Borderline Changes in Kidney Allografts Represents a Non-Homogenous Cohort with Different Outcome

P. Hruba¹, J. Maluskova¹, Z. Krejcik², M. Merkerova-Dostalova², V. Stranecky³, J. Klema⁴, K. Osickova¹, M. Wohlfahrtova¹, E. Honsova¹, O. Viklicky¹

¹Institute for Clinical and Experimental Medicine, Prague, Czech Republic, ²Institute of Hematology and Blood Transfusion, Prague, Czech Republic, ³Institute of Inherited Metabolic Disorders, Prague, Czech Republic, ⁴Czech Technical University, Prague, Czech Republic

Meeting: 2019 American Transplant Congress

Abstract number: C148

Keywords: Biopsy, Gene expression, Graft survival, Kidney transplantation

Session Information

Session Name: Poster Session C: Kidney: Acute Cellular Rejection

Session Type: Poster Session

Date: Monday, June 3, 2019

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall C & D

*Purpose: Borderline changes (BL) represent a frequent histological finding in kidney allograft with unclear prognosis.

*Methods: In this single center, retrospective, observational study, the BL were diagnosed in 12.6% of biopsies (n=6197) performed in 2005-2017, all patients received steroid pulses. Risk factors for 5-years (5y) graft failure were evaluated in cases where BL was the first pathology (Early BL: <3M, n=269, Late BL: >3M, n=61, Subclinical 3M-BL, n=193) and compared with normal findings at 3M (controls, n=251). Molecular patterns of BL with later progression to TCMR were evaluated using RNA microarray (Agilent SurePrintG3) in early BL (n=10) and compared with stable patients (n=11). The enrichment of differentially expressed genes in biological processes was analyzed using DAVID database.

*Results: Patients with case biopsy diagnosed BL had worse renal function compared to subclinical BL and controls (p<0.0001). Early BL had highest risk of TCMR development (OR=10.6, 95% CI: 4.3-24.3, p<0.0001 compared to controls; OR=5.1, 95% CI: 2.5-10.7, p<0.0001 compared to subclinical BL). Five-year graft survival was shorter in Early BL: 85.9% compared to Late BL: 98.2%, Subclinical BL: 93.3%, and controls: 97.8%; log rank test p< 0.0001). In the model adjusted for cold ischemia time, HLA mismatch and ECD donor category, the risk of 5y graft failure after BL was higher in patients with delayed graft function (DGF) (HR=2.7, 95% CI: 1.5-4.9, p=0.001), higher donor age (HR=1.04, 95% CI: 1.01-1.07, p=0.008) and longer dialysis vintage (HR=1.04, 95% CI: 1.0-1.02, p=0.028). Longer follow-up to BL was associated with improved 5y graft survival (HR=0.81, 95% CI: 0.68-0.96, p=0.016). These risk factors have remained significant also in a model adjusted for retransplantation and rATG induction. More severe tubulitis (t2, t3) in Early BL was associated with TCMR onset (log rank test p=0.017). This corresponds to higher expression of transcripts associated with immune and inflammation processes in Early BL with TCMR development (GO terms: leukocyte migration in inflammatory response (p=0.03), antigen processing and presentation via MHC class (p=0.048), lymphocyte, monocyte and neutrophil chemotaxis (p=0.003, p=0.041 and p<0.0001, respectively).

*Conclusions: Early BL and BL in patients with DGF, older donors and longer dialysis vintage, respectively, represent risk factors for premature graft loss. Severe inflammation in means of tubulitis or molecular profiles is associated with progression to TCMR regardless steroid treatment. Therefore, BL represents a non-homogenous cohort with different outcome.

To cite this abstract in AMA style:

Hruba P, Maluskova J, Krejcik Z, Merkerova-Dostalova M, Stranecky V, Klema J, Osickova K, Wohlfahrtova M, Honsova E, Viklicky O. Borderline Changes in Kidney Allografts Represents a Non-Homogenous Cohort with Different Outcome [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/borderline-changes-in-kidney-allografts-represents-a-non-homogenous-cohort-with-different-outcome/. Accessed November 21, 2024.

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