The relationship between inflammatory status and cardiovascularoutcomes, progression to end-stage renal disease, and mortality in patients with cardiorenal syndrome

Cardiorenal syndrome is a bidirectional pathophysiological process in which acute or chronic loss of function in the heart or kidney precipitates dysfunction in the contralateral organ. Cardiac structural or functional abnormalities reduce renal perfusion and impair kidney function; in turn, decreased glomerular filtration, fluid retention, and accumulation of uremic toxins increase cardiac workload and exacerbate heart failure. Inflammation is a key determinant within this reciprocal interplay: a sustained inflammatory response accelerates cellular injury, fibrosis, and functional decline in both organs, thereby driving disease progression. Thus, in cardiorenal syndrome, inflammation should be regarded not merely as a consequence but as a central mechanism that initiates, maintains, and aggravates the process. This retrospective study included 101 patients with chronic cardiorenal (Type 2) or chronic renocardiac (Type 4) syndrome who were followed at the Nephrology and Cardiology outpatient clinics of Alanya Training and Research Hospital between 1 August 2022 and 31 July 2024. Classification was based on the Acute Dialysis Quality Initiative (ADQI) 16th Consensus Report; only chronic subtypes were analyzed. Type 2 cardiorenal syndrome comprised patients with a diagnosis of heart failure for ≥3 months and consequent persistent renal dysfunction (eGFR < 60 mL/min/1.73 m2). Type 4 renocardiac syndrome comprised patients with chronic kidney disease (KDIGO stage ≥3) whose left ventricular ejection fraction (EF) declined to <60% during follow-up. Systemic inflammation was assessed using the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII = [neutrophils × platelets]/lymphocytes). These biomarkers were evaluated as indicators of systemic inflammatory response and analyzed in relation to changes in cardiac and renal function. The median age of participants was 68 years, and 81.2% were male. During follow-up, 6 patients died, 6 progressed to end-stage kidney disease (ESKD), and 29 experienced an acute cardiovascular event (ACE). Regarding cardiac function, EF decreased in 36.6% of patients, remained unchanged in 48.5%, and increased in 14.9%. With respect to renal function, estimated glomerular filtration rate (eGFR) decreased in 77.2% and increased in 20.8%. Although NLR, PLR, and SII levels were higher among patients who died or developed ESKD, these differences were not statistically significant (all p > 0.05). Notably, second-visit NLR values were significantly higher in patients who experienced an ACE (p = 0.025). Receiver operating characteristic analyses demonstrated limited discriminative ability of these inflammatory markers for predicting clinical outcomes. In conclusion, the inflammatory response appears to play a pivotal role in the progression and clinical outcomes of cardiorenal syndrome; however, routine indices such as NLR, PLR, and SII alone are insufficient to reliably predict risk. Larger, prospective studies are warranted to develop inflammation-based prognostic models and to strengthen risk stratification. Keywords: Cardiorenal syndrome, Chronic renocardiac syndrome, Chronic cardiorenal syndrome, Inflammation, Systemic immune-inflammation index (SII), Neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), Ejection fraction (EF), Glomerular filtration rate (GFR), Prognostic markers, Clinical outcomes, Mortality, End-stage renal disease (ESRD)