Crystalluria and Chronic Kidney Disease.

Crystalluria can involve the kidney and lower urinary tract, can produce acute and chronic effects, and occurs in all mammalian species. Most commonly urinary crystals contain calcium. Numerous other endogenous and exogenous substances can produce crystalluria. Crystals are identified in kidneys of many species, up to 100% in certain rat strains. More severe renal disease (acute tubular necrosis and chronic renal disease) can be secondary to crystal accumulation, such as observed with melamine-cyanuric acid in cats and dogs. Aggregation of crystals leads to calculi that act as urothelial abrasives with consequent regenerative proliferation. Accumulation in the kidney pelvis or bladder can lead to partial or complete obstruction and hydronephrosis. Long-term presence of urinary tract calculi in rodents leads to increased risk of urothelial tumors, but not in humans. Crystals in the lower urinary tract can act as irritants in rodents, but not in humans. It is critical that specific procedures are followed to optimize the presence of crystals in urine for diagnosis, including not fasting the animals. Numerous factors have been identified which can enhance or inhibit crystal formation. Extrapolation from animals for the threshold toxicity of crystals/calculi is appropriate but is not relevant for cancer risk assessment.