Acute kidney injury (AKI) is a common significant complication following cardiac surgery [1]. The development of AKI is associated with prolonged hospital stays, an increased need for renal replacement therapy, and higher mortality rates both in the short and long term [2]. The incidence of postoperative AKI in patients receiving tricuspid valve (TV) surgery and cardiac valve replacement is estimated to be 30% and 46.8%, respectively [3, 4]. Patients demonstrated a 1.58-fold increased risk of AKI after tricuspid valve replacement [3]. Although some novel biomarkers, such as urinary liver fatty acid binding protein (L-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule 1 (KIM-1) have been studied for AKI stratification and prediction [5], the cost-effectiveness of using these in clinical practice remains unclear [6]. Therefore, predicting AKI with readily calculable markers before tricuspid valve surgery is essential for identifying high-risk patients and implementing preventative strategies.

Inflammation and oxidative stress are key pathophysiologies in cardiac surgery-related AKI [7]. Uric acid enhances proinflammatory mediators, leading to glomerulosclerosis and tubular damage [8]. The redox state of serum albumin, indicative of systemic antioxidant capacity, is associated with reduced renal function [9]. Both serum uric acid and albumin serve as an independent risk marker for AKI [10, 11]. However, conditions such as malnutrition, sepsis, inflammation, congestive heart failure, and chronic kidney disease can influence their levels [12, 13, 14]. The serum uric acid/albumin ratio (UAR), comprising serum uric acid and serum albumin levels, has emerged as a novel inflammatory biomarker for predicting the onset of AKI [14] and is associated with short-term mortality in patients with acute kidney injury [15]. This marker has been evaluated for its predictive value in post-contrast acute kidney injury following percutaneous coronary intervention (PCI) [16]. However, the clinical features and underlying pathophysiological processes differ between contrast-induced acute kidney injury after PCI and acute kidney injury associated with cardiac surgery. There is a notable absence of research validating the predictive value of this marker in patients following tricuspid valve surgery. Consequently, this study aimed to determine whether the UAR can predict the risk of AKI in those who have undergone such surgery.

Our study confirms that the UAR can be used as an independent predictor of AKI in patients undergoing isolated tricuspid valve repair or replacement surgery. A linear relationship between the UAR levels and AKI incidence suggests that an elevated UAR is linked to an increased risk of AKI, even after accounting for confounding factors. The UAR has a moderate predictive value for AKI, with its predictive efficacy equivalent to uric acid.

Our study found that individuals in the higher UAR tertile were older, predominantly male, and had elevated levels of creatinine and uric acid and lower levels of albumin. These findings are consistent with previous studies [15, 18]. For example, the study by Li et al. [18] observed that patients with unstable angina pectoris who underwent percutaneous coronary intervention and had a high UAR of $\ge$8.38 and exhibited a higher all-cause mortality rate during follow-up outside the hospital compared to those with a UAR 8.38. Similarly, the study by Özgür et al. [15] reported that patients with a UAR greater than 2.36 had an increased 30-day mortality rate compared to those with a UAR below 2.36. However, our study did not find a correlation between the UAR and ICU mortality. There are a couple of reasons for this discrepancy. Firstly, an international cross-study by Hoste et al. [19] reported that the mortality rate for patients with AKI in the ICU is approximately 24%. Given this benchmark, the relatively low mortality rate observed in our study may not be sufficient to demonstrate a statistically significant difference. Secondly, this discrepancy could suggest that the UAR is more strongly associated with long-term mortality outcomes than short-term mortality in the ICU.

Acute kidney injury is characterized by a sudden decline in renal function within hours to days, indicated by a rapid rise in serum creatinine levels, a decrease in urine output, or both [7]. The incidence of AKI related to cardiac surgery is estimated to be between 20% and 30% [2, 7, 20, 21]. In this study, 18.3% of patients developed AKI following surgery. Several risk factors, including age, male gender, hypertension, cardiac arrhythmia, transfusion, and preoperative serum creatinine levels, have been associated with the development of AKI following cardiac surgery [21, 22, 23]. Our study corroborates these associations, demonstrating that older male patients with higher creatinine levels, lower platelet counts, history of transfusion, hypertension, and atrial fibrillation are at an increased risk of AKI development. Our study determined that the UAR is a risk factor for AKI, with a linear relationship indicating that higher UAR levels are associated with an increased risk of AKI. Furthermore, elevated uric acid and decreased albumin levels may contribute to this condition. Serum uric acid has been widely evaluated as a predictive biomarker for AKI after cardiac surgery. A study of 190 patients undergoing coronary artery bypass surgery revealed that for each 1-unit increase in serum uric acid concentration, the risk of AKI rose by 1.18 times [24]. Another study involving 247 cardiac surgery patients showed that, after adjusting for confounders with multivariate logistic regression, a preoperative uric acid level of $\ge$373 µmol/L was linked to a 5.4-fold increase in AKI risk compared to levels $\le$373 µmol/L [25]. However, a study conducted by Lapsia et al. [26] analyzed the incidence of AKI and all available uric acid values in 4949 adult patients who underwent cardiovascular surgery, starting from the lowest value with incremental increases of 0.5 mg/dL, and found that a J-shaped relationship appears to exist between uric acid (UA) and AKI. These data suggest that both hypouricemia and hyperuricemia are linked to an increased risk of acute kidney injury; however, the study did not specify the predictive threshold for uric acid levels. Thus, detecting a new biomarker or considering their combination may be needed for AKI prediction. Lower serum albumin is an independent factor for both the development of AKI and post-AKI mortality [10]. In a study of 634 diabetes mellitus patients undergoing coronary bypass grafting, low preoperative serum albumin levels predicted AKI independently, with an albumin level below 3 mg/dL showing an AUC of 0.621 for AKI prediction (p 0.001) [27]. Furthermore, a separate study of 1182 patients undergoing off-pump coronary artery bypass surgery found that preoperative serum albumin levels below 4.0 g/dL were associated with a 1.83-fold higher risk of AKI than levels above this threshold [28]. Elevated uric acid and reduced albumin levels indicate an increased UAR, which is associated with a higher risk of AKI.

