Targeting the Endothelin A Receptor in IgA Nephropathy

Kohan, Donald E.; Barratt, Jonathan; Heerspink, Hiddo J.L.; Campbell, Kirk N.; Camargo, Mariannne; Ogbaa, Ike; Haile-Meskale, Ruth; Rizk, Dana V.; King, Andrew

doi:10.1016/j.ekir.2023.07.023

Cited by 9 publications

(1 citation statement)

References 88 publications

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“…Recent evidence has linked IgAN to the activity of the complement system [118]. RASis were the standard of care for patients with IgAN and proteinuria; however, even with the addition of sodium-glucose cotransporter-2 inhibition or steroids (systemic or gut targeted), significant residual proteinuria, renal functional deterioration, and continued risk of kidney failure occurs [110,119,120]. Activation of the renal ET system in IgAN is supported by several lines of evidence.…”

Section: Overview Of Iganmentioning

confidence: 99%

Mechanism of protective actions of sparsentan in the kidney: lessons from studies in models of chronic kidney disease

Kohan,

Bedard,

Jenkinson

et al. 2024

Clinical Science

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Simultaneous inhibition of angiotensin II AT1 and endothelin ETA receptors has emerged as a promising approach for treatment of chronic progressive kidney disease. This therapeutic approach has been advanced by the introduction of sparsentan, the first dual AT1 and ETA receptor antagonist. Sparsentan is a single molecule with high affinity for both receptors. It is US Food and Drug Administration approved for immunoglobulin A nephropathy (IgAN) and is currently being developed as a treatment for rare kidney diseases, such as focal segmental glomerulosclerosis. Clinical studies have demonstrated the efficacy and safety of sparsentan in these conditions. In parallel with clinical development, studies have been conducted to elucidate the mechanisms of action of sparsentan and its position in the context of published evidence characterizing the nephroprotective effects of dual ETA and AT1 receptor inhibition. This review summarizes this evidence, documenting beneficial anti-inflammatory, antifibrotic, and hemodynamic actions of sparsentan in the kidney and protective actions in glomerular endothelial cells, mesangial cells, the tubulointerstitium, and podocytes, thus providing the rationale for the use of sparsentan as therapy for focal segmental glomerulosclerosis and IgAN and suggesting potential benefits in other renal diseases, such as Alport syndrome.

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Section: Overview Of Iganmentioning

confidence: 99%