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Previous Volume 353:2342-2351 December 1, 2005 Number 22 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Strom, T. B. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background The outcome of renal transplantation after an episode of acute rejection is difficult to predict, even with an allograft biopsy.

Methods We studied urine specimens from 36 subjects with acute rejection, 18 subjects with chronic allograft nephropathy, and 29 subjects with normal biopsy results. Levels of messenger RNA (mRNA) for FOXP3, a specification and functional factor for regulatory T lymphocytes, and mRNA for CD25, CD3, perforin, and 18S ribosomal RNA (rRNA) were measured with a kinetic, quantitative polymerase-chain-reaction assay. We examined associations of mRNA levels with acute rejection, rejection reversal, and graft failure.

Results The log-transformed mean (±SE) ratio of FOXP3 mRNA copies to 18S ribosomal RNA copies was higher in urine from the group with acute rejection (3.8±0.5) than in the group with chronic allograft nephropathy (1.3±0.7) or the group with normal biopsy results (1.6±0.4) (P<0.001 by the Kruskal–Wallis test). FOXP3 mRNA levels were inversely correlated with serum creatinine levels measured at the time of biopsy in the acute-rejection group (Spearman's correlation coefficient = –0.38, P=0.02) but not in the group with chronic allograft nephropathy or the group with normal biopsy results. Analyses of receiver-operating-characteristic curves demonstrated that reversal of acute rejection can be predicted with 90 percent sensitivity and 73 percent specificity with use of the optimal identified cutoff for FOXP3 mRNA of 3.46 (P=0.001). FOXP3 mRNA levels identified subjects at risk for graft failure within six months after the incident episode of acute rejection (relative risk for the lowest third of FOXP3 mRNA levels, 6; P=0.02). None of the other mRNA levels were predictive of reversal of acute rejection or graft failure.

Conclusions Measurement of FOXP3 mRNA in urine may offer a noninvasive means of improving the prediction of outcome of acute rejection of renal transplants.

Source Information

From the Division of Nephrology, Departments of Medicine (T.M., D.D., R.D., C.S., R.N., J.B.L., C.H., B.L., V.K.S., M.S.), Pathology (S.V.S.), and Surgery (S.K.), Weill Medical College of Cornell University; the Department of Transplantation Medicine, New York Presbyterian Hospital–Weill Cornell Medical Center (D.D., C.H., S.K., M.S.); and the Rogosin Institute (D.D., C.H., V.K.S.) — all in New York; the Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia (W.W.H.); and the Department of Psychiatry, State University of New York at Stony Brook, Stony Brook (J.E.S.).

Address reprint requests to Dr. Suthanthiran at the Division of Nephrology and Department of Transplantation Medicine, 525 E. 68th St., Box 3, New York, NY 10021, or at msuthan{at}med.cornell.edu.

Full Text of this Article

Related Letters:

Urinary FOXP3 Messenger RNA and Renal-Allograft Rejection
Kamoun M., Boyd J. C., Strehlau J., Podolskaya A., Ehrich J., Muthukumar T., Schwartz J. E., Suthanthiran M.
Extract | Full Text | PDF  
N Engl J Med 2006; 354:2291-2293, May 25, 2006. Correspondence

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