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.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: Empagliflozin

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:

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.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Carlos Martínez Salgado, PhD; Phone Number: +34616129633; Email: carlosms@usal.es

Study Locations

• Spain
  • Salamanca, Spain
    • Hospital Universitario De Salamanca
    • Contact: Carlos Martínez Salgado, PhD; Phone Number: +34616129633; Email: carlosms@usal.es
    • Contact: Pilar Fraile Gómez, MD, PhD; Phone Number: +34923291100; Email: pilarfg@usal.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Participants with chronic kidney disease (CKD) stages 2-4.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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.	Drug: Empagliflozin; Oral empagliflozin (10-25 mg daily) for 12 months
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in urinary biomarker panel expression (proteomic fingerprint)	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.	Baseline, 6 months, 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in estimated glomerular filtration rate (eGFR)	Evaluation of renal function improvement or stabilization during SGLT2 inhibitor treatment.	Baseline, 6 months, 12 months
Histopathological improvement of renal tissue (animal study)	Monthly analysis of renal fibrosis, inflammation, and extracellular matrix accumulation in preclinical models treated with empagliflozin.	Monthly up to 9 months
Monitoring of adverse events of empagliflozin in CKD patients without diabetes	Adverse events (AEs) will be recorded and classified according to Common Terminology Criteria for Adverse Events (CTCAE, latest version), including severity grading and assessment of causality related to treatment. Serious adverse events (SAEs) and discontinuations due to AEs will be specifically tracked by the investigator.	From baseline to 12 months
Change in estimated glomerular filtration rate (eGFR)	Change in renal function assessed by estimated glomerular filtration rate (eGFR) calculated using the CKD-EPI equation during empagliflozin treatment using the Serum creatinine-based CKD-EPI equation.	From baseline to 12 months
Change in serum creatinine	hange in serum creatinine levels to assess renal safety during treatment with empagliflozin by standard clinical laboratory assay (mg/dL).	From baselinte to 12 months
Change in urinary albumin-to-creatinine ratio	Change in urinary albumin-to-creatinine ratio as a marker of renal damage and safety during empagliflozin treatment by standard urine laboratory testing (mg/g creatinine).	From baseline to 12 months
Change in serum electrolyte levels	Change in serum sodium and potassium levels to evaluate electrolyte safety during empagliflozin treatment by standard clinical laboratory testing (mmol/L).	From baseline to 12 months
Change in liver function tests	Change in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels to assess hepatic safety by standard clinical laboratory assays (U/L).	From baseline to 12 months
Change in glycated hemoglobin (HbA1c)	Change in HbA1c levels to monitor metabolic safety in non-diabetic CKD patients treated with empagliflozin by standard laboratory assay (%).	From baseline to 12 months.
Change in hematological parameters	Change in complete blood count parameters to evaluate hematological safety during treatment by standard clinical laboratory testing.	From baseline to 12 months
Change in blood pressure	Assessment of changes in both blood pressures (systolic and diastolic), by Standard sphygmomanometer measurement (mmHg).	From baseline to 12 months
Change in body weight	Change in body weight to assess tolerability and volume status during empagliflozin treatment by calibrated clinical scale (kg).	From baseline to 12 months
Discontinuation due to treatment intolerance	Number and proportion of participants who permanently discontinue empagliflozin due to treatment-related intolerance or adverse events. It will be achieved trough clinical visit records and adverse event reporting.	From baseline to 12 months

Collaborators and Investigators

• Sponsor: Instituto de Investigación Biomédica de Salamanca
• Investigators: Principal Investigator: Carlos Martínez Salgado, PhD, University of Salamanca; Principal Investigator: Pilar Fraile Gómez, MD, PhD, University of Salamanca

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: January 12, 2026
• First Posted (Estimated): January 16, 2026

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: SGLT2 inhibitors; empagliflozin; urinary biomarker
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Renal Insufficiency, Chronic; empagliflozin
• Other Study ID Numbers: PI25/00053

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized datasets and analytic code will be available upon reasonable request, following approval by the Ethics Committee and IBSAL data governance board.
• IPD Sharing Time Frame: Data will be available starting 12 months after publication of primary results and for a minimum of 5 years thereafter.
• IPD Sharing Access Criteria: Qualified researchers with a methodologically sound proposal, as determined by the study steering committee, will be able to access the data. Requests should be directed to the study PI. A data access agreement will be required.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No