Melamine has very low toxicity Why does it cause kidney failure and death in children

The recent melamine-contaminated milk powder incident in Sanlu received a lot of attention and caused many infants and children to have kidney stones, hydronephrosis and eventually kidney failure. As a medical practitioner, it is necessary to clarify how melamine causes these pathological changes from a biochemical perspective. To this end, I have searched for relevant articles published in pubmed, and I hope that they will be helpful to you. 1. The toxicity of melamine is in fact very low, with studies showing an acute LD50 of >1 g/kg body weight. No nephrotoxicity was found in sheep, rabbits and rats. Moreover, there is evidence that melamine is not biotransformed and metabolized by the liver in mammals. 2. If melamine is not nephrotoxic, why can it cause kidney failure and eventually lead to death in children? 3. In fact, melamine alone cannot cause serious consequences in the body. However, if melamine is ingested together with melamine, it can have very serious consequences. Melanic acid and melamine are similar in structure, and they are often present together in the chemical production process. Therefore, if melamine is added directly to the production process of milk powder, melanic acid is in fact mixed with melamine at the same time. 4. When melamine and cyanuric acid are present at the same time, they can be connected by the formation of a hydration bond between the hydroxyl group and the amino group in the molecular structure. This connection can be made repeatedly, eventually forming a lattice structure. The most important thing is that this structure is very difficult to dissolve in water, so please remember this first. 5. When this lattice structure mixed in milk powder is ingested into the human body, melamine and melanic acid dissociate from each other due to the acidic effect of gastric juice, thus destroying this complex, and melamine and melanic acid are then absorbed into the blood separately. 6. Since the body cannot transform these two substances, eventually melamine and melanic acid are transported by the blood to the kidneys, ready to be eliminated from the body with the urine. However, right in the kidney cells, the two substances meet again, so they interact again, re-forming insoluble macromolecular complexes in a lattice structure and depositing them to form stones, resulting in physical blockage of the kidney tubules, which prevents the smooth elimination of urine and makes the kidneys waterlogged, eventually leading to kidney failure. 7. It is not quite clear why melamine and melinic acid cannot combine with each other to form complexes in the blood. A possible explanation is that only in the kidney, due to the concentration effect, the two substances can reach the critical concentration for the formation of insoluble complexes. Another explanation is that uric acid may play the role of the starting seed in the formation of the complex, as in the role of the dust core during the formation of raindrops.