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.
Study Type
OBSERVATIONAL
Enrollment
300
Oral empagliflozin (10-25 mg daily) for 12 months
Hospital Universitario de Salamanca
Salamanca, Spain
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.
Time frame: Baseline, 6 months, 12 months
Change in estimated glomerular filtration rate (eGFR)
Evaluation of renal function improvement or stabilization during SGLT2 inhibitor treatment.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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 (%).
Time frame: 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.
Time frame: From baseline to 12 months
Change in blood pressure
Assessment of changes in both blood pressures (systolic and diastolic), by Standard sphygmomanometer measurement (mmHg).
Time frame: 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).
Time frame: 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.
Time frame: From baseline to 12 months
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