Studies by Şaylık et al. [29] and Yeter et al. [14] have demonstrated the predictive value of the UAR for kidney impairment post-percutaneous coronary intervention. Şaylık et al. [29] identified a UAR cutoff of $>$1.62 for detecting contrast-induced nephropathy (CIN), while Yeter et al. [14] found that a UAR $>$1.7 correlates with AKI in critically ill patients. In our study, a UAR value exceeding 8.89 was the optimal threshold for AKI detection in patients undergoing TV surgery. The discrepancy in our study may stem from different units for uric acid and albumin: µmol/L for UA and g/L for albumin (ALB), contrasting with mg/dL for UA and g/dL for ALB in their studies. In our study, the UAR demonstrated a moderate predictive value for AKI following TV surgery. Comparative analysis of the ROC curves revealed that the predictive accuracy of the UAR did not exceed that of serum uric acid. This outcome contrasts previous studies suggesting UAR as a superior predictor for post-contrast kidney injury or nephropathy in PCI [16, 29]. The differences in albumin levels can explain this. In contrast to the study by Zhang et al. [16], which documented the lowest albumin level at 33.3 $\pm$ 0.45 g/L, our study reported a median level of 38 g/L, with a 95% CI ranging from 35.8 to 40.3 g/L. A previous study explored the relationship between serum albumin and AKI in 624 patients undergoing surgery for acute type A aortic dissection and noted that the risk of AKI does not significantly increase once albumin levels exceed a threshold of 32 g/L [30]. Furthermore, the AUC for albumin in predicting AKI in our study was 0.583, with a p-value of 0.952, suggesting a poor predictive value. Consequently, the predictive efficacy of the UAR appears to be more reliant on uric acid levels than albumin levels. Therefore, our study found the predictive accuracy of the UAR and uric acid level to be quite comparable.

The metabolic disorder of uric acid and decreased albumin synthesis before cardiac surgery may underlie the mechanism through which the UAR predicts AKI. Firstly, the kidney plays a significant role in uric acid excretion and absorption. Therefore, before undergoing cardiac surgery, most patients grapple with diminished cardiac function, potentially triggering a cascade of events known as cardiorenal syndrome, which in turn can impair kidney function [31]. Consequently, this leads to reduced excretion of uric acid in the urine and increased reabsorption, resulting in elevated uric acid levels in the bloodstream [32]. Secondly, sustained elevation in uric acid levels may promote pathogenic inflammation, cellular proliferation, and maladaptive changes. These pathological changes can result in glomerulosclerosis and fibrosis in the tubulointerstitium, resulting in renal damage even after cardiac surgery [33]. Chronic kidney disease is characterized by persistent chronic inflammation, which may decrease albumin concentration due to a reduced synthesis rate [31, 34]. As a result, low serum albumin levels indicate the severity of the inflammation [35] and reflect the extent of kidney function impairment.

The UAR has a wide range of applications. Moreover, it is effective in predicting AKI and has demonstrated significant prognostic value in forecasting outcomes for patients with ST-elevation myocardial infarction (STEMI) [36] and complications following various procedures, including cryoballoon catheter ablation [37], coronary artery bypass grafting (CABG) [38], and PCI. Compared with single markers, the UAR provides stronger results and a multidimensional impact, making it particularly advantageous in clinical practice.

The current study has several inherent limitations. Firstly, the retrospective design of the study prevents us from establishing a causality relationship between the UAR and AKI. Secondly, the study focuses solely on patients who underwent isolated TV surgery, which may limit the generalizability of our findings to other cardiac surgery populations. Additionally, the absence of long-term follow-up data limits our understanding of AKI incidence over an extended period. Finally, despite applying a multivariate analysis, residual confounders, such as the duration of tricuspid valve disease, right heart failure, and diuretic therapy, could not be fully addressed. For these reasons, future research should be prospective and include diverse patient populations to validate our findings. We strongly recommend incorporating long-term follow-up data to gain a deeper understanding of the incidence and progression of AKI.

Our analysis establishes a clear linear correlation between preoperative UAR levels and the incidence of AKI in patients undergoing isolated tricuspid valve repair or replacement. An elevated UAR is linked to an increased risk of AKI. The UAR demonstrates a moderate level of predictive accuracy for AKI; while it is comparable to uric acid alone, it has wider clinical application value. As a cost-effective biomarker, UAR could be instrumental in identifying patients at risk of AKI who may require closer monitoring and management.

All data relevant to the study are included in the article. Data can also be requested from the corresponding author.

CJZ: Conceptualization, Formal analysis, and Writing—review & editing; YJL: Conceptualization and Writing—original draft; LYL: Conceptualization, Writing—review & editing and Project administration; JL and FFZ: Investigation, Data curation, and Writing—review & editing. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects.

This study was performed in accordance with the principle of the Declaration of Helsinki, and the research protocol was approved by the Ethics Committee of Guangdong Provincial People’s Hospital (KY2024-605–02), and all of the participants provided signed informed consent.

This research received no external funding.

The authors declare no conflict of interest.