Kidney Week

Abstract: FR-PO909

Predictive Role of Histological and Immunological Parameters in ABMR in a Cohort of Renal Transplanted Patients

Session Information

• Transplantation: Translational and Transplant Pathology
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1802 Transplantation: Clinical

Authors

• Regalia, Anna, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milan, Milan, Italy

Anna Regalia,

• Campise, Mariarosaria, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milan, Milan, Italy

Mariarosaria Campise,

• Alfieri, Carlo M., Fondazione IRCCS Ca' Granda Ospedale Policlinico Milan, Milan, Italy

Carlo M. Alfieri,

• Cresseri, Donata, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milan, Milan, Italy

Donata Cresseri,

• Moroni, Gabriella, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milan, Milan, Italy

Gabriella Moroni,

• Gandolfo, Maria Teresa, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milan, Milan, Italy

Maria Teresa Gandolfo,

• Binda, Valentina, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milan, Milan, Italy

Valentina Binda,

• Messa, Piergiorgio, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milan, Milan, Italy

Piergiorgio Messa,

Background

In clinical practice, the diagnosis of antibody-mediated rejection (ABMR) is based on three main components: specific histological lesions, presence of peri-tubular capillaries C4d and of circulating anti-HLA donor specific antibodies (cDSA). Our study aims to evaluate the concordance between histological and immunological diagnostic elements of ABMR and their predictive role on renal transplant (RTx) prognosis.

Methods

Among the 486 RTx patients transplanted from deceased donors in our Unit (2004-2015), 115 patients were submitted to renal biopsy (RBx) on clinical indications and evaluated for tissue C4d and cDSA (Luminex). Follow-up time was 3.7±2.7 yrs. According to histological lesions, RBx were categorized in: ABMR (hABMR), T-cell mediated rejection (hTCMR) or other lesions (hO). In addition, a categorization according to C4d positivity (C4d+/C4d-) and presence of cDSA at RBx (cDSA+/cDSA-) was made. In the relationship between histological and immunological elements, we considered 4 groups: cDSA-/C4d- (gr-A); cDSA-/C4d+ (gr-B); cDSA+/C4d- (gr-C); cDSA+/C4d+ (gr-D).

Results

Among the 115 RBx, 20%, 21% and 59% were respectively hABMR, hTCMR and hO. Compared to others, hABMR had higher PRA at RTx (p=0.03), higher Prot-U at RBx (p=0.01), more prevalence of C4d+ and cDSA+ (both p <0.0001) and shorter follow-up after RBx (p=0.03). In hABMR, 17.4% and 8.7% were in gr-A and gr-B, 30.4% and 43.5% in gr-C and gr-D (p<0.0001); in hTCMR, 95.8% and 0% were in gr-A and gr-B, 4.2% and 0% in gr-C and gr-D (p<0.0001); in hO, 80.9% and 2.9% were in gr-A and gr-B, 14.7% and 1.5% in gr-C and gr-D (p<0.0001); hABMR, C4d+ and DSA+ were singularly associated with graft loss, but among them h-ABMR was the only independent predictive factor for graft loss (HR 2.64 - p=0.01). Kaplan Meier analysis showed a worse graft outcome in hABMR compared to other histological diagnoses (p<0.001). h-ABMR had also higher graft loss discriminative power than C4d+ and cDSA+ (AUC 0.70, p<0.001). No discriminative informative advantages were found considering together h-ABMR and/or C4d+ and/or cDSA+.

Conclusion

Our data suggest that the histological evaluation of RTx is an unavoidable test for the diagnosis of graft dysfunction and represents the best prognostic parameter.