Alport syndrome is an inherited condition caused by a mutation in one of the genes that encode for a structural protein called type 4 collagen. This protein is a major part of a structure called the basement membrane, present in many organs, including the kidneys, inner ear, and eyes.
In the kidneys, the basement membrane is an essential part of the filtration unit required to remove waste products and excess water from the blood. When there is little or no functioning type 4 collagen, the kidneys cannot work as normal and progressively become more damaged.
Mutations in three different genes encoding for collagen 4 (COL4A3, COL4A4, and COL4A5) can lead to Alport syndrome. The severity of the disease depends on the type of mutation and the gene affected.
What is end-stage kidney disease
End-stage kidney disease, sometimes referred to as kidney failure or end-stage renal disease (ESRD), is the last stage of chronic kidney disease, the most common symptom of Alport syndrome. This is the point where the kidneys are so damaged that they can no longer function.
When the kidneys can no longer filter the blood, the patient requires dialysis to remove waste from the blood.
Risk of end-stage kidney disease in Alport syndrome
The risk of end-stage kidney disease depends on the type of Alport syndrome the patient has. Men with the X-linked disease, where the mutation is in the COL4A5 gene, are most likely to develop it. Around 90 percent of men with X-linked Alport syndrome develop end-stage kidney disease around age 40. How quickly kidney disease progresses depends on the mutation in the COL4A5 gene.
About 12 percent of women with X-linked Alport syndrome progress to end-stage kidney disease around age 40, with this chance increasing to 30 percent by age 60 and to 40 percent by age 80. Progressive kidney disease is more likely to occur if the patient has proteinuria (proteins in the urine) and/or hearing loss.
Some women with X-linked Alport syndrome may be at risk for early onset end-stage kidney disease, depending on how their body has inactivated one of their two X chromosomes. This can result in women with Alport having symptoms that mirror men in severity.
Both men and women with Alport syndrome caused by COL4A3 and/or COL4A4 mutations are at high risk of progressing to end-stage kidney disease before age 40.
End-stage kidney disease symptoms
End-stage kidney disease is associated with a range of symptoms, including fatigue, itchy or dry skin, headaches, weight loss, loss of appetite, nausea, insomnia, and muscle cramps.
End-stage kidney disease can also cause either high or no urine output, along with recurrent urinary tract infections and possible urinary incontinence.
The kidneys are also involved in the production of new blood cells, control of blood pressure, and management of levels of some chemicals in the body. As a result, end-stage kidney disease can cause problems not related to filtering blood. These include:
- Anemia, or reduced red blood cell levels
- Bone problems, due to high phosphorus that can weaken bones and cause them to break easily
- Heart disease
- Hyperkalemia, or high potassium levels in the blood
- Fluid retention, leading to swelling, organ damage, and increased heart rate
- High blood pressure
End-stage kidney disease diagnosis
Alport patients should be monitored regularly for changes in kidney function. Guidelines published by the Alport syndrome research program recommend assessing protein levels in the urine of these patients at least once a year.
Blood tests can be used to check for reduced blood cell counts, electrolyte levels, and markers of kidney function. Urine tests can include checking for the presence of proteins and blood in urine.
Imaging tests, including an ultrasound or computed tomography (CT) scan, can be used to confirm kidney damage. These produce an image of the kidneys that can be used to assess the size of the organs and any abnormalities.
A kidney biopsy, where a small piece of the tissue is removed and checked in a laboratory, may be used to rule out other conditions or to determine the level of damage.
Treatment of end-stage kidney disease
End-stage kidney disease is often managed using dialysis to remove excess fluid and waste products from the blood before they reach toxic levels. There are two types of dialysis, hemodialysis and peritoneal dialysis. The patient’s diet may have to be altered to cope with end-stage kidney disease, as dialysis cannot fully replace the work of the kidneys.
Some patients may be able to get a kidney transplant, replacing their damaged kidneys with those of a healthy donor. If the transplant is successful, the patient may no longer need to undergo dialysis. A recent study reports that a kidney transplant can also help reverse some of the complications associated with end-stage kidney disease, including platelet dysfunction, or bleeding due to the blood not clotting correctly.
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