Diagnostic and Monitoring System for Chronic Kidney Disease Based on Urinary Biomarkers and Preventive Treatment With the SGLT2 Inhibitor Empagliflozin
Overview
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Instituto de Investigación Biomédica de Salamanca
- Enrollment
- 300
- Locations
- 1
- Primary Endpoint
- Change in urinary biomarker panel expression (proteomic fingerprint)
Overview
Brief Summary
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.
Detailed Description
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:
- validation of a urinary biomarker panel obtained through differential proteomics for early detection and monitoring of CKD progression, and
- 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.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 16 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
Arms & Interventions
Empagliflozin Treatment Group
Participants with chronic kidney disease (CKD) stages 2-4 will receive oral empagliflozin (10-25 mg daily) for 12 months. Urinary and plasma samples will be collected at baseline, 6 months, and 12 months to evaluate the urinary biomarker panel, renal function (eGFR), and treatment safety.
Intervention: Empagliflozin (Drug)
Control group
Adults with chronic kidney disease (CKD) stages 2-4 (KDIGO classification) managed in nephrology outpatient clinics without initiation of SGLT2 inhibitors at baseline or during follow-up.
These patients receive standard clinical care according to local and national guidelines.
They are followed on the same schedule (baseline, 6, and 12 months) and have identical variables collected from electronic health records and laboratory systems.
Reasons for non-initiation of SGLT2i are documented systematically and may include:
Not meeting indication criteria established by the Spanish National Health System (e.g., albumin-to-creatinine ratio <200 mg/g, eGFR <20 mL/min/1.73 m² for empagliflozin or <25 for dapagliflozin), or
Clinical contraindications or conditions such as significant hypovolemia or hypotension, recurrent urinary or genital infections, or hypersensitivity.
Control patients will be censored in the primary analysis if they later start SGLT2i therapy (cross-over).
Outcomes
Primary Outcomes
Change in urinary biomarker panel expression (proteomic fingerprint)
Time Frame: Baseline, 6 months, 12 months
Quantitative assessment of urinary biomarkers (including KIM-1, transferrin, IGFBP7, TIMP-2, among others) to evaluate disease progression and treatment response. Urinary biomarkers will be assessed using liquid chromatography-mass spectrometry (LC-MS/MS)-based differential proteomic analysis. Biomarker expression will be quantified as log2 fold change with false discovery rate (FDR) correction. Selected biomarkers will be validated using enzyme-linked immunosorbent assay (ELISA) or equivalent immunoassays. Biomarker concentrations will be normalized to urinary creatinine levels.
Secondary Outcomes
- Change in estimated glomerular filtration rate (eGFR)(Baseline, 6 months, 12 months)
- Histopathological improvement of renal tissue (animal study)(Monthly up to 9 months)
- Monitoring of adverse events of empagliflozin in CKD patients without diabetes(From baseline to 12 months)
- Change in estimated glomerular filtration rate (eGFR)(From baseline to 12 months)
- Change in serum creatinine(From baselinte to 12 months)
- Change in urinary albumin-to-creatinine ratio(From baseline to 12 months)
- Change in serum electrolyte levels(From baseline to 12 months)
- Change in liver function tests(From baseline to 12 months)
- Change in glycated hemoglobin (HbA1c)(From baseline to 12 months.)
- Change in hematological parameters(From baseline to 12 months)
- Change in blood pressure(From baseline to 12 months)
- Change in body weight(From baseline to 12 months)
- Discontinuation due to treatment intolerance(From baseline to 12 months)