Mechanism underlying hypokalemia induced by trimethyltin chloride: Inhibition of H+/K+-ATPase in renal intercalated cells

Does a Proton Pump Inhibitor Cause Hypokalemia?

“…In case 2, urinary pH stayed around 7 even in reduced serum bicarbonate levels due to the pre-exsting impairment of renal function, which may suggest a disturbance in H + -secretion by suppressed HKα1 activity, as reported previously (6). Metabolic acidosis also enhances the expression of HKα1 (1) and PPI-affinity to HKα1 (2).…”

“…Whereas, we recently encountered two cases of hypokalemia associated with administration of omeprazole in their clinical courses, not accompanied by hypomagnesemia. These cases showed hypokalemia and relatively higher levels of urinary pH ( 6.0) that were similar to the previous case report that showed trimethyltin chloride inhibited renal H + ,K + -ATPase activity to induce hypokalemic renal tubular acidosis (6), as predicted by Kurtzman in his review (7). The two cases reported here presented with some differences in their clinical parameters other than serum potassium, which may reflect heterogeneity in developing hypokalemia associated with the use of omeprazole.…”

Chronic low level trimethyltin exposure and the risk of developing nephrolithiasis

“…From 1994 to 2008, there were at least 20 published reports of acute occupational accidents involving methyltin exposures in this region12 13 (figure 1). We identified two plants located in the city of Qingyuan, Guangdong, which use methyltins as the heat stabiliser for PVC production to manufacture plastic window blinds.…”

“…We previously reported that over 80% of the poisoning cases involving acute occupational TMT exposures developed hypokalaemia before showing more deleterious neurobehavioural symptoms, and that treatment of hypokalaemia can delay and significantly improve the neurobehavioural symptoms 12. We subsequently showed that hypokalaemia was likely due to the direct inhibition of H + /K + -ATPase by TMT in renal intercalated cells 13. The inhibition of renal H + /K + -ATPase by TMT can disrupt the regulation of urinary pH and alter electrolyte concentrations and deposition in the kidney and urinary tract, which are known risk factors for crystal deposition and kidney stones formation 23…”

“…Methyltin-stabilised PVC has extensive applications including packaging materials, foils, piping of potable water, waste and drainage water, window frames and coating materials. With increasing use of methyltin stabilisers in PVC production in developing countries, such as in China, a dramatic increase in occupational poisoning accidents has occurred due to acute exposures to methyltin compounds 12 13. Moreover, leaching of methyltin ingredients from PVC and related materials can contaminate foodstuffs, beverages, drinking water, municipal water and sewage sludge 9.…”