Molecular Marker Strategies Supporting the Novartis US92 Study- A Discovery Study of Protein Biomarkers for Kidney Function (eGFR) and Acute Rejection in Serum from Renal Transplant Patients

U. Christians,¹ J. Klepacki,¹ A. Karimpour-fard,¹ G. Ingle,² D. Patel,² K. Johnson,³ D. Cibrik,³ J. Klawitter.¹

¹University of Colorado, Anschutz Medical Campus, Aurora, CO
²Novartis Pharmaceuticals, East Hanover, NJ
³University of Michigan Medical School, Ann Arbor, MI.

Meeting: 2015 American Transplant Congress

Abstract number: C255

Keywords: Kidney transplantation, Monitoring, Renal injury

Session Information

Session Name: Poster Session C: Translational Biomarkers and Immune Monitoring

Session Type: Poster Session

Date: Monday, May 4, 2015

Session Time: 5:30pm-6:30pm

Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Purpose. Protein biomarkers have the potential to allow for earlier and more specific diagnosis of kidney injury in kidney transplant patients than established clinical markers such as creatinine and transplant biopsies. We assayed 28 serum protein markers which are involved in kidney transplant rejection in a prospective, multicenter trial (CRAD100AUS92, Novartis Pharmaceuticals, NJ).

Methods. Serum was collected longitudinally (baseline, 1, 2, 4 and 6 months) from 120 de novo kidney transplant patients. A custom protein microchip was developed and measured activin A, BCAM, CD30, E-Cadherin, GRO alpha, IFNγ, IL-1 beta, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, KIM-1, lactoferrin, MCP-1, MCP-2, MIP-1 alpha, MMP-13, osteopontin, TGF-beta 2, TIMP-4, TNF-alpha, VEGF and VEGFR2.

Results. Regression analysis showed that the pattern of protein markers correlating with eGFR was different before and after transplantation, e.g. KIM-1 (p< 0.025 before transplantation, not significant after transplantation). After transplantation, the following protein markers were correlated with eGFR (n=388): activin A (p< 0.007), BCAM (0.035), IL-10 (0.0001), IL-1beta (0.016), IL-2R (0.040), IL-8 (0.017), MMP-13 (0.02), osteopontin (0.04), VEGF (0.0013) and VEGFR2 (p<0.037). When serum samples collected during biopsy proven acute rejection (BPAR, n=14) were compared to samples from stable patients with eGFRs >60 mL/min/1.73m² (n=58), the following markers were significantly different: MIP-alpha/CCL3 (p<0.0001) and VEGFR2 (p<0.016, log-transformed data, T-Test). When samples collected before the BPAR episode were compared with the samples from stable patients with eGFRs 60 mL/min/1.73 m², TNF-alpha was found higher in the pre-BPAR samples (p<0.002).

Summary. These results suggest that in kidney transplant patients, serum protein markers change depending on the patients' status (pre-transplantation, post-transplantation, pre-BPAR, during BPAR).

Conclusions. An array of protein biomarkers may be more useful and specific to monitor pathology in kidney transplant patients than single markers.

To cite this abstract in AMA style:

Christians U, Klepacki J, Karimpour-fard A, Ingle G, Patel D, Johnson K, Cibrik D, Klawitter J. Molecular Marker Strategies Supporting the Novartis US92 Study- A Discovery Study of Protein Biomarkers for Kidney Function (eGFR) and Acute Rejection in Serum from Renal Transplant Patients [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/molecular-marker-strategies-supporting-the-novartis-us92-study-a-discovery-study-of-protein-biomarkers-for-kidney-function-egfr-and-acute-rejection-in-serum-from-renal-transplant-patients/. Accessed November 21, 2024.

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