Experimental studies in animals have shown that PDE5 inhibitors may reverse kidney damage independently of their effects on blood pressure through intra-renal mechanisms. In humans, PDE5 inhibitors have also been shown to reduce proteinuria, a marker of kidney damage. However, the successful introduction of SGLT2 inhibitors and endothelin receptor antagonists to the field of renal therapeutics makes the development of PDE5 inhibitors for this purpose unlikely.