Renal tubular acidosis
Name = PAGENAME
Caption = 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.
DiseasesDB = 11687
DiseasesDB_mult = DiseasesDB2|11673 DiseasesDB2|11705
ICD10 = ICD10|N|25|8|n|25
ICD9 = ICD9|588.89
OMIM = 179800
eMedicineSubj = med
eMedicineTopic = 1071
MeshID = 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 the
urine.cite journal |author=Laing CM, Toye AM, Capasso G, Unwin RJ |title=Renal tubular acidosis: developments in our understanding of the molecular basis |journal=Int. J. Biochem. Cell Biol. |volume=37 |issue=6 |pages=1151–61 |year=2005|pmid=15778079 |doi=10.1016/j.biocel.2005.01.002 |url=] When blood is filtered by the kidney, the passes through the tubulesof the nephron, allowing for exchange of salts, acid equivalents, and other before it drains into the bladder as urine. The metabolic acidosisthat results from RTA may be caused either by failure to recover sufficient ( alkaline) bicarbonateions from the filtrate in the early portion of the nephron ( proximal tubule) or by insufficient secretion of ( acid) hydrogen ionsinto 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
Distal RTA (dRTA) is 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 ductof the distal nephron.This leads to a failure to acidify the urine to a pHof 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;
anion gap metabolic acidosis/acidemia
Hypokalemia(which may be severe)
*Urinary stone formation (related to alkaline urine,
hypercalciuria, and low urinary citrate).cite journal
author = Buckalew VM Jr
title = Nephrolithiasis in renal tubular acidosis
journal = Journal of Urolology
volume = 141
issue = 3 (part 2)
pages = 731-737
year = 1989
pmid = 2645431]
Nephrocalcinosis(deposition of calciumin the substance of the kidney)
Bonedemineralisation (causing ricketsin children and osteomalaciain adults)
The acidosis is variable, and one may have dRTA with
alpha intercalated cellfailure without necessarily being acidemic, this is termed "incomplete dRTA". The diagnosis of dRTA can be made by the observation of a urinary pHof 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 chloridetest", [cite journal |quotes= |last=Wrong |first= O|authorlink= |coauthors=Davies HEF |year= 1959|month= |title=The Excretion of Acid in Renal Disease |journal=QJM |volume= 28|issue= |pages=259–313 |id= |url= |accessdate= ] in which ammonium chloride capsules are used as the acid load. More recently, an alternative test using furosemide and fludrocortisone has been described. [cite journal |author=Walsh SB, Shirley DG, Wrong OM, Unwin RJ |title=Urinary acidification assessed by simultaneous furosemide and fludrocortisone treatment: an alternative to ammonium chloride |journal=Kidney Int. |volume=71 |issue=12 |pages=1310–6 |year=2007 |pmid=17410104 |doi=10.1038/sj.ki.5002220 |url=]
The symptoms and sequelae of dRTA are variable and ranging from being completely
asymptomatic, through loinpain and hematuriafrom kidney stonesto failure to thriveand severe ricketsin childhood forms as well as possible renal failureand even death.
