On the Mechanism of Toluene-Induced Renal Tubular Acidosis

Abstract

This study was aimed to investigate the pathogenesis of toluene-induced renal tubular acidosis (RTA). In 5 individuals addicted to toluene sniffing we documented the occurrence of hypokalemia and hyperchloremic metabolic acidosis associated with inability to lower urine pH below 5.5 (6.06 ± 0.24). Overall kidney bicarbonate reabsorption was normal or enhanced, a feature characteristic of the distal form of RTA (DRTA). These findings resemble those found during the administration of amphotericin B, a drug felt to cause DRTA by increasing hydrogen ion (H⁺) back-diffusion in the collecting tubule. In toluene sniffers, the urine pCO₂ measured in a highly alkaline urine was reduced (47 ± 8.8 mm Hg), suggesting a decrease in the rate of collecting tubule H⁺ secretion rather than H⁺ back-diffusion. To investigate these two mechanisms of altered distal acidification more directly we studied the effect of toluene on acidification by the urinary turtle bladder, an epithelial analogue of the mammalian collecting tubule. In this preparation, toluene resulted in a decrease in the rate of H⁺ secretion measured by either the pH stat technique or the reverse short circuit current. When mucosal pH was progressively lowered to examine H⁺ secretion against an H⁺ gradient, toluene-treated bladders displayed a significant decrease in proton conductance but the lowest mucosal pH required to nullify H⁺ secretion, (MpH) JH = O, was not different from that of control bladders (4.05 ± 0.29 and 3.90 ± 0.13, respectively). In contrast, in amphotericin B-treated bladders (MpH) JH =·was 5.15 ± 0.39, a value more than 1 pH unit higher than that of control and toluene-treated bladders (p < 0.05). Thus, amphotericin B, but not toluene, reduced the pH gradient that could be generated across the turtle bladder. These findings suggest that toluene, unlike amphotericin B, does not cause H⁺ back-diffusion. Decreased conductance of protons through the active transport pathway is the mechanism that best explains the toluene-induced defect in distal acidification.

Clinical presentation and management in acute toluene intoxication: a case series

“…The mechanism involved is an inability of the distal tubule to excrete hydrogen ions as ammonium. This defect in distal acidification could be mediated by decreased proton conductance through the active conduction pathway (Batlle et al, 1988). However, other authors have suggested that overproduction of hippuric acid by toluene metabolism also contributes to acidosis in toluene poisoning (Carlisle et al, 1991), and could explain the finding of high anion gaps in the other 12 patients in this series.…”

Decreased Renal Expression of H⁺-ATPase and Pendrin in a Patient with Distal Renal Tubular Acidosis Associated with Sj&ouml;gren's Syndrome

“…It can be speculated that decreased immunoreactivity of pendrin in the collecting duct plays a compensatory role, acting to decrease the secretion of HCO3 -and prevent the development of acidosis, but the change is not able to fully compensate for the acidosis (thus, H + -ATPase might play a key role). Patients with secondary distal RTA require a diagnostic work-up to determine the etiology, which can include such drugs as ifosfamide, amphotericin B, or lithium, hypercalciuric conditions, medullary sponge kidney, nephrocalcinosis, obstructive uropathy and autoimmune diseases, including Sjögren's syndrome (2,(9)(10)(11). Distal RTA occurs in up to 25% of patients with Sjögren's syndrome (12).…”

Histopathological Changes of Rat Kidney with Exposure to Chronic Thinner Inhalation

“…There are studies reporting hepatic, renal, cardiovascular, and hemopoietic system damages in thinner addicts. 1,6,14,15 In a study conducted in 2000, two types of rats were exposed to inhalation of 2-butoxyethanol chemical which is also present in thinner, for defined periods every day for 14 weeks and 2 years, respectively. At the end of the period in the kidneys of the sacrificed subjects, renal tubular degeneration and increase in hemosiderin pigmentation were detected.…”

“…In some of them, besides renal tubular acidosis, aminoaciduria, hypophosphoremia, and hypocalcemia had developed. 15 In a case report by Erramouspe et al, it was established that the infant of a mother who has smelled dye thinner containing toluene during her pregnancy was born with renal tubular acidosis. 16 The reason for renal toxicity due to smelling of adhesives seems to be toluene.…”