Dapagliflozin to Reduce the Decline in Renal Function in Patients Newly Diagnosed With Lupus Nephritis

**Description of Procedures**

Participants who meet the inclusion and exclusion criteria and provide written informed consent will be randomly assigned in a 1:1 ratio to one of two study groups: standard treatment plus dapagliflozin 10 mg/day or standard treatment alone.

Participants in the intervention group will receive a three-month supply of dapagliflozin (84 tablets). All participants will continue routine outpatient follow-up for a period of three months.

The primary evaluation will include baseline and 3-month measurements of proteinuria (using either the urine protein-to-creatinine ratio in a spot urine sample or 24-hour urine protein quantification) and kidney function assessed by estimated glomerular filtration rate (eGFR). These laboratory tests are part of the standard clinical monitoring of patients with lupus nephritis.

Renal response will be classified according to the KDIGO 2024 recommendations as complete remission, primary renal response, partial response, or no response, based on changes in proteinuria and kidney function during follow-up.

Additionally, cardiovascular-kidney-metabolic health status will be assessed at baseline and at the end of the study using the 2023 American Heart Association classification, to determine improvement, stability, or progression of cardiovascular, renal, and metabolic risk.

The use of other antiproteinuric medications will be allowed at the discretion of the treating physician, except for SGLT2 inhibitors in the control group.

Adverse events and safety outcomes will be monitored throughout the study. If adverse effects or contraindications related to dapagliflozin occur, the medication will be discontinued and appropriate medical care will be provided.

Inclusion criteria

• Patients over 18 years of age.
• Patients who agree to participate in the study after signing an informed consent form.
• Patients who meet the classification criteria for systemic lupus erythematosus proposed by the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) 2019.
• Patients diagnosed with active lupus nephritis based on one or a combination of the following:

• Renal biopsy: based on a report of the following histological classes: I, II, III, IV, V, or mixed (combinations of the aforementioned classes), following the recommendations of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis and modified National Institutes of Health (ISN/RPS) 2018 (Appendix 1). -Clinical: diagnostic variables of renal domain activity according to the SELENA-SLEDAI or Mex-SLEDAI composite clinical criteria (Appendix 2), with proteinuria always estimated on more than two occasions.
• Patients with proteinuria greater than 500 mg/dL per day, quantified by the protein/creatinine ratio in a single urine sample or by quantification of protein in a 24-hour urine collection.

Exclusion criteria

• 1. Pacientes con diagnóstico por biopsia o a integración del clínico de nefritis lúpica con temporalidad mayor a 6 meses.

• Pacientes bajo tratamiento actual con algún inhibidor iSGLT2, sulfonilureas, bombas de infusión continua de insulina.

• Pacientes con contraindicación del uso de inhibidor SGLT2. (Estadio clínico de enfermedad renal crónica KDIGO IV o tasa de filtrado glomerular estimada <20 ml/min, estado de deshidratación moderado a severo, sospecha de infección grave aguda, requerimiento de evento quirúrgico en días próximos. Infecciones del tracto urinario o genitales severas, recurrentes (>3 eventos/año), o con uso de dispositivos urinarios permanentes.

• Pacientes en embarazo en curso, puerperio o lactancia. 5. Paciente con requerimiento de reanimación hídrica agresiva, uso de aminas vasoactivas, requerimiento de dispositivos de ventilación mecánica invasiva o de alto flujo, terapias de sustitución orgánica, falla orgánica múltiple, infección grave o complicada, o cualquier estado patológico que por criterio clínico se considere al paciente como crítico.

• Estado de acidosis metabólica (por gasometría venosa pH <7.30) o sospecha de cetoacidosis euglucémica.

• Pacientes con diagnóstico previo de Diabetes Mellitus tipo 1, tipo 2 o con el reporte al tamizaje de HbA1c > 6.5%, glucemia en ayuno ≥126 mg/dL o glucemia ≥200 mg/dL asociado a síntomas de hiperglucemia.

• TFGe <20 mL/min o requerimiento de terapia de sustitución renal previa o inminente.