Interestingly, dRTA has been proposed as a possible diagnosis for the unknown malady plaguing Tiny Tim in Charles Dickens'
A Christmas Carol. [cite journal | author = Lewis D | title = What was wrong with Tiny Tim? | journal = Am J Dis Child | volume = 146 | issue = 12 | pages = 1403–7 | year = 1992 | pmid = 1340779] [ [http://www.time.com/time/magazine/article/0,9171,977391,00.html What Ailed Tiny Tim - TIME ] ]
Autoimmune disease. Classically Sjögren's syndrome, but it is also associated with systemic lupus erythematosus, rheumatoid arthritisand even hypergammaglobulinemia. Hypokalaemia is often severe in these cases. [cite journal |author=Wrong OM, Feest TG, MacIver AG |title=Immune-related potassium-losing interstitial nephritis: a comparison with distal renal tubular acidosis |journal=Q. J. Med. |volume=86 |issue=8 |pages=513–34 |year=1993 |pmid=8210309 |doi= |url=http://qjmed.oxfordjournals.org/cgi/content/abstract/86/8/513]
*Hereditary causes include mutations of
Band 3[cite journal |author=Bruce LJ, Cope DL, Jones GK, "et al" |title=Familial distal renal tubular acidosis is associated with mutations in the red cell anion exchanger (Band 3, AE1) gene |journal=J. Clin. Invest. |volume=100 |issue=7 |pages=1693–707 |year=1997 |pmid=9312167 |pmc=508352 |doi=10.1172/JCI119694 |url=http://www.jci.org/cgi/content/abstract/100/7/1693] the basolateral bicarbonate transporter of the intercalated cell, which may transmit in an autosomal dominantfashion in western European cases, or in an autosomal recessivefashion in South East Asian cases. The South East Asian cases are associated with more severe hypokaemia. [cite journal |author=Bruce LJ, Wrong O, Toye AM, "et al" |title=Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in Malaysia and Papua New Guinea: loss of up to 95% band 3 transport in red cells |journal=Biochem. J. |volume=350 Pt 1 |issue= |pages=41–51 |year=2000 |pmid=10926824 |pmc=1221222 |doi=10.1042/0264-6021:3500041 |url=http://www.biochemj.org/bj/350/0041/bj3500041.htm] Other Hereditary causes include mutations of subunits of the apical proton pumpvH+-ATPase, [cite journal|last=Wagner|first=CA |year=2004 |month=Oct|title=Renal Vacuolar H+-ATPase|journal=Physiological Reviews|volume=84 |issue=4 |pages=1263–314|url=http://physrev.physiology.org/cgi/content/full/84/4/1263|pmid=15383652|doi=10.1152/physrev.00045.2003] which transmit in an autosomal recessive fashion, and may be associated with sensorineural deafness. [cite journal |author=Karet FE, Finberg KE, Nelson RD, "et al" |title=Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness |journal=Nat. Genet. |volume=21 |issue=1 |pages=84–90 |year=1999 |pmid=9916796 |doi=10.1038/5022 |url=http://www.nature.com/ng/journal/v21/n1/abs/ng0199_84.html]
*Nephrocalcinosis. While it is a consequence of dRTA, it can also be a cause; related to calcium-induced damage of the
cortical collecting duct.
Sickle cell anemia.
ifosfamide, [cite journal |author=Skinner R, Pearson AD, English MW, "et al" |title=Risk factors for ifosfamide nephrotoxicity in children |journal=Lancet |volume=348 |issue=9027 |pages=578–80 |year=1996 |pmid=8774570 |doi=10.1016/S0140-6736(96)03480-0 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673696034800] toluene, [cite journal |author=Batlle DC, Sabatini S, Kurtzman NA |title=On the mechanism of toluene-induced renal tubular acidosis |journal=Nephron |volume=49 |issue=3 |pages=210–8 |year=1988 |pmid=3135502 |doi= |url=] lithium carbonate[cite journal |author=Boton R, Gaviria M, Batlle DC |title=Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy |journal=Am. J. Kidney Dis. |volume=10 |issue=5 |pages=329–45 |year=1987 |pmid=3314489 |doi= |url=] and amphotericin B. [cite journal |author=McCurdy DK, Frederic M, Elkinton JR |title=Renal tubular acidosis due to amphotericin B |journal=N. Engl. J. Med. |volume=278 |issue=3 |pages=124–30 |year=1968 |pmid=5634966 |doi= |url=]
urinary tract obstruction.
