Get access

Urinary cell mRNA profiles predictive of human kidney allograft status

Authors

  • John R. Lee,

    1. Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, USA
    2. Department of Transplantation Medicine, New York Presbyterian Hospital – Weill Cornell Medical Center, New York, NY, USA
    Search for more papers by this author
  • Thangamani Muthukumar,

    1. Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, USA
    2. Department of Transplantation Medicine, New York Presbyterian Hospital – Weill Cornell Medical Center, New York, NY, USA
    Search for more papers by this author
  • Darshana Dadhania,

    1. Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, USA
    2. Department of Transplantation Medicine, New York Presbyterian Hospital – Weill Cornell Medical Center, New York, NY, USA
    Search for more papers by this author
  • Ruchuang Ding,

    1. Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, USA
    2. Department of Transplantation Medicine, New York Presbyterian Hospital – Weill Cornell Medical Center, New York, NY, USA
    Search for more papers by this author
  • Vijay K. Sharma,

    1. Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, USA
    Search for more papers by this author
  • Joseph E. Schwartz,

    1. Department of Psychiatry and Behavioral Science, Stony Brook School of Medicine, Stony Brook, NY, USA
    Search for more papers by this author
  • Manikkam Suthanthiran

    Corresponding author
    1. Division of Nephrology and Hypertension, Department of Medicine, Weill Cornell Medical College, New York, NY, USA
    2. Department of Transplantation Medicine, New York Presbyterian Hospital – Weill Cornell Medical Center, New York, NY, USA
    • Correspondence to:

      Manikkam Suthanthiran

      Division of Nephrology and Hypertension

      Department of Medicine

      525 East 68th Street, Box 3

      New York, NY 10065, USA

      Tel.: +1 212 746 4430

      Fax: +1 212 746 6894

      e-mail: msuthan@med.cornell.edu

    Search for more papers by this author

Summary

Kidney allograft status is currently characterized using the invasive percutaneous needle core biopsy procedure. The procedure has become safer over the years, but challenges and complications still exist including sampling error, interobserver variability, bleeding, arteriovenous fistula, graft loss, and even death. Because the most common type of acute rejection is distinguished by inflammatory cells exiting the intravascular compartment and gaining access to the renal tubular space, we reasoned that a kidney allograft may function as an in vivo flow cytometer and sort cells involved in rejection into urine. To test this idea, we developed quantitative polymerase chain reaction (PCR) assays for absolute quantification of mRNA and pre-amplification protocols to overcome the low RNA yield from urine. Here, we review our single center urinary cell mRNA profiling studies that led to the multicenter Clinical Trials in Organ Transplantation (CTOT-04) study and the discovery and validation of a 3-gene signature of 18S rRNA-normalized measures of CD3ε mRNA and IP-10 mRNA and 18S rRNA that is diagnostic and predictive of acute cellular rejection in the kidney allograft. We also review our development of a 4-gene signature of mRNAs for vimentin, NKCC2, E-cadherin, and 18S rRNA diagnostic of interstitial fibrosis/tubular atrophy (IF/TA).

Ancillary