Epidemiology

All forms of RTA are uncommon but the disease is under-reported and incomplete forms are not often recognized, which limits precision regarding incidence and prevalence. A retrospective analysis of healthcare data in the UK extrapolated the prevalence of distal RTA in Europe to be between 0.46/10,000 using recorded cases and 1.60/10,000 when including suspected cases.[13] Inherited disorders are much rarer than acquired forms.[14][15] The prevalence of hereditary distal RTA is unclear, although it is certainly rare with around 350 individuals reported in the literature.[5] The autosomal recessive inherited disorders cystinosis and galactosemia are seen in approximately 1 to 2:100,000 children and 1:60,000 births, respectively, with selected populations having a higher incidence rate.[16][17]

Patients with chronic kidney disease are also at risk of developing RTA because of progressive nephron loss.[3] In the initial stages of declining kidney function, there is an adaptive increase in ammonium production and acid secretion. However, as renal function declines to a glomerular filtration rate of <30 mL/min/1.73 m², this adaptive increase in ammonium production fails to keep up with endogenous acid production. This results in a hyperchloremic normal anion gap acidosis referred to as the RTA of kidney insufficiency.[18] The most common form of RTA found in patients with chronic kidney disease is probably hyperkalemic distal RTA in urinary tract obstruction, but hyperkalemic distal RTA secondary to aldosterone deficiency in diabetes may be nearly as common.[19][20] Small studies have placed the occurrence of RTA after renal transplant at over 20%.[21][22]

Fanconi syndrome is exceedingly rare as a primary disease, and the metabolic diseases in which it develops (e.g., Lowe syndrome, Wilson disease, Dent disease, cystinosis, galactosemia, hereditary fructose intolerance, von Gierke disease) are also rare.[7][23] Lead exposure and cadmium exposure vary significantly with location, residence, and occupation (as well as with social status in the case of lead).

Drug-induced RTA and Fanconi syndrome are rising in incidence. Increasing use of over-the-counter nonsteroidal anti-inflammatory medications has resulted in life-threatening hypokalemia, due to mixed RTA.[24][25] Use of carbonic anhydrase inhibitors, to reduce intraocular pressure in glaucoma or for the treatment of mountain sickness, has become more prevalent, and they have the potential to cause isolated proximal RTA.[2] Up to 5% of patients treated with the chemotherapy agent ifosfamide may develop Fanconi syndrome.[2] The worldwide use of combination antiviral therapy for HIV infection may be anticipated to produce a significant number of cases of drug-related proximal tubule dysfunction and RTA. The incidence of Fanconi syndrome in patients taking tenofovir is around 1 in every 1000 patients per year and this increases fivefold when tenofovir is co-administered with ritonavir.[26] Similar antiviral agents are also used for treatment of hepatitis B and C.

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