Cardiorenal Syndrome: Pathophysiology, Management, and the Challenge of Therapeutic Inertia

Cardiorenal syndrome describes the clinical consequences of the bidirectional influence that cardiac and renal dysfunction exert on each other—a domain in which single-organ care proves insufficient. A 2024 meta-analysis estimated the pooled prevalence of chronic kidney disease among patients with heart failure at 49%. Across individual cohorts, this figure ranges between 30% and 60%, with the spread reflecting the population studied and the threshold used to define kidney disease. Among acute heart failure admissions, 64% of cases have an estimated glomerular filtration rate below 60 mL/min/1.73 m2, and mortality reaches 7.6% once it falls into the severe range (15–29 mL/min/1.73 m2). The same can be described in the other “direction”: congestive heart failure is reported in 28% of adults aged 66 years or older with chronic kidney disease, compared to 6% of those without. The Acute Dialysis Quality Initiative distinguishes a five-subtype framework by direction and chronicity of organ injury, and each subtype shows characteristic prescribing failure patterns. In types 1 and 2, the dominant problem is premature de-escalation of neurohormonal therapy at the first creatinine rise. In type 4, the failure is upstream in the cascade: cardiovascular surveillance lags behind the increasing rate of chronic kidney disease. Randomized trials over the past decade have expanded the therapeutic options. Sodium-glucose cotransporter 2 inhibitors showed cardiorenal benefit across every ejection fraction studied and at estimated glomerular filtration rate values down to 20 mL/min/1.73 m2. These findings have expanded treatment eligibility to patients with advanced CKD. The FINE-HEART pooled analysis of finerenone suggested a nominal reduction in all-cause mortality, alongside fewer heart failure hospitalizations and improvement in the kidney composite outcome. In the FLOW trial, semaglutide showed a reduction in the composite of major kidney events and cardiovascular death in diabetic adults with chronic kidney disease. In this cohort, the estimated glomerular filtration rate slope was slower in the active arm and secondary outcomes showed reductions in major adverse cardiovascular events and in all-cause mortality. However, observational registries show that these classes of drugs are less used in patients with the highest baseline risk, with advancing renal disease identified as an independent predictor of under-prescription. Therapeutic inertia in this setting reflects determinants at the patient, clinician, and system levels, which is compounded because each prescribing decision must be justified for both the heart and the kidney. The primary objective of the present narrative review is the therapeutic inertia that separates this evidence from routine prescribing: the sections on pathophysiology, imaging and biomarker tools, and subtype-specific pharmacotherapy supply the clinical rationale, and the closing sections cover the implementation strategies and the multidisciplinary framework required to act on the trial findings.