This is relatively straightforward. It involves correction of the acidemia with oral
sodium bicarbonateor sodium citrate. This will correct the acidemia and reverse bone demineralisation. Hypokalemia and urinary stone formation and nephrocalcinosis can be treated with potassium citratetablets which not only replace potassium but also inhibit calcium excretion and thus do not exacerbate stone disease as sodium bicarbonate or citrate may do. [cite journal |author=Morris RC, Sebastian A |title=Alkali therapy in renal tubular acidosis: who needs it? |journal=J. Am. Soc. Nephrol. |volume=13 |issue=8 |pages=2186–8 |year=2002 |pmid=12138154 |doi=10.1097/01.ASN.0000027973.07189.00 |url=http://jasn.asnjournals.org/cgi/reprint/13/8/2186.pdf]
Type 2-Proximal RTA
Proximal RTA (pRTA) is caused by a failure of the
proximal tubularcells 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. [cite journal |author=Rodriguez Soriano J, Boichis H, Stark H, Edelmann CM |title=Proximal renal tubular acidosis. A defect in bicarbonate reabsorption with normal urinary acidification |journal=Pediatr. Res. |volume=1 |issue=2 |pages=81–98 |year=1967 |pmid=6029811 |doi= |url=] 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 syndromewhere there is also phosphaturia, glycosuria, aminoaciduria, uricosuria and tubular proteinuria.The principal feature of Fanconi's syndrome is bone demineralization ( osteomalaciaor rickets) due to phosphate wasting.
Cystinosis[cite journal |author=Gahl WA, Thoene JG, Schneider JA |title=Cystinosis |journal=N. Engl. J. Med. |volume=347 |issue=2 |pages=111–21 |year=2002 |pmid=12110740 |doi=10.1056/NEJMra020552 |url=http://content.nejm.org/cgi/content/extract/347/2/111]
Galactosemia[cite journal |author=Golberg L, Holzel A, Komrower GM, Schwarz V |title=A clinical and biochemical study of galactosaemia; a possible explanation of the nature of the biochemical lesion |journal=Arch. Dis. Child. |volume=31 |issue=158 |pages=254–64 |year=1956 |pmid=13363463 |pmc=2011923 |doi= |url=]
Glycogen storage disease(type I) [cite journal |author=Matsuo N, Tsuchiya Y, Cho H, Nagai T, Tsuji A |title=Proximal renal tubular acidosis in a child with type 1 glycogen storage disease |journal=Acta Paediatr Scand |volume=75 |issue=2 |pages=332–5 |year=1986 |pmid=3457521 |doi=10.1111/j.1651-2227.1986.tb10210.x |url=]
Hereditary fructose intolerance[cite journal |author=Morris RC |title=An experimental renal acidification defect in patients with hereditary fructose intolerance. I. Its resemblance to renal tubular acidosis |journal=J. Clin. Invest. |volume=47 |issue=6 |pages=1389–98 |year=1968 |pmid=5653216 |pmc=297294 |doi=10.1172/JCI105830 |url=]
*Lowe syndrome [cite journal |author=Hodgson SV, Heckmatt JZ, Hughes E, Crolla JA, Dubowitz V, Bobrow M |title=A balanced de novo X/autosome translocation in a girl with manifestations of Lowe syndrome |journal=Am. J. Med. Genet. |volume=23 |issue=3 |pages=837–47 |year=1986 |pmid=3953680 |doi=10.1002/ajmg.1320230311 |url=]
Wilson's disease[cite journal |last=Weibers |first=DO |authorlink= |coauthors= |year=1979 |month=Aug |title=Renal stones in Wilson's disease |journal=Am J Med |volume=67 |issue=2 |pages=249–54 |id= |url=http://www.md-journal.com/pt/re/medicine/abstract.00005792-200005000-00002.htm;jsessionid=GJqhJ2BT5PpykNC8TdC42PFLB1RXHMtrf2YyZLnQWhD0G8p6zxML!1888299356!-949856144!8091!-1 |accessdate= |quote= |doi=10.1016/0002-9343(79)90399-1 ]
Amyloidosis[cite journal |last=Rochman |first=J |authorlink= |coauthors= |year=1980 |month=Oct |title=Adult Fanconi's syndrome with renal tubular acidosis in association with renal amyloidosis: occurrence in a patient with chronic lymphocytic leukemia |journal=Arch Int Med |volume=140 |issue=10 |pages= |id= |url=http://archinte.ama-assn.org/cgi/content/abstract/140/10/1361 |accessdate= |quote= |pmid=6775610 |doi=10.1001/archinte.140.10.1361 ]
