Implications of Immunohistochemical Detection of C4d along Peritubular Capillaries in Late Acute Renal Allograft Rejection

Poduval, Rajiv D.; Kadambi, Pradeep V.; Josephson, Michelle A.; Cohn, Richard A.; Harland, Robert C.; Javaid, Basit; Huo, Dezheng; Manaligod, José R.; Thistlethwaite, J. Richard; Meehan, Shane M.

doi:10.1097/01.tp.0000148987.13199.10

Cited by 64 publications

(63 citation statements)

References 28 publications

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“…9 Moreover, in specific settings, such as protocol biopsies 11 or late acute renal allograft rejection, 24,25 there is controversy if C4d deposition is associated or not with poor function and higher rates of graft loss.…”

Section: Discussionmentioning

confidence: 99%

“…15,21,28 Moreover, the staining of plasma proteins in PTCs that results from soluble C4 fixation sometimes makes interpretation of C4d less reliable. 24 Nonetheless, potential advantages of paraffin-IHC are better preservation of morphologic features, and most important, IHC can be done retrospectively in stored paraffin sections when diagnosis of ABMR is doubtful. 3,22 We investigated the internal consistency of C4d interpretation in paraffin-IHC, by measuring its reproducibility.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical and pathological correlations of C4d immunostaining and its infl uence on the outcome of kidney transplant recipients

Carpio¹,

Rech²,

Eickhoff³

et al. 2011

J. Bras. Nefrol.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical and pathological correlations of C4d immunostaining and its infl uence on the outcome of kidney transplant recipients

Carpio¹,

Rech²,

Eickhoff³

et al. 2011

J. Bras. Nefrol.

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“…IHC also has artifacts, such as staining of the plasma in the capillaries and interstitium as a result of fixation of soluble C4, which can render the sample uninterpretable. In one series, 8% of the samples showed this artifact, which was alleviated by decreasing the microwave treatment time (23). However, IHC in fixed tissue has a great advantage over IF: Glomerular deposits can be assessed, because the normal mesangium does not stain for C4d in fixed tissue but does in frozen.…”

Section: Comparison Of C4d Techniquesmentioning

confidence: 99%

“…The dilemma has been what to do with those not uncommon cases with focally positive PTC that do not exceed 50%. In one study, Meehan and colleagues (23) found that diffuse C4d (Ն50% of PTC) had a higher rate of graft loss 1 yr later (65%) than those with focal or no C4d (33% graft loss in both cases). In contrast, Magil and Tinckam (24) found that the outcome with diffuse or focal C4d was not distinguishable and was worse than those without C4d.…”

Section: Definition Of Positive C4d Stainingmentioning

confidence: 99%

Antibody-Mediated Renal Allograft Rejection

Colvin

2007

Journal of the American Society of Nephrology

493

447

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Alloantibodies to HLA class I or II and other antigens expressed by endothelium cause a variety of effects on renal transplants, ranging from acute to chronic rejection, and even apparent graft acceptance (accommodation). Recognition of these conditions and appropriate therapy requires demonstration of C4d in biopsies, commonly confirmed by tests for circulating alloantibody. Substantial practical experience by pathologists in the interpretation and pitfalls of C4d stains are reviewed along with considerations of the clinical significance and pathologic mechanisms of the different effects of antibody on the endothelium of the renal allograft. Clinical trials will be needed to ascertain the optimal treatment for the newly appreciated conditions chronic humoral rejection and accommodation.

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“…The prognostic value of this hallmark is confirmed for early rejection episodes [10,11] however it is not generally accepted as a negative prognostic factor in the late acute and chronic transplant rejection. Even though several studies showed that renal graft survival in C4d-positive late AMR was significantly lower compared to C4d-negative cases [19][20][21][22], other authors did not confirm this association [23][24][25]. Keiran et al, who studied the renal graft biopsies performed late (>10 years) after transplantation, demonstrated prognostic value of C4d expression only in its association with TG, while in the absence of the latter C4d-positivity did not influence the prognosis [26].…”

Section: Discussionmentioning

confidence: 99%

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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Implications of Immunohistochemical Detection of C4d along Peritubular Capillaries in Late Acute Renal Allograft Rejection

Abstract: Evidence of acute cellular with occult humoral rejection is identified in more than 40% of late AR episodes. Late acute humoral rejection may be associated with interstitial hemorrhage and plasma cells and contributes significantly to graft loss.

Cited by 64 publications

References 28 publications

Clinical and pathological correlations of C4d immunostaining and its infl uence on the outcome of kidney transplant recipients

Clinical and pathological correlations of C4d immunostaining and its infl uence on the outcome of kidney transplant recipients

Antibody-Mediated Renal Allograft Rejection

The Prognostic Value of Late Kidney Transplant Rejection Pathology Characteristics

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