What is Alport ?

What is Alport ?

Alport syndrome is an genetic disease of the kidneys that manifest several other symptoms of other serious disorders such as hearing loss, blood in the urine (hematuria), end stage kidney disease, an eye disease (lenticonus), and glomerulonephritis.

Three categories of Alport syndrome

The most common form is X-linked inherited mutation of the alpha chain 5 (XLAS). The two other forms of Alport syndrome are autosomal recessive (ARAS) and autosomal dominant (ADAS). Both conditions involve mutations of the genes for alpha-3 or alpha-4 chains of collagen IV, which are both located on chromosome 2.

Causes of Alport syndrome

Alport syndrome is caused by changes in the genetic patterns of the COL4A3, COL4A4 and COL4A5 proteins.

The changes in the genetic patterns hinder the successful production of what is called the type IV collagen system.

The type IV collagen system are key structures of basement membranes found in the kidneys, eyes and the inner parts of the ears.

Basement membranes are thin sheets that serve as divisions between cells.

When type IV collagen cannot be produced to gene mutation, the basement membrane cannot perform their role in removing waste materials from the blood and in producing urine leading to hematuria and protein in the blood.

Alport syndrome always affects the kidneys. Hearing loss and visual changes may also occur. If you suspect that you may have inherited Alport syndrome, look for these symptoms:

Blood in the urine (hematuria)

Alport syndrome damages the filtering system of the kidneys so people may have blood in urine in the early course. Typically, blood in the urine is the first sign of kidney problems. Because type IV collagen proteins contribute to the normal functioning of the eye and the inner ear, many individuals with Alport syndrome will experience vision and hearing loss.

Protein in the urine (proteinuria)

Symptoms of Alport syndrome are usually attributed to urinary tract infections, but repeated infections are signs and reflux nephropathy. Some common clinical symptoms of the disease are blood in the urine, back pain or side pain in the kidney area, cloudy urine and increased frequency of urination.

High blood pressure (also called hypertension)

Alport syndrome makes the heart work harder than normal to circulate blood through the blood vessels. Blood pressure is summarised by two measurements, systolic and diastolic,which depend on whether the heart muscle is contracting or relaxed between beats and equate to a maximum and minimum pressure, respectively.

Edema

The most common sign of swelling is excess fluid in the body. This may take several forms. Leg swelling can occur in any part of the legs, including the feet, ankles, calves or thighs. And swelling can occur around the eyes, even all over the body.

Micro Chinese medicine treatment

Micro Chinese medicine may block renal fibrosis infiltration .Practices have proven that the treatment has definite effect on repairing epithelial cells of glomerular capillary. We can be sure that you will get better as long as the damaged epithelial cells get repaired. Now that you get better, the function of epithelial cells can return to normal, and then urinary proteins will disappear. When the function return to normal and urinary proteins disappear, the probability of relapse will reduce certainly.

Medicated bath

Toxins and wasted products in the blood are excreted through skin by sweating, which reduced the burden of the kidney.

Alleviate some clinical symptoms including skin disease and itching.

•Improve blood circulation in different organs including kidney and liver, which helps repair the damaged kidney function and slow down the atrophy of the kidney.

•Alleviate fatigue; reduce the pain of the muscle and joint; enhance microcirculation of the whole body so as to help remove the metabolic products and bring more oxygen.

•Improve sleep quality.

Hemodialysis

Hemodialysis (HD), blood perfusion (HP), plasma exchange, etc. but the continuous blood purification (CBP), blood lipid,and artificial liver support system (ALSS) is combined application by multiple technologies above, Though peritoneal dialysis without extracorporeal circulation, only in ascites exchange to achieve the purpose of purifying the blood, but from broadly speaking, also should be included within the blood purification therapy.

Elevated blood urea nitrogen (BUN) and creatinine (CR) in people with Alport Syndrome suggests that renal damage has worsened. The kidneys are filters of the body. When creatinine, BUN and other wastes accumulate in the body, they will be carried through bloodstream to damage varying systems, such as gastrointestinal tract, cardiovascular system, endocrine system, etc.

Molecular genetic testing

● COL4A5 genetic testing

Diagnostic testing for symptomatic individuals – COL4A5 sequencing and deletion/duplication testing is most sensitive.

Use to exclude diagnosis of Alport syndrome in patients with positive thin basement membrane nephropathy on biopsy.
Should not be used for prenatal testing.

For more information on COL4A5 gene variants and their clinical significance, refer to ARUP's Alport syndrome and COL4A5 mutation database.

● Detailed family and personal history to rule out other possible diseases.

● Audiologic and ophthalmologic exams – may be abnormal.

Histology

● Immunohistochemical analysis of collagen IV expression using renal or skin biopsies.

   Skin biopsies have a higher incidence of false negatives than renal biopsies.

● Electron microscopy of renal biopsy specimen

Differential Diagnosis

● Thin basement membrane nephropathy

● Other glomerular diseases

● Inherited hearing loss syndromes

● Fechtner-Epstein syndrome

]The people who suffer from Alport syndrome experience problem related to the dysfunctional kidney. Sometimes they also suffer from deafness and some eye problems. this disease is one of the main causes, which are associated with the failure of the kidney. The other common associated problems with this disease are diabetes and high blood pressure. A person suffers from Alport syndrome when a particular collagen is missing from the kidney. This missing collagen causes inflammation in the kidney and as a consequence hampers the normal functioning of the kidney.

Prognosis

For a male with X-linked Alport's syndrome (XLAS), the disease follows a consistent but variable course. At present this seems to be uninfluenced by any intervention except when renal failure develops and renal replacement therapy (dialysis or transplantation) can be offered. This is a lifesaving intervention. Microscopic haematuria with episodic gross haematuria develops from an early age. Proteinuria then develops, which is a prelude to the development of hypertension and progressive renal failure. All males will eventually develop chronic renal failure. The rate of progression to chronic renal failure is mutation dependent in XLAS. Over 90% will develop chronic renal failure before age 30 if they have a loss-of-function mutation in COL4A5.In women with XLAS 12% may develop chronic renal failure before age 40; significant hearing loss may also develop in 10%. In autosomal-recessive Alport's syndrome, the natural history of the disease is less well characterised. Once chronic renal failure has developed, patients with all types of Alport's syndrome can be offered renal replacement therapy.

Follow a healthy-eating plan

You may need to keep health care with changing the diet, such as limiting fluids, avoiding high salt and fat foods. That can keep the patients out of the risks of the disease. The foods should be avoided are following:

● High-potassium: oranges, banana, kiwis, avocado, papayas, cantaloupe, potatoes, tomatoes, spinach, fellow leafy vegetables, sweet potato and animal protein.

● High-sodium: canned foods, pickles, smoked meat, processed cheese, packed chips, crackers.

● High-phosphorus: dairy products, nuts, beans, cocoa, cold drinks, and beer.

● High-fluid: apples, orange, grapes, lettuce.

Stop smoking

Smoking is an important factor that has been shown to hasten the progression of kidney disease. In addition, smoking increases the risk of high blood pressure and cardiovascular. Therefore smoking is on ban due to above risks.

Avoid noises

Hearing loss is likely to be permanent. Counseling and education to increase coping skills can be helpful. Learning new skills such as lip reading or sign language and getting hearing aids may help. Young men with Alport syndrome should use hearing protection in noisy environments.