Chronic Kidney Disease
Conditions
Keywords
SGLT2 inhibitors, empagliflozin, urinary biomarker
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: 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.
Interventions
DRUGEmpagliflozin
Oral empagliflozin (10-25 mg daily) for 12 months
Sponsors
Instituto de Investigación Biomédica de Salamanca
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in urinary biomarker panel expression (proteomic fingerprint) | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in estimated glomerular filtration rate (eGFR) | Baseline, 6 months, 12 months | Evaluation of renal function improvement or stabilization during SGLT2 inhibitor treatment. |
| Histopathological improvement of renal tissue (animal study) | Monthly up to 9 months | Monthly analysis of renal fibrosis, inflammation, and extracellular matrix accumulation in preclinical models treated with empagliflozin. |
| Monitoring of adverse events of empagliflozin in CKD patients without diabetes | 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. |
| Change in serum creatinine | 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). |
| Change in urinary albumin-to-creatinine ratio | 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). |
| Change in serum electrolyte levels | 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). |
| Change in liver function tests | 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). |
| Change in glycated hemoglobin (HbA1c) | 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 (%). |
| Change in hematological parameters | From baseline to 12 months | Change in complete blood count parameters to evaluate hematological safety during treatment by standard clinical laboratory testing. |
| Change in blood pressure | From baseline to 12 months | Assessment of changes in both blood pressures (systolic and diastolic), by Standard sphygmomanometer measurement (mmHg). |
| Change in body weight | From baseline to 12 months | Change in body weight to assess tolerability and volume status during empagliflozin treatment by calibrated clinical scale (kg). |
| Discontinuation due to treatment intolerance | 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. |
Countries
Spain
Contacts
CONTACTCarlos Martínez Salgado, PhD
PRINCIPAL_INVESTIGATORCarlos Martínez Salgado, PhD
University of Salamanca
PRINCIPAL_INVESTIGATORPilar Fraile Gómez, MD, PhD
University of Salamanca
Outcome results
None listed