|Project outline

PARASOL – Detection of Renal Allograft Rejection by NMR-based Urine Metabolomics

Objective:
Quantitative evaluation of the diagnostic accuracy (AUC value, sensitivity, and specificity) of AXINON® renalTX-SCORE-U100® for the detection of acute renal allograft rejections

“A non-invasive diagnostic test for close-monitoring of kidney transplant patients and minimizing the number of potential graft-harming biopsies for earliest therapy intervention to preserve the kidney“,
Dr. Eric Schiffer, Head of Clinical Development, numares AG

Kidney transplantation is the treatment method of choice for patients with terminal kidney failure [1]. Transplant patients require frequent follow-up examinations to detect potential complications at an early stage. Therefore, biopsies are performed during aftercare. They are generally considered to be safe, but it remains an invasive procedure with a risk for complications, at worst of losing the transplant [2; 3]. A metabolite based, non-invasive test for the detection of acute rejection after transplantation would improve clinical detection of asymptomatic rejection to arrange a control biopsy or to supplement the physician’s assessment of patients with non-specific symptoms such as fever.

Study design:
PARASOL is an open-label multicenter prospective observational (non-interventional) study w/o follow-up

Partners:
Regensburg University Hospital (Prof. Dr. Bernhard Banas); Medical University Vienna (Prof. Dr. Georg Böhmig); Institute for Clinical and Experimental Medicine Prague (Prof. MUDr. Ondřej Viklický, CSc.); Centre Hospitalier Universitaire Grenoble Alpes (Prof. Dr. Lionel Rostaing); Bellvitge University Hospital Barcelona (Dr. Oriol Bestard)

Material:
Urine samples from renal allograft patients ≥14 days after transplantation

Reference standard:
Routine kidney biopsy

Approach: 
Metabolomics studies make it possible to analyze the entire metabolite spectrum (metabolome) to detect rising and falling concentrations of endogenous substances and associate them with pathological processes. Previous results from the UMBRELLA study, which was performed in collaboration with Bernhard Banas and co-workers from the Department of Nephrology at the University Hospital Regensburg, showed that it is possible to diagnose acute renal allograft rejection from urine using alanine, citrate, lactate, and urea normalized to urine creatinine. This metabolic constellation is further validated in the PARASOL study in a pan-European multicentre study. The diagnostic accuracy for the metabolic constellations will be determined based on their AUC value, sensitivity, and specificity depending on the cut-off value.

Success:
In 2017, numares launched the AXINON® renalTX-SCORE-U100®* for use in clinical routine. 

References:
1.    Suthanthiran, M. and T.B. Strom, Renal transplantation. N Engl J Med, 1994. 331(6): p. 365-76.
2.    Schwarz, A., et al., Safety and adequacy of renal transplant protocol biopsies. Am J Transplant, 2005. 5(8): p. 1992-6.
3.    Furness, P.N., et al., Protocol biopsy of the stable renal transplant: a multicenter study of methods and complication rates. Transplantation, 2003. 76(6): p. 969-73.

*numares’ products are not yet available for sale within the United States; they have not yet been approved or cleared by the U.S. Food and Drug Administration.