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

January 12, 2026 updated by: Instituto de Investigación Biomédica de Salamanca

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

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline, 6 months, 12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in estimated glomerular filtration rate (eGFR)
Time Frame: Baseline, 6 months, 12 months
Evaluation of renal function improvement or stabilization during SGLT2 inhibitor treatment.
Baseline, 6 months, 12 months
Histopathological improvement of renal tissue (animal study)
Time Frame: Monthly up to 9 months
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
Time Frame: From baseline to 12 months

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)
Time Frame: From baseline to 12 months
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
Time Frame: From baselinte to 12 months
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
Time Frame: From baseline to 12 months
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
Time Frame: From baseline to 12 months
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
Time Frame: From baseline to 12 months
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)
Time Frame: From baseline to 12 months.
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
Time Frame: From baseline to 12 months
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
Time Frame: From baseline to 12 months
Assessment of changes in both blood pressures (systolic and diastolic), by Standard sphygmomanometer measurement (mmHg).
From baseline to 12 months
Change in body weight
Time Frame: From baseline to 12 months
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
Time Frame: From baseline to 12 months
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Instituto de Investigación Biomédica de Salamanca

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Carlos Martínez Salgado, PhD, University of Salamanca
  • Principal Investigator: Pilar Fraile Gómez, MD, PhD, University of Salamanca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 18, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2026

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 16, 2026

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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