Clinical trial NCT00337220: Urine Testing to Detect Kidney Transplant Rejection
Official title: Noninvasive Diagnosis of Renal Allograft Rejection by Urinary Cell mRNA Profiling
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Kidney Transplantation
Kidney Disease
Kidney Failure, Chronic
Keywords: allograft
graft
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2006-06-15
Enrollment: 492
Sex: ALL
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who have recently undergone kidney transplant

Brief summary: The purpose of this study is to determine if analysis of urine samples for specific markers can predict transplant rejection in people who have received kidney transplants.

Detailed description: Innovations in kidney transplantation have improved short-term outcomes for transplant patients. However, organ rejection remains as an important threat to the long-term survival of the transplanted organ. An increase in the serum creatinine level is often the first clinical indicator of kidney transplant rejection; however, this marker lacks sensitivity and specificity. Rejection is currently diagnosed using an invasive transplant biopsy procedure; in addition to being expensive, transplant biopsies can result in bleeding from the transplant and even graft loss. In early studies, it has been observed that significant increases in the levels of perforin, granzyme B, and CD3 messenger RNA (mRNA) in urinary cells signal the development of acute transplant rejection. The purpose of this study is to evaluate whether the noninvasive procedure of measuring perforin, granzyme B, and CD3 mRNA levels in urine samples can accurately diagnose and predict kidney transplant rejection, make transplant biopsy unnecessary, and provide an opportunity to initiate treatment for early rejection with the aim to minimize damage to the kidney.

This study will last 3 years post-transplant. There will be a total of 14 study visits. Blood and urine collection will occur at all visits. Additional visits may be necessary for those participants who develop abnormal kidney function.

Eligibility criteria: Inclusion Criteria:

* Scheduled to undergo primary or redo deceased- or living-donor kidney transplantation
* Ability to provide informed consent

Exclusion Criteria:

* Requires combined organ transplantation
* Previously received a solid organ transplant (other than kidney transplant) or islet cell transplant
* HCV infected
* HIV infected

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: New York
country: United States
facility: Cornell University
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Department of Surgery, University of Pennsylvania Medical Center
name: Abraham Shaked, MD, PhD
role: STUDY_CHAIR
affiliation: Northwestern University
name: John Friedewald, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Surgery, University of Wisconsin
name: Stuart Knechtle, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Surgery, Columbia University
name: Jean Emond, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cornell University
name: Darshana Dadhania, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dadhania D, Muthukumar T, Ding R, Li B, Hartono C, Serur D, Seshan SV, Sharma VK, Kapur S, Suthanthiran M. Molecular signatures of urinary cells distinguish acute rejection of renal allografts from urinary tract infection. Transplantation. 2003 May 27;75(10):1752-4. doi: 10.1097/01.TP.0000063931.08861.56.
citation: Ding R, Li B, Muthukumar T, Dadhania D, Medeiros M, Hartono C, Serur D, Seshan SV, Sharma VK, Kapur S, Suthanthiran M. CD103 mRNA levels in urinary cells predict acute rejection of renal allografts. Transplantation. 2003 Apr 27;75(8):1307-12. doi: 10.1097/01.TP.0000064210.92444.B5.
citation: Li B, Hartono C, Ding R, Sharma VK, Ramaswamy R, Qian B, Serur D, Mouradian J, Schwartz JE, Suthanthiran M. Noninvasive diagnosis of renal-allograft rejection by measurement of messenger RNA for perforin and granzyme B in urine. N Engl J Med. 2001 Mar 29;344(13):947-54. doi: 10.1056/NEJM200103293441301.
citation: Tatapudi RR, Muthukumar T, Dadhania D, Ding R, Li B, Sharma VK, Lozada-Pastorio E, Seetharamu N, Hartono C, Serur D, Seshan SV, Kapur S, Hancock WW, Suthanthiran M. Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine. Kidney Int. 2004 Jun;65(6):2390-7. doi: 10.1111/j.1523-1755.2004.00663.x.
citation: 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. doi: 10.1056/NEJMoa1215555.