Subclinical Antibody Mediated Rejection in Kidney Transplantation: Protocol Biopsy for De Novo Donor Specific Antibody, a Single-Center Experience.

Abstract

The prevalence and treatment of subclinical antibody mediated rejection associated with de novo donor specific antibody (dn DSA) have not yet been well defined. Since october 2010, a renal biopsy was systematically performed in all newly detected dnDSA kidney transplant recipients. DSA were tested by routine surveillance 3, 6, 12 months then yearly after transplantation (Luminex single antigen). Demographic, clinical and pathologic data were collected. Thirteen patients (24-46 years) were biopsied with a mean delay of 41,7 months after transplantation. Dn DSA were in all case a class II HLA antibody, and mean fluorescence intensity (MFI) was 8026 (1874-17000). Graft function was stable in the last 3 months before biopsy (mean serum creatinin: 110 ± 20 μmol/L;Modification of Diet in Renal Disease formula (MDRD): 64.4 ± 6.6 mL/min). Pathologic findings (Banff 2009 classification) of renal biospies showed a mean microcirculation inflammation score glomerulitis + peri tubular capilaritis (g+ cpt) of 3.0 ± 1.6 and was ≥ 3 in 9 cases (70%). Peritubular C4d deposition was positive in 5 cases (38%). Transplant glomerulopathy was detected in 7 cases. All patients with g + cpt ≥ 3 were treated with plasma exchange, rituximab, corticosteroids and intravenous immunoglobulins, followed by a repeat biopsy after a median follow-up of 4.6 ± 3.4 months. There was an improvement of microcirculation inflammation score in 8/9 cases (2.5 ± 1 versus 3.9 ± 0.9; p = 0.0017). The MFI of the dn DSA decreased from 7836 to 4162 (p = 0.02). After a mean follow up of 19 months (11.6-35.6), mean serum creatinin increased from 108 ± 22 to 122 ±18 μmol/L (p=NS) (MDRD: 66.1±19 versus 54.2 mL/min ± 7.7, p=NS) with stable proteinuria (0.17 to 0.10 g/day; p=NS). Pathologic findings of renal biopsy performed for dnDSA detection without graft dysfunction very often show antibody mediated rejection lesions. Preemptive treatment is associated with improved microcirculation inflammation score and decreased MFI of dnDSA. The real impact of such a strategy on long term kidney allograft function needs to be confirmed by specifically designed studies.