Dynamic Prognostic Score to Predict Kidney Allograft Survival in Patients with Antibody-Mediated Rejection

Abstract

No tool is available for the early assessment of response to antibody-mediated rejection (ABMR) therapies in kidney allograft recipients. This study was designed to define a dynamic composite prognostic ABMR score to predict kidney allograft survival, integrating the disease characteristics at diagnosis and the response to treatment. Among 1978 kidney recipients who underwent transplant between 2008 and 2014, we included 278 patients diagnosed with active ABMR and receiving standard treatment, including plasma exchange, intravenous Ig, and rituximab. Patients were prospectively assessed at diagnosis and after treatment for clinical data, histologic characteristics (allograft biopsy specimen), and donor-specific anti-HLA antibodies (DSA). The dynamic ABMR prediction model included GFR (<0.001) and presence of interstitial fibrosis/tubular atrophy (=0.003) at diagnosis and changes in GFR (<0.001), peritubular capillaritis Banff score (=0.002), and DSA mean fluorescence intensity (<0.001) after treatment. Overall, this model showed good calibration and discrimination (C-statistic=0.84). The ABMR prognostic score derived from the prediction model identified three risk strata with 6-year kidney allograft survival rates of 6.0% (high-risk group, =40), 44.9% (intermediate-risk group,=36), and 84.4% (low-risk group, =202), and it provided greater net clinical benefit to patients than did considering them all to have the same level of risk of allograft loss. The performance of the ABMR prognostic score was validated in an independent cohort of 202 kidney recipients with ABMR (C-statistic=0.79). The ABMR prognostic score could be used to inform therapeutic decisions in clinical practice and for the design of clinical trials.

Microvascular inflammation in renal allograft biopsies assessed by endothelial and leukocyte co‐immunostain: a retrospective study on reproducibility and clinical/prognostic correlates

“…Indeed, we deliberately included ABO-and HLA-incompatible transplants, of whom almost 32% had at least one previous kidney transplant. Our results are in line with observations of Viglietti and colleagues who recently developed a prognostic score for patients with AMR: the score includes eGFR at the time of diagnosis, presence of chronic allograft glomerulopathy, IF/TA degree, de novo HLA-DSA and intensity of peritubular capillaritis; the authors suggest that this score should drive therapeutic approach to patients with AMR [25]. Our iptcr score alone can predict DSA strength as well as graft survival, an improvement on the ptc score used by Viglietti.…”

Predictors of graft survival at diagnosis of antibody‐mediated renal allograft rejection: a retrospective single‐center cohort study

“…In agreement with Viglietti et al . , our results indicate that both eGFR at diagnosis and chronic glomerulopathy are significant predictors of renal allograft loss. In addition, microvascular inflammation and the applied treatment regimen also seem to influence graft loss.…”

“…In a recent review, Böhmig and colleagues summarized the underlying pathogenesis, the clinical impact as well as currently available options and future concepts for the treatment of late ABMR . Apart from that, it is becoming more and more clear that graft survival following diagnosis of ABMR may not only be dependent on the applied treatment protocol, but also on the underlying functional and morphological parameters at diagnosis . Consequently, before subjecting an individual to an intensified immunosuppressive anti‐ABMR treatment protocol, a risk‐benefit analysis based on independent predictors of graft survival should be performed, in order to avoid high‐dose immunosuppressive treatment, when the anticipated graft survival benefit is questionable.…”

Failure to removede novodonor-specific HLA antibodies is influenced by antibody properties and identifies kidney recipients with late antibody-mediated rejection destined to graft loss - a retrospective study

“…In addition, criteria based on change in Ab strength, represented by MFI categories , were also tested. In detail, we analyzed (i) strength category shift: MFI >10 000 to MFI from 5000 to 10 000; from MFI comprised between 5000 and 10 000 to MFI < 5000; from MFI comprised between 5000 and 1000 to negative; (ii) MFI relative change value, calculated according to a previously described formula (MFI at 1 year from treatment initiation ─ MFI at treatment/MFI at treatment), and reported as a continuous variable .…”

“…Analysis of these antibody biological properties could also provide meaningful insight into the response to anti‐humoral treatment in late AMR. In particular, pre‐ and post‐treatment variations of DSA properties, such as antibody strength or ability to fix complement, are the parameters that have been found associated with outcome in kidney recipients treated for AMR . These studies included large proportions of patients with early acute AMR, thus, the role of these predictors in late AMR is unclear and needs to be further assessed.…”