P1601COMPLEMENT MEMBRANE ATTACK COMPLEX DURING THE FIRST WEEK AFTER KIDNEY TRANSPLANTATION AS SEVERITY BIOMARKER TO DELAYED GRAFT FUNCTION
Authors: Arias-Cabrales Carlos , Riera Marta , Pérez-Sáez Maria José , Gimeno Javier , Burballa Carla , Buxeda Anna , Benito David , Redondo Pachon Dolores , Crespo Marta , Pascual Julio , Rodríguez-Garcia Eva 
Published: June 2020

Abstract

Background and Aims
Ischemia-reperfusion (I/R) damage is a relevant cause of delayed graft function (DGF). Complement activation is involved in experimental I/R injury, but few data are available about the expression of the complement cascade final component -membrane attack complex (MAC)- and I/R injury in KT patients. We studied the dynamics of membrane attack complex (MAC) as plasma fraction (pMAC) and the histological deposit pattern of C3b, complement factor H (FH) and MAC in DGF patients.

Method
We evaluated pMAC levels in 59 recipients, 38 with immediate graft function and 21 without serum creatinine decreased at day 7 (DGF). pMAC was measured at admission for KT (day 0) and 7 days after KT (day 7). Sandwich ELISAs were used to measure MAC. Additionally, we performed imunohistoquimical stained for MAC, C3b and kidney biopsies (KB) with DGF (n=12) and a control group of one-year protocol biopsies without damage (n=4)

Results
Patients in the DGF group were older, more frequently diabetics and received kidneys from older donors and more frequently controlled cardio-circulatory death type.
Day0 and day7 post-KT pMAC levels were similar in non-DGF patients 5902±3049 mAu/L vs 6178±2882 mAu/L; p=0.686). However, patients with DGF showed a significant increase of pMAC levels between day0 and day7 (6621±2202 mAu/L vs 9625±4142 mAu/L; p=0.006. Figure 1
Percentage pMAC levels increase (Δ0-7 pMAC%) discriminative assessment analyzed by ROC curve showed a good discriminative value for DGF with an AUC of 0.78; p&lt;0.001 (sensitivity 81%, specificity 66% by cut-off point of 5%). In patients with DGF longer than ten days, we found more frequently patients with a Δ0-7 pMAC &gt;5% (83% vs 17% Δ0-7 pMAC &lt;5% ; p=0.003).Patients with DGF showed renal function at 3 and 6 months, but worse renal function 1 year after KT (serum creatinine 1.78±0.61 vs 1.35±0.30 mg/dl in non-DGF patients). DGF patients with Δ0-7 pMAC &gt;5% displayed worse renal function 1 and 2 year after KT compared to DGF patients with Δ0-7 pMAC &lt;5%.
MAC, C3b and FH stains were observed in tubular epithelial cells basal membrane. DGF-kidney biopsies showed more frequently high-intensity stain for MAC and FH than controls, without differences to C3b stain. DGF-kidney biopsies also showed a higher number of tubules with positive stain and larger perimeter of tubules with positive stains for MAC, C3b and FH than the controls. Figure 2.
Among the 12 patients with DGF-biopsies, three (25%) never recovered renal function, all of them presented Δ0-7 pMAC &gt;5% and intense, diffuse and positive staining in more than 50% of tubular perimeter for MAC, FH and C3b

Conclusion
Complement activation during peritrasplant period could be related with the severity of graft injury and the presence of DGF. Therefore, the determination of MAC levels could be useful to identify patients with possible complement dependent graft injury that might benefit from complement inhibitor therapies