Elevation of multiple cytokines/chemokines in urine of human renal transplant recipients with acute and chronic injuries: potential usage for diagnosis and monitoring

Early diagnosis and intervention of acute dysfunction caused by both immune and nonimmune factors in the kidney transplant are crucial for the long-term well-being of the recipient. The monitoring and diagnosis of acute dysfunction and chronic allograft nephropathy in kidney transplant are currently based on clinical symptoms, serum creatinine (Cr), proteinuria, and renal biopsy. A renal biopsy can indicate infiltration of inflammatory cells, structural damage, and fibrosis in the kidney. It is currently the gold standard for the diagnosis of acute and chronic injury. Nonetheless, the biopsy tissue is only a tiny sample of the kidney and may miss focal inflammation or damages. Furthermore, the biopsy procedure is invasive and has potential complications. A sensitive noninvasive test that is able to detect acute and chronic injuries in the kidney transplant will be a very useful adjunct in clinical practice to monitor the renal graft and to help guide the performance of biopsies. We and others have observed a significant elevation of cytokines and chemokines in urine of kidney transplant recipients with acute and chronic injuries. For example, CXCR3 binding chemokines elevate in urine samples of recipients with acute dysfunction in the kidney transplant. Furthermore, the elevation of these chemokines predicts the occurrence of acute rejection earlier than the rise of serum Cr. A rapid fall of the chemokines in urine indicates response to antirejection therapy, which is more sensitive than the serum Cr. Cytokines and chemokines excreted into the urine are made by both the infiltrating inflammatory cells and the kidney cells, and therefore the elevation of these factors in urine may indicate inflammation and renal tissue injury. Based on these observations, we think that cytokines and chemokines in urine may become useful biomarkers in the clinic for monitoring the kidney graft. © 2006 Elsevier Inc. All rights reserved.

Duke Scholars

Author Stuart Johnston Knechtle Surgery, Abdominal Transplant Surgery