Multiple myeloma[cite journal |author=Messiaen T, Deret S, Mougenot B, "et al" |title=Adult Fanconi syndrome secondary to light chain gammopathy. Clinicopathologic heterogeneity and unusual features in 11 patients |journal=Medicine (Baltimore) |volume=79 |issue=3 |pages=135–54 |year=2000 |pmid=10844934 |doi=10.1097/00005792-200005000-00002 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0025-7974&volume=79&issue=3&spage=135]
Paroxysmal nocturnal hemoglobinuria[cite journal |author=Riley AL, Ryan LM, Roth DA |title=Renal proximal tubular dysfunction and paroxysmal nocturnal hemoglobinuria |journal=Am. J. Med. |volume=62 |issue=1 |pages=125–9 |year=1977 |pmid=13653 |doi=10.1016/0002-9343(77)90357-6 |url=]
*Toxins, such as
HAART, ifosfamide, [cite journal |author=Skinner R |title=Chronic ifosfamide nephrotoxicity in children |journal=Med. Pediatr. Oncol. |volume=41 |issue=3 |pages=190–7 |year=2003 |pmid=12868118 |doi=10.1002/mpo.10336 |url=] 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 bicarbonatemay exacerbate urinary potassium losses and precipitate hypokalemia. [cite journal |author=Rodríguez Soriano J |title=Renal tubular acidosis: the clinical entity |journal=J. Am. Soc. Nephrol. |volume=13 |issue=8 |pages=2160–70 |year=2002 |pmid=12138150 |doi=10.1097/01.ASN.0000023430.92674.E5 |url=http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=12138150] As with dRTA, reversal of the chronic acidosis should reverse bone demineralisation. [cite journal |author=McSherry E |title=Renal tubular acidosis in childhood |journal=Kidney Int. |volume=20 |issue=6 |pages=799–809 |year=1981 |pmid=7038264 |doi=10.1038/ki.1981.213 |url=]
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
calcificationand subsequent mental impairment;It is very rare and cases from all over the world have been reported, of which about 70% are from the Magrebregion of North Africa, possibly due to the high prevalence of consanguinitythere. [cite journal |author=Fathallah DM, Bejaoui M, Lepaslier D, Chater K, Sly WS, Dellagi K |title=Carbonic anhydrase II (CA II) deficiency in Maghrebian patients: evidence for founder effect and genomic recombination at the CA II locus |journal=Hum. Genet. |volume=99 |issue=5 |pages=634–7 |year=1997 |pmid=9150731 |doi=10.1007/s004390050419 |url=http://www.springerlink.com/content/7fvlgeehvxf5d5rt/fulltext.pdf] The kidney problems are treated as described above. There is no treatment for the osteopetrosis or cerebral calcification.
Type 4 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
ammoniumexcretion, which is secondary to hypoaldosteronism.Its cardinal feature is hyperkalemia, and measured urinary acidification is normal.
Congenital adrenal hyperplasia
*Hyporeninemic hypoaldosteronism (due to decreased angiotensin 2 production as well as intra-adrenal dysfunction)cite journal |author=DeFronzo RA |title=Hyperkalemia and hyporeninemic hypoaldosteronism |journal=Kidney Int. |volume=17 |issue=1 |pages=118–34 |year=1980 |pmid=6990088 |doi=10.1038/ki.1980.14 |url=]
#Renal dysfunction-most commonly
Amiloride, Spironolactone, Trimethoprim, Pentamidine)
*Aldosterone deficiency should be treated with a
mineralocorticoid(such as fludrocortisone), as well as possibly a glucocorticoidfor cortisoldeficiency, if present.
*Hyporeninemic hypoaldosteronism is ammenable to
fludrocortisonetreatment, but the accompanying hypertensionand edemacan prove a problem in these patients, so often a diuretic(such as the thiazidediuretic, bendrofluazide,or a loop diuretic, such as furosemide) is used to control the hyperkalemia. [cite journal |author=Sebastian A, Schambelan M, Sutton JM |title=Amelioration of hyperchloremic acidosis with furosemide therapy in patients with chronic renal insufficiency and type 4 renal tubular acidosis |journal=Am. J. Nephrol. |volume=4 |issue=5 |pages=287–300 |year=1984 |pmid=6524600 |doi= |url=]
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