C-Reactive Protein as a Biomarker of Inflammation and Graft Injury After Kidney and Heart Allo- and Xenotransplantation Into Non-Human Primates.

Abstract

Introduction: C-reactive protein (CRP) is a widely used inflammatory biomarker. We evaluated CRP alongside tissue injury markers in non-human primate (NHP) models of kidney and heart allo- and xeno-transplantation to assess CRP's sensitivity in detecting graft-specific inflammatory responses (acute rejection), and explored CRP elevations in the absence of clinically evident graft injury. A secondary objective compared CRP dynamics between NHP species.

Methods: Forty-two baboon or cynomolgus monkey NHPs received kidney (n = 12) or heart (n = 7) xenografts, or kidney (n = 12) or heart (n = 11) allografts. In serum obtained before transplant, after graft revascularization on the day of transplant, and at defined post-operative intervals, CRP, creatinine (kidney), and troponin-I (heart) were measured and correlated with clinical events and histopathology.

Results: Baboons exhibited higher baseline and pre-transplant CRP levels than cynomolgus monkeys (p < 0.05). Following kidney xenotransplantation, CRP rose to higher levels in baboons than cynomolgus monkeys (p < 0.05). In association with episodes of histologically confirmed graft rejection, CRP elevations preceded rises in creatinine (kidney) or troponin-I (heart) by 7-14 days. Additionally, CRP elaboration was observed in association with opportunistic infection and surgical procedures such as graft biopsies.

Conclusion: As reflected by CRP dynamics, systemic inflammation is associated with organ allo- and xenotransplantation in NHPs. We conclude that CRP is a potentially valuable marker of inflammation that, when interpreted alongside organ-specific biomarkers, quantifies the severity of immune activation associated with graft injury and detects additional inflammatory events, which may be clinically occult but influence experimental outcomes. CRP could be a valuable biometric adjunct in multi-parametric inflammation monitoring in transplantation and other disease models.