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Published on: May 7, 2019
Plasma exchange-sensitive syncytial glomerulopathy in a kidney transplant patient
Marco Delsante1, Elena Martinelli2, Chiara Foroni3
1Unità Operativa di Nefrologia, Azienda Ospedaliero-Universitaria Parma and Dipartimento Di Medicina E Chirurgia, Università Di Parma, Via Gramsci 14, 43100, Parma, Italy. delsantem@gmail.com.
Abstract:
Microvascular inflammation (MVI), defined as the presence of glomerulitis and/or peritubular capillaritis, is the key histological lesion of anti-HLA donor-specific antibodies (DSA)-related antibody mediated rejection, but recently other possible mechanisms of MVI have emerged. However, except for peritubular capillary C4d deposition that is more frequently observed in the presence of anti-HLA-DSA, histological features are similar regardless of MVI origin. Therefore, accurately describing patterns of MVI may help differentiate etiologies and drive therapeutic choices. We describe the case of a kidney transplant recipient (primary nephropathy: autosomal dominant polycystic kidney disease) who underwent kidney biopsy for worsening renal function and new onset hypertension. Histologic findings showed severe microvascular inflammation with intense glomerulitis and presence of intracapillary multinucleated cells, positive on immunostaining for endothelial marker ETS-related gene (ERG). Focal intense peritubular capillaritis and early glomerular basement membrane reduplication, C4d negative, were observed, consistent with early chronic active ABMR. HLA-DSA were absent, but high level of anti-angiotensin II type-1 receptor (AT1R) antibodies (Ab) were detected (78 U/L, normal levels < 10 U/L). Two subsequent biopsies showed intense microvascular inflammation with diffuse peritubular capillaritis, and multinucleated, ERG-positive, endothelial cells were still seen in glomerular capillary loops. The patient was started on angiotensin receptor blockers (ARBs) and plasma exchange (PEX) sessions obtaining normalization of blood pressure and AT1R Ab and proteinuria reduction, but, after subsequent liver transplant, rituximab therapy failed to maintain remission and the patient remained PEX-dependent.
Insights
Microvascular inflammation in kidney transplants can stem from various causes, not just anti-HLA antibodies. Identifying specific patterns, like those linked to anti-AT1R antibodies, is crucial for targeted treatment and improved outcomes.
Area of Science:
- Nephrology
- Transplant Immunology
- Histopathology
Background:
- Microvascular inflammation (MVI) is a key feature of antibody-mediated rejection in kidney transplants, often linked to anti-HLA donor-specific antibodies (DSA).
- Histological features of MVI can be similar regardless of its origin, making differentiation challenging.
- Emerging evidence suggests non-HLA antibody mechanisms contribute to MVI, necessitating refined diagnostic approaches.
Purpose of the Study:
- To describe a case of kidney transplant recipient with microvascular inflammation.
- To investigate the potential role of non-HLA antibodies, specifically anti-angiotensin II type-1 receptor (AT1R) antibodies, in driving MVI.
- To highlight the diagnostic and therapeutic implications of identifying specific MVI etiologies.
Main Methods:
- Case report of a kidney transplant recipient with worsening renal function and new-onset hypertension.
- Analysis of kidney biopsy findings, including glomerulitis, peritubular capillaritis, and immunostaining for ERG.
- Detection of anti-HLA-DSA and anti-AT1R antibodies (Ab).
- Monitoring of therapeutic response to angiotensin receptor blockers (ARBs) and plasma exchange (PEX).
Main Results:
- Histology revealed severe MVI with glomerulitis, intracapillary multinucleated cells (ERG-positive), and peritubular capillaritis, C4d negative.
- Anti-HLA-DSA were absent, but high levels of anti-AT1R antibodies were detected.
- Treatment with ARBs and PEX led to blood pressure normalization, reduced AT1R Ab, and proteinuria.
- Rituximab therapy after a subsequent liver transplant failed to maintain remission, with the patient remaining PEX-dependent.
Conclusions:
- This case suggests that anti-AT1R antibodies can cause significant microvascular inflammation in kidney allografts, mimicking features of antibody-mediated rejection.
- Accurate histological pattern description and etiological differentiation are vital for guiding therapeutic strategies in MVI.
- Non-HLA antibodies represent an important target for understanding and managing kidney transplant dysfunction.
