Renal Tubular Acidosis

Definition:-Your body’s cells use chemical reactions to carry out tasks such as turning food into energy and repairing tissue. These chemical reactions generate acids. But too much acid in the blood—acidosis—can disturb many bodily functions. Healthy kidneys help maintain acid-base balance by excreting acids into the urine and returning bicarbonate—an alkaline, or base, substance—to the blood. This “reclaimed” bicarbonate neutralizes much of the acid that is created when food is broken down in the body.

Renal tubular acidosis (RTA) is a disease that occurs when the kidneys fail to excrete acids into the urine, which causes a person’s blood to remain too acidic. Without proper treatment, chronic acidity of the blood leads to growth retardation, kidney stones, bone disease, and progressive renal failure.

One researcher, pediatric neurologist Donald Lewis, has theorized that Charles Dickens may have been describing a child with RTA when he created the character of Tiny Tim in his famous story, “A Christmas Carol.” Tiny Tim’s small stature, malformed limbs, and periods of weakness are all possible consequences of the chemical imbalance caused by RTA. Among the evidence cited to support this theory is the fact that Tiny Tim’s condition, while fatal in one scenario, is reversible when Scrooge pays for medical treatments, which in those times would likely have included sodium bicarbonate and sodium citrate, which are alkaline agents that would neutralize the acid in Tiny Tim’s blood. Whether the literary diagnosis of Tiny Tim is correct or not, the good news is that medical treatment can indeed reverse the effects of RTA.

Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. When blood is filtered by the kidney, the filtrate passes through the tubules of the nephron, allowing for exchange of salts, acid equivalents, and other solutes before it drains into the bladder as urine. The metabolic acidosis that results from RTA may be caused either by failure to recover sufficient (alkaline) bicarbonate ions from the filtrate in the early portion of the nephron (proximal tubule) or by insufficient secretion of (acid) hydrogen ions into the latter portions of the nephron (distal tubule). Although a metabolic acidosis also occurs in those with renal insufficiency, the term RTA is reserved for individuals with poor urinary acidification in otherwise well-functioning kidneys. Several different types of RTA exist, which all have different syndromes and different causes.

The word acidosis refers to the tendency for RTA to lower the blood’s pH. When the blood pH is below normal (7.35), this is called acidemia. The metabolic acidosis caused by RTA is a normal anion gap acidosis.

Diagnosis :-
To diagnose RTA, your doctor will check the acid-base balance in samples of your blood and urine. If the blood is more acidic than it should be and the urine less acidic than it should be, RTA may be the reason, but additional information is needed first to rule out other causes. If RTA is suspected, additional information about the sodium, potassium, and chloride levels in the urine and the potassium level in the blood will help identify which of the three types of RTA you have. In all cases, the first goal of therapy is to neutralize acid in the blood, but different treatments may be needed to address the different underlying causes of acidosis .
Types of RTA:-
At one time, doctors divided RTA into four types.

*Type 1 is also called classic distal RTA. “Distal,” which means distant, refers to the point in the urine-forming tube where the defect occurs. It is relatively distant from the point where fluid from the blood enters the tiny tube, or tubule, that collects fluid and wastes to form urine.

*Type 2 is 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.

*Type 3 is rarely used as a classification today because it is now thought to be a combination of type 1 and type 2.

*Type 4 RTA is caused by another defect in the distal tubule, but it is different from classic distal RTA and proximal RTA because it results in high levels of potassium in the blood instead of low levels. Either low potassium (hypokalemia) or high potassium (hyperkalemia) can be a problem because potassium is important in regulating heart rate.

Type I-Distal RTA:-
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 now discovered the abnormal gene responsible for the inherited form. More often, however, classic distal RTA is a complication of diseases that affect many organ systems (systemic diseases), like the autoimmune disorders Sjögren’s syndrome and lupus.

