In order to understand how kidney
function is impaired in cystinosis, one needs to understand how it works
normally. There are two kidneys, one on each side in the back. Each kidney is
made up of one million nephrons, the working unit of the kidney.
Each
nephron has two parts:
1. a glomerulus or
filter.
2. a tubule, a long collecting duct
for the urine.
Blood comes into the kidney to be filtered. Blood
consists of :
1. a water part with various
dissolved chemicals, such as salt, sodium bicarbonate, potassium, sugar,
calcium, etc. and
2. protein particles and
white and red blood cells, too big to dissolve in the water. As the blood comes
through the kidney, the water part of blood and the dissolved chemicals are
filtered and start down the long tube.
Along the tube are cells that
have hooks that recognize if you need to take back (reabsorb) the water, salt
and bicarbonate, etc. If you need more water, it is reabsorbed, and similarly
for the other chemicals. If you drink alot, you urinate a lot and if you don't
drink as much, you don't urinate as much. In essence, 99% of everything that
starts down the tube is reabsorbed, otherwise an adult would have to urinate
and, therefore drink 50 gallons per day.
In cystinosis, these hooks
don't work normally. For some reason, the cystine crystals deposit in the cells
lining the tubules and alter their function. This is a long slow process, but
by interfering even a little bit, with the normal mechanisms of control, the
balance of chemicals in the body is disturbed tremendously. Fortunately, the
kidneys are mainly reserve and medications can control most of the chemical
disturbance until 90% of the kidney function is lost.
What happens
then? Another function of the kidney is to filter waste products. When you eat
protein, some is used to rebuild new cells, ect., and some is not (since your
body is not 100% efficient). The excess protein and waste products are usually
handled by the kidneys, resulting in the characteristic yellow color and
ammonia smell of urine. After progressive renal deterioration, the damaged
tubules collapse, causing a backup that destroys the filters (glomeruli),
resulting in a loss of the ability to rid the body of normal waste products.
The substances appear in the blood as blood urea nitrogen (BUN), or creatinine,
and with build up in the body are toxic (poisonous). The long slow buildup is
tolerated until approximately 10% of the kidney function remains. At this
point, further intervention is necessary to prevent uremic (literally urine in
the blood) poisoning. This therapy is called dialysis and cleans the blood of
these waste products and usually corrects most of the metabolic disturbances of
the body.
The kidney actually also has other functions since it
controls water excretion, acid and base excretion, high blood pressure, bone
minerals, etc., which need to be discussed at a future time.
At this
time, experimental therapy is aimed at using substances to remove the cystine
from the cells and, therefore prevent or slow down this relentless and
progressive decline of kidney function in cystinosis.
Sheldon
Orloff, MD Sub-Chief of Renal Medicine/Kaiser Hospitals