Implications of immunohistochemical detection of C4d along peritubular capillaries in late acute renal allograft rejection

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

*Corresponding author for this work

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Background. Immunohistochemical detection of the C4d complement product along peritubular capillaries (PC) may indicate humoral rejection of renal allografts. We examined the frequency of PC C4d expression in renal-allograft biopsies with acute rejection (AR) arising more than 6 months after transplantation and the impact of this finding. Methods. C4d was detected by immunoperoxidase in 2-micron paraffin sections of consecutive biopsies obtained over a 3-year period. The extent was classified as diffuse (≥50% PC C4d+), focal (<50% C4d+), and negative (C4d-). Clinical data were obtained by retrospective chart review. Fifty-five AR episodes with Banff 97 types 1A (n = 13), 1B (n = 26), 2A (n = 11), 2B (n = 3), and 3 (n = 2) met inclusion criteria. Results. PC C4d expression was diffuse in 23 (42%), focal in 9 (16%), and negative in 23 (42%) biopsies. AR episodes with focal and diffuse C4d expression had higher proportionate elevation of serum creatinine at biopsy and 4 weeks after diagnosis (P≤0.05). Biopsies with diffuse PC C4d had interstitial hemorrhage (56.5%) and plasmacytic infiltrates (52%) more frequently than C4d- biopsies (22% and 16%), P = 0.02, but had no other distinctive histologic features. Graft loss was greater in diffuse (65%) compared with focal C4d+ (33%) and C4d- (33%) groups 1 year after diagnosis, P = 0.03. Other clinical and pathologic parameters did not differ significantly, including treatment received for AR. Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)228-235
Number of pages8
JournalTransplantation
Volume79
Issue number2
DOIs
StatePublished - Jan 27 2005

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Allografts
Kidney
Biopsy
Hemorrhage
Transplants
Plasma Cells
Paraffin
Creatinine
Transplantation
Serum

Keywords

  • Allograft
  • C4d
  • Kidney
  • Late acute rejection

ASJC Scopus subject areas

  • Transplantation

Cite this

Poduval, Rajiv D. ; Kadambi, Pradeep V. ; Josephson, Michelle A. ; Cohn, Richard A. ; Harland, Robert C. ; Javaid, Basit ; Huo, Dezheng ; Manaligod, Jose R. ; Thistlethwaite, J. Richard ; Meehan, Shane M. / Implications of immunohistochemical detection of C4d along peritubular capillaries in late acute renal allograft rejection. In: Transplantation. 2005 ; Vol. 79, No. 2. pp. 228-235.
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title = "Implications of immunohistochemical detection of C4d along peritubular capillaries in late acute renal allograft rejection",
abstract = "Background. Immunohistochemical detection of the C4d complement product along peritubular capillaries (PC) may indicate humoral rejection of renal allografts. We examined the frequency of PC C4d expression in renal-allograft biopsies with acute rejection (AR) arising more than 6 months after transplantation and the impact of this finding. Methods. C4d was detected by immunoperoxidase in 2-micron paraffin sections of consecutive biopsies obtained over a 3-year period. The extent was classified as diffuse (≥50{\%} PC C4d+), focal (<50{\%} C4d+), and negative (C4d-). Clinical data were obtained by retrospective chart review. Fifty-five AR episodes with Banff 97 types 1A (n = 13), 1B (n = 26), 2A (n = 11), 2B (n = 3), and 3 (n = 2) met inclusion criteria. Results. PC C4d expression was diffuse in 23 (42{\%}), focal in 9 (16{\%}), and negative in 23 (42{\%}) biopsies. AR episodes with focal and diffuse C4d expression had higher proportionate elevation of serum creatinine at biopsy and 4 weeks after diagnosis (P≤0.05). Biopsies with diffuse PC C4d had interstitial hemorrhage (56.5{\%}) and plasmacytic infiltrates (52{\%}) more frequently than C4d- biopsies (22{\%} and 16{\%}), P = 0.02, but had no other distinctive histologic features. Graft loss was greater in diffuse (65{\%}) compared with focal C4d+ (33{\%}) and C4d- (33{\%}) groups 1 year after diagnosis, P = 0.03. Other clinical and pathologic parameters did not differ significantly, including treatment received for AR. Conclusion. 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.",
keywords = "Allograft, C4d, Kidney, Late acute rejection",
author = "Poduval, {Rajiv D.} and Kadambi, {Pradeep V.} and Josephson, {Michelle A.} and Cohn, {Richard A.} and Harland, {Robert C.} and Basit Javaid and Dezheng Huo and Manaligod, {Jose R.} and Thistlethwaite, {J. Richard} and Meehan, {Shane M.}",
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Poduval, RD, Kadambi, PV, Josephson, MA, Cohn, RA, Harland, RC, Javaid, B, Huo, D, Manaligod, JR, Thistlethwaite, JR & Meehan, SM 2005, 'Implications of immunohistochemical detection of C4d along peritubular capillaries in late acute renal allograft rejection', Transplantation, vol. 79, no. 2, pp. 228-235. https://doi.org/10.1097/01.TP.0000148987.13199.10

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, Jose R.; Thistlethwaite, J. Richard; Meehan, Shane M.

