Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Hereditary Podocytopathies, Alport Syndrome, and FSGS: A Case Series to Better Plan a Large-Scale Study.

Abstract

Hereditary diseases of the glomerular filtration barrier are characterized by a more vulnerable glomerular basement membrane and dysfunctional podocytes. Recent clinical trials have demonstrated the nephroprotective effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in chronic kidney disease (CKD). SGLT2-mediated afferent arteriole vasoconstriction is hypothesized to correct the hemodynamic overload of the glomerular filtration barrier in hereditary podocytopathies. To test this hypothesis, we report data in a case series of patients with Alport syndrome and focal segmental glomerulosclerosis (FSGS) with respect of the early effect of SGLT2i on the kidney function. Mean duration of treatment was 4.5 (±2.9) months. Mean serum creatinine before and after SGLT-2i initiation was 1.46 (±0.42) and 1.58 (±0.55) mg/dL, respectively, with a median estimated glomerular filtration rate of 64 (±27) before and 64 (±32) mL/min/1.73 m2 after initiation of SGLT2i. Mean urinary albumin-creatinine ratio in mg/g creatinine before SGLT-2i initiation was 1827 (±1560) and decreased by almost 40% to 1127 (±854) after SGLT2i initiation. To our knowledge, this is the first case series on the effect and safety of SGLT2i in patients with hereditary podocytopathies. Specific large-scale trials in podocytopathies are needed to confirm our findings in this population with a tremendous unmet medical need for more effective, early on, and safe nephroprotective therapies.

• Authors: Jan Boeckhaus, Oliver Gross
• Journal: Cells (Cells) Vol. 10 Issue 7 (07 18 2021) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 34359984 (Publication Type: Case Reports, Journal Article, Observational Study)

Chemical References

• SLC5A2 protein, human
• Sodium-Glucose Transporter 2
• Sodium-Glucose Transporter 2 Inhibitors

Topics

• Adult
• Aged
• Female
• Glomerular Filtration Rate (physiology)
• Glomerulosclerosis, Focal Segmental (complications, drug therapy, pathology, physiopathology)
• Humans
• Male
• Middle Aged
• Nephritis, Hereditary (complications, drug therapy, pathology, physiopathology)
• Podocytes (drug effects, pathology)
• Proteinuria (complications, drug therapy, physiopathology)
• Sodium-Glucose Transporter 2 (metabolism)
• Sodium-Glucose Transporter 2 Inhibitors (pharmacology, therapeutic use)