Radiograph of a rickets sufferer, a complication of both distal and proximal RTA.
Distal renal tubular acidosis (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.
Contents
1Symptoms
2Causes
3Diagnosis
4Treatment
5See also
6References
7External links
Symptoms
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]
Normal anion gap metabolic acidosis/acidemia
Hypokalemia
Urinary stone formation (related to alkaline urine, hypercalciuria, and low urinary citrate).[2]
Nephrocalcinosis (deposition of calcium in the substance of the kidney)
Bone demineralisation (causing rickets in children and osteomalacia in adults)
The symptoms and sequelae of dRTA are variable and range from being completely asymptomatic, to 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.
dRTA commonly leads to sodium loss and volume contraction, which causes a compensatory increase in blood levels of aldosterone.[3] Aldosterone causes increased resorption of sodium and loss of potassium in the collecting duct of the kidney, so these increased aldosterone levels cause the hypokalemia which is a common symptom of dRTA.[3]
Causes
Diagram depicting an alpha intercalated cell with the apical proton pump and basolateral band 3 (kAE1)
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.[4]
Hereditary causes include mutations of Band 3[5] the basolateral bicarbonate transporter of the intercalated cell, which may be transmitted 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 hypokalemia.[6] Other hereditary causes include mutations of subunits of the apical proton pump vH+-ATPase,[7] which are transmitted in an autosomal recessive fashion, and may be associated with sensorineural deafness.[8]
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 (more commonly causing pRTA than dRTA),[9] lithium carbonate[10] and amphotericin B.[11]
Chronic urinary tract obstruction.
Toluene causes a non-anion gap metabolic acidosis with hypokalemia and a positive urinary anion gap that looks a lot like distal RTA but there is no hydrogen secretion defect and the acidosis is due to acid production during the metabolism of toluene.[12]
Diagnosis
The pH of patient's blood is highly variable, and acidemia is not necessarily characteristic of sufferers of dRTA at any given time. One may have dRTA caused by alpha intercalated cell failure without necessarily being acidemic; termed incomplete dRTA, which is characterized by an inability to acidify urine, without affecting blood pH or plasma bicarbonate levels.[13] 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,[14] in which ammonium chloride capsules are used as the acid load. More recently, an alternative test using furosemide and fludrocortisone has been described.[15]
dRTA has been proposed as a possible diagnosis for the unknown malady plaguing Tiny Tim in Charles Dickens' A Christmas Carol.[16][17]
Treatment
This is relatively straightforward. It involves correction of the acidemia with oral sodium bicarbonate, sodium citrate or potassium 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.[18]
See also
Renal tubular acidosis
Proximal renal tubular acidosis
Ifosfamide
References
^Laing CM, Toye AM, Capasso G, Unwin RJ (2005). "Renal tubular acidosis: developments in our understanding of the molecular basis". Int. J. Biochem. Cell Biol. 37 (6): 1151–61. doi:10.1016/j.biocel.2005.01.002. PMID 15778079.
^Buckalew VM Jr (1989). "Nephrolithiasis in renal tubular acidosis". The Journal of Urology. 141 (3 (part 2)): 731–737. doi:10.1016/S0022-5347(17)40997-9. PMID 2645431.
^ abWein, Alan, J (2011). Campbell-walsh Urology Expert Consult(PDF) (10th ed.). Philadelphia, PA: W B Saunders Co. p. 1045. ISBN 978-1-4160-6911-9.
^Wrong OM, Feest TG, MacIver AG (1993). "Immune-related potassium-losing interstitial nephritis: a comparison with distal renal tubular acidosis". Q. J. Med. 86 (8): 513–34. doi:10.1093/qjmed/86.8.513. PMID 8210309.
^Bruce LJ, Cope DL, Jones GK, et al. (1997). "Familial distal renal tubular acidosis is associated with mutations in the red cell anion exchanger (Band 3, AE1) gene". J. Clin. Invest. 100 (7): 1693–707. doi:10.1172/JCI119694. PMC 508352. PMID 9312167.
^Bruce LJ, Wrong O, Toye AM, et al. (2000). "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". Biochem. J. 350 Pt 1 (Pt 1): 41–51. doi:10.1042/0264-6021:3500041. PMC 1221222. PMID 10926824.
^Karet FE, Finberg KE, Nelson RD, et al. (1999). "Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness". Nat. Genet. 21 (1): 84–90. doi:10.1038/5022. PMID 9916796.