Other diseases and conditions associated with distal RTA include hyperparathyroidism, a hereditary form of deafness, analgesic nephropathy, rejection of a transplanted kidney, renal medullary cystic disease, obstructive uropathy, and chronic urinary tract infections

Distal RTA (dRTA) is the most common and also the classical form of RTA, being the first described. It has a number of causes which cause a common underlying problem, which is a failure of acid secretion by the alpha intercalated cells of the cortical collecting duct of the distal nephron. This leads to a failure to acidify the urine to a pH of less than 5.3 even if the blood is too acidic (ie there is systemic acidemia), and consequently there is a tendency towards acidemia. This leads to the clinical features of dRTA;

*Normal anion gap metabolic acidosis/acidemia

*Hypokalemia (which may be severe)

*Urinary stone formation

*Nephrocalcinosis (deposition of calcium in the substance of the kidney)

*Bone demineralisation (causing rickets in children and osteomalacia in adults)

The acidosis is variable, and one may have dRTA with alpha intercalated cell failure without necessarily being acidemic, this is termed incomplete dRTA. The diagnosis of dRTA can be made by the observation of a urinary pH of greater than 5.3 in the face of a systemic acidemia (usually taken to be a serum bicarbonate of 20 mmol/l or less). In the case of an incomplete dRTA, failure to acidify the urine following an oral acid loading challenge is often used as a test. The test usually performed is the short ammonium chloride test, in which ammonium chloride capsules are used as the acid load. More recently, an alternative test using furosemide and fludrocortisone has been described.

The symptoms and sequelae of dRTA are variable and ranging from being completely asymptomatic, through loin pain and hematuria from kidney stones to failure to thrive and severe rickets in childhood forms as well as possible renal failure and even death.

Interestingly, dRTA has been proposed as a possible diagnosis for the unknown malady plaguing Tiny Tim in Charles Dickens’ A Christmas Carol.

*Autoimmune disease. Classically Sjögren’s syndrome, but it is also associated with systemic lupus erythematosus, rheumatoid arthritis and even hypergammaglobulinemia. Hypokalaemia is often severe in these cases.

*Hereditary causes include mutations of Band 3 the basolateral bicarbonate transporter of the intercalated cell, which may transmit in an autosomal dominant fashion in western European cases, or in an autosomal recessive fashion in South East Asian cases. The South East Asian cases are associated with more severe hypokaemia. Other Hereditary causes include mutations of subunits of the apical proton pump vH+-ATPase, which transmit in an autosomal recessive fashion, and may be associated with sensorineural deafness.

*Liver cirrhosis.

*Nephrocalcinosis. While it is a consequence of dRTA, it can also be a cause; related to calcium-induced damage of the cortical collecting duct.

*Renal transplantation.

*Sickle cell anemia.

*Toxins, including ifosfamide, toluene, lithium carbonate and amphotericin B.

*Chronic urinary tract obstruction.

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Click to enlarge >..alpha_intercalated_cell_cartoon.jpg
Cartoon of the alpha intercalated cell, showing the apical proton pump and the basolateral band 3 (kAE1)

This is relatively straightforward. It involves correction of the acidemia with oral sodium bicarbonate or sodium citrate. This will correct the acidemia and reverse bone demineralisation. Hypokalemia and urinary stone formation and nephrocalcinosis can be treated with potassium citrate tablets which not only replace potassium but also inhibit calcium excretion and thus exacerbate stone disease as sodium bicarbonate or citrate may do.

Type 2-Proximal RTA:-
This form of RTA occurs most frequently in children as part of a disorder called Fanconi’s syndrome. The symptoms of Fanconi’s syndrome include high levels of glucose, amino acids, citrate, and phosphate in the urine, as well as vitamin D deficiency and low blood-potassium.

Proximal RTA (pRTA) is caused by a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the urine can acidify to a pH of less than 5.3. pRTA also has several causes, and may occasionally be present as a solitary defect, but is usually associated with a more generalised dysfunction of the proximal tubular cells called Fanconi’s syndrome where there is also phosphaturia, glycosuria, aminoaciduria, uricosuria and tubular proteinuria. The principal feature of Fanconi’s syndrome is bone demineralisation due to phosphate wasting.


