PTM Fetuin-A and SGLT2 inhibition: a clinical perspective on nephroprotection – experience from a single center
Keywords:
fetuin-A, GLT2 inhibitors, dapagliflozin, chronic kidney disease, diabetes mellitusAbstract
Introduction: Fetuin-A is a hepatocyte-derived glycoprotein that plays a key role in metabolic regulation, insulin signaling, and inhibition of ectopic calcification. Reduced fetuin-A levels are associated with increased cardiovascular risk and an unfavorable prognosis in patients with chronic kidney disease (CKD). Evidence from the literature suggests that sodium–glucose cotransporter 2 (SGLT2) inhibitors may indirectly influence fetuin-A through anti-inflammatory and metabolic mechanisms. The aim of the present study was to assess the dynamics of urinary post-translationally modified fetuin-A (uPTM-FA) in patients with diabetes treated with dapagliflozin, compared with insulin therapy and other antidiabetic treatments, and to explore its potential as a biomarker of nephroprotection in chronic kidney disease.
Materials and Methods: Seventy adult patients with type 1 and type 2 diabetes mellitus were followed and stratified into three therapeutic groups: dapagliflozin (n = 23), insulin (n = 24), and other antidiabetic therapy (n = 23). Biomarkers were measured at three time points: baseline (V0), month 3 (V3), and month 6 (V6). The groups were comparable in terms of age, sex, phenotype, diabetes duration, renal function, degree of albuminuria, and baseline fetuin-A levels.
Results: Patients treated with dapagliflozin demonstrated the most pronounced and consistent reduction in median urinary PTM fetuin-A levels, with a higher proportion of clinically significant responders compared with the control groups. Dapagliflozin resulted in favorable modulation of uPTM-FA over the six-month follow-up period, with the effect being most pronounced in high-risk patients (A2 albuminuria, elevated baseline fetuin-A levels, and CKD stages G2–G3b).
Conclusion: Urinary PTM fetuin-A emerges as a clinically interpretable biomarker that complements information obtained from estimated glomerular filtration rate and albuminuria and may support personalized monitoring and therapeutic decision-making in patients with diabetes and chronic kidney disease.
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