ASSAYS TO PREDICT ALLOGRAFT REJECTION

J. Kers¹, Y. Xu-dubois², F. Bemelman³, J. Roelofs¹, M. Idu⁴, E. Rondeau⁵, I. Ten berge³, S. Florquin^1
1Pathology, Academic Medical Center, Amsterdam/NETHERLANDS, ²Inserm Unit 702, Tenon Hospital, Paris/FRANCE, ³Renal Transplant Unit, Department Of Internal Medicine, Academic Medical Center, Amsterdam/NETHERLANDS, ⁴Surgery, Academic Medical Center, Amsterdam/NETHERLANDS, ⁵Nephrology & Kidney Transplantation, Tenon Hospital, Paris/FRANCE

Body: Introduction: The development of interstitial fibrosis and tubular atrophy (IF/TA) is the main histological feature involved in long-term renal allograft deterioration. We hypothesize that de novotubular expression of CD44, a glycoprotein receptor for hyaluronan and osteopontin and involved in renal fibrosis, can operate as a surrogate marker to predict the late development of IF/TA anddecline in renal function. Methods: Six months protocol renal allograft biopsies (n = 30 for matching 12 months GFR and n = 20 for matching 12 months protocolar biopsy) were immunostained for CD44,semi-quantitatively scored by three raters of two centres and compared with 12 months Banff scores and eGFR (calculated with the MDRD formula). The inter-observer agreement was calculated on thetotal set of biopsies (n = 50). Results: De novo CD44 tubular expression at 6 months was correlated with both Banff IF/TA score (r = 0,471 and p = 0,042) and eGFR (r = -0,544 and p = 0,002) at 12months. Patients with CD44 expression in more than 10% of tubules (positive) at 6 months had a more pronounced decline in renal function than patients with CD44 expression in less than 10% of tubules(negative) (GFR at 12 months: median 38,5 ml/min versus 58,5 ml/min positive versus negative group respectively, p < 0,001). The inter-observer agreement was excellent (Kendall's W-coefficient:0,69, p < 0,001). Conclusion: In summary, de novo tubular expression of CD44 is a surrogate marker for development of IF/TA in renal allograft and declined renal function. The semi-quantitativescoring system used in this study is reproducible among raters of different medical centers. Future area under the receiver operating characteristic analysis (AUROC) on large patient cohorts mustvalidate predictive value for tubular epithelial CD44 expression in the long-term follow-up after renal transplantation.

Disclosure: All authors have declared no conflicts of interest.