KEGG   DISEASE: H00243Help
Entry
H00243                      Disease                                

Name
Hyperkalemic distal renal tubular acidosis (RTA type 4), including:
Pseudohypoaldosteronism type I  (PHA1);
Pseudohypoaldosteronism type II (Gordon's syndrome)
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
Endocrine disease; Urinary system disease
BRITE hierarchy
Pathway
Aldosterone-regulated sodium reabsorption
Gene
SCNN1A [HSA:6337] [KO:K04824]
SCNN1B [HSA:6338] [KO:K04825]
SCNN1G [HSA:6340] [KO:K04827]
NR3C2 [HSA:4306] [KO:K08555]
WNK1 [HSA:65125] [KO:K08867]
WNK4 [HSA:65266] [KO:K08867]
Env factor
Cyclo-oxygenase inhibitors
Converting enzyme inhibitors
Heparin [DR:D07510]
Potassium-retaining diuretics
Trimethoprim [DR:D00145]
Pentamidine [DR:D08333]
Cyclosporin A [DR:D00184]
Insulin antagonists
Beta-adrenergic antagonists
Alpha-adrenergic agonists
Digitalis [DR:D03819]
Succinylcholine [DR:D00766]
Marker
Plasma K+ [CPD:C00238]
Urinary anion gap [CPD:C01330 C00238 C00698]
Urine pH
Urinary NH4+
Drug
Fludrocortisone [DG:DG00506]
Furosemide [DG:DG00272]
Sodium bicarbonate [DR:D01203]
Other DBs
ICD-10: 
MeSH: 
OMIM: 
Reference
PMID:19721811 (gene)
  Authors
Pereira PC, Miranda DM, Oliveira EA, Silva AC
  Title
Molecular pathophysiology of renal tubular acidosis.
  Journal
Curr Genomics 10:51-9 (2009)
Reference
PMID:11045400 (gene)
  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)
Reference
PMID:12138150 (gene, env_factor, marker, drug)
  Authors
Rodriguez Soriano J
  Title
Renal tubular acidosis: the clinical entity.
  Journal
J Am Soc Nephrol 13:2160-70 (2002)
Reference
(marker, drug)
  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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