INFLAMMATION + FIBROSIS IN CKD
KIDNEY FILTRATION FURTHER DETERIORATES AS INFLAMMATION AND FIBROSIS PROGRESS1
MR OVERACTIVATION SIGNIFICANTLY TRIGGERS INFLAMMATION AND FIBROSIS, CONTRIBUTING TO A DECLINE IN KIDNEY FUNCTION1
For patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), unaddressed inflammation and fibrosis can lead to a variety of cellular changes that permanently alter the structure of the kidney.2
MR: mineralocorticoid receptor.
Cellular expansion
Cells within the glomerulus proliferate and expand, resulting in mesangial matrix expansion. There is a strong link between this process and CKD progression3
Thickening around tubules
Thickening and scarring in and around the renal tubules, which decreases renal function and increases pressure3
Scarring of kidney blood vessels
The hardening and scarring of the glomerulus, a tuft of capillaries that removes waste from blood, leads to an excessive loss of protein3
Kidney fibrosis
Structural damage to the kidney impairs the organ’s functionality3
In the kidney, inflammation and fibrosis can lead to tissue expansion, increased pressure within the vasculature and internal structure, and eventually, to scarring that makes effective filtration increasingly difficult.2
INFLAMMATORY AND FIBROTIC DAMAGE IS A MAJOR CONSEQUENCE OF MR OVERACTIVATION IN THE KIDNEY1
Under normal conditions, MR signaling regulates electrolyte and fluid balance within the kidneys.1
However, under certain conditions, like T2D, the MR within the kidney can become pathologically overactivated. As MR activators proliferate and the cell begins producing:
- Proinflammatory proteins
- Profibrotic proteins
These factors eventually lead to inflammation and fibrosis in the kidneys, causing damage. Kidney damage, as shown by increased albuminuria, raises the risk of a cardiovascular (CV) event and declining kidney function.1,4
Normal MR Function
MR Overactivation
MR OVERACTIVATION CONTRIBUTES TO THE RISK OF A CV EVENT1
Though CV risk is a reality from the beginning of CKD in T2D, as CKD progresses, there is an increased chance a patient might experience a CV event like myocardial infarction or stroke. There is evidence in both preclinical and clinical trials to support the connection of MR overactivation with CV dysfunction.1,4,5
References:
- Bauersachs J, et al. Hypertension. 2015;65(2):257–263. Return to content
- Alicic RZ, et al. Clin J Am Soc Nephrol. 2017;12(12):2032–2045. Return to content
- Thomas MC, et al. Nat Rev Dis Primers. 2015;1:15018. Return to content
- Fox, C. et al. Lancet. 380(9854):1662–1673. Return to content
- Scirica BM, et al. JAMA Cardiol. 2018;3(2):155–163. Return to content