KEGG   DISEASE: Hyperkalemic distal renal tubular acidosis (RTA type 4)
Entry
H00243                      Disease                                

Name
Hyperkalemic distal renal tubular acidosis (RTA type 4)
  Subgroup
Pseudohypoaldosteronism type I (PHA1)
Pseudohypoaldosteronism type II (PHA2)
  Supergrp
Renal tubular acidosis [DS:H02310]
Description
Renal tubular acidosis (RTA) is characterized by metabolic acidosis, a severe disturbance of extracellular pH homeostasis, due to renal impaired acid excretion. Type 4 RTA is a heterogeneous group of disorders associated with hyperkalemia due to aldosterone deficiency or impairment in aldosterone molecular signaling. Primary pseudohypoaldosteronism type 1 (PHA1) is characterized by salt-wasting, hyperkalemia, and metabolic acidosis in the presence of markedly elevated plasma renin activity and aldosterone concentration. In the autosomal dominant form, aldosterone resistance is due to heterozygous mutations in the mineralocorticoid receptor gene. In the autosomal recessive form, aldosterone resistance is caused by loss-of-function homozygous mutations in the genes encoding one of the three constitutive subunits (alpha, beta, and gamma) of the epithelial Na+ channel (SCNN1A, SCNN1B, and SCNN1G). Other inherited cause of type 4 RTA includes hyperkalaemia associated with hypertension and low or normal levels of plasma aldosterone. This syndrome is called pseudohypoaldosteronism type 2 (PHA2), or Gordon's syndrome, which results in a renal aldosterone resistance. Mutations in the genes encoding WNK1 and WNK4 kinases (WNK1 and WNK4), which regulate ion-transportors on renal tubules, were identified in patients with PHA2. Acquired hyperkalemic RTA is observed in the context of mineralocorticoid deficiency, systemic lupus erythematosus, and AIDS nephropathy. It is also often seen in a number of tubulointerstitial renal diseases. Finally, a great number of drugs may induce hyperkalemic RTA.
Category
Urinary system disease
Brite
Human diseases [BR:br08402]
 Urinary system diseases
  Kidney diseases
   H00243  Hyperkalemic distal renal tubular acidosis (RTA type 4)
Human diseases in ICD-11 classification [BR:br08403]
 16 Diseases of the genitourinary system
  Diseases of the urinary system
   GB90  Certain specified disorders of kidney or ureter
    H00243  Hyperkalemic distal renal tubular acidosis (RTA type 4)
Pathway
hsa04960  Aldosterone-regulated sodium reabsorption
Gene
(PHA1A) NR3C2 [HSA:4306] [KO:K08555]
(PHA1B) SCNN1A [HSA:6337] [KO:K04824]
(PHA1B) SCNN1B [HSA:6338] [KO:K04825]
(PHA1B) SCNN1G [HSA:6340] [KO:K04827]
(PHA2B) WNK4 [HSA:65266] [KO:K08867]
(PHA2C) WNK1 [HSA:65125] [KO:K08867]
(PHA2D) KLHL3 [HSA:26249] [KO:K10443]
(PHA2E) CUL3 [HSA:8452] [KO:K03869]
Env factor
Cyclo-oxygenase inhibitors
Converting enzyme inhibitors
Heparin [CPD:C00374]
Potassium-retaining diuretics
Trimethoprim [CPD:C01965]
Pentamidine [CPD:C07420]
Cyclosporin A [CPD:C05086]
Insulin antagonists
Beta-adrenergic antagonists
Alpha-adrenergic agonists
Digitalis
Succinylcholine
Drug
Sodium bicarbonate [DR:D01203]
Other DBs
ICD-11: GB90.44
ICD-10: N25.8
MeSH: D011546
OMIM: 264350 177735 145260 614491 614492 614495 614496
Reference
  Authors
Pereira PC, Miranda DM, Oliveira EA, Silva AC
  Title
Molecular pathophysiology of renal tubular acidosis.
  Journal
Curr Genomics 10:51-9 (2009)
DOI:10.2174/138920209787581262
Reference
  Authors
Rodriguez-Soriano J
  Title
New insights into the pathogenesis of renal tubular acidosis--from functional to molecular studies.
  Journal
Pediatr Nephrol 14:1121-36 (2000)
DOI:10.1007/s004670000407
Reference
  Authors
Wilson FH, Disse-Nicodeme S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP
  Title
Human hypertension caused by mutations in WNK kinases.
  Journal
Science 293:1107-12 (2001)
DOI:10.1126/science.1062844
Reference
  Authors
Boyden LM, Choi M, Choate KA, Nelson-Williams CJ, Farhi A, Toka HR, Tikhonova IR, Bjornson R, Mane SM, Colussi G, Lebel M, Gordon RD, Semmekrot BA, Poujol A, Valimaki MJ, De Ferrari ME, Sanjad SA, Gutkin M, Karet FE, Tucci JR, Stockigt JR, Keppler-Noreuil KM, Porter CC, Anand SK, Whiteford ML, Davis ID, Dewar SB, Bettinelli A, Fadrowski JJ, Belsha CW, Hunley TE, Nelson RD, Trachtman H, Cole TR, Pinsk M, Bockenhauer D, Shenoy M, Vaidyanathan P, Foreman JW, Rasoulpour M, Thameem F, Al-Shahrouri HZ, Radhakrishnan J, Gharavi AG, Goilav B, Lifton RP
  Title
Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities.
  Journal
Nature 482:98-102 (2012)
DOI:10.1038/nature10814
Reference
  Authors
Rodriguez Soriano J
  Title
Renal tubular acidosis: the clinical entity.
  Journal
J Am Soc Nephrol 13:2160-70 (2002)
DOI:10.1097/01.ASN.0000023430.92674.E5
Reference
  Authors
McPhee SJ, Papadakis MA (ed).
  Title
Current Medical Diagnosis & Treatment 2010, Forty-Ninth Edition
  Journal
The McGraw-Hill Companies, Inc. (2010)
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