Early Detection Of Renal Injury

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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 rats 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. This paper was accepted by Kidney International. 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 filed a provisional patent, and submitted the work for publication. 2) Is inflammation involved in ARF? We can detect renal inflammation using MRI with ultra-small iron oxide particles (USPIO). This work has been submitted for publication. 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; Provisional patent submitted; MS accepted to Kidney International) is upregulated in kidney tissue within 1 hour of injury, and detectable in urine within 3-6 hours of injry. We have begun to test it on human samples (some we have collected, some from 2-3 collaborating groups outside NIH), and in preliminary studies, find it is goes up after injury. 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.