C4d-Positive Chronic Rejection: A Frequent Entity With a Poor Outcome

David‐Neto, Elias; Prado, Elisângela; Beutel, Abram; Ventura, Carlucci Gualberto; Siqueira, Sheila Aparecida Coelho; Hung, James; Lemos, Francine Brambate Carvalinho; Souza, N. A.; Nahas, William Carlos; Ianhez, L E; David, Débora Leite

doi:10.1097/01.tp.0000288807.52520.5e

Cited by 39 publications

(29 citation statements)

References 18 publications

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“…We found that in this unique cohort of renal allograft recipients Ն10 yr after transplantation, identified on review of our pathology database, 25% were C4d ϩ , which is similar to the prevalence of C4d positivity in allograft biopsies performed at earlier times. 21,28 Diffuse positive C4d staining (C4d3 Ͼ50%) as defined by Banff 2007 27 was seen in 23 patients; two patients had focal PTC C4d staining (C4d2 10 to 50%) in their index biopsies. Evaluation of historical samples, retrospectively stained for C4d, revealed that the great majority of pervious biopsies from C4d ϩ patients were also positive.…”

Section: Discussionmentioning

confidence: 99%

Combination of Peritubular C4d and Transplant Glomerulopathy Predicts Late Renal Allograft Failure

Kieran

Wang²,

Perkins

et al. 2009

Journal of the American Society of Nephrology

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The histologic associations and clinical implications of peritubular capillary C4d staining from long-term renal allografts are unknown. We identified 99 renal transplant patients who underwent an allograft biopsy for renal dysfunction at least 10 yr after transplantation, 25 of whom were C4d-positive and 74 of whom were C4d-negative. The average time of the index biopsy from transplantation was 14 yr in both groups. Compared with C4d-negative patients, C4d-positive patients were younger at transplantation (29 Ϯ 13 versus 38 Ϯ 12 yr; P Ͻ 0.05) and were more likely to have received an allograft from a living donor (65 versus 35%; P Ͻ 0.001). C4d-positive patients had more inflammation, were more likely to have transplant glomerulopathy, and had worse graft outcome. The combined presence of C4d positivity, transplant glomerulopathy, and serum creatinine of Ͼ2.3 mg/dl at biopsy were very strong predictors of rapid graft loss. C4d alone did not independently predict graft loss. Retrospective staining of historical samples from C4d-positive patients demonstrated C4d deposition in the majority of cases. In summary, these data show that in long-term renal allografts, peritubular capillary staining for C4d occurs in approximately 25% of biopsies, can persist for many years after transplantation, and strongly predicts graft loss when combined with transplant glomerulopathy.

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Section: Discussionmentioning

confidence: 99%

Combination of Peritubular C4d and Transplant Glomerulopathy Predicts Late Renal Allograft Failure

Kieran

Wang²,

Perkins

et al. 2009

Journal of the American Society of Nephrology

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“…and function, some did not confirm this association (10)(11)(12)(13)(14)(15)(16)(17)(18)(19) (20,(20)(21)(22)(23)(24) …”

Section: C4d−/dsa+ (N = 39 149%) C4d+/dsa− (N = 49 187%) and C4dmentioning

confidence: 99%

The Impact of C4d Pattern and Donor-Specific Antibody on Graft Survival in Recipients Requiring Indication Renal Allograft Biopsy

Haririan

Kiangkitiwan

Kukuruga

et al. 2009

American Journal of Transplantation

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“…That might be explained by the different sensitivity of C4d detection methods and also by the dynamic nature of the rejection, in which course C4d expression may appear and disappear over the time depending on the activity of the process. Beyond that, there are some findings confirming the enhancing role of other mechanisms of DSA-driven endothelial damage in late chronic rejection, which are not directly associated with complement activation [36,37]. However in general the literature data concerning this issue are controversial -while some authors describe important influence of C4d-positivity on chronic rejection prognosis [26,38], the others indicate that prognosis for C4d-posistive chronic rejection does not differ from such for C4d-negative or even is better [17,39].…”

Section: Discussionmentioning

confidence: 75%

The Prognostic Value of Late Kidney Transplant Rejection Pathology Characteristics

Stolyarevich¹,

Artyukhina²,

Zakharova³

et al. 2016

J Transplant Technol Res

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Renal allograft rejection, represented by the wide spectrum of lesions with different pathogenesis, pathology patterns, clinical course and prognosis, still remains the most often cause of late graft dysfunction. Moreover, a combination of several factors, either of which may impact the post-transplant course, generally take place. We aimed to analyze the incidence of late renal allograft rejection variants, and to determine clinical factors and pathology features, influencing prognosis in the specific types of late renal allograft rejection.The data obtained from 361 patients with acute (n=227) or chronic (n=134) late allograft rejection (mean time after kidney transplantation 48.8 ± 46.1 months) were analyzed retrospectively. C4d expression was found in 34% cases of acute rejection and in 58% cases of chronic rejection (64% in chronic transplant glomerulopathy and 52% in transplant vasculopathy). 5-year graft survival comprised 48% and 24% for acute and chronic transplant rejection respectively (Р<0.01). Combination of acute cell-mediated rejection with chronic transplant rejection did not influence significantly the prognosis for the latter. Diffuse C4d expression on peritubular capillaries turned to be an independent prognostic factor regardless the pathology variant of renal allograft rejection. In contrast, focal C4d expression had no impact on the prognosis, which did not differ significantly from C4d-negative type. On the other hand, in acute rejection prognosis for C4d-positive forms was worse compared to C4d-negative (55% vs 25%; P <0.01), while in chronic rejection there was no difference between C4d-positive and C4d-negative forms (26% vs 24%; P=NS). In multivariate Cox-model analysis, the following factors appeared to influence the prognosis: presence of chronic transplant glomerulopathy, features of vasculitis, severity of tubulitis, presence of thrombotic micrioangiopathy and prominence of interstitial fibrosis.

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C4d-Positive Chronic Rejection: A Frequent Entity With a Poor Outcome

Abstract: These data indicate that C4d positive chronic rejection is very common, associated with proteinuria, and has a poor outcome. A larger study is warranted to identify which immunosuppressive regimen may modify the poor course of this entity.

Cited by 39 publications

References 18 publications

Combination of Peritubular C4d and Transplant Glomerulopathy Predicts Late Renal Allograft Failure

Combination of Peritubular C4d and Transplant Glomerulopathy Predicts Late Renal Allograft Failure

The Impact of C4d Pattern and Donor-Specific Antibody on Graft Survival in Recipients Requiring Indication Renal Allograft Biopsy

The Prognostic Value of Late Kidney Transplant Rejection Pathology Characteristics

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