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Volume 344:947-954 March 29, 2001 Number 13 Next

	Full Text PDF Editorial by Soulillou, J.-P. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Acute rejection is a serious and frequent complication of renal transplantation, and its diagnosis is contingent on the invasive procedure of allograft biopsy. A noninvasive diagnostic test for rejection could improve the outcome of transplantation.

Methods We obtained 24 urine specimens from 22 renal-allograft recipients with a biopsy-confirmed episode of acute rejection and 127 samples from 63 recipients without evidence of acute rejection. RNA was isolated from the urinary cells. Messenger RNA (mRNA) encoding the cytotoxic proteins perforin and granzyme B and a constitutively expressed cyclophilin B gene were measured with the use of a competitive, quantitative polymerase-chain-reaction assay, and the level of expression was correlated with allograft status.

Results The log-transformed mean (±SE) levels of perforin mRNA and granzyme B mRNA, which encode cytotoxic proteins, but not the levels of constitutively expressed cyclophilin B mRNA, were higher in the urinary cells from the 22 patients with a biopsy-confirmed episode of acute rejection than in the 63 recipients without an episode of acute rejection (perforin, 1.4±0.3 vs. –0.6±0.2 fg per microgram of total RNA; P<0.001; and granzyme B, 1.2±0.3 vs. –0.9±0.2 fg per microgram of total RNA; P<0.001). Analysis involving the receiver-operating-characteristic curve demonstrated that acute rejection can be predicted with a sensitivity of 83 percent and a specificity of 83 percent with the use of a cutoff value of 0.9 fg of perforin mRNA per microgram of total RNA, and with a sensitivity of 79 percent and a specificity of 77 percent with the use of a cutoff value of 0.4 fg of granzyme B mRNA per microgram of total RNA. Sequential urine samples were obtained from 37 patients during the first nine days after transplantation, and measurements of the levels of mRNA that encoded cytotoxic proteins identified those in whom acute rejection developed.

Conclusions Measurement of mRNA encoding cytotoxic proteins in urinary cells offers a noninvasive means of diagnosing acute rejection of renal allografts.

Source Information

From the Division of Nephrology, Department of Medicine (B.L., C.H., R.D., V.K.S., R.R., B.Q., D.S., M.S.), and the Department of Pathology (J.M.), Weill Medical College of Cornell University, New York; the Department of Transplantation Medicine, New York–Presbyterian Hospital, New York (C.H., D.S., M.S.); 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.

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