Kidney Disease

Noelle Thompson & Julie Eldridge

The Basics

The kidneys are two vital organs located on either side of your spine just above the waste.
The kidneys cleanse your blood by removing waste and excess fluid, maintain the balance of salt and minerals in your blood, and help regulate blood pressure.
When the kidneys malfunction, fluid and waste buildup in the body and can cause symptoms such as swelling in your ankles, vomiting, weakness, poor sleep, and shortness of breath.
If left untreated, it can lead to kidney failure.
  • Kidney damage and decreased function that lasts longer than 3 months is called chronic kidney disease (CKD). THis is particularly dangerous, because you may not have any symptoms until irreparable, kidney damage has occurred. Diabetes(types 1 and 2) and high blood pressure are the most common causes of CKD.


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Mechanism

Slit-diaphragm-mediated signaling to the podocyte cytoskeleton is the mechanism. Podocytes interdigitate and cover the capillary walls of the glomerulus. At the site of interdigitation, a specialized intercellular junction is formed that is commonly called the “slit diaphragm". When the podocyte is damaged it allows protein out of the body through waste.

Alterations in the molecular composition cause the dysfunction of of the podocyte.


"The glomerulus is a complex structure, the stability of which depends on the cooperative function of the basement membrane, mesangial cells and podocytes, counteracting the distending forces originating from the high glomerular hydrostatic pressures. Failure of this system leads to quite uniform architectural lesions. (2) There is strong evidence that the podocyte is incapable of regenerative replication post-natally; when podocytes are lost for any reason they cannot be replaced by new cells. Loss of podocytes may therefore lead to areas of "bare" GBM, which represent potential starting points for irreversible glomerular injury"

One specific type of kidney disease is called focal segmental glomerulosclerosis.
FSGS is the cause of Nephrotic Syndrome in children and adolescents and the leading cause of kidney failure in adults.
Nephrotic Syndrome is a nonspecific kidney disease that is characterized by Edema, or the loss of protein through the kidneys.
There is no direct way of treatment but they can treat the symptoms.
The prognosis for nephrotic syndrome under treatment is generally good although this depends on the underlying cause, the age of the patient and their response to treatment.
children and adolescents are easier treated because they tend to respond to steroid treatment better than adults and because the disease is progressive, the younger the patient the less damage.
children 5 and under and adults 30 and over usually have the worst prognosis because they are at greater risk of kidney failure.
focal segmental glomerulosclerosis frequently lead to end stage renal disease.
nephrotic syndrome has a very bad prognosis especially rapidly progressing glomerulonephritis, which leads to acute kidney failure after a few months.

Once the kidneys have failed, dialysis or a kidney transplant is required.

(sources: https://en.wikipedia.org/wiki/Focal_segmental_glomerulosclerosis

https://en.wikipedia.org/wiki/Nephrotic_syndrome)

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These are normal kidneys compared to kidneys affected by FSGS

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Genetics

FSGS is an autosmal dominant disease. The most common causative gene is INF2 (up to 17%), other mutations include TRPC6 (up to 12%) and ACTN4 (3.5%)
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Where is research going?

Is the podocyte the one cause and if so how is it fixed?

Scientist are working on advancements in treatment. Currently they can only treat the symptoms to decrease the progression in patients.