The Role Of The Neutrophil-Lymphocyte Ratio For Pre-Operative Risk Stratification Of Acute Kidney Injury After Tetralogy Of Fallot Repair

Manuel V, Miana LA, Turquetto A, et al.

Cardiol Young. 2021 Jun;31(6):1009-1014.

doi: 10.1017/S1047951121001943.

PMID: 34016219.


Take-Home Points

  • Acute kidney injury (AKI) is a frequent complication after cardiopulmonary bypass (CPB) in children.
  • AKI can have long-term implications leading to chronic kidney disease.
  • Therapeutic options for AKI after CPB are limited and, therefore, low-cost, easy-to-measure biomarkers may help to preoperatively identify patients at risk of AKI after CPB.
  • The preoperative neutrophil/lymphocyte ratio may be useful in predicting serious AKI in children with tetralogy of Fallot (TOF) undergoing cardiac surgery. However, larger prospective studies are required to confirm these findings.

Commentary by Ingrid Moreno-Duarte, MD Adult Cardiothoracic Anesthesiologist and Intensivist/Pediatric Cardiothoracic Anesthesia Fellow in Children’s Medical Center/UT Southwestern, Dallas, TX; Sana Ullah MD, Associate Professor in Anesthesiology, UT Southwestern Medical Center and Children’s Medical Center, Dallas, TX.

Acute kidney injury (AKI) is a well-known complication after CPB. Children, particularly patients with congenital heart disease, have a higher incidence of AKI (5-45%). The presence of AKI is associated with increased in-hospital morbidity and mortality – including increased length of stay in the intensive care unit, increased mechanical ventilation, and increased mortality. Postoperative AKI is an independent risk factor for prognosis in surgical patients and can have long-term implications leading to chronic kidney disease (1). Although patients with Tetralogy of Fallot (TOF) have excellent long-term survival, more than half of these patients present with chronic kidney disease (CKD) in adulthood (2). Identifying which patients with AKI are at risk of CKD is challenging. Due to limited therapeutic options for AKI, the ability to prospectively identify high-risk patients could be very useful in implementing prevention strategies to reduce the impact of renal injury after congenital cardiac surgery.


The absolute neutrophil/lymphocyte count ratio (NLR) reflects the balance between inflammation (neutrophils) and immunity (lymphocytes) (3). An increase in the NLR suggests an acute or chronic inflammatory response that can suppress lymphocyte function. The NLR is simple, inexpensive, and easily calculated. The ratio has been used to predict multiple cardiovascular, respiratory, and hospital outcomes in adults but has not been studied in children. Higher NLR values are associated with disease progression and worse prognosis.


The authors explored the utility of the use of the preoperative NLR in predicting AKI in children undergoing TOF repair. A single center retrospective analysis of 116 patients less than 18 years old undergoing TOF repair between January 2014 and December 2018 was performed (4). AKI was defined according to the Acute Kidney Injury Network definition, where percentage changes in serum creatinine level from baseline are used to classify acute kidney injury as grade I (≥150–200%), grade II (≥200–300%), or grade III (>300%).


Patients were excluded if they had any other hemodynamically significant concomitant congenital heart defect, pre-operative hemodynamic instability, surgical complications leading to increased CPB and cross-clamp times, suspected or evidenced infection (leukocytosis), prior antibiotic administration during the same hospital admission, primary hematological or other immunological diseases, or a positive viral screening.


The patients were assigned into two groups depending on the presence (n=39) or absence (n=77) of AKI according to the AKI Network definition. In the AKI group, the median neutrophil-lymphocyte ratio was 0.71 (interquartile range: 0.50–1.36); in the group without AKI, the neutrophil-lymphocyte ratio was 0.61 (interquartile range: 0.34–1.18).


There was no statistical difference in the NLR between groups. However, a subgroup analysis comparing the non-AKI group with the grade III AKI subpopulation (10 patients) showed an association between the NLR and its ability to predict more severe stages of AKI. A high preoperative NLR was also significantly associated with a high postoperative serum creatinine level. The study also re-confirmed the association of AKI with the presence of longer periods of postoperative mechanical ventilation, intensive care length of stay, hospital stay, and increased mortality during the first 48 hours after TOF repair.


The authors propose that the higher level of the pre-operative NLR may be influenced by the presence of cyanosis and chronic vascular stress, which may lead to a chronically activated innate immune system. CPB may exacerbate this activation and lead to adverse outcomes, including AKI. The authors conclude that the pre-operative NLR can be used to identify patients at risk of developing grade III acute kidney injury after TOF repair. 


The NLR is inexpensive and easy to measure; however, it is not truly specific to AKI. Many other conditions unrelated to the kidney may increase this ratio. This retrospective study included a small sample size and the groups were numerically unbalanced (39 vs. 77 patients), which limits the study’s conclusions. In addition, the retrospective design, the relatively small number of patients, and a sensitivity and specificity of approximately 70% undercuts the utility of this test as a predictor of renal injury after CPB. Since measuring the white cell count is a routine blood test before cardiac surgery, it should be relatively easy to conduct a much larger prospective study to assess the usefulness of the NLR as a predictive risk-stratification tool.


Nonetheless, AKI does affect outcomes after congenital heart surgery. A low-cost, easy-to-measure biomarker such as the NLR may have a role in identifying high-risk patients with congenital heart disease that could develop AKI after cardiopulmonary bypass. Identifying such patients could lead to early prevention strategies, such as avoidance of fluid depletion, hypotension, mindful use of nephrotoxic agents, and prophylactic dialysis catheters placed at the time of surgery (5, 6).



1. Trongtrakul K, Sawawiboon C, Wang AY, Chitsomkasem A, Limphunudom P, Kurathong S, et al. Acute kidney injury in critically ill surgical patients: Epidemiology, risk factors and outcomes. Nephrology (Carlton). 2019;24(1):39-46.

2. Buelow MW, Dall A, Bartz PJ, Tweddell JS, Sowinski J, Rudd N, et al. Renal dysfunction is common among adults after palliation for previous tetralogy of Fallot. Pediatr Cardiol. 2013;34(1):165-9.

3. Song M, Graubard BI, Rabkin CS, Engels EA. Neutrophil-to-lymphocyte ratio and mortality in the United States general population. Sci Rep. 2021;11(1):464.

4. Manuel V, Miana LA, Turquetto A, Guerreiro GP, Fernandes N, Jatene MB. The role of the neutrophil-lymphocyte ratio for pre-operative risk stratification of acute kidney injury after tetralogy of Fallot repair. Cardiol Young. 2021:1-6.

5. Koo CH, Eun Jung D, Park YS, Bae J, Cho YJ, Kim WH, et al. Neutrophil, Lymphocyte, and Platelet Counts and Acute Kidney Injury After Cardiovascular Surgery. J Cardiothorac Vasc Anesth. 2018;32(1):212-22.

6. Vanmassenhove J, Kielstein J, Jörres A, Biesen WV. Management of patients at risk of acute kidney injury. Lancet. 2017;389(10084):2139-51.