Urinary Biomarker-Based Diagnostic and Monitoring System for Chronic Kidney Disease and Real-World Effectiveness of SGLT2 Inhibitors

Diagnostic and Monitoring System for Chronic Kidney Disease Based on Urinary Biomarkers and Preventive Treatment With the SGLT2 Inhibitor Empagliflozin

This prospective observational study aims to assess the association between real-world use of sodium-glucose co-transporter 2 inhibitors (SGLT2i; e.g., empagliflozin, dapagliflozin) and renal function decline in adults with chronic kidney disease (CKD) stages 2-4 (KDIGO classification). The study will also validate a urinary biomarker panel for early diagnosis and monitoring of CKD progression.

No investigational product is assigned, and medical practice or prescription patterns are not altered.

This is a real-world, observational study with prospective follow-up and retrospective baseline data when available, conducted at the Nephrology Department of the University Hospital of Salamanca, Spain.

The project integrates translational and clinical components:

1. validation of a urinary biomarker panel obtained through differential proteomics for early detection and monitoring of CKD progression, and
2. evaluation of the effectiveness and safety of SGLT2i in routine clinical practice.

A total of 300 adults with CKD stages 2-4 will be included (150 initiating SGLT2i and 150 matched controls). Participants will be followed for 12 months (baseline, 6, and 12 months). Data will be extracted exclusively from electronic health records and laboratory systems.

The primary outcome is the annual decline rate of estimated glomerular filtration rate (eGFR, CKD-EPI 2021). Secondary outcomes include a composite renal endpoint (≥40% sustained eGFR decline, renal replacement therapy, transplantation, or renal death), cardiovascular hospitalization, all-cause mortality, adverse drug reactions (ADRs), and real-world patterns of SGLT2i use.

Exploratory analyses will assess associations between urinary biomarkers and clinical outcomes.

The study follows Spanish regulations for observational studies with medicinal products (Real Decreto 957/2020), with ethics approval and informed consent for biological samples.

Inclusion Criteria:

• ≥18 years old
• Diagnosed with chronic kidney disease (KDIGO stages 2-4)
• Life expectancy ≥12 months
• Available clinical and laboratory data in the electronic medical record

Exclusion Criteria:

• Current or recent renal replacement therapy or kidney transplantation
• End-stage renal disease
• Participation in interventional trials that may affect outcomes
• Allergy or intolerance to SGLT2i (for exposed cohort)