Renal disease is difficult to detect, particularly in a form called acute renal failure. We are developing new methods to detect renal disease involving either MRI, or urine or blood tests. 1)Detection of proximal tubule damage in mice MRI using dendrimer gadolinium chelates. We found that a G4 dendemer accumulates in the proximal tubule, and can be used to detect renal structure, function, and injury. Because this dendrimer remains in the kidney too long, we have made a library of similar compounds. One of these (PADAM G3) has excellent imaging properites, but rapidly leaves the kidney. We have now used these methods to detect small renal cysts, and decreased cortical thickness seen in chronic renal disease. 2) Is inflammation involved in ARF? We can detect renal inflammation using MRI with ultra-small iron oxide particles (USPIO). Unfortunately, this method is not as sensitive as we would like. 3) Markers for early diagnosis We have seached for new genes that are up-regulated following injury in humans and animals. One of the markers (cyr61) is upregulated in kidney tissue within 1 hour of injury, and detectable in urine within 3-6 hours of injry. We have sent detailed methods and antibodies to several groups who are searcing for this in human samples. 4) We found another protein that is elevated in kidney tissue and serum as early as 5-30 min after renal injury. This protein was first found because it was a 'non-specific' band from a poly-clonal antibody we generated against something else. We are currently trying to purify and chacterize the protein.
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