Proximal renal tubular acidosis: a not so rare disorder of multiple etiologies

Abstract

Proximal renal tubular acidosis (RTA) (Type II RTA) is characterized by a defect in the ability to reabsorb HCO3 in the proximal tubule. This is usually manifested as bicarbonate wastage in the urine reflecting that the defect in proximal tubular transport is severe enough that the capacity for bicarbonate reabsorption in the thick ascending limb of Henle's loop and more distal nephron segments is overwhelmed. More subtle defects in proximal bicarbonate transport likely go clinically unrecognized owing to compensatory reabsorption of bicarbonate distally. Inherited proximal RTA is more commonly autosomal recessive and has been associated with mutations in the basolateral sodium-bicarbonate cotransporter (NBCe1). Mutations in this transporter lead to reduced activity and/or trafficking, thus disrupting the normal bicarbonate reabsorption process of the proximal tubules. As an isolated defect for bicarbonate transport, proximal RTA is rare and is more often associated with the Fanconi syndrome characterized by urinary wastage of solutes like phosphate, uric acid, glucose, amino acids, low-molecular-weight proteins as well as bicarbonate. A vast array of rare tubular disorders may cause proximal RTA but most commonly it is induced by drugs. With the exception of carbonic anhydrase inhibitors which cause isolated proximal RTA, drug-induced proximal RTA is associated with Fanconi syndrome. Drugs that have been recently recognized to cause severe proximal RTA with Fanconi syndrome include ifosfamide, valproic acid and various antiretrovirals such as Tenofovir particularly when given to human immunodeficiency virus patients receiving concomitantly protease inhibitors such as ritonavir or reverse transcriptase inhibitors such as didanosine.

Drug-induced acid-base disorders

“…This disturbance is characterized by a decrease in the threshold value for HCO 3 − reabsorption [90,110]. A more frequent ABD in patients receiving ifosfamide is RFS [111,112], a disorder of the proximal tubule cell associated with RTA in combination with glycosuria, aminoaciduria, phosphaturia, and normal AG [113]. Proximal RTA in the context of RFS is not rare in patients treated with ifosfamide (4.6 % of patients).…”

The Potential Effect of Using the Cockcroft-Gault Method on Tenofovir-Associated Renal Impairment Reports and on Clinical Decisions Regarding Tenofovir Use in Individual Patients: Implications for the Future

“…The use of the urine dipstick in this regard is based on the fact that the normal nephron would reabsorb all the filtered glucose except in hyperglycaemic patients, who at the detection of glycosuria have plasma glucose levels above the normal threshold for glucose reabsorption: 180 mg/dl [26]. Consequently, the cART guidelines rest on the understanding of the pathophysiology of TDFassociated proximal tubulopathy, during which the reabsorption of glucose is likely interrupted resulting in glycosuria in euglycaemic patients [13,27]. The addition of the urine dipstick is promising to partly or fully negate the possible mis-categorisation of renal impairment by the C-G method in patients receiving TDF-containing cART.…”

Hypophosphatemia in patients with chronic HBV

“…Ne possono conseguire acidosi metabolica, ipouricemia, aminoaciduria, glicosuria (con glicemia nella norma) e ipofosfatemia. Può riconoscere sia cause ereditarie che acquisite; tra le ereditarie ricordiamo una forma primaria causata da una mutazione missense del cotrasportatore NaPi-II e una forma secondaria in cui sono incluse la cistinosi, la galattosemia, la tirosinemia, la sindrome di Lowe, la sindrome di Alport, la malattia di Wilson e i disordini mitocondriali [22]. Tra le forme acquisite ci sono quelle causate da amiloidosi, mieloma multiplo, emoglobinuria parossistica notturna, trapianto renale, metalli pesanti e farmaci.…”

“…Infine può essere raramente associata ad alcuni antibiotici (tetracicline e aminoglicosidi), ad acido valproico e acido fumarico [23]. Nel box sono riportate le caratteristiche cliniche e laboratoristiche della sindrome di Fanconi [22,23].…”