Cardiac surgery on cardiopulmonary bypass (CPB) is strongly correlated with postoperative renal dysfunction, which represents one of the most frequent complications in this surgical population. This spectrum encompasses acute kidney injury (AKI), acute kidney disease (AKD), and chronic kidney disease (CKD), with AKI serving as a critical precursor to subsequent renal morbidity.^1,2 Before potential progression to AKD or CKD, AKI is independently associated with elevated short-term morbidity and mortality, as well as adverse long-term outcomes. Given its critical role in both early and late disease burden, cardiac surgery-associated acute kidney injury (CSA-AKI) has emerged as a priority research domain. CSA-AKI is operationally defined by the Kidney Disease: Improving Global Outcomes (KDIGO) consensus criteria as AKI occurring within seven days after cardiac surgery.^3,4 Its pathogenesis involves multifactorial mechanisms, prominently including CPB-induced systemic inflammatory responses. Blood contact with the extracorporeal circuit during CPB activates innate immune pathways through bio-incompatibility reactions with artificial surfaces, triggering the release of pro-inflammatory mediators.⁵ Concurrently, ischemia-reperfusion injury and oxidative stress synergistically potentiate inflammatory cascades, resulting in endothelial dysfunction and immune cell activation, which drives the systemic release of inflammatory cytokines including Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6) and Interleukin-8 (IL-8) and complement activation products.⁶ Notably, reactive oxygen species (ROS) also induce transcriptional activation of pro-inflammatory pathways via nuclear factor kappa B (NF-κB) upregulation.^5–8 The resultant microvascular dysregulation compromises renal hemodynamic autoregulation, while chemokine-mediated leukocyte infiltration promotes direct tubular injury and interstitial inflammation, ultimately culminating in the pathogenesis of AKI. Persistent inflammation may also contribute to progressive renal fibrosis through maladaptive repair mechanisms.³

Red cell distribution width (RDW), a routine parameter in complete blood count (CBC), has evolved beyond its traditional role in anemia diagnosis and classification. Emerging evidence positions RDW as a biomarker of chronic inflammatory states, with elevated values reflecting underlying pathophysiological stress. Clinically, RDW demonstrates prognostic utility for cardiovascular morbidity, including hypertension progression, decompensated heart failure, atherosclerotic disease severity, and postoperative cerebrovascular events.⁹ Platelets (PLT), beyond their hemostatic functions, play a pivotal role in systemic inflammation, injury, and stress responses. Pro-inflammatory mediators such as IL-6 and IL-1β stimulate thrombopoiesis while enhancing platelet reactivity.¹⁰ The resultant thrombocytosis exacerbates microcirculatory dysfunction through multiple pathways: amplified platelet-leukocyte aggregate formation, increased vascular permeability, and perpetuation of pro-thrombotic inflammatory feedback loops. The red cell distribution width-to-platelet ratio (RPR), a novel composite biomarker integrating inflammatory and thrombotic dimensions, has demonstrated prognostic value in critical illnesses including septic shock and acute pancreatitis.^11,12 However, its association with CSA-AKI pathogenesis remains insufficiently characterized. This study is aimed at identifying the value of RPR for diagnosing CSA-AKI and evaluating the value of RPR combined with other factors for diagnosing CSA-AKI.

RPR has been demonstrated to correlate significantly with various infectious and cardiovascular disorders. This prospective cohort study investigated the association between preoperative RPR levels and postoperative AKI in 252 patients undergoing open-heart surgery with CPB. Our findings revealed a dose-dependent association between elevated RPR concentrations and increased AKI incidence. In predictive performance analyses, RPR exhibited superior diagnostic accuracy compared to CRP, UA, Hs-cTnI and Mb, though marginally lower than BUN. These findings collectively suggest RPR may serve as a promising predictor for CPB-associated AKI risk stratification. Notably, the integration of RPR with conventional varieties demonstrated augmented predictive efficacy, highlighting the clinical potential of RPR in perioperative renal protection strategies.

Cardiopulmonary bypass establishes a bloodless surgical field through cardiac arrest, enabling intricate intracardiac procedures. Distinct from conventional surgery, CPB induces multifaceted pathophysiological alterations encompassing extracorporeal oxygenation, systemic inflammation activation, and obligatory anticoagulation. Chenoweth et al. first demonstrated complement system activation during CPB, which was a critical early-phase response in inflammatory cascades triggered by diverse pathological stimuli including trauma, thermal injury, infection, and notably, CPB itself.¹³ Chemotactic factors are released from activated complement components that drive inflammatory cascades within local tissues. Notably, Factor XII participates in bradykinin generation through the contact system, establishing a coagulation-inflammation interplay. CPB circuit bioincompatibility predominantly activates alternative complement pathways through blood-material interactions, independent of Factor XII activation.^14–16 Mechanistic studies reveal IL-6 as a pivotal cytokine with dual-phase immunomodulatory properties in AKI pathogenesis. Experimental evidence from genetically engineered murine ischemia models demonstrates IL-6-mediated regulation of IL-10, which exerts compensatory anti-inflammatory effects. Clinically, CPB patients exhibit significant perioperative elevation of both IL-6 and IL-10 serum levels.^17,18

RDW has been established as a novel inflammatory prognosticator across diverse pathologies, including functional bowel disorders, autoimmune conditions, malignancies, and chronic diseases requiring recurrent hospitalization.^19–21 Mechanistically, RDW was elevated because of AKI-induced oxidative stress, metabolic dysregulation, and hemodynamic instability which collectively enhance erythrocyte destruction rates, promoting immature reticulocyte release into circulation.^22,23 Platelets exacerbate inflammatory progression through pro-inflammatory cytokine secretion and immunocyte interactions.^24,25 Of clinical significance, thrombocytopenia in critically ill patients demonstrates strong correlation with adverse outcomes.²⁶ RPR integrates these pathophysiological dynamics, emerging as a robust inflammatory indicator across multiple disease.^27,28 Clinically validated as a novel prognostic biomarker, RPR demonstrates predictive capacity for disease trajectories in neonatal sepsis, acute pancreatitis, and advanced hepatic fibrosis and hepatic cirrhosis.^11,29–31 Its clinical utility is enhanced by its routine accessibility through standard complete blood count parameters, non-invasive acquisition with rapid analytical turnaround, and superior diagnostic accuracy compared to conventional inflammatory markers.^28,32 These characteristics make RPR as a cost-effective prognostic tool with significant translational potential in resource-constrained settings.

This investigation has several methodological constraints requiring critical consideration. First, the retrospective single-center design relying on electronic health records inherently limits generalizability, compounded by an underpowered sample size that increases susceptibility to selection bias. Then, the observational nature of data introduces unavoidable risks of measurement inaccuracies and residual confounding, particularly regarding undocumented perioperative variables. These limitations collectively constrain causal inference and external validity of our predictive models. Crucially, the diagnostic performance of RPR requires external validation through prospective multicenter trials employing standardized data collection protocols.

Elevated RPR upon admission is substantially associated with high risk of CSA-AKI. Therefore, RPR may serve as a novel predictor and its combination with other biomarks may facilitate the clinical decision making in these patients undergoing CPB. However, the result are not conclusive because of lacking of further larger sizes of samples to validate it for the effectiveness. So in the future larger samples will be needed to verify the outcomes.