Background: Over time grafts develop arteriosclerosis (ART)and arteriolar hyalinosis (AH). Previous studies associated AH with calcineurin inhibitors (CNI), diabetes (DM), kidney age and hypertension. Other studies suggested that ART may relate to the presence of donor specific antibodies (DSA). We re-examine the development of new ART and AH post-KTX using protocol and clinical biopsies in a large KTX cohort.

Methods: Included 1721 adult, conventional single center KTX (1998-2014),51+14.4 yo, 61% males, 81.4% living donors, 25% DM. None had moderate-severe ART or AH at time 0 biopsy. T cell depletion used in 83% and CNI maintenance in 95%. End points were de novo moderate-severe ART_m/s or AH_m/s in protocol or clinical biopsy and death-censored graft survival.

Results: The incidence of ART_m/s and AH_m/s increased with time. At 1,5 and 8 years the cumulative incidence of ART_m/s was 11.6%, 43% and 66% and for AH_m/s 4.4%, 35% and 69.7%. AH_m/s was associated with reduced death-censored graft survival (time dependent, HR=3.89 (2.54-5.94), p<0.0001) independent of recipient/donor age, HLAmm, DSA, graft function and acute rejection. ART_m/s also independently related to reduced graft survival (time dependent HR=2.21 (1.47-3.33), p<0.0001). AH_m/s developed more commonly in older donor grafts (HR=1.36 (1.32-1.41), p<0.0001 multivariate Cox), DSA class II at KTX (HR=1.81 (1.37-2.38), p<0.0001) and younger recipients (HR=0.88 (0.85-0.91), p=0.005). ART_m/s also developed more commonly in older donor grafts (HR=1.43 (1.39-1.48), p<0.0001) and DSAII (HR=1.84 (1.46-2.36)). In contrast neither ART_m/s or AH_m/s related to DM, DSA class I, donor type, blood pressure or lipid levels at one year. DSAII at KTX related to earlier and more rapid development of ART_m/s (1 & 5 years: DSAII+, 23.2% and 64.6% vs DSAII-, 13.2% and 48.0%) and AH_m/s (1 & 5 years: DSAII+, 5.7% and 51.7% vs DSAII-, 3.6% and 31.5%). When divided into quartiles by donor age (<34,34-44,45-53,>53) the incidence of ART_m/s at 5 years was 29%, 38%, 44% and 69%, and incidence of AH_m/s was 13.9%, 30.5%, 33% and 62%.

Conclusions: ART_m/s and AH_m/s develop progressively and relate to reduced graft survival. DSAII relate to earlier and more rapid ART_m/s and AH_m/s. Increasing donor age related to lesion development suggesting that the graft is programmed to respond to injuries according to their age at transplant. Identifying grafts at risk for vascular lesions will allow testing for vascular protective maneuvers.

CITATION INFORMATION: El Ters M., Cornell L., Grande J., Cosio F. Kidney Allograft Vascular Disease Post-Transplant (KTX): Risk Factors and Implications Am J Transplant. 2017;17 (suppl 3).

« Back to 2018 American Transplant Congress