In: Transplantation, Vol. 79, No. 2, 27.01.2005, p. 228-235.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Implications of immunohistochemical detection of C4d along peritubular capillaries in late acute renal allograft rejection

AU - Poduval, Rajiv D.

AU - Kadambi, Pradeep V.

AU - Josephson, Michelle A.

AU - Cohn, Richard A.

AU - Harland, Robert C.

AU - Javaid, Basit

AU - Huo, Dezheng

AU - Manaligod, Jose R.

AU - Thistlethwaite, J. Richard

AU - Meehan, Shane M.

PY - 2005/1/27

Y1 - 2005/1/27

N2 - Background. Immunohistochemical detection of the C4d complement product along peritubular capillaries (PC) may indicate humoral rejection of renal allografts. We examined the frequency of PC C4d expression in renal-allograft biopsies with acute rejection (AR) arising more than 6 months after transplantation and the impact of this finding. Methods. C4d was detected by immunoperoxidase in 2-micron paraffin sections of consecutive biopsies obtained over a 3-year period. The extent was classified as diffuse (≥50% PC C4d+), focal (<50% C4d+), and negative (C4d-). Clinical data were obtained by retrospective chart review. Fifty-five AR episodes with Banff 97 types 1A (n = 13), 1B (n = 26), 2A (n = 11), 2B (n = 3), and 3 (n = 2) met inclusion criteria. Results. PC C4d expression was diffuse in 23 (42%), focal in 9 (16%), and negative in 23 (42%) biopsies. AR episodes with focal and diffuse C4d expression had higher proportionate elevation of serum creatinine at biopsy and 4 weeks after diagnosis (P≤0.05). Biopsies with diffuse PC C4d had interstitial hemorrhage (56.5%) and plasmacytic infiltrates (52%) more frequently than C4d- biopsies (22% and 16%), P = 0.02, but had no other distinctive histologic features. Graft loss was greater in diffuse (65%) compared with focal C4d+ (33%) and C4d- (33%) groups 1 year after diagnosis, P = 0.03. Other clinical and pathologic parameters did not differ significantly, including treatment received for AR. Conclusion. 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.

AB - Background. Immunohistochemical detection of the C4d complement product along peritubular capillaries (PC) may indicate humoral rejection of renal allografts. We examined the frequency of PC C4d expression in renal-allograft biopsies with acute rejection (AR) arising more than 6 months after transplantation and the impact of this finding. Methods. C4d was detected by immunoperoxidase in 2-micron paraffin sections of consecutive biopsies obtained over a 3-year period. The extent was classified as diffuse (≥50% PC C4d+), focal (<50% C4d+), and negative (C4d-). Clinical data were obtained by retrospective chart review. Fifty-five AR episodes with Banff 97 types 1A (n = 13), 1B (n = 26), 2A (n = 11), 2B (n = 3), and 3 (n = 2) met inclusion criteria. Results. PC C4d expression was diffuse in 23 (42%), focal in 9 (16%), and negative in 23 (42%) biopsies. AR episodes with focal and diffuse C4d expression had higher proportionate elevation of serum creatinine at biopsy and 4 weeks after diagnosis (P≤0.05). Biopsies with diffuse PC C4d had interstitial hemorrhage (56.5%) and plasmacytic infiltrates (52%) more frequently than C4d- biopsies (22% and 16%), P = 0.02, but had no other distinctive histologic features. Graft loss was greater in diffuse (65%) compared with focal C4d+ (33%) and C4d- (33%) groups 1 year after diagnosis, P = 0.03. Other clinical and pathologic parameters did not differ significantly, including treatment received for AR. Conclusion. 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.

KW - Allograft

KW - C4d

KW - Kidney

KW - Late acute rejection

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U2 - 10.1097/01.TP.0000148987.13199.10

DO - 10.1097/01.TP.0000148987.13199.10

M3 - Article

VL - 79

SP - 228

EP - 235

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 2

ER -