^Skinner R, Pearson AD, English MW, et al. (1996). "Risk factors for ifosfamide nephrotoxicity in children". Lancet. 348 (9027): 578–80. doi:10.1016/S0140-6736(96)03480-0. PMID 8774570.
^Boton R, Gaviria M, Batlle DC (1987). "Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy". Am. J. Kidney Dis. 10 (5): 329–45. doi:10.1016/s0272-6386(87)80098-7. PMID 3314489.
^McCurdy DK, Frederic M, Elkinton JR (1968). "Renal tubular acidosis due to amphotericin B". N. Engl. J. Med. 278 (3): 124–30. doi:10.1056/NEJM196801182780302. PMID 5634966.
^Carlisle, E. J.; Donnelly, S. M.; Vasuvattakul, S.; Kamel, K. S.; Tobe, S.; Halperin, M. L. (February 1991). "Glue-sniffing and distal renal tubular acidosis: sticking to the facts". Journal of the American Society of Nephrology. 1 (8): 1019–1027. ISSN 1046-6673. PMID 1912400.
^Batlle, D.; Haque, S. K. (2012). "Genetic causes and mechanisms of distal renal tubular acidosis". Nephrology Dialysis Transplantation. 27 (10): 3691–3704. doi:10.1093/ndt/gfs442. PMID 23114896.
^Wrong, O; Davies HEF (1959). "The Excretion of Acid in Renal Disease". QJM. 28 (110): 259–313. PMID 13658353.
^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/sj.ki.5002220. PMID 17410104.
^Lewis D (1992). "What was wrong with Tiny Tim?". Am J Dis Child. 146 (12): 1403–7. doi:10.1001/archpedi.1992.02160240013002. PMID 1340779.
^Morris RC, Sebastian A (2002). "Alkali therapy in renal tubular acidosis: who needs it?" (PDF). J. Am. Soc. Nephrol. 13 (8): 2186–8. doi:10.1097/01.ASN.0000027973.07189.00. PMID 12138154.
External links
Classification
D
OMIM: 179800
MeSH: D000141
External resources
MedlinePlus: 000493
v
t
e
Diseases of the urinary system (N00–N39, 580–599)
Kidney disease
Glomerules
Primarily nephrotic
Non-proliferative
Minimal change
Focal segmental
Membranous
Proliferative
Mesangial proliferative
Endocapillary proliferative
Membranoproliferative/mesangiocapillary
By condition
Diabetic
Amyloidosis
Primarily nephritic, RPG
Type I RPG/Type II hypersensitivity
Goodpasture's syndrome
Type II RPG/Type III hypersensitivity
Post-streptococcal
Lupus
DPGN
IgA/Berger's
Type III RPG/Pauci-immune
Granulomatosis with polyangiitis
Microscopic polyangiitis
Eosinophilic granulomatosis with polyangiitis
General
glomerulonephritis
glomerulonephrosis
Tubules
Renal tubular acidosis
proximal
distal
Acute tubular necrosis
Genetic
Fanconi syndrome
Bartter syndrome
Gitelman syndrome
Liddle's syndrome
Interstitium
Interstitial nephritis
Pyelonephritis
Balkan endemic nephropathy
General
General syndromes
Nephritis
Nephrosis
Renal failure
Acute renal failure
Chronic kidney disease
Uremic pericarditis
Uremia
Diabetes insipidus
Nephrogenic
Renal papilla
Renal papillary necrosis
Major calyx/pelvis
Hydronephrosis
Pyonephrosis
Reflux nephropathy
Vascular
Renal artery stenosis
Renal ischemia
Hypertensive nephropathy
Renovascular hypertension
Renal cortical necrosis
Other
Analgesic nephropathy
Renal osteodystrophy
Nephroptosis
Abderhalden–Kaufmann–Lignac syndrome
Urinary tract
Ureter
Ureteritis
Ureterocele
Megaureter
Bladder
Cystitis
Interstitial cystitis
Hunner's ulcer
Trigonitis
Hemorrhagic cystitis
Neurogenic bladder dysfunction
Bladder sphincter dyssynergia
Vesicointestinal fistula
Vesicoureteral reflux
Urethra
Urethritis
Non-gonococcal urethritis
Urethral syndrome
Urethral stricture/Meatal stenosis
Urethral caruncle
Any/all
Obstructive uropathy
Urinary tract infection
Retroperitoneal fibrosis
Urolithiasis
Bladder stone
Kidney stone
Renal colic
Malakoplakia
Urinary incontinence
Stress
Urge
Overflow
v
t
e
Electrolyte imbalance and acid–base imbalance (E86–E87, 276)
Volume status
Volume contraction (dehydration/hypovolemia)
Hypervolemia
Electrolyte
Sodium
High
Hypernatremia
Salt poisoning
Low
Hypotonic
Isotonic
Potassium
High
Low
Chloride
High
Low
Calcium
