Renal tubular acidosis


Renal tubular acidosis is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately the urine. In renal physiology, when blood is filtered by the kidney, the passes through the tubules of the nephron, allowing for exchange of salts, acid equivalents, and other before it drains into the bladder as urine. The metabolic acidosis that results from RTA may be caused either by failure to reabsorb sufficient bicarbonate ions from the filtrate in the early portion of the nephron or by insufficient secretion of hydrogen ions into the latter portions of the nephron. 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.
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, 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 :
TypeType 1Type 2Type 4
LocationCollecting Tubules, distal tubulesProximal tubulesAdrenal
AcidemiaYes YesMild when present
PotassiumHypokalemiaHypokalemiaHyperkalemia
PathophysiologyFailure of α intercalated cells to secrete H+ and reclaim K+Failure of proximal tubular cells to reabsorb Deficiency of aldosterone, or a resistance to its effects,

Type 1: distal

Distal RTA 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 cells of the medullary 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. Because renal excretion is the primary means of eliminating from the body, there is consequently a tendency towards acidemia. There is an inability to excrete H+ while cannot be reclaimed by the cell, leading to acidemia and hypokalemia.
This leads to the clinical features of dRTA; 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, the substance of the kidney develops stones bilaterally; this does not occur in the other RTA types.
Proximal RTA is caused by a failure of the proximal tubular cells to reabsorb filtered bicarbonate from the urine, leading to urinary bicarbonate wasting and subsequent acidemia. Reabsorption of bicarbonate is typically 80-90% in the proximal tubule and failure of this process leads to decreased systemic buffer and metabolic acidosis. The distal intercalated cells function normally, so the acidemia is less severe than dRTA and the alpha intercalated cells can produce H+ to acidify the urine to a pH of less than 5.3. pRTA also has several causes, and may occasionally be present as a solitary defect, but is usually associated with a more generalized dysfunction of the proximal tubular cells called Fanconi syndrome, in which there is also phosphaturia, glycosuria, aminoaciduria, uricosuria, and tubular proteinuria.
The principal feature of Fanconi syndrome is bone demineralization due to phosphate wasting.

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 and is no longer observed. This form of RTA has also been referred to as juvenile RTA.
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. 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.
The kidney problems are treated as described above. There is no treatment for the osteopetrosis or cerebral calcification.
Type 3 is rarely discussed. 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 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 metabolic acidosis due to a physiological reduction in proximal tubular ammonium excretion, 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.
Causes include:
  1. Drugs: NSAIDs, ACE inhibitors and 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. Baines et al. first described it in adults in 1945.
Donald L. Lewis postulated the character Tiny Tim, of A Christmas Carol, was suffering from renal tubular acidosis.
Researchers published 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.