Anti-complement therapies are currently being tested in human kidney transplantation to prevent DGF. In this large prospective, cohort study of 469 deceased organ donors, we measured complement proteins C3a and C5a in donor urine collected at procurement and determined outcomes in 902 kidney recipients.

The complement proteins C3a and C5a were detectable at high levels in the deceased donor urine. Of 469 donors, 114 (23%) had AKI stage 1 or higher (AKI: serum creatinine elevation from admission to terminal value). Urine C5a was strongly positively associated with donor AKI (p<0.001). Compared to no AKI, median C5a concentration was 3-fold higher in AKI stage 2/3. 291 (32%) of the 902 kidney transplant recipients experienced DGF (DGF: any dialysis in the first post-transplant week). Donor Urine C5a was higher for the recipients with DGF compared to non-DGF (median 0.42 mg/ml, [interquartile range 0.15, 1.28] vs. 0.28 mg/ml [0.13, 0.87], p=0.002). Donor urine C5a levels remained independently associated with DGF after adjusting for known DGF risk factors. As C5a was associated with donor AKI stage, we examined the correlation between donor AKI and recipient DGF. 680 donor kidneys (72%) did not have AKI but 28% of these non-AKI kidneys developed DGF. In the absence of donor AKI, C5a levels remained strongly correlated and independently associated with recipient DGF. 216 donor kidneys (28%) had at least AKIN stage 1 and 45% of these AKI kidneys developed DGF. However, C5a was no longer associated with recipient DGF in the subgroup of kidneys from donors with AKI. Urine C3a in donors was not associated with AKI or DGF. Urine complement C3a and C5a levels were not associated with 6-month eGFR.

These data demonstrate that despite the absence of clinical donor AKI, C5a is able to predict recipient DGF. This data implies the potential use of urine C5a as a marker in kidneys without clinical AKI to predict subsequent DGF in the recipients. Targeting C5a signaling using stratification based on this biomarker may have value in preventing or treating post-ischemic acute kidney injury after transplantation.

CITATION INFORMATION: Schroppel B, Heeger P, Hall I, Doshi M, Weng F, Reese P, Parikh C. Deceased Donor Urine C5a Predicts Donor and Recipient Acute Kidney Injury. Am J Transplant. 2016;16 (suppl 3).

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