oxalates and melamine

Drug and xenobiotic toxicity is an important cause of kidney injury, especially in vulnerable patients. Nephrotoxic syndromes include functional disorders; vascular injury, such as thrombotic microangiopathy; glomerular injury resulting in nephrotic syndrome or glomerulonephritis; acute tubular necrosis; acute interstitial nephritis; and crystalopathy/nephrolithiasis. Recently reported nephrotoxins are reviewed in the context of these syndromes of kidney injury.

Topics: Adenine; Alcohols; Angiogenesis Inhibitors; Anticonvulsants; Antipsychotic Agents; Dasatinib; Diphosphonates; Glutamates; Guanine; HIV Protease Inhibitors; Humans; Indoles; Kidney Diseases; Organophosphonates; Oxalates; Pamidronate; Pemetrexed; Phenindione; Plants, Toxic; Proton Pump Inhibitors; Pyrimidines; Pyrroles; Selective Serotonin Reuptake Inhibitors; Sunitinib; Tenofovir; Thiazoles; Triazines

Exposure to melamine, which is ubiquitous in daily life, is linked to adverse kidney outcomes. The melamine tolerable daily intake in humans is based on the no-observed-effect-level (NOEL) established in a single-toxicant murine model. However, humans are often simultaneously exposed to multiple environmental nephrotoxicants. The NOEL of melamine during coexposure with other toxicants needs to be evaluated. Oxalate is a potentially nephrotoxic terminal metabolite, and hyperoxaluria is reportedly associated with chronic kidney disease. We explored whether these two potential nephrotoxicants can interact and enhance kidney injury. We established a Sprague-Dawley rat model of coexposure to the melamine NOEL (63 mg/kg/day) and 2% hydroxy-L-proline (HLP, an oxalate precursor) in drinking water to simulate human environmental melamine exposure. Melamine/oxalate coexposure increased proximal tubular cell mitochondrial reactive oxygen species levels, lipid peroxidation and oxidative DNA damage. The degrees of mitochondrial damage, tubular cell apoptosis, tubular atrophy, and interstitial fibrosis were elevated in coexposed rat kidneys. The evidence indicated that exposure to the melamine NOEL can cause renal tubular injury via oxidative stress and that this effect may be enhanced via interaction of melamine with other environmental factors, such as oxalate. Thus, melamine risk assessment and toxicity prevention should be conducted carefully in different susceptible populations.

Topics: Animals; Kidney; Mice; Oxalates; Oxidative Stress; Rats; Rats, Sprague-Dawley; Triazines

Several animal species are used to study calcium oxalate urolithiasis; however, an ideal model has yet to be identified. We used Drosophila as a model organism and fed the flies lithogenic agents such as ethylene glycol, hydroxyl-L-proline, and sodium oxalate. At different times, the Malpighian tubules, the kidney equivalent of insects, were dissected and a polarized light microscope used to highlight the birefringent crystals. Scanning electron microscopy and energy-dispersive X-ray spectroscopy confirmed that the crystal composition was predominately calcium oxalate. Furthermore, administration of potassium citrate successfully reduced the quantity of and modulated the integrity of the ethylene glycol-induced crystals. Thus, the Drosophila model of bio-mineralization produces crystals in the urinary system through many lithogenic agents, permits observation of crystal formation, and is amenable to genetic manipulation. This model may mimic the etiology and clinical manifestations of calcium oxalate stone formation and aid in identification of the genetic basis of this disease.

Topics: Aging; Animals; Calcium Oxalate; Crystallization; Disease Models, Animal; Drosophila melanogaster; Ethylene Glycol; Female; Hydroxyproline; Longevity; Male; Malpighian Tubules; Microscopy, Electron, Scanning; Microscopy, Polarization; Nephrolithiasis; Oxalates; Potassium Citrate; Spectrometry, X-Ray Emission; Triazines; Urolithiasis