Renal tubular acidosis

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Renal tubular acidosis
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
SpecialtyNephrology Edit this on Wikidata

Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of

alkaline) from the filtrate in the early portion of the nephron (the proximal tubule). Although a metabolic acidosis also occurs in those with chronic kidney disease, 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. RTA is usually an incidental finding based on routine blood draws that show abnormal results. Clinically, patients may present with vague symptoms such as dehydration, mental status changes, or delayed growth in adolescents.[2]

The word acidosis refers to the tendency for RTA to cause an excess of acid, which lowers 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.

Types

An overview of types 1, 2, and 4 is presented below (type 3 is usually excluded from modern classifications):

Type Type 1 Type 2 Type 4
Location Collecting Tubules, distal tubules Proximal tubules Adrenal
Acidemia Yes (very severe) Yes Mild when present
Potassium
Hypokalaemia
 Hypokalemia Hyperkalemia
Pathophysiology Failure of α intercalated cells to secrete H+ and reclaim K+ Failure of proximal tubular cells to reabsorb HCO−
3 		Deficiency of aldosterone, or a resistance to its effects, (hypoaldosteronism or pseudohypoaldosteronism)
Prevalence/Incidence Prevalence of 46 per 1 million people[3] Autosomal dominant: 1 family described[4]

Type 1: distal

Main article: Distal renal tubular acidosis

Distal RTA (dRTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of H+ secretion into lumen of nephron by the alpha intercalated

medullary collecting duct of the distal nephron.[citation needed
]

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

acidemia. There is an inability to excrete H+ while K+
 cannot be reclaimed by the cell, leading to acidemia (as H+
 builds up in the body) and hypokalemia (as K+
 cannot be reabsorbed by the alpha cell).[citation needed
]

This leads to the clinical features of dRTA;[1] In other words, the intercalated cells' apical H+/K+ antiporter is non-functional, resulting in proton retention and potassium excretion. Since calcium phosphate stones demonstrate a proclivity for deposition at higher pHs (alkaline), the substance of the kidney develops stones bilaterally; this does not occur in the other RTA types[citation needed].

Distal RTA has also been linked to specific genetic mutations that will alter when the disease will present in the patient's life. Patient's with mutations in ATP6V1B1 and ATP6V0A4 will present with symptoms within the first year of life, while those with mutation of the SLC4A1 have delayed onset around 10 years of age.[6] Electrolyte imbalances remain the same, while in severe cases symptoms can advance to amino aciduria and hyperammonemia.[7] In a large Asian series of Distal renal Tubular Acidosis in Sjogren's Syndrome, late diagnosis is a rule in spite of overt hypokalemic periodic paralysis in a vast majority of them[8]

dRTA is the most common form of RTA diagnosed in Western countries, and can be classified as either hereditary (primary) or acquired (secondary). Primary RTA generally results from systemic and autoimmune diseases[9] or drug and toxin exposure in adults, whereas pediatric RTA results from genetic defects in the proteins that facilitate urine acidification at the distal tubule. Hereditary dRTA generally presents as failure to thrive during the first several months of life. Other common clinical manifestations in children include a variety of gastrointestinal and urinary symptoms, including polyuria, polydipsia, constipation, diarrhea, bouts of dehydration, and decreased appetite.[10]

Type 2: proximal

Radiograph of a child with rickets
, a complication of both proximal and, less commonly, distal RTA.
Main article: Proximal renal tubular acidosis

Proximal RTA (pRTA) is caused by a failure of the

phosphaturia, glycosuria, aminoaciduria, uricosuria, and tubular proteinuria.[citation needed
]

The principal feature of Fanconi syndrome is bone demineralization (osteomalacia or rickets) due to phosphate wasting.[citation needed]

Type 3: combined proximal and distal

In some patients, 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.[13] This form of RTA has also been referred to as juvenile RTA.[14]

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.[15][16][17] It is very rare and cases from all over the world have been reported, of which about 70% are from the Maghreb region of North Africa, possibly due to the high prevalence of consanguinity there.[18] The kidney problems are treated as described above. There is no treatment for the osteopetrosis or cerebral calcification.

Type 3 is rarely discussed.[19] Most comparisons of RTA are limited to a comparison of types 1, 2, and 4.

Type 4: absolute hypoaldosteronism or aldosterone insensitivity

Type 4 RTA is due either to a deficiency of Aldosterone, or to a resistance to its effects.

Type 4 RTA is not actually a tubular disorder at all 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 proximal tubular ammonium excretion (impaired ammoniagenesis), which is secondary to hypoaldosteronism, and results in a decrease in urine buffering capacity. Its cardinal feature is hyperkalemia, and measured urinary acidification is normal, hence it is often called hyperkalemic RTA or tubular hyperkalemia.[19]

Causes include:

  1. Drugs:
    ARBs, Eplerenone, Spironolactone, Trimethoprim, Pentamidine
  2. Pseudohypoaldosteronism

History

Renal tubular acidosis was first described in 1935 by Lightwood and 1936 by Butler et al. in children.[20][21] Baines et al. first described it in adults in 1945.[22]

Donald L. Lewis postulated the character Tiny Tim, of A Christmas Carol, was suffering from renal tubular acidosis.[23]

Researchers published in

PLOS ONE in 2009 speculated that the infamously afflicted Charles II of Spain may have suffered from renal tubular acidosis in tandem with combined pituitary hormone deficiency.[24]

See also

References

  1. ^
    PMID 15778079
    .
  2. PMID 27999512
    .
  3. S2CID 235713623.{{cite journal}}: CS1 maint: multiple names: authors list (link
    )
  4. ^ "Prevalence and incidence of rare diseases: Bibliographic data" (PDF). Orphanet. 2022-01-01.
  5. PMID 2645431
    .
  6. S2CID 19096598
    .
  7. S2CID 3291184
    .
  8. PMID 25584094
    .
  9. PMID 25823989
    .
  10. PMID 27188519
    .
  11. PMID 19721811
    .
  12. PMID 6029811
    .
  13. PMID 12138150
    .
  14. ^ de Jong PE, Koomans HA, Weening JJ (2000). Klinische Nefrologie (3rd ed.). Maarssen: Elsevier. pp. 141–2.
  15. PMID 3925334
    .
  16. PMID 15300855
    .
  17. PMID 15218065
    .
  18. S2CID 24978813
    .
  19. ^ a b Hyporeninemic Hypoaldosteronism at eMedicine
  20. PMC 1975385
    .
  21. doi:10.1016/s0022-3476(36)80111-5
    .
  22. ^ Baines AM, Barelay JA, Cooke WT (1945). "Nephrocalcinosis associated with hyperchloremia and low plasma-bicarbonate". Q J Med. 14: 113–23.
  23. PMID 1340779
    .
  24. PMID 19367331
    .

External links

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