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URINE IP-10 AND MIG AS POTENTIAL INDICATORS FOR ACUTE KIDNEY INJURYFollowing urine sample collection, IP-10 and MIG levels are quantified with Renovar's immunoassay. Preliminary results in a limited trial indicated that IP-10 and MIG levels were elevated significantly in kidney transplant recipients with cell-mediated acute rejection, antibody-mediated acute rejection, acute tubular necrosis and BK viral nephritis. In contrast, urinary levels of IP-10 and MIG were minimal in patients with stable graft function, with chronic allograft nephropathy, and in healthy controls. (1)

Prior research has shown that IP-10 and MIG are produced by injured kidney tubular cells, infiltrating inflammatory cells, or both. (2-4) Renovar's preliminary research suggests that the diagnosis of acute injury by detection of elevated IP-10 and MIG levels provides sensitivity and specificity of approximately 85%. The research also shows that IP-10 and MIG levels decline several days earlier than serum creatinine, indicating that measuring these urinary chemokines may be more sensitive and predictive for monitoring anti-rejection therapy. (1) Independent research confirms that elevated IP-10 and MIG levels may also be used for predicting the occurrence of acute rejection. Detection of these elevated levels may enable earlier clinical intervention, which may decrease the likelihood of severe damage to the transplanted kidney. (2,5,6)

Renovar is in the process of establishing the clinical utility of and seeking FDA clearance for a Renokine I human urinary chemokine assay.
For Research Use Only. Not For Use in Diagnostic Procedures.
- Hu HZ, Aizenstein BD, Puchalski A, Burmania JA, Hamawy MM, Knechtle SJ. "Elevation of CXCR3-binding chemokines in urine indicates acute renal-allograft dysfunction." American Journal of Transplantation 2004 4:432-7.
- Kanmaz T, Feng P, Torrealba J, Kwan J, Fechner JH, Schultz JM, Dong Y, Kim HT, Dar W, Hamawy MM, Knechtle SJ, Hu HZ. "Surveillance of acute rejection in baboon renal transplantation by elevation of interferon-gamma inducible protein-10 and monokine induced by interferon-gamma in urine. Transplantation 2004 78:1002-7.
- Tatapudi RR, Muthukumar T, Dadhania D, Ding R, Li B, Sharma VK, Lozada-Pastorio E, Seetharamu N, Hartono C, Serur D, Seshan SV, Kapur S, Hancock WW, Suthanthiran M. "Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine" Kidney International 2004; 65:2390-7.
- Panzer U, Reinking RR, Steinmetz OM, Zahner G, Sudbeck U, Fehr S, Pfalzer B, Schneider A, Thaiss F, Mack M, Conrad S, Huland H, Helmchen U, Stahl RA. "CXCR3 and CCR5 positive T-cell recruitment in acute human renal allograft rejection." Transplantation 2004 78:1341-50.
- Hauser IA, Spiegler S, Kiss E, Gauer S, Sichler O, Scheuermann EH, Ackermann H, Pfeilschifter JM, Geiger H, Grone HJ, Radeke HH. "Prediction of acute renal allograft rejection by urinary monokine induced by IFN-gamma (MIG)." Journal of American Society of Nephrology. 2005 16:1849-58.
- Matz M, Beyer J, Wunsch D, Mashreghi MF, Seiler M, Pratschke J, Babel N, Volk HD, Reinke P, Kotsch K. "Early post-transplant urinary IP-10 expression after kidney transplantation is predictive of short- and long-term graft function." Kidney International 2006 69:1683-90.
- Avihingsanon Y, Phumesin P, Benjachat T, Akkasilpa S, Kittikowit V, Praditpornsilpa K, Wongpiyabavorn J, Eiam-Ong S, Hemachudha T, Tungsanga K, Hirankarn N. "Measurement of urinary chemokine and growth factor messenger RNAs: a noninvasive monitoring in lupus nephritis." Kidney International 2006 69:747-53.
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