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Renal tubular acidosis
Classification and external resources

Significant bilateral nephrocalcinosis (calcification of the kidneys) on a frontal X-ray (radiopacities (white) in the right upper and left upper quadrant of the image), as seen in distal renal tubular acidosis.
ICD-10 N25.8
ICD-9 588.89
OMIM 179800
DiseasesDB 11687 11673 11705
eMedicine med/1071
MeSH D000141

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.[1] 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.


Type I-Distal RTA

Radiograph of a rickets sufferer, a complication of both distal and proximal RTA.

Distal RTA (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cells of the cortical collecting duct of the distal nephron. This failure of acid secretion may be due to a number of causes, and it leads to an inability to acidify the urine to a pH of less than 5.3. Because renal excretion is the primary means of eliminating acid from the body, there is consequently a tendency towards acidemia. This leads to the clinical features of dRTA;[1]

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,[3] in which ammonium chloride capsules are used as the acid load. More recently, an alternative test using furosemide and fludrocortisone has been described.[4]

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.[5][6]



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 do not exacerbate stone disease as sodium bicarbonate or citrate may do.[16]

Type 2-Proximal RTA

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.[17] 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 demineralization (osteomalacia or rickets) due to phosphate wasting.


Familial disorders

Acquired disorders


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.[28] As with dRTA, reversal of the chronic acidosis should reverse bone demineralization.[29]

Type 3 RTA-Combined proximal and distal RTA

In some patients, their RTA shares features of both dRTA and pRTA. This rare pattern was observed in the 1960s and 1970s as a transient phenomenon in infants and children with dRTA, possibly in relation with some exogenous factor such as high salt intake, and is no longer observed.[30] This form of RTA has also been referred to as juvenile RTA.[31]

Combined dRTA and pRTA is also observed as the result of inherited carbonic anhydrase II deficiency. Mutations in the gene encoding this enzyme give rise to an autosomal recessive syndrome of osteopetrosis, renal tubular acidosis, cerebral calcification, and mental retardation. [32][33][34] It is very rare and cases from all over the world have been reported, of which about 70% are from the Magreb/West region of North Africa, possibly due to the high prevalence of consanguinity there.[35] The kidney problems are treated as described above. There is no treatment for the osteopetrosis or cerebral calcification.

Type 4 RTA (hyperkalemic RTA)

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 molecule


  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)[36]
  1. Renal dysfunction-most commonly diabetic nephropathy
  2. HIV infection
  3. ACE inhibitors
  4. NSAIDs
  5. Cyclosporine
  • Aldosterone resistance
  1. Drugs (Amiloride, Spironolactone,Trimethoprim, Pentamidine)
  2. Pseudohypoaldosteronism



Renal tubular acidosis was first described in 1935 by Lightwood and 1936 by Butler et al. in children.[38][39] Baines et al. first described it in adults in 1945.[40]

See also


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  2. ^ Buckalew VM Jr (1989). "Nephrolithiasis in renal tubular acidosis". Journal of Urolology 141 (3 (part 2)): 731–737. PMID 2645431.  
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  4. ^ Walsh SB, Shirley DG, Wrong OM, Unwin RJ (2007). "Urinary acidification assessed by simultaneous furosemide and fludrocortisone treatment: an alternative to ammonium chloride". Kidney Int. 71 (12): 1310–6. doi:10.1038/ PMID 17410104.  
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  6. ^ What Ailed Tiny Tim - TIME
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  40. ^ Baines AM, Barelay JA, Cooke WT. Nephrocalcinosis associated with hyperchloremia and low plasma-bicarbonate. Q J Med 1945;14:113–23.


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