*Purpose: In preclinical studies, ischemia reperfusion injury and older donor age are associated with renal inflammation in the early phase after transplantation. In human kidney transplantation, impaired renal allograft function in the first days after transplantation is often adjudicated to donor- and procedure-related characteristics such as donor age, type of donor and cold ischemia time. However, the contribution of ischemia reperfusion injury to the histology of early kidney transplant biopsies remains unstudied.

*Methods: In a cohort of 1000 kidney recipients, transplanted between March 2004 and February 2013, a total of 335 indication biopsies were performed in 297 patients within the first 14 days after transplantation. The histological picture of these biopsies and its relation with donor- and procedure-related characteristics were studied.

*Results: Early indication biopsies were more often performed in allografts from older donors, with more HLA mismatches and more often pretransplant HLA-DSA, with recipients more often on a standard immunosuppression regimen, having higher body mass index, and of Caucasian descent. Patients with an early indication biopsy experienced more often graft failure during follow-up compared to patients without biopsy in the first 14 days (23.9% vs. 11.8% respectively, p<0.0001). Biopsies displayed microvascular inflammation (g + ptc) score ≥2 in 29.6% and tubulo-interstitial score (t + i) ≥2 in 49.6%. Rejection (TCMR, ABMR or mixed rejection) was diagnosed in 190 of 335 (56.7%) biopsies and associated with pretransplant HLA-DSA (HR 3.40, p <0.0001) and HLA mismatches (HR 1.29, p <0.0001) in multivariate Cox regression analysis. Cold ischemia time, donor age and donor type (living donor vs. donor after brain death vs. donor after cardiac death) were not identified as independent risk factors for early rejection, microvascular inflammation or tubulo-interstitial inflammation.

*Conclusions: These data illustrate that the contribution of ischemia-reperfusion injury to renal inflammation after human kidney transplantation needs to be revisited. Indication biopsies performed in the earliest days after kidney transplantation often display inflammatory changes, related to allo-immune risk factors. In contrast to preclinical observations, non-immune factors like cold ischemia time, older donor age and donor type do not explain such early inflammation in the human setting.

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