Kidney International (1995) 48, 1542–1548; doi:10.1038/ki.1995.444
Insights into the biochemical mechanism of maleic acid-induced Fanconi syndrome
1The Combined Program in Nephrology and Renal Physiology, Departments of Physiology and Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
Correspondence: Sandra Sabatini PhD MD, Department of Physiology, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.
Received 6 October 1993; Revised 8 June 1995; Accepted 12 June 1995.
Top of page
Insights into the biochemical mechanism of maleic acid-induced Fanconi syndrome. Maleic acid administration is known to produce the Fanconi syndrome, although the biochemical mechanism is incompletely understood. In this study the effect of a single injection of maleic acid (50 mg/kg body wt, i.v.) on the rat renal ATPases was examined. Maleic acid rapidly caused bicarbonaturia, natriuresis, and kaliuresis. When nephron segments were microdissected, there was an 81 2% reduction in proximal convoluted tubule (PCT) Na-K-ATPase activity (P < 0.005) and a 48 4% reduction in PCT H-ATPase activity (P < 0.01). Enzyme activity (Na-K-ATPase, H-ATPase, H-K-ATPase) in the medullary thick ascending limb of Henle's loop and distal nephron segments was normal. In vitro, maleic acid (1 and 10 mM) inhibited Na-K-ATPase in PCT, but it had no effect on H-ATPase in PCT. Prior phosphate infusion to maleic acid-treated rats attenuated urinary bicarbonate wastage by 50% (P < 0.05); activity of proximal tubule Na-K-ATPase and H-ATPase activities were partially protected as compared to the animals given maleic acid alone (P < 0.05). Renal cortical ATP levels were not altered at the concentration of maleic acid used in this study (that is, 50 mg/kg body wt), but higher doses of maleic acid (that is, 500 and 1000 mg/kg body wt) caused ATP levels to fall. Maleic acid did not affect cortical medullary total phosphate concentration, however, P32 turnover (1 and 24 hr) was altered by prior phosphate infusion. A protective effect of prior phosphate loading on the membrane bound Pi pool (insoluble) was seen while the cytosolic Pi pool (soluble) was not different from control. Thus, maleic acid-induced "Fanconi" syndrome likely results from both direct inhibition of proximal tubule Na-K-ATPase activity and membrane-bound phosphorus depletion. The former mechanism would reduce activity of the sodium-dependent transporters (that is, Na/H antiporter), while the latter would inhibit the electrogenic proton pump (H-ATPase). The combination of reduced proximal tubule Na-H exchange and H-ATPase activities would markedly inhibit bicarbonate reabsorption and result in the metabolic acidosis universally seen in the Fanconi syndrome.
范可尼綜合徵(Fanconi syndrome)是由於近端腎小管對多種物質再吸收障礙，氨基酸、葡萄糖、磷酸鹽、碳酸氫鹽及其他物質自尿中大量丟失，導致近端腎小管酸中毒、低鉀血 症、佝僂病、骨質稀疏和生長發育遲滯等表現的一個綜合徵。本徵可因多種遺傳性或獲得性疾病引起。導致本徵的共同機制可能有二：一是腎小管膜的完整性改變致 發生泄漏而不能有效地重吸收多種溶質；二是腎小管細胞內代謝改變，不能產生足夠的能量以維持物質的轉運。這兩者有時不可截然分開，因為維持細胞間的完整性 和保持小管上皮需要細胞內的能量。
Maleic acid found in food products in Taiwan
The chemical was added to products including tapioca balls and rice noodles to give them more elasticity. A health official said maleic acid is not known to have adverse effects on human health, and has not been linked to cancer, adding that an average-sized adult could consume 30mg of maleic acid in a day without their health being affected.
Health authorities were alerted in March and April that certain food manufacturers have been adding maleic acid to their products and launched an investigation into the tip-offs.
After the seizure, concentrations of maleic acid of under 800ppm was found in the food, an amount deemed within a safe range. A doctor specializing in clinical toxicology at Chang Gung Memorial Hospital in New Taipei, said maleic acid is a poisonous industrial chemical and it is therefore unethical to add it to food, even in small amounts.
The authorities will conduct a further investigation into the manufacturers involved and decide whether to issue a fine of NT$30,000 to NT$150,000 (US$1,000-$5,000).