Topic Discussion: Aldosterone

Aldosterone, the hormone that seems to be forgotten in the nephrology world with the emergence of ACEI and ARBS and renin inhibitors.  Aldosterone has so many direct actions that having an aldo antagonist as part of your medication regimen is handy. And we have had it for years but its sparingly used partly because of in experience and partly because of better marketing of other drugs.

Well, Nature Review Nephrology this month had a nice review on aldo's mechanisms and effects on the kidney and cardiovascular system.
Few take home points
1. We all know well how aldo effects the salt reabsorption in the distal collecting duct
2. Aldosterone regulates the EnAc channel in the distal duct via a distinct molecular mechanism
3. Aldosterone increases the expression of inflammatory cytokines namely Il-6, Il-1 and MCP-1.
4. Aldosterone via a sgk1 pathway activates NKfB which leads to activation of TGF-B.
5. Due to the above cascade of events, it induces inflammation and fibrosis
6. Aldosterone induces PAI1 expression in mesangial cells and this act can be mitigated using aldo antagonists atleast in a model of radiation injury in rats
7. Aldo can induces fibrosis from a TGF-B independent pathway as well.
8. Aldo can induce mesangial cell proliferation and podocyte injury via reactive oxidative stress and the mTor pathway.
9. Aldosterone can lead to senescence of vascular smooth muscle cells through the ROS and RAS pathways
10. In a setting of high salt diet, the fibrosis or damage is even worse.
11. Too much aldo can lead to endothelial damage - shown in coronary vasculature
12. Large clinical trials such as RALES AND EPHESUS have shown that effects of blocking the mineralocorticoid receptor pathway has good effects on the heart, specifically LVH and reduction in cardiovascular endpoints.
13.We need more large studies in CKD and renal patients of a angiotensin blockade + aldo blockade modality.  We have to keep in mind the Hyperkalemia with those trials; as that's where they ran into problems with the RALES trial