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Is Early Complement Activation in Renal Transplantation Associated with Later Graft Outcome?
Kidney Blood Press Res. 2018; 43(5):1488-1504.KB

Abstract

BACKGROUND/AIMS

Complement activation is important in post-transplantation renal injury, but data on its role as predictor of transplant outcome/complications when assessed in donor kidneys are lacking.

METHODS

In human renal transplant biopsies with delayed graft function (DGF, n=12), antibody mediated rejection (ABMR, n=8), T-cell mediated rejection (TCMR, n=11), 1 year protocol biopsies (control, n=10) and corresponding zero-biopsies we performed immunohistochemical analyses of 6 complement factors using FFPE sections and correlated the findings with kidney function, as assessed by serum creatinine, and morphological changes including interstitial fibrosis and tubular atrophy (IF/TA).

RESULTS

In DGF, TCMR and ABMR significant complement deposition was observed, which was less pronounced in corresponding zero-biopsies. Zero-biopsies with subsequent ABMR showed glomerular complement factor D and C3c expression. Moreover, glomerular C3c and C9 and tubular MASP-2 and Collectin-11 expression in zero-biopsies significantly correlated with serum creatinine at diagnosis of DGF, TCMR or ABMR. Glomerular C1q was significantly increased in ABMR, but not in DGF and TCMR. In contrast, peritubular C1q was significantly enhanced in DGF and TCMR compared to zero-biopsies. Using C3d as a surrogate marker for complement activity we could confirm that stained complement factors are frequently associated with complement activity.

CONCLUSION

Complement deposition strongly correlated with histopathological changes observed in renal transplants. All 3 complement pathways were operational in biopsies with DGF, TCMR and ABMR albeit with differential abundance and localization. Since complement deposition in zero-biopsies correlated with graft function and morphological changes, early specific complement inhibition in renal transplantation may be a new therapeutic option to prevent graft loss.

Authors+Show Affiliations

Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Erlangen, Germany.Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Erlangen, Germany.Roche Pharma Research & Early Development, Roche Innovation Center Basel, Basel, Switzerland.Department of Nephrology and Hypertension, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Erlangen, Germany.Department of Nephrology and Hypertension, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Erlangen, Germany.Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Erlangen, Germany.Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Erlangen, Germany.Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Erlangen, GermanyChristoph.Daniel@uk-erlangen.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30286468

Citation

Bobka, Steffen, et al. "Is Early Complement Activation in Renal Transplantation Associated With Later Graft Outcome?" Kidney & Blood Pressure Research, vol. 43, no. 5, 2018, pp. 1488-1504.
Bobka S, Ebert N, Koertvely E, et al. Is Early Complement Activation in Renal Transplantation Associated with Later Graft Outcome? Kidney Blood Press Res. 2018;43(5):1488-1504.
Bobka, S., Ebert, N., Koertvely, E., Jacobi, J., Wiesener, M., Büttner-Herold, M., Amann, K., & Daniel, C. (2018). Is Early Complement Activation in Renal Transplantation Associated with Later Graft Outcome? Kidney & Blood Pressure Research, 43(5), 1488-1504. https://doi.org/10.1159/000494014
Bobka S, et al. Is Early Complement Activation in Renal Transplantation Associated With Later Graft Outcome. Kidney Blood Press Res. 2018;43(5):1488-1504. PubMed PMID: 30286468.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Is Early Complement Activation in Renal Transplantation Associated with Later Graft Outcome? AU - Bobka,Steffen, AU - Ebert,Nadja, AU - Koertvely,Eloed, AU - Jacobi,Johannes, AU - Wiesener,Michael, AU - Büttner-Herold,Maike, AU - Amann,Kerstin, AU - Daniel,Christoph, Y1 - 2018/10/04/ PY - 2018/03/24/received PY - 2018/09/25/accepted PY - 2018/10/5/pubmed PY - 2019/1/10/medline PY - 2018/10/5/entrez KW - C1q KW - C3c KW - C3d KW - C9 KW - CFD KW - Collectin 11 KW - Complement KW - MASP-2 KW - Renal biopsy KW - Renal transplantation SP - 1488 EP - 1504 JF - Kidney & blood pressure research JO - Kidney Blood Press. Res. VL - 43 IS - 5 N2 - BACKGROUND/AIMS: Complement activation is important in post-transplantation renal injury, but data on its role as predictor of transplant outcome/complications when assessed in donor kidneys are lacking. METHODS: In human renal transplant biopsies with delayed graft function (DGF, n=12), antibody mediated rejection (ABMR, n=8), T-cell mediated rejection (TCMR, n=11), 1 year protocol biopsies (control, n=10) and corresponding zero-biopsies we performed immunohistochemical analyses of 6 complement factors using FFPE sections and correlated the findings with kidney function, as assessed by serum creatinine, and morphological changes including interstitial fibrosis and tubular atrophy (IF/TA). RESULTS: In DGF, TCMR and ABMR significant complement deposition was observed, which was less pronounced in corresponding zero-biopsies. Zero-biopsies with subsequent ABMR showed glomerular complement factor D and C3c expression. Moreover, glomerular C3c and C9 and tubular MASP-2 and Collectin-11 expression in zero-biopsies significantly correlated with serum creatinine at diagnosis of DGF, TCMR or ABMR. Glomerular C1q was significantly increased in ABMR, but not in DGF and TCMR. In contrast, peritubular C1q was significantly enhanced in DGF and TCMR compared to zero-biopsies. Using C3d as a surrogate marker for complement activity we could confirm that stained complement factors are frequently associated with complement activity. CONCLUSION: Complement deposition strongly correlated with histopathological changes observed in renal transplants. All 3 complement pathways were operational in biopsies with DGF, TCMR and ABMR albeit with differential abundance and localization. Since complement deposition in zero-biopsies correlated with graft function and morphological changes, early specific complement inhibition in renal transplantation may be a new therapeutic option to prevent graft loss. SN - 1423-0143 UR - https://www.unboundmedicine.com/medline/citation/30286468/Is_Early_Complement_Activation_in_Renal_Transplantation_Associated_with_Later_Graft_Outcome L2 - https://www.karger.com?DOI=10.1159/000494014 DB - PRIME DP - Unbound Medicine ER -