<b>Low dose sGC stimulator (BAY 41-8543) combined with a low dose PDE9 inhibitor (BAY 73-6691)</b><b> reduces renal fibrosis in 5/6 nephrectomized rats</b>

Results: 5/6Nx caused an increase of cystatin C, increased proteinuria and glomerulosclerosis, as well as renal interstitial fibrosis. Neither low-dose sGC stimulation nor low-dose PDE9 inhibition alone improved kidney function and morphology in 5/6Nx rats, whereas BAY 41-8543 in combination with BAY 73-6691 attenuated renal interstitial fibrosis in 5/6Nx rats. This beneficial effect could not be explained by alterations of blood pressure (BP) and renal immune system. BP did not differ between groups. BAY 41-8543 in combination with BAY 73-6691 had no effect on renal macrophage, CD4+ T-cell and CD8+ T-cell infiltration in the late-stage of 5/6Nx. RNA sequencing, however, revealed that BAY 41-8543 in combination with BAY 73-6691 down-regulated the expression of several fibrosis-related genes such as Collagen Type I Alpha 1, Collagen Type III Alpha 1 Chain, Collagen Type XIV Alpha 1 Chain, Lumican, Integrin Subunit Alpha 11, as well as Transforming Growth Factor Beta 3.