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Capillary C4d and Kidney Allograft Outcome in Relation to Morphologic Lesions Suggestive of Antibody-Mediated Rejection.
Clin J Am Soc Nephrol. 2015 Aug 07; 10(8):1435-43.CJ

Abstract

BACKGROUND AND OBJECTIVES

Recent studies highlighting a role of C4d- antibody-mediated rejection (ABMR) have debated whether C4d staining has independent value as a rejection marker. Considering the presumed role of complement as an important effector of graft injury, this study hypothesized that capillary C4d, a footprint of antibody-triggered complement activation, indicates a particularly severe manifestation of ABMR.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS

This large retrospective clinicopathologic study sought to assess the clinical predictive value of C4d staining in relation to ABMR morphology. Overall, 885 renal allograft recipients who underwent transplantation between 1999 and 2006 (median duration of follow-up, 63.3 [interquartile range, 40.6-93.5] months; 206 graft losses) were included if they had had one or more indication biopsies. A total of 1976 biopsy specimens were reevaluated for capillary C4d staining (C4d data were available for 825 patients) and distinct morphologic lesions suggestive of ABMR, including glomerulitis, peritubular capillaritis, capillary microthrombi, transplant glomerulopathy, and severe intimal arteritis.

RESULTS

C4d+ patients, with or without ABMR features, had worse death-censored 8-year graft survival (53% or 67%) than C4d- patients (66% or 81%; P<0.001). In Cox regression analysis, C4d was associated with a risk of graft loss independently of baseline confounders and ABMR morphology (hazard ratio, 1.85 [95% confidence interval, 1.34 to 2.57]; P<0.001). The risk was higher than that observed for C4d- patients, a finding that reached statistical significance in patients showing fewer than two different ABMR lesions. Moreover, in a mixed model, C4d was independently associated with a steeper decline of eGFR (slope per year, -8.23±3.97 ml/min per 1.73 m(2); P<0.001).

CONCLUSIONS

These results suggest that detection of intragraft complement activation has strong independent value as an additional indicator of ABMR associated with adverse kidney transplant outcomes.

Authors+Show Affiliations

Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria;Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria; Department of Medicine III, Hospital of Elisabethinen Linz, Linz, Austria; and.Clinical Institute of Pathology, Medical University Vienna, Vienna, Austria.Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria; Department of Medicine III, Hospital of Elisabethinen Linz, Linz, Austria; and.Clinical Institute of Pathology, Medical University Vienna, Vienna, Austria.Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria;Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria; georg.boehmig@meduniwien.ac.at.

Pub Type(s)

Evaluation Study
Journal Article

Language

eng

PubMed ID

26071493

Citation

Kikić, Željko, et al. "Capillary C4d and Kidney Allograft Outcome in Relation to Morphologic Lesions Suggestive of Antibody-Mediated Rejection." Clinical Journal of the American Society of Nephrology : CJASN, vol. 10, no. 8, 2015, pp. 1435-43.
Kikić Ž, Kainz A, Kozakowski N, et al. Capillary C4d and Kidney Allograft Outcome in Relation to Morphologic Lesions Suggestive of Antibody-Mediated Rejection. Clin J Am Soc Nephrol. 2015;10(8):1435-43.
Kikić, Ž., Kainz, A., Kozakowski, N., Oberbauer, R., Regele, H., Bond, G., & Böhmig, G. A. (2015). Capillary C4d and Kidney Allograft Outcome in Relation to Morphologic Lesions Suggestive of Antibody-Mediated Rejection. Clinical Journal of the American Society of Nephrology : CJASN, 10(8), 1435-43. https://doi.org/10.2215/CJN.09901014
Kikić Ž, et al. Capillary C4d and Kidney Allograft Outcome in Relation to Morphologic Lesions Suggestive of Antibody-Mediated Rejection. Clin J Am Soc Nephrol. 2015 Aug 7;10(8):1435-43. PubMed PMID: 26071493.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Capillary C4d and Kidney Allograft Outcome in Relation to Morphologic Lesions Suggestive of Antibody-Mediated Rejection. AU - Kikić,Željko, AU - Kainz,Alexander, AU - Kozakowski,Nicolas, AU - Oberbauer,Rainer, AU - Regele,Heinz, AU - Bond,Gregor, AU - Böhmig,Georg A, Y1 - 2015/06/12/ PY - 2014/10/06/received PY - 2015/04/16/accepted PY - 2015/6/14/entrez PY - 2015/6/14/pubmed PY - 2016/5/11/medline KW - C4d KW - antibody-mediated rejection KW - complement KW - kidney transplantation KW - transplant outcomes SP - 1435 EP - 43 JF - Clinical journal of the American Society of Nephrology : CJASN JO - Clin J Am Soc Nephrol VL - 10 IS - 8 N2 - BACKGROUND AND OBJECTIVES: Recent studies highlighting a role of C4d- antibody-mediated rejection (ABMR) have debated whether C4d staining has independent value as a rejection marker. Considering the presumed role of complement as an important effector of graft injury, this study hypothesized that capillary C4d, a footprint of antibody-triggered complement activation, indicates a particularly severe manifestation of ABMR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This large retrospective clinicopathologic study sought to assess the clinical predictive value of C4d staining in relation to ABMR morphology. Overall, 885 renal allograft recipients who underwent transplantation between 1999 and 2006 (median duration of follow-up, 63.3 [interquartile range, 40.6-93.5] months; 206 graft losses) were included if they had had one or more indication biopsies. A total of 1976 biopsy specimens were reevaluated for capillary C4d staining (C4d data were available for 825 patients) and distinct morphologic lesions suggestive of ABMR, including glomerulitis, peritubular capillaritis, capillary microthrombi, transplant glomerulopathy, and severe intimal arteritis. RESULTS: C4d+ patients, with or without ABMR features, had worse death-censored 8-year graft survival (53% or 67%) than C4d- patients (66% or 81%; P<0.001). In Cox regression analysis, C4d was associated with a risk of graft loss independently of baseline confounders and ABMR morphology (hazard ratio, 1.85 [95% confidence interval, 1.34 to 2.57]; P<0.001). The risk was higher than that observed for C4d- patients, a finding that reached statistical significance in patients showing fewer than two different ABMR lesions. Moreover, in a mixed model, C4d was independently associated with a steeper decline of eGFR (slope per year, -8.23±3.97 ml/min per 1.73 m(2); P<0.001). CONCLUSIONS: These results suggest that detection of intragraft complement activation has strong independent value as an additional indicator of ABMR associated with adverse kidney transplant outcomes. SN - 1555-905X UR - https://www.unboundmedicine.com/medline/citation/26071493/Capillary_C4d_and_Kidney_Allograft_Outcome_in_Relation_to_Morphologic_Lesions_Suggestive_of_Antibody_Mediated_Rejection_ L2 - http://cjasn.asnjournals.org/cgi/pmidlookup?view=long&amp;pmid=26071493 DB - PRIME DP - Unbound Medicine ER -