Abstract
Background and Aims
Protocol biopsies following kidney transplantation (KT) allow the histological diagnosis of antibody-mediated rejection (ABMR) with stable renal function (RF). Controversy arises when considering isolated proteinuria as a clinical biomarker. Currently, there is no effective treatment for ABMR and transplant units may decide on treatment independently of the clinical expression.
Method
KT recipients (1987-2017) with post-KT biopsies (2008-2018) showing ABMR graft lesions (category 2-Banff’2015) >1year post-KT were included. Cases were grouped into phenotypes of ABMR according to the clinical picture at biopsy : 1) acute RF impairment (↑creatinine >15% three weeks before biopsy) with/without proteinuria and with/without DSA detection. 2) sub-acute RF impairment (↑creatinine >15% six months before biopsy) with/without proteinuria and with/without DSA detection, 3) performed for DSA detection with stable RF and no proteinuria or 4) protocol biopsy, with stable RF, no proteinuria or DSA detection. We considered an additional category: 5) isolated proteinuria (↑>500 mg or x2 six months before biopsy). Categories 1), 2) and 5) were considered clinical ABMR. Categories 3) and 4) were considered subclinical ABMR. We aimed to evaluate graft outcomes in the different ABMR phenotypes.
Results
In a cohort of 105 KT recipients with histologic lesions of ABMR, biopsies corresponded to phenotypes 1) in 35 (33%), 2) 10 (9,5%), 3) 21 (20,3%), 4) 14 (13,4%) and y 5) in 25 23,8%). No differences between clinical and subclinical ABMR were found in baseline characteristics except for donors ‘age, who were older within the clinical group (51.8±18.8 vs. 43.88 ±16.1; p=0.04). At time of biopsy, subclinical had better RF than clinical ABMR (creatinine 1.3±0.4 mg/dl vs. 2.2±1.1 mg/dl; p=0.02) and less proteinuria (161 mg/g [IQR 93-269] vs 939 mg/g [IQR 412-2000]; p=0.001)
Graft survival was worse in those patients with acute and sub-acute RF impairment, followed by those with isolated proteinuria (Figure 1). In comparison to subclinical ABMR, those with RF impairment and isolated proteinuria had an increased risk of graft lost; HR 9.4 (95% IC 2.2-40.7, p=0.002) and 4.8 (95% IC 1.01-23.2, P=0.05) respectively. DSA detection in these groups did not impact graft survival. Specific treatment was not different among groups, except for steroid pulses, which were more frequently applied in cases of ABMR with clinical manifestation.
Conclusion
The clinical phenotypes of ABMR influence long-term graft survival independently from treatment. Understanding graft evolution according to clinical phenotype at the time of histologic diagnosis should guide the therapeutic strategy, to balance risk-benefit ratio.