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Urinary-cell mRNA profile and acute cellular rejection in kidney allografts.

Publication ,  Journal Article
Suthanthiran, M; Schwartz, JE; Ding, R; Abecassis, M; Dadhania, D; Samstein, B; Knechtle, SJ; Friedewald, J; Becker, YT; Sharma, VK; Chang, CS ...
Published in: N Engl J Med
July 4, 2013

BACKGROUND: The standard test for the diagnosis of acute rejection in kidney transplants is the renal biopsy. Noninvasive tests would be preferable. METHODS: We prospectively collected 4300 urine specimens from 485 kidney-graft recipients from day 3 through month 12 after transplantation. Messenger RNA (mRNA) levels were measured in urinary cells and correlated with allograft-rejection status with the use of logistic regression. RESULTS: A three-gene signature of 18S ribosomal (rRNA)-normalized measures of CD3ε mRNA and interferon-inducible protein 10 (IP-10) mRNA, and 18S rRNA discriminated between biopsy specimens showing acute cellular rejection and those not showing rejection (area under the curve [AUC], 0.85; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 by receiver-operating-characteristic curve analysis). The cross-validation estimate of the AUC was 0.83 by bootstrap resampling, and the Hosmer-Lemeshow test indicated good fit (P=0.77). In an external-validation data set, the AUC was 0.74 (95% CI, 0.61 to 0.86; P<0.001) and did not differ significantly from the AUC in our primary data set (P=0.13). The signature distinguished acute cellular rejection from acute antibody-mediated rejection and borderline rejection (AUC, 0.78; 95% CI, 0.68 to 0.89; P<0.001). It also distinguished patients who received anti-interleukin-2 receptor antibodies from those who received T-cell-depleting antibodies (P<0.001) and was diagnostic of acute cellular rejection in both groups. Urinary tract infection did not affect the signature (P=0.69). The average trajectory of the signature in repeated urine samples remained below the diagnostic threshold for acute cellular rejection in the group of patients with no rejection, but in the group with rejection, there was a sharp rise during the weeks before the biopsy showing rejection (P<0.001). CONCLUSIONS: A molecular signature of CD3ε mRNA, IP-10 mRNA, and 18S rRNA levels in urinary cells appears to be diagnostic and prognostic of acute cellular rejection in kidney allografts. (Funded by the National Institutes of Health and others.).

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Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

July 4, 2013

Volume

369

Issue

1

Start / End Page

20 / 31

Location

United States

Related Subject Headings

  • Transcriptome
  • Sensitivity and Specificity
  • Real-Time Polymerase Chain Reaction
  • ROC Curve
  • RNA, Ribosomal, 18S
  • RNA, Ribosomal
  • RNA, Messenger
  • RNA Polymerase I
  • Prospective Studies
  • Middle Aged
 

Citation

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Suthanthiran, M., Schwartz, J. E., Ding, R., Abecassis, M., Dadhania, D., Samstein, B., … Clinical Trials in Organ Transplantation 04 (CTOT-04) Study Investigators. (2013). Urinary-cell mRNA profile and acute cellular rejection in kidney allografts. N Engl J Med, 369(1), 20–31. https://doi.org/10.1056/NEJMoa1215555
Suthanthiran, Manikkam, Joseph E. Schwartz, Ruchuang Ding, Michael Abecassis, Darshana Dadhania, Benjamin Samstein, Stuart J. Knechtle, et al. “Urinary-cell mRNA profile and acute cellular rejection in kidney allografts.N Engl J Med 369, no. 1 (July 4, 2013): 20–31. https://doi.org/10.1056/NEJMoa1215555.
Suthanthiran M, Schwartz JE, Ding R, Abecassis M, Dadhania D, Samstein B, et al. Urinary-cell mRNA profile and acute cellular rejection in kidney allografts. N Engl J Med. 2013 Jul 4;369(1):20–31.
Suthanthiran, Manikkam, et al. “Urinary-cell mRNA profile and acute cellular rejection in kidney allografts.N Engl J Med, vol. 369, no. 1, July 2013, pp. 20–31. Pubmed, doi:10.1056/NEJMoa1215555.
Suthanthiran M, Schwartz JE, Ding R, Abecassis M, Dadhania D, Samstein B, Knechtle SJ, Friedewald J, Becker YT, Sharma VK, Williams NM, Chang CS, Hoang C, Muthukumar T, August P, Keslar KS, Fairchild RL, Hricik DE, Heeger PS, Han L, Liu J, Riggs M, Ikle DN, Bridges ND, Shaked A, Clinical Trials in Organ Transplantation 04 (CTOT-04) Study Investigators. Urinary-cell mRNA profile and acute cellular rejection in kidney allografts. N Engl J Med. 2013 Jul 4;369(1):20–31.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

July 4, 2013

Volume

369

Issue

1

Start / End Page

20 / 31

Location

United States

Related Subject Headings

  • Transcriptome
  • Sensitivity and Specificity
  • Real-Time Polymerase Chain Reaction
  • ROC Curve
  • RNA, Ribosomal, 18S
  • RNA, Ribosomal
  • RNA, Messenger
  • RNA Polymerase I
  • Prospective Studies
  • Middle Aged