Key result
Stage- and phenotype-based sequencing in CKM syndrome prioritizes early initiation of broad organ-protective therapies.
Why the study?
Recommendations for therapies managing cardiovascular, kidney, and metabolic diseases are distributed across separate disease-specific guidelines, leaving clinicians to decide on the order and combination of initiation based on CKM stage and clinical factors.
Provides a practical, stage- and phenotype-based framework for prioritizing and sequencing multi-organ pharmacotherapies across the cardiovascular-kidney-metabolic syndrome spectrum.
Answers are grounded in this paper and cite their sources.
May guide CKM therapy sequencing in practice; extends staging frameworks with phenotype-specific tailoring.
Cardiovascular-kidney-metabolic (CKM) syndrome refers to the intertwined effects of increased adiposity, metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). Although many therapies have been developed for the management of cardiovascular, kidney, and metabolic diseases, recommendations for their use are distributed across separate disease-specific guidelines. The clinician needs to decide on the order of initiation of therapies, whether therapies can be taken together, and how the order of initiation changes based on the stage of CKM, predominant phenotype, level of renal function, presence of albuminuria, hypertension, hyperkalemia, congestion, obesity, drug tolerance, treatment access, and feasibility. This review suggests a stage- and phenotype-oriented therapeutic sequence across CKM conditions. It includes lifestyle and obesity therapy, renin-angiotensin system (RAS) inhibition, sodium-glucose cotransporter-2 inhibition, mineralocorticoid receptor antagonism, incretin therapies, heart failure drugs, hypertension management, and lipid-lowering therapies.
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Senapati et al. (2026) conducted a review in Cardiovascular-kidney-metabolic (CKM) syndrome (stages 0-4). Stage- and phenotype-oriented therapeutic sequencing (lifestyle, RAS inhibitors, SGLT2 inhibitors, MRAs, incretin therapies, heart failure pharmacotherapy, antihypertensives, and lipid-lowering therapy) was evaluated. Stage- and phenotype-oriented therapeutic sequencing in cardiovascular-kidney-metabolic syndrome prioritizes early, breadth-focused initiation of organ-protective therapies tailored to clinical risk.
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