinase-associated lipocalin.^[22] Uric acid appears to be involved in renal vasoconstriction and disruption of renal self-regulation mechanisms which both affect the glomerular filtration rate^[17]
Urgent cardiac surgery or existence of a precedent one^[8],[13]
Nephrotoxic medication: As expected, nephrotoxic medication preoperatively such as nonsteroidal anti-inflammatory drugs (NSAIDs) or aminoglycosides increases the incidence of AKI. The same correlation is presented with the administration of the angiotensin-converting enzyme inhibitors (ACEIs) or the angiotensin receptor blockers (ARBs) regardless of any intra- or postoperative drop in blood pressure.^[23],[24] Increased incidence of AKI has also been reported after preoperative use of intravenous CM even 5 days before surgery.^[25],[26]

Although by definition, CS-AKI appears after CS, in some of the aforementioned cases, such as acute heart failure and preoperative nephrotoxic medication including CM, the AKI may have started much earlier.^[27]

Intraoperative

Type of surgery: According to the use or not of extracorporeal circulation, CS is distinguished as on-pump or off-pump, respectively, with the first associated with an increased incidence of AKI.^[28],[29] A duration of extracorporeal circulation >2 h^[16] and a continuous over pulsatile blood flow have been both blamed for AKI.^[30],[31] In addition, risk factors have been proposed the activation of immune mechanisms, the atherosclerotic disease after catheterization of the aorta, the increased surgical time, and the hypothermia.^[24]

At the same time, other large randomized trials do not confirm the above findings.^[32] Until sufficient documentation comes, according to the KDIGO guidelines, the choice of the off-pump technique is not justified exclusively for the avoidance of CS-AKI.^[2]

The incidence of AKI is reported as 37% after coronary artery bypass graft surgery, 49% in valve replacement, and 55% in aortic surgery.^[33] In combined surgeries, the risk is doubled or even tripled^[34]
Blood transfusions: Blood transfusions (BTs) during surgery have been blamed for the development of AKI.^[11],[35] Transfused red blood cells are thought to promote oxidative stress and show increased adhesion to the vascular endothelium as well as some degree of hemolysis.^[24],[36] The outcome is decreased tissue oxygenation.^[11]

Postoperative

After CS, the main etiologic factors for AKI are nephrotoxic medication with the predominance of NSAIDs, hypovolemia, low cardiac output, and low blood pressure. The resulting glomerular ischemia increases the production of angiotensin II and finally prolongs the vicious cycle of ischemia.^[6],[34]

Treatment

Since there is not any specified treatment yet, the management of CS-AKI is focused on the one hand on prevention and the other on alleviation of the complications. Prevention of CS-AKI is mainly based on the avoidance of CM, ACEI, and ARB preoperatively and the administration of balanced crystalloid solutions, and the restriction of BT perioperatively. In addition to the absolute goal of complete reversal of AKI, the therapeutic effort aims to prevent the transition of injury to chronic KD (CKD). Hemodynamic support focuses on improving the performance of the cardiac ventricles, maintaining the mean blood pressure and sinus rhythm, controlling the preload and afterload of the right ventricle, and achieving the best ventilation.^[3] The pillars of bedside treatment are medication, dialysis, and nutrition, while at the research level, modern data focus on stem cells and alkaline phosphatase.

Medication

Despite the promising variety of medicines that applied in the past decades, nowadays treatment of CS-AKI cannot rely on medication since almost all of the old and extensively used drugs are not considered beneficial.

Heart medication

The primary goal is to maintain a satisfactory mean arterial pressure ranging ideally from 65 to 75 mmHg with sinus rhythm.^[4] Any need for intravascular volume replacement should be achieved by the administration of balanced crystalloid solutions rather than saline ones. Having sustained a euvolemic status next step should focus on increasing cardiac output while reducing afterload on the ventricles. Diuretics, dopamine, fenoldopam, mannitol, and natriuretic peptide are no longer recommended since they have not improved clinical outcomes.^[3],[4] On the contrary, the appropriate medication includes mainly catecholamines while phosphodiesterase Type III inhibitors (milrinone and enoximone) and inhaled pulmonary vasodilators (nitric oxide and prostacyclin) though not contraindicated are still far from routine use.^{[3],[37],[38],[39]} It is of note that loop diuretics retain their indication in an overhydrated status.^[2]

