Renal transplant patients with preformed anti-HLA antibodies: early biopsy findings and clinical outcomes

Abstract

Introduction: Renal fibrosis is the end point of a process that begins at transplant, with ischemia reperfusion and early inflammation, and progresses over time with immunological and non-immunological phenomena. Early identification of morphological markers and intervention could improve graft function and survival. Objective: to evaluate the correlation between intensity and specificity of pre-transplant anti-HLA antibodies and kidney allograft pathology in order to identify early risk factors or markers of allograft dysfunction. Methods: A retrospective cohort of kidney transplant recipients with pre-transplant anti-HLA antibodies who underwent graft biopsy within the first two years post-transplant was divided into two groups according to the specificity of anti-HLA antibodies: nonspecific (non-DSA, n = 29) and specific (DSA+, n = 16). Kidney graft pathology, renal function, and proteinuria were analyzed. Results: general characteristics were similar in both groups, except for the higher dose of thymoglobulin in DSA+ group (p < 0.05). The non-DSA group had higher scores for glomerulosclerosis, interstitial inflammation (i) and interstitial fibrosis (ci) (p < 0.05) and higher incidence of cell-mediated acute rejection. No statistical difference in incidence of antibody-mediated rejection, renal function, and proteinuria was observed during follow up. Discussion and conclusions: the difference in inflammation scores and interstitial fibrosis may be associated to the higher incidence of acute cell-mediated rejection and polyomavirus nephropathy in the Non-DSA group. We also should take into account the protective effect of higher doses of thymoglobulin, reducing ischemia reperfusion injury in the DSA+ group. The short follow-up might have been insufficient to detect long-term changes in allograft tissue, renal function, and proteinuria.

Treatment of Antibody-Mediated Rejection After Kidney Transplantation: Immunological Effects, Clinical Response, and Histological Findings

“…All transplant recipients were HLA-typed and screened for anti-HLA antibodies with solid-phase tests, as previously described [ 13 , 14 ]. HLA was typed by polymerase chain reaction (PCR) amplification of genomic deoxyribonucleic acid (DNA) samples, and anti-HLA antibodies were screened with solid-phase tests (LABScreen™ Single Antigen HLA Class I LS1A04 and LABScreen™ Single Antigen HLA Class II LS2A01).…”

Bone marrow mesenchymal stem cell-derived extracellular vesicles containing miR-181d protect rats against renal fibrosis by inhibiting KLF6 and the NF-κB signaling pathway

“…Unfortunately, existing treatments only slow the progression of renal fibrosis but do not cure the disease [ 3 ]. The identification of morphological markers as well as early interventions is important for improving graft function and survival [ 4 ].…”

Pre-formed DSA and kidney allograft outcomes

“…Using solid-phase, single antigen bead assays, we are now able to identify anti-HLA antibody specificity with high precision and sensitivity. Although there are compelling data for kidney transplants that preexisting DSA is associated with increased risk of rejection, it remains controversial whether antibodies that are detected exclusively by solid-phase assays, and not detected by crossmatch assays, influence long-term graft outcome 1 , 2 .…”