TOPIC DISCUSSION: Mechanism of Proteinuria in Diabetic Kidney Disease

What is the mechanism behind this entity that we see so frequently?

If we look at it from different sites of injury, there is data to support each one of these theories.

 Proximal Tubule injury:  leading to decreased protein reabsorption leading to proteinuria.

Hemodynamic injury: leading to glomerular hyperfiltration leading to increase glomerular pressure and proteinuria

Mesangial cell injury: leads to hypertrophy, matrix expansion, and mesangiolysis leading to glomerular hypefiltration and proteinuria

Endothelial cell injury: leading to altered VEGF leading to podocyte damage

GBM injury: leading to decreased negative charge and proteinuria

Podocyte injury: leading to podocytopenia or foot process effacement and leading to apoptosis, degradation or lack of proliferation.

Vascular insult:- leads to ischemia that can lead to tubular injury leading to proteinuria.

Which one is primary and which is secondary mechanism?  Can diabetic disease progress without albuminuria? Yes it can.

Current literature supports that diabetic kidney disease is mainly due to glomerular filtration barrier changes, changes in endothelial damage and GBM and direct injury to podocytes, Mesangial involvement is more of secondary role.   Tubular interstitial damage is also playing a role but it the former factors that if disrupted lead to ongoing proteinuria.  This explains why when we have accelerated HTN on top of diabetic nephropathy, there is increase in proteinuria likely due to increasing glomerular endothelial damage.

A nice review on this topic can be found in an article in KIfrom 2008.