Treatment of Kidney Disease in Alport Syndrome

Renal Anatomy and Physiology

Each kidney consists of one million tiny filters (glomeruli) each of which drains into a fine tubule that conveys the urine to the renal pelvis. From the pelvis it drains via the ureter to the bladder. The glomeruli create a large volume (120 ml/min) filtrate from the blood and the tubules return most of this filtrate to the blood, but leave in the urine substances that need to be removed from the body.

Measurement of kidney function

The best overall measure of kidney function is the rate at which all the glomeruli make the filtrate of blood—the glomerular filtration rate (GFR). This can be estimated by the creatinine clearance, or the volume of blood that has creatinine removed from it. Creatinine is a normal body waste product and is useful as a marker of kidney function. The better the kidney function the higher the GFR and the creatinine clearance. Because the kidneys remove creatinine from the blood, the better they work, the lower the serum creatinine and the worse they are working, the higher the serum creatinine. Serum creatinine is the most useful simple way to estimate kidney function. It has two big disadvantages. It is slow to detect early loss of kidney function, and it rises disproportionately fast as kidney failure progresses

Treatment of Hematuria in Alport Syndrome

A microscopic trace of blood in the urine (microhematuria) is almost invariable in Alport Syndrome. From time to time, blood may be visible. This is expected at time of fever or exercise, particularly in "juvenile" types of Alport Syndrome and does not require treatment.

Treatment of Progressive Renal Insufficiency

By far the most important way to retard worsening of kidney failure is excellent control of high blood pressure. This begins with attaining ideal weight. Limiting salt intake is fundamental in getting good control of blood pressure. Most people with Alport syndrome will require medication for high blood pressure and it is likely better to start this as early as practicable and to strive for blood pressure as low as tolerable.

Angiotensin converting enzyme (ACE) inhibitors are the preferred form of treatment for high blood pressure. If they are not tolerated, then angiotensin receptor blocking agents (ARBs) are a reasonable substitute. As time goes by, additional antihypertensive medications will likely be needed. Diuretics are often a good choice to add to ACE-inhibitors.

Moderate restriction of dietary protein intake will be needed as renal failure advances and there is no apparent harm in starting this early. Dietary preferences are hard to change and it is sensible to make adjustments slowly.

Gene Therapy

Although there have been some attempts of gene therapy in human disease, Alport syndrome is a more difficult problem than diseases of the blood or the liver and it will be some time before gene therapy becomes practicable in humans.