Kidney Week

Abstract: SA-PO022

Predictors of Graft Survival at Diagnosis of Antibody-Mediated Renal Allograft Rejection

Session Information

• Transplantation: Clinical Outcomes
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1802 Transplantation: Clinical

Authors

• Duerr, Michael, Charité Universitaetsmedizin Berlin, Berlin, Germany

Michael Duerr,

• Bachmann, Friederike, Charité Universitaetsmedizin Berlin, Berlin, Germany

Friederike Bachmann,

• Lachmann, Nils, Charité Universitaetsmedizin Berlin, Berlin, Germany

Nils Lachmann,

• Klotsche, Jens, German Rheumatism Research Center Berlin, a Leibniz Institute, Berlin, Germany

Jens Klotsche,

• Halleck, Fabian, Charité Universitaetsmedizin Berlin, Berlin, Germany

Fabian Halleck,

• Wu, Kaiyin, Institut für Pathologie, Charite Campus Mitte, Berlin, Berlin, Germany

Kaiyin Wu,

• Liefeldt, Lutz, Charité Universitaetsmedizin Berlin, Berlin, Germany

Lutz Liefeldt,

• Budde, Klemens, Charité Universitaetsmedizin Berlin, Berlin, Germany

Klemens Budde,

• Waiser, Johannes, Charité Universitaetsmedizin Berlin, Berlin, Germany

Johannes Waiser,

Group or Team Name

• AG Duerr & Waiser

Background

Treatment of antibody-mediated rejection (ABMR) after renal transplantation is unsatisfactory. In order to improve treatment efficacy, it is necessary to identify parameters, which independently predict graft survival at diagnosis.

Methods

We investigated 54 consecutive renal allograft recipients with a diagnosis of ABMR between 2005 and 2015. Patients were treated with five different consecutive treatment groups of 10-12 patients. Patient characteristics, renal function and HLA antibody status at diagnosis, baseline renal biopsy results and immunosuppressive treatment were thoroughly recorded. The identification of diverse risk factors of graft loss at 24 months after diagnosis was investigated uni- and multivariate by a Cox proportional hazard model.

Results

Concerning the underlying patient characteristics including baseline parameters at diagnosis, we found no major differences between treatment groups. Multivariable analysis showed that transplant glomerulopathy, microvascular inflammation, and eGFR were predictive for graft loss at 24 months after diagnosis (table 1). In our analysis proteinuria (per 500mg/day) was statistically not a risk factor in the univariate analysis (HR 1.12; 95% CI 0.99-1.27; p=0.072). Notably, a significant (>10%) decrease of DSAmax (HR 0.62; 95% CI 0.25-1.52; p=0.294) following treatment was not associated with an improved graft survival compared to patients with no significant DSA decrease. Treatment with cyclophosphamide (6x15mg/m²) plus high-dose intravenous immunoglobulins (IVIG) (1.5g/kg) was superior compared to treatment with rituximab (1x500mg) (HR 0.10; 95% CI 0.02-0.54; p=0.008) or bortezomib (4x1.3mg/m²) plus low-dose IVIG (30g) (HR 0.16; 95% CI 0.02-0.99; p=0.049).

Conclusion

Histopathological signs of acute and chronic ABMR as well as renal function at diagnosis are independent risk factors for graft survival. Treatment with cyclophosphamide plus high-dose IVIG seems to be advantageous. Prospective studies including patients with defined risk factors are needed in order to further improve treatment efficacy.

Funding

• Clinical Revenue Support