Kidney medication

Despite the ongoing research, no specific treatment has been established. Several medications from the past such as dopamine, mannitol, or diuretics are no longer indicated.^[3],[4] Similarly, atrial natriuretic peptide, fenoldopam, and N-acetylcysteine (NAC) have been abandoned due to poor results or even an increase in mortality.^{[2],[3],[4],[40]} As for NAC, although it has been extensively proposed for the prevention of contrast-induced AKI (CI-AKI) in the case of CS-AKI, NAC has failed to improve renal outcomes after CS. KDIGO suggested oral NAC for the prevention of CI-AKI but recommended not using either oral or iv NAC for the prevention of CS-AKI, especially in critically ill patients.^[2] Newer studies and systematic reviews confirmed this negative recommendation.^{[41],[42],[43]} Moreover, the Acute Disease Quality Initiative group has recently reaffirmed the contraindication of NAC for the prevention of CS-AKI.^[3]

Dialysis

AKI will require dialysis in the cases of overhydration, hyperkalemia, metabolic acidosis, and uremic symptoms.^[44] The decision to initiate dialysis is based on clinical criteria and not on the level of renal function or the stage of AKI.^[3]

According to recent meta-analyses, early onset of dialysis has a positive effect on mortality and length of stay in the intensive care unit.^[45],[46] The most suitable type of hemodialysis is continuous versus intermittent as it offers better control of overhydration and hemodynamic stability.^[47] The intermittent method has been associated with a greater likelihood of CKD as well as higher AKI relapse rates.^[48] Duration of continuous hemodialysis longer than 50 h has been associated with reduced mortality,^[49] while according to the KDIGO guidelines, the recommended dose of replacement fluid is 20–25 ml/kg/h.^[50]

Nutrition

Diet plays an important role in improving AKI as mortality increases in malnourished patients. The appropriate diet takes into account the postoperative metabolic needs and the inflammatory condition associated with AKI. According to the KDIGO guidelines and regardless of the stage of AKI, the patient should receive 20–30 kcal/kg by enteral or parenteral nutrition daily and should correct any resultant hyperglycemia over 149 mg/dL. Protein administration should not be avoided as a reason for the prevention of CKD. On the contrary, the amount of daily required protein is 0.8–1 g/kg for noncatabolic patients who do not undergo dialysis, 1–1.5 g/kg for dialyzed patients with a maximum of 1.7 g/kg for patients undergoing continuous hemodialysis or hypercatabolic.^[3]

Stem cells

Stem cells through the release of immunoregulatory, anti-inflammatory, pro-mitotic, and anti-apoptotic agents appear to contribute to a rapid reversal of renal injury.^{[51],[52],[53]} Allogeneic stem cells have been tested with conflicting results in patients with a high probability of CS-AKI.^[54],[55]

Alkaline phosphatase

Alkaline phosphatase is being researched, especially in septic patients with promising results.^[56] It converts adenosine triphosphate to adenosine which has anti-inflammatory effects.^[57]

Prognosis

AKI can reverse or progress to CKD or even become lethal. The more advanced the stage of AKI, the more the expected postoperative complications and the worse the outcome.^[58]

CS-AKI is associated with increased morbidity and overall mortality which ranges from 2% to 3%.^[59] The manifestation of AKI even at Stage I doubles mortality, while in the case of dialysis, mortality reaches 60%.^[60] AKI is an independent factor of both short and long-term mortalities.^{[33],[61],[62],[63]} In a study of 426 patients after heart surgery, it was found that in the case of reversal of the postoperative AKI during hospitalization, the mortality rate was 4%, while otherwise, the mortality rate was 26%.^[64]

It is noteworthy that the manifestation of AKI increases the incidence of infections, affects the function of other organs,^[61],[65] and subsequently increases hospitalization.^[63]

CS-AKI can fall into acute KD (AKD) or finally into CKD. The more severe the stage of AKI, the greater the chance of AKD or CKD, especially in cases that require dialysis.^[66]

Conclusion

CS-AKI is a typical AKI model which gathers research interest as, on the one hand, it is a well-known complication of heart surgeries and, on the other hand, it can be studied extensively due to the expected time of onset. Its increased morbidity and mortality renders prevention necessary mainly by deterring predisposing factors and also by applying appropriate treatment methods to prevent complications and transition to CKD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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