Endocrine and Metabolic Crosstalk in Non-Diabetic Chronic Kidney Disease: Current Mechanisms, Biomarkers, and Therapeutic Perspectives

Resumen

Chronic kidney disease (CKD) without diabetes mellitus has become an increasingly recognized clinical entity whose progression cannot be explained exclusively by traditional hemodynamic mechanisms. Growing evidence indicates that endocrine dysregulation, metabolic remodeling, mitochondrial dysfunction, chronic inflammation, oxidative stress, and altered communication between the kidney and other organ systems play fundamental roles throughout disease development and progression. The present review critically analyzes current scientific evidence regarding the endocrine and metabolic mechanisms involved in non-diabetic CKD, integrating findings from nephrology, endocrinology, and internal medicine while incorporating information relevant to Latin American populations. A narrative review based on the Scientific Method was conducted using high-quality publications retrieved from internationally recognized databases and clinical practice guidelines. The available evidence demonstrates that persistent activation of the renin–angiotensin–aldosterone system, disruption of the fibroblast growth factor 23–Klotho axis, impaired vitamin D metabolism, insulin resistance, obesity-related endocrine alterations, mitochondrial dysfunction, and gut–kidney interactions contribute substantially to renal fibrosis, progressive loss of kidney function, and cardiovascular complications. Contemporary therapeutic approaches, particularly sodium–glucose cotransporter-2 inhibitors, have significantly modified disease management by providing nephroprotective effects beyond glycemic control. Emerging biomarkers and precision medicine strategies also show considerable potential for improving early diagnosis, individualized risk assessment, and targeted therapeutic interventions. Nevertheless, additional multicenter studies, particularly involving underrepresented regions such as Latin America, remain necessary to strengthen the current evidence base. Overall, non-diabetic CKD should be regarded as a complex multisystem disorder requiring an integrated clinical approach that combines endocrine, metabolic, cardiovascular, and nephrological perspectives to optimize patient outcomes.