Topic: Renal Tubular Acidosis
Question: What is (are) Renal Tubular Acidosis ?
Answer: Type 1: Classical Distal RTA
                
Type 1 is also called classical distal RTA. "Distal," which means distant, refers to the point in the urine-forming tube of the kidney where the defect occursrelatively distant from the point where fluid from the blood enters the tiny tube, or tubule, that collects fluid and wastes to form urine.
                
This disorder may be inherited as a primary disorder or may be one symptom of a disease that affects many parts of the body. Researchers have discovered abnormal genes responsible for the inherited forms of the disease. More often, however, classical distal RTA occurs as a result of systemic diseasesdiseases that affect many organ systemslike the autoimmune disorders Sjgren's syndrome and lupus, which also attack the distal tubule.
                
Other diseases and conditions associated with classical distal RTA include sickle cell anemia, hyperparathyroidism, hyperthyroidism, chronic active hepatitis, primary biliary cirrhosis, a hereditary form of deafness, analgesic nephropathy, rejection of a transplanted kidney, renal medullary cystic disease, obstructive uropathy, and chronic urinary tract infections. Many of these conditions cause abnormal calcium deposits to build up in the kidney and impair distal tubule function.
                
A major consequence of classical distal RTA is a low blood potassium level. The level drops if the kidneys excrete too much potassium into urine instead of returning it to the blood supply. Because potassium helps regulate nerve and muscle health and heart rate, low levels can cause extreme weakness, irregular heartbeat, paralysis, and even death.
                
Untreated classical distal RTA causes growth retardation in children and progressive kidney and bone disease in adults. Restoring normal growth and preventing kidney stones are the major goals of therapy. If acidosis is corrected with sodium bicarbonate or sodium citrate, then low blood-potassium, salt depletion, and calcium leakage into urine will be corrected. This alkali therapy also helps decrease the development of kidney stones and stabilizes kidney function so kidney failure does not progress. Infants may need potassium supplements, but older children and adults rarely do because alkali therapy prevents the kidney from excreting potassium into the urine.
                
Type 2: Proximal RTA
                
Type 2 is also called proximal RTA. The word "proximal," which means near, indicates that the defect is closer to the point where fluid and wastes from the blood enter the tubule.
                
This form of RTA occurs most frequently in children as part of a disorder called Fanconi's syndrome. The features of Fanconi's syndrome include the abnormal excretion of glucose, amino acids, citrate, and phosphate into the urine, as well as vitamin D deficiency and low blood-potassium.
                
Proximal RTA can also result from inherited disorders that disrupt the body's normal breakdown and use of nutrients. Examples include the rare disease cystinosis, in which cystine crystals are deposited in bones and other tissues; hereditary fructose intolerance; and Wilson disease.
                
Proximal RTA also occurs in patients treated with ifosfamide, a drug used in chemotherapy. A few older drugssuch as acetazolamide or outdated tetracyclinecan also cause proximal RTA. In adults, proximal RTA may complicate diseases like multiple myeloma, or it may occur in people who experience chronic rejection of a transplanted kidney.
                
When possible, identifying and correcting the underlying causes are important steps in treating the acquired forms of proximal RTA. The diagnosis is based on the chemical analysis of blood and urine samples. Children with this disorder would likely receive large doses of an oral alkali, such as sodium bicarbonate or potassium citrate, to treat acidosis and prevent bone disorders, kidney stones, and growth failure. Correcting acidosis and low potassium levels restores normal growth patterns, allowing bone to mature while preventing further renal disease. Vitamin D supplements may also be needed to help prevent bone problems.
                
Type 3
                
Type 3 is rarely used as a classification because it is now thought to be a combination of type 1 and type 2.
                
Type 4: Hyperkalemic RTA
                
Type 4 is also called hyperkalemic RTA and is caused by a generalized transport abnormality of the distal tubule. The transport of electrolytes such as sodium, chloride, and potassium that normally occurs in the distal tubule is impaired. This form is distinguished from classical distal RTA and proximal RTA because it results in high levels of potassium in the blood instead of low levels. Either low potassiumhypokalemiaor high potassiumhyperkalemiacan be a problem because potassium is important in regulating heart rate.
                
Type 4 RTA occurs when blood levels of the hormone aldosterone are low or when the kidneys do not respond to it. Aldosterone directs the kidneys to regulate the levels of sodium, potassium, and chloride in the blood. Type 4 RTA also occurs when the tubule transport of electrolytes such as sodium, chloride, and potassium is impaired due to an inherited disorder or the use of certain drugs.
                
Drugs that may cause type 4 RTA include
                
- diuretics used to treat congestive heart failure such as spironolactone or eplerenone  - blood pressure drugs called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)  - the antibiotic trimethoprim  - the antibiotic pentamidine, which is used to treat pneumonia  - an agent called heparin that keeps blood from clotting  - a class of painkillers called nonsteroidal anti-inflammatory drugs (NSAIDs)  - some immunosuppressive drugs used to prevent rejection
                
Type 4 RTA may also result from diseases that alter kidney structure and function such as diabetic nephropathy, HIV/AIDS, Addison's disease, sickle cell disease, urinary tract obstruction, lupus, amyloidosis, removal or destruction of both adrenal glands, and kidney transplant rejection.
                
For people who produce aldosterone but cannot use it, researchers have identified the genetic basis for their body's resistance to the hormone. To treat type 4 RTA successfully, patients may require alkaline agents to correct acidosis and medication to lower the potassium in their blood.
                
If treated early, most people with any type of RTA will not develop permanent kidney failure. Therefore, the goal is early recognition and adequate therapy, which will need to be maintained and monitored throughout the person's lifetime.
Source: NIDDK