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.
