Chronic kidney disease is a broad term that includes subtle decreases in kidney function
that develop over a minimum of three months.
In contrast, acute kidney injury refers to any deterioration in kidney function that
happens in less than three months.
Now the kidney’s job is to regulate what’s in the blood, so they might remove waste,
or make sure electrolyte levels are steady, or regulate the overall amount of water, and
even make hormones - the kidneys do a lot of stuff!
Blood gets into the kidney through the renal artery, and once inside it goes gets into
tiny clumps of arterioles called glomeruli where it’s initially filtered, and the filtrate
which is the stuff that gets filtered out, moves into the renal tubule.
The rate at which this filtration takes place is known as glomerular filtration rate or
GFR.
In a normal healthy person, this is somewhere around 100-120 milliliter of fluid filtered
per minute per 1.73 m2 of body surface area.
The value is slightly less in women than men and it decreases slowly in all of us as we
grow older.
One of the most common causes of chronic kidney disease is hypertension.
In hypertension, the walls of arteries supplying the kidney begin to thicken in order to withstand
the pressure, and that results in a narrow lumen.
A narrow lumen means less blood and oxygen gets delivered to the kidney, resulting in
ischemic injury to the nephron’s glomerulus.
Immune cells like macrophages and fat-laden macrophages called foam cells slip into the
damage glomerulus and start secreting growth factors like Transforming Growth Factor ß1
or TGF-ß1.
These growth factors cause the mesangial cells to regress back to their more immature stem
cell state known as mesangioblasts and secrete extracellular structural matrix.
This excessive extracellular matrix leads to glomerulosclerosis, hardening and scarr,
and diminishes the nephron’s ability to filter the blood - over time leading to chronic
kidney disease.
The most common cause of CKD is diabetes, excess glucose in the blood starts sticking
to proteins in the blood — a process called non-enzymatic glycation because no enzymes
are involved.
This process of glycation particularly affects the efferent arteriole and causes 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,
and increases pressure within the glomerulus leading to hyperfiltration.
In response to this high-pressure state, the supportive mesangial cells secrete more and
more structural matrix expanding the size of the glomerulus.
Over many years, this process of glomerulosclerosis, once again, diminishes the nephron’s ability
to filter the blood and leads to chronic kidney disease.
Although diabetes and hypertension are responsible for the vast majority of CKD cases, there
are other systemic diseases like lupus and rheumatoid arthritis, can also cause glomerulosclerosis.
Other causes of chronic kidney disease include infections like HIV, as well as long-term
use of medications like NSAIDs, and toxins like the ones in tobacco.
Now, normally urea in the body gets excreted in the urine, but when there’s a decreased
glomerular filtration fate, less urea get filtered out, and therefore it accumulates
in the blood, a condition called azotemia, which can cause general symptoms like It nausea
and a loss of appetite.
As the toxin levels really build up, they can affect the functioning of the central
nervous system - causing encephalopathy.
This results in asterixis, a tremor of the hand that kind of resembles a bird flapping
its wings and is best seen when the person attempts to extend their wrists.
Further accumulation of these toxins in the brain can even progress to coma and death.
The buildup of toxins can also cause pericarditis which is inflammation of the lining of the
heart.
In addition, there can be increased tendency for bleeding, since excess urea in the blood
makes platelets less likely to stick to each other, and so there’s less clot formation.
Finally, in some cases, someone can develop uremic frost, where urea crystals can deposit
in the skin and they look like powdery snowflakes.
In addition to getting rid of waste, the kidneys play an important role in electrolyte balance.
Potassium levels are particularly important, and normally the kidney helps with potassium
excretion.
In chronic kidney disease, just like with urea, less potassium is excreted and more
builds up in the blood, and it leads to hyperkalemia, which is worrisome because it can cause cardiac
arrhythmias.
Another key role of the kidneys relates to balancing calcium levels.
Normally, the kidney helps to activate vitamin D which helps to increase absorption of calcium
from the diet.
In chronic kidney disease, there’s less activated vitamin D, so less calcium is absorbed
into the blood, resulting in hypocalcemia - low calcium levels.
As calcium levels in the blood falls, parathyroid hormone is released, causing the bones to
lose calcium.
Over time, this resorption of calcium from the bones leaves them weak and brittle, a
condition known as renal osteodystrophy.
The kidneys also release key hormones.
For example, normally when the kidneys start sensing a lower than normal amount of fluid
getting filtered, they respond by releasing the hormone renin to increase the blood pressure.
In chronic kidney disease, the falling glomerular filtration rate leads to more and more renin
secretion which leads to hypertension.
Now, remember that hypertension is a cause of chronic kidney disease itself, so this
creates quite the vicious cycle.
The kidney also secretes the hormone erythropoietin which stimulates the production of red blood
cells from the bone marrow.
In chronic kidney disease, erythropoietin levels fall and this leads to lowered production
of red blood cells, and ultimately anemia.
Ultimately the diagnosis of chronic kidney disease comes down to looking at changes in
the glomerular filtration rate over time.
Chronic kidney disease might be suspected with a GFR of less than 90 ml/min/1.73 m2
, and irreversible kidney damage might happen with a GFR below 60 ml/min/1.73 m2.
To confirm the diagnosis a kidney biopsy can be done to look for changes like glomerulosclerosis.
Treatment for chronic kidney disease often involves managing the underlying cause.
In severe situations, dialysis or a kidney transplant might be needed.
Alright, as a quick recap… chronic kidney disease is when the glomerular filtration
rate falls below 90 ml/min/1.73 m2 over at least three months.
Chronic kidney disease is mainly caused by diabetes and hypertension, and complications
include electrolyte abnormalities, accumulation of toxins in the body, hypertension, and bone
abnormalities.