Proteins are not normally found in the urine of healthy individuals as the filtering units of the kidney prevent the loss of large proteins and smaller ones are typically reabsorbed. A team of researchers at the University of Sao Paulo in Brazil and Ohio State University recently searched for biomarkers indicative of early stages of kidney disease in dogs. They discovered that the urine of dogs in stages 1 or 2 of chronic kidney disease contained vitamin D-binding proteins and retinol-binding proteins. By stage 4 the presence of Tamm-Horsfall protein in the urine had declined. Vitamin D-binding protein is responsible for transporting vitamin D in the blood. Perhaps not surprisingly, therefore, some studies have found that vitamin D deficiency may be associated with the progression of chronic kidney disease. Similarly, retinol-binding protein transports retinol from the liver to the blood. Tamm-Horsfall protein, on the other hand, is a normal constituent of urine and is thought to help prevent the formation of calcium oxalate kidney stones. Thus lower levels of this protein in urine is a marker of more advanced kidney disease.