Assoc.Prof.Priv. Doz. Dr. Željko Kikić
MedUni Wien RESEARCHER OF THE MONTH October 2024
In the present retrospective multicenter study, a new quantitative method for assessing the progression of transplant glomerulopathy (TG) using digital pathology as a potential endpoint for clinical trials on chronic active antibody-mediated rejection of kidney transplants was investigated. The authors developed a digital scoring method that quantifies duplication of the capillary basement membrane in glomeruli at 100x magnification and correlates it with clinical outcomes, rejection lesions, and gene transcripts. In a multicenter setting, 75 patients from Vienna, Linz, Paris, Los Angeles, Boston, and Edmonton with 2 sequential biopsies were included to evaluate the clinical relevance of the new scoring method. Digital pathological assessment of TG demonstrated better depiction of progression compared to conventional Banff assessment. It correlated with transplant loss and Banff-ABMR lesions but was not associated with changes in gene transcripts. In the multivariate model, digital pathology emerged as the best predictor for the endpoint of transplant loss. This reproducible method could serve as a surrogate endpoint in clinical trials.
Selected Literature
- Kikic Ž, Adam BA, Buxeda Porras A, Lefaucheur C, Loupy A, Regele H, Cejka D,Haas M, Colvin RB, Mengel M. Quantitative scoring of progression in transplant glomerulopathy using digital pathology may be superior to Banff cg scoring. Kidney Int. 2022 Nov 24:S0085-2538(22)00967-X. doi: 10.1016/j.kint.2022.10.024. Epub ahead of print. PMID: 36436680.
- Naesens M, Roufosse C, Haas M, Lefaucheur C, Mannon RB, Adam BA, Aubert O, Böhmig GA, Callemeyn J, Clahsen-van Groningen M, Cornell LD, Demetris AJ, Drachenberg CB, Einecke G, Fogo AB, Gibson IW, Halloran P, Hidalgo LG, Horsfield C, Huang E, Kikić Ž, Kozakowski N, Nankivell B, Rabant M, Randhawa P, Riella LV, Sapir-Pichhadze R, Schinstock C, Solez K, Tambur AR, Thaunat O, Wiebe C, Zielinski D, Colvin R, Loupy A, Mengel M. The Banff 2022 Kidney Meeting Report: Reappraisal of microvascular inflammation and the role of biopsy-based transcript diagnostics. Am J Transplant. 2023 Oct 28:S1600-6135(23)00818-3. Doi:10.1016/j.ajt.2023.10.016. Epub ahead of print. PMID: 38032300.
- Roufosse C, Naesens M, Haas M, Lefaucheur C, Mannon RB, Afrouzian M, Alachkar N, Aubert O, Bagnasco SM, Batal I, Bellamy COC, Broecker V, Budde K, Clahsen-VanGroningen M, Coley SM, Cornell LD, Dadhania D, Demetris AJ, Einecke G, Farris AB, Fogo AB, Friedewald J, Gibson IW, Horsfield C, Huang E, Husain SA, Jackson AM, Kers J, Kikić Ž, Klein A, Kozakowski N, Liapis H, Mangiola M, Montgomery RA, Nankinvell B, Neil DAH, Nickerson P, Rabant M, Randhawa P, Riella LV, Rosales I, Royal V, Sapir-Pichhadze R, Sarder P, Sarwal M, Schinstock C, Stegall M, Solez K, van der Laak J, Wiebe C, Colvin RB, Loupy A, Mengel M. The Banff 2022 Kidney Meeting Work Plan: Data-driven refinement of the Banff Classification for renal allografts. Am J Transplant. 2023 Nov 4:S1600-6135(23)00855-9. doi: 10.1016/j.ajt.2023.10.031. Epub ahead of print. PMID: 37931753.
- Kikić Ž, Kainz A, Kozakowski N, Oberbauer R, Regele H, Bond G, Böhmig GA. 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.
- Kozakowski N, Herkner H, Böhmig GA, Regele H, Kornauth C, Bond G, Kikić Ž. The diffuse extent of peritubular capillaritis in renal allograft rejection is an independent risk factor for graft loss. Kidney Int. 2015 Aug;88(2):332-40.
- Kozakowski N, Herkner H, Eskandary F, Eder M, Winnicki W, Bond G, Kikić Ž. An integrative approach of assessing peritubular capillaritis extent and score in low-grade microvascular inflammation – associations with transplant glomerulopathy and graft loss. Nephrol Dial Transplant. 2019 Jan 1;34(1):166-174