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

Jan Boeckhaus,Oliver Gross

doi:10.3390/cells10071815

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.

Highlights

Hereditary diseases of the glomerular filtration barrier are characterized by a more vulnerable glomerular basement membrane (GBM) and dysfunctional podocytes, which are unable to permanently tolerate hyperfiltration and elevated capillary pressure [1]
We report data on the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in a case series of patients with Alport syndrome (AS) and focal segmental glomerulosclerosis (FSGS)
As a working hypothesis for our case series, we postulate that SGLT2-mediated correction of the hemodynamic overload of the glomerular filtration barrier represents a new and highly promising therapeutic approach in podocytopathies

Summary

Introduction

Hereditary diseases of the glomerular filtration barrier are characterized by a more vulnerable glomerular basement membrane (GBM) and dysfunctional podocytes, which are unable to permanently tolerate hyperfiltration and elevated capillary pressure [1]. Variants in the slit-diaphragm genes NPHS1 and NPHS2, as well as INF2, are other classical hereditary causes of FSGS in adolescents and young adults [2,3] In these hereditary diseases of the glomerular filtration barrier, angiotensin-converting-enzyme inhibitors (ACEis) have evolved as the cornerstone of treatment, starting pre-emptively in oligo-symptomatic toddlers with isolated microhematuria [4,5]. The goal of our investigation was to characterize the early effect on the kidney function and to assess the safety of initiation of therapy [7,8] To our knowledge, this is the first case series on the effect of SGLT2i in patients with hereditary causes of CKD

Materials and Methods

Results

Discussion