Diabetic nephropathy

Chapters:

Watch video only

Introduction0:00–0:19

Diabetic nephropathy refers to the kidney damage caused by both type I and type II diabetes. Because of the growing number of people affected by diabetes, diabetic nephropathy is currently the leading cause of end-stage renal disease in most developed countries around the world.

Physiology0:19–1:25

Each kidney has millions of nephrons, each of which is served by a tiny capillary bed called a glomerulus. The tiny arteriole that approaches the glomerulus is called the afferent arteriole - a for approaching, and the arteriole that exits the glomerulus is called the efferent arteriole - e for exits.
The glomeruli are a tiny cluster of capillaries that are physically supported by mesangial cells. So when blood is filtered it moves through the endothelium lining the capillary, then through the basement membrane, and then through the epithelium lining the nephron, and finally into the nephron itself - at which point its called filtrate.
The endothelium has pores that keep cells from entering the filtrate, and the basement membrane is negatively charged and repels other negatively charged molecules and proteins, like the protein albumin.
The epithelium has of special cell type called a podocyte which looks like an octopus because it has foot processes that wrap around the basement membrane, leaving tiny gaps between its octopus-like projections called filtration slits.

Pathology1:25–3:56

In diabetes mellitus, there’s an excess of glucose in the blood, because it can’t get into cells, and when blood gets filtered through the kidneys, some of that excess glucose starts to spill into the urine, called glycosuria.
In addition, when there’s a lot of glucose in the blood, it also starts sticking to proteins in the blood — a process called non-enzymatic glycation because no enzymes are involved.
Because glucose can get through the endothelium, this process of glycation can also involve the basement membrane of small blood vessels making it thicken.
The process particularly affects the efferent arteriole causing it to get stiff and more narrow - a process called hyaline arteriosclerosis.
This creates an obstruction that makes it difficult for blood to leave the glomerulus, increasing pressure within the glomerulus.
At the same time, the afferent arteriole dilates, allowing more blood flow into the glomerulus and increasing pressure further.
High pressure in the glomerulus leads to an increase in the glomerular filtration rate--which is simply the amount of blood filtered through per minute.
This is the first stage of diabetic nephropathy, called hyperfiltration. In response to this high-pressure state, the supportive mesangial cells secrete more and more structural matrix expanding the size of the glomerulus.
This matrix deposition and mesangial expansion happen uniformly, or it can result in little nodules within the mesangium called Kimmelstiel-Wilson nodules - which are tiny little balls of protein.
The thickening of the basement membrane counterintuitively makes it more permeable—allowing proteins like albumin through that otherwise would have been filtered out.
It makes sense if you think about our octopus friend once more - as the glomerulus expands, the legs of the octopus naturally have larger gaps between them, in other words the filtration slits widen, making it easier for substances to slip through.
So in the end, the key abnormalities in diabetic nephropathy are a thickened glomerular basement membrane, mesangial expansion, Kimmelstiel-Wilson nodules, and disruption of the podocytes.
Eventually, these changes damage the glomerulus so much that it's unable to filter blood normally, and the glomerular filtration rate decreases.

Symptoms3:56–4:24

Typically, diabetic nephropathy starts quietly with no symptoms during the hyperfiltration phase, but over time as more and more of the nephrons are affected, the kidney becomes less and less effective and filtering the blood into the urine, and the glomerular filtration rate decreases dramatically .
Once the kidneys no longer can do their job of filtering the blood, end stage renal disease results. Because there are no overt symptoms of diabetic nephropathy, regularly screening the urine of individuals with diabetes is super important.

Diagnosis4:24–4:52

Microalbuminuria, which means excreting 30 to 300 mg of albumin in a day, is a reliable signal that diabetic nephropathy has started to set in.
Excreting above 300 mg per day is considered macroalbuminuria, and is a sure sign of a problem. Unfortunately, diabetic nephropathy is a progressive complication that can be significantly slowed down but not completely stopped.

Treatment4:52–5:29

Keeping tight control on hypertension and hyperglycemia is critical. Specifically, angiotensin-converting enzymes (ACE) inhibitors or angiotensin receptor blockers can be particularly useful.
These not only lower blood pressure as a whole, but they also specifically reduce constriction of the efferent arteriole.
By reducing this constriction, the pressure within the glomerulus and the damage that comes from it. Alright, as a quick recap, diabetic nephropathy is kidney damage that is caused by diabetes, resulting in glomerular basement membrane thickening, mesangial expansion, and sclerosis.

Review5:29–7:23

An initial phase of increased glomerular filtration rate is followed by progressive albuminuria, then a gradual decline in glomerular filtration rate, and finally renal failure.
This progression can be slowed by tight control of blood sugar and blood pressure and the use of ACE-inhibitors or angiotensin receptor blockers to decrease pressure specifically within the glomerulus.
Thanks for watching, you can help support us by donating on patreon, or subscribing to our channel, or telling your friends about us on social media.