Familial disorders

* Cystinosis
*Glycogen storage disease (type I)
*Hereditary fructose intolerance
*Lowe’s syndrome
*Wilson’s disease

Acquired disorders

*Multiple myeloma
*Paroxysmal nocturnal hemoglobinuria
*Toxins, such as HAART, ifosfamide, lead, and cadmium

Again this depends on oral bicarbonate supplementation. However, this will increase urinary bicarbonate wasting and may well promote a bicarbonate diuresis. The amount of bicarbonate given may have to be very large, to stay ahead of the urinary losses. Correction with oral bicarbonate may exacerbate urinary potassium losses and precipitate hypokalemia.As with dRTA, reversal of the chronic acidosis should reverse bone demineralisation.

Type 3 RTA:-
This was previously used to designate a rare and transient mixed dRTA and pRTA of uncertain aetiology. Now it is used to describe a genetic defect in type 2 carbonic anhydrase (CA2), which is found in both the proximal and distal tubular cells, as well in bone. As a result it causes;

*proximal renal tubular acidosis
*distal renal tubular acidosis
*cerebral calcification and subsequent mental impairment;

It is very rare and cases from all over the world have been reported, of which about 70% are from the Magreb region of North Africa, possibly due to the high prevalence of consanguinity there. The kidney problems are treated as described above. There is no treatment for the osteopetrosis or cerebral calcification.

Type 4 RTA (Hypoaldosteronism):-
This form of RTA is most often referred to as type 4. It 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 is distinguished by a high blood-potassium level.

Hyperkalemic distal RTA may result from sickle cell disease, urinary tract obstruction, lupus, amyloidosis, or transplantation.

Type 4 RTA is not actually a tubular disorder at all, and nor does it have a clinical syndrome similar to the other types of RTA described above. It was included in the classification of renal tubular acidoses as it is associated with a mild (normal anion gap) metabolic acidosis due to a physiological reduction in distal tubular ammonium excretion, which is secondary to hypoaldosteronism. Its cardinal feature is hyperkalemia, and measured urinary acidification is normal.

*Aldosterone deficiency-Primary (rare)

1.Primary adrenal insufficiency
2.Congenital adrenal hyperplasia
3.Aldosterone synthase deficiency

*Hyporeninemic hypoaldosteronism (due to decreased angiotensin 2 production as well as intra-adrenal dysfunction)

1.Renal dysfunction-most commonly diabetic nephropathy
2..HIV infection
3..ACE inhibitors

*Aldosterone resistance

1.Drugs (Amiloride, Spironolactone,Trimethoprim, Pentamidine)

*Aldosterone deficiency should be treated with a mineralocorticoid (such as fludrocortisone), as well as possibly a glucocorticoid for cortisol deficiency, if present.

*Hyporeninemic hypoaldosteronism is ammenable to fludrocortisone treatment, but the accompanying hypertension and edema can prove a problem in these patients, so often a diuretic (such as the thiazide diuretic, bendrofluazide,or a loop diuretic, such as furosemide) is used to control the hyperkalemia.

Hope through Research:-
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) conducts and supports research into many kinds of kidney disease, including renal tubular acidosis. NIDDK-supported researchers are exploring the genetic and molecular mechanisms that control acid-base regulation in the kidney. These studies will point the way to more effective treatments for RTA.

Click to See also:-
Hyperchloremic acidosis
Kidney stone

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

For More Information you may contact:

American Association of Kidney Patients
3505 East Frontage Road
Suite 315
Tampa, FL 33607
Phone: 1–800–749–2257 or 813–636–8100
Fax: 813–636–8122

American Kidney Fund
6110 Executive Boulevard
Suite 1010
Rockville, MD 20852
Phone: 1–800–638–8299 or 301–881–3052

National Kidney Foundation
30 East 33rd Street
New York, NY 10016
Phone: 1–800–622–9010 or 212–889–2210
Fax: 212–689–9261

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