Delayed spironolactone administration prevents the transition from acute kidney injury to chronic kidney disease through improving renal inflammation

Abstract

We propose that MRB, administered 24 h after the ischemic injury that leads to AKI, reduces inflammation and promotes efficient tissue repair that avoids the AKI to CKD transition. These data highlight a therapeutic window to preclude CKD development after AKI.

The safety and efficiency of low-dose mineralocorticoid receptor antagonists in dialysis patients: a meta-analysis

“…MRAs play an important role in chronic HF, especially in patients with left ventricular function changes and HF after myocardial infarction. In terms of kidney disease, MRAs also play a critical role, such as preventing the transition from acute kidney injury to chronic kidney disease [16,17], protecting against diabetic nephropathy [18], and delaying the progression of glomerulonephritis [19]. The underlying mechanism by which MRAs work may be by reduction of oxidative stress [20], reduction of inflammation [21], regulation of vascular tone [22], or antifibrosis [23].…”

Potential Benefit of Mineralocorticoid Receptor Antagonists in Kidney Diseases

“…The use of genetically modified mouse model deficient of MR in myeloid cells revealed that myeloid MR contributes to renal injury in a glomerulonephritis mouse model [8]. Moreover, our recent work showed that myeloid MR participates to CKD progression induced by AKI [34].…”

“…The deletion of MR in myeloid cells favored M2 polarization of renal macrophages leading to improved tissue repair and prevention of renal scaring, decreased function, and interstitial fibrosis. Interestingly MRA administration using the nonsteroidal MRA finerenone has similar effects, blunting CKD development after ischemia-reperfusion injury in rodents [22,34] and in the large white pig [34]. The role of myeloid MR in the progression of CKD in other models of kidney disease has to be further studied.…”

“…MR antagonism also prevents CKD induced by a mild ischemic period even when administered 3 hours after the ischemia episode [48]. The underlying mechanisms rely on the limitation of inflammatory events and the promotion of repair mechanisms held by M2-type macrophages and interleukin-4 receptor signaling [34]. Importantly, these benefits are also observed in the Large White Pig model: short-term soludactone administration before/after the ischemic event indeed prevents CKD progression at 3 months, with a reduction in fibrosis and proteinuria and improved renal function [34].…”

“…The underlying mechanisms rely on the limitation of inflammatory events and the promotion of repair mechanisms held by M2-type macrophages and interleukin-4 receptor signaling [34]. Importantly, these benefits are also observed in the Large White Pig model: short-term soludactone administration before/after the ischemic event indeed prevents CKD progression at 3 months, with a reduction in fibrosis and proteinuria and improved renal function [34]. The data indicate that MRA treatment is an encouraging therapeutic option to prevent the AKI to CKD transition which identifies the MR expressed in inflammatory cells as a specific target in this setting.…”