Transplant glomerulopathy and post-transplant de novo thrombotic microangiopathy: common features and pathologic mechanisms

• Autor(a) principal: Costa,Rui M
• Data de Publicação: 2014
• Outros Autores: Vazquez-Martul,Eduardo, Reboredo-Mosquera,Juan, Rivera,Constantino
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://scielo.pt/scielo.php?script=sci_arttext&pid=S0872-01692014000300005
• topic: Antibody-mediated rejection; kidney transplant; thrombotic microangiopathy; transplant glomerulopathy

Aim: Comparison between transplant glomerulopathy (TG) and de novo thrombotic microangiopathy (TMA) in renal allograft biopsies in a 10 -year retrospective analysis. Results: Out of a total of 627 biopsies, TG (6.2%) was diagnosed at a later stage (6.9 ± 5.9 vs. 3.5 ± 6.5 years, p = 0.01) and presented higher proteinuria (4.0 ± 3.6 vs. 2.3 ± 1.6 gr/24h, p = 0.02), advanced glomerulosclerosis, interstitial fibrosis/tubular atrophy and interstitial plasma cells (30.8% vs. 0%, p = 0.02). De novo TMA (2.2%) was associated to worse graft disfunction (sCr 4.9 ± 1.8 vs. 2.7 ± 0.2mg/dl, p < 0.01), older donors (53 ± 10 vs. 41 ± 17 years, p = 0.04), PRA levels ≥ 25% (16.7% vs. 3.1%, p = 0.07) and previous rejection events (21.4% vs. 5.3%, p = 0.08). Diffuse glomerular lesions were observed in all TMA cases, with capillary congestion (100 vs. 35.1%, p < 0.01), microthrombi (50% vs. 5.4, p = 0.01), schistocytes (42.8% vs. 7.7%, p = 0.01) and mesangiolysis (85.7% vs. 29.7%, p < 0.01). Positive C4d in de novo TMA cases was similar to TG (71.4% vs. 53.8%, p = ns) but presented arteriolar C4d deposition (35.7 % vs. 8.7%, p = 0.042). Donor -specific antibodies detection was equally found (TG: 41.6%; TMA: 57.1%, p = ns), mainly anti-HLA Class II. In ultrastructural analysis only TG cases presented glomerular basement membrane (GBM) multilayering. Graft loss was similar, but de novo MAT cases had worst first year survival (73.3% vs. 97%, p = 0.013). Conclusion: Both pathologies belong within the spectrum of microcirculatory injury: TG results from subclinical lesion, presenting chronic cyclic accommodation, de novo TMA represents severe form of lytic endothelial lesion