Kidney Week

Abstract: SA-PO726

SGLT2 Inhibition in Nondiabetic CKD: Results in Experimental Lupus Nephritis (LN)

Session Information

• Glomerular Diseases: Therapeutic Strategies
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Vilardell, Jordi, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus. Nephrology and Transplantation Research Group., Barcelona, Spain

Jordi Vilardell, PhD

• Jacobs Cachá, Conxita, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus. Nephrology and Transplantation Research Group., Barcelona, Spain

Conxita Jacobs Cachá, PhD

• Martos, Nerea, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus. Nephrology and Transplantation Research Group., Barcelona, Spain

Nerea Martos

• Llorens Cebrià, Carmen, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus. Nephrology and Transplantation Research Group., Barcelona, Spain

Carmen Llorens Cebrià, MS

• Motto, Aku Enam, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus. Nephrology and Transplantation Research Group., Barcelona, Spain

Aku Enam Motto, PhD

• Lech, Maciej, University Hospital, Ludwig-Maximilians-University. Department of Medicine IV, Division of Nephrology, Munich, Germany

Maciej Lech, PhD

• Martínez Díaz, Irene, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus. Nephrology and Transplantation Research Group., Barcelona, Spain

Irene Martínez Díaz

• Anders, Hans J., University Hospital, Ludwig-Maximilians-University. Department of Medicine IV, Division of Nephrology, Munich, Germany

Hans J. Anders, MD

• Soler, Maria Jose, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus. Nephrology and Transplantation Research Group., Barcelona, Spain

Maria Jose Soler, MD, PhD

Group or Team Name

• Nephrology and Transplantation Research Group.

Background

Sodium glucose cotransporter type 2 inhibitors (SGLT2i) attenuate cardiovascular morbidity and progression of CKD in type 2 diabetes patients. It has been proposed that SGLT2i may also elicit renoprotection in non-diabetic CKD. Our goal is to evaluate if the SGLT2i treatment improves kidney disease progression in a mouse model of LN.

Methods

Female MRLlpr/lpr mice were randomly assigned to (1) vehicle (VH) or (2) empagliflozin (EMP) (10 mg/kg/day) treatment once signs of active systemic lupus erythematosus appeared: proteinuria >100mg/dL or lymphadenopathy in minimum 2 bilateral sites with proteinuria >30mg/dL. 13 mice/group were treated for 4 weeks. Reduction of urinary albumin to creatine ratio (UACR) was the primary endpoint. Glomerular Filtration Rate (GFR), renal histology (LN activity/chronicity index, glomerulosclerosis, interstitial fibrosis) and SLE markers (total serum IgG, anti-dsDNA IgG, IgG deposits, lymph node and spleen weight) were considered secondary endpoints.

Results

After 4 weeks of treatment, no significant differences in glicemia were found between groups. Empagliflozin inhibited SGLT2 in the tubular cells supported by a significant increase of glucosuria (EMP 12.3±5.3 mg/g; VH 1.2±5.3 mg/g, p<0.001) and reflected with the increased water intake observed in this group (EMP 7.0±0.95 mg/g; VH 5.0±0.3 mg/g; p<0.001). At the end of the experiment, vehicle treated mice showed a significant increase in UACR (post-UACR 3.3±0.7 vs pre-UACR 2.2±0.7mg/g; p<0.001) consistent with LN progression that was not reduced by empagliflozin. Empagliflozin did not modify GFR and LN activity/chronicity indexes, glomerulosclerosis or interstitial fibrosis. Regarding SLE markers, empagliflozin was not able to decrease total serum IgG, anti-dsDNA IgG, glomerular IgG deposits or lymph node weight. Only spleen weight decreased significantly in empagliflozin treated mice (EMP 8.5±1.6mg/g; VH 12.1±3.4 mg/g; p<0.001).

Conclusion

In our experimental setting, empagliflozin reduced spleen weight suggesting a protective role in SLE in MRLlpr/lpr mice. However, empagliflozin did not modify LN progression probably because the acute LN phase. It is expected that positive effect in terms of reducing proteinuria will be observed in patients with LN and residual proteinuria.

Funding

• Government Support – Non-U.S.