High
Low
Acid–base
Acidosis
Metabolic: High anion gap
Ketoacidosis
Diabetic ketoacidosis
Alcoholic ketoacidosis
Lactic
Normal anion gap
Hyperchloremic
Renal tubular
Respiratory
Alkalosis
Metabolic
Contraction alkalosis
Respiratory
Both
Mixed disorder of acid-base balance
UpToDate Contents
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…concentration . Some patients with incomplete distal RTA progress to overt distal RTA, and some have a family history of RTA. Patients with incomplete distal RTA have reduced urine citrate levels and may …
…determined by the primary defect in these disorders: decreased distal tubule acidification with distal (type 1) RTA and impaired proximal bicarbonate reabsorption in proximal (type 2) RTA . Correction of the acidosis …
…RTA, which is sometimes considered a subtype of distal RTA. These major forms of RTA differ in their pathophysiology and clinical manifestations : Distal RTA is caused by defects in distal hydrogen ion excretion …
…urine pH (greater than 5.5) The etiology of distal RTA in children can be divided into genetic and acquired disorders Genetic primary causes of distal RTA include mutations of genes that encode the …
…nephrocalcinosis, and skeletal abnormalities are frequently associated with untreated distal (type 1) renal tubular acidosis (RTA) . Stone disease is also seen with carbonic anhydrase inhibitors but typically not …
English Journal
Distal renal tubular acidosis: genetic causes and management.
Soares SBM, de Menezes Silva LAW, de Carvalho Mrad FC, Simões E Silva AC.
World journal of pediatrics : WJP. 2019 May;().
Distal renal tubular acidosis (dRTA) is a kidney tubulopathy that causes a state of normal anion gap metabolic acidosis due to impairment of urine acidification. This review aims to summarize the etiology, pathophysiology, clinical findings, diagnosis and therapeutic approach of dRTA, with emphasis
Prevalence of distal renal tubular acidosis in patients with calcium phosphate stones.
Guimerà J, Martínez A, Tubau V, Sabate A, Bauza JL, Rios A, Lopez M, Piza P, Grases F, Pieras E.
World journal of urology. 2019 May;().
Distal renal tubular acidosis (DRTA) is a metabolic disorder that associates urolithiasis and urinary pH > 6. The prevalence of DRTA in patients with calcium phosphate stones is not well known. The objective is to determine the prevalence of DRTA in patients with calcium phosphate stones and uri
Intrinsic hydrogen evolution capability and a theoretically supported reaction mechanism of a paddlewheel-type dirhodium complex.
Kataoka Y, Yano N, Handa M, Kawamoto T.
Dalton transactions (Cambridge, England : 2003). 2019 Feb;().
The intrinsic capability of the paddlewheel-type dirhodium tetraacetate complex, [Rh2(O2CCH3)4(H2O)2] ([1(H2O)2]), as a hydrogen evolution catalyst (HEC) for photochemical hydrogen evolution from aqueous solution was illustrated. This was achieved by using an optimized artificial photosynthesis (AP)
… Background: Autosomal recessive distal renal tubular acidosis (dRTA) is a rare hereditary disease caused by pathogenic variants in the ATP6V0A4 gene or ATP6V1B1 gene, and characterized by hyperchloremic metabolic acidosis with normal anion gap, hypokalemia, hypercalciuria, hypocitraturia and nephrocalcinosis. … Methods: We investigated a sporadic case of dRTA with a compound heterozygous mutation in the ATP6V0A4 gene, revealed by next generation sequencing. …
… We herein report the case of a 64-year old woman with recurrent attacks of hypokalemic quadriparesis which resulted from distal renal tubular acidosis (dRTA) secondary to Sjögren syndrome. … Severe hypokalemia (1.8 mEq/L), accompanied by normal anion gap metabolic acidosis, a positive urine anion gap and an inappropriately high urine pH pointed toward the diagnosis of dRTA. …
