Chronic Histologic Changes Are Present Regardless of HLA Mismatches: Evidence from HLA Identical Living Donor Kidney Transplants

BACKGROUND At 5 and 10 years after kidney transplantation, chronic histologic changes such as arteriolar hyalinosis and mesangial expansion are common, however, determining etiology is difficult. We compared surveillance biopsies in living donor kidney transplants (LDKTx) from HLA matched siblings (termed HLA-identical (HLA-ID)) to HLA non-ID to investigate which histologic changes were likely due to alloimmune injury and which were due to non-alloimmune injury. METHODS We performed a retrospective, cohort study comparing HLA-ID sibling LDKTx (n=175) to HLA non-ID LDKTx (n=175; matched for age, sex and year of transplant +/- 2 years) performed at a single institution from 03/1999 to 11/2018. RESULTS Baseline characteristics and maintenance immunosuppression were similar. Mortality rates were similar, but in the HLA-ID group, 10-year death-censored graft survival was higher (93.8% vs 80.9% HLA non-ID LDKTx, p<0.001), rejection rates were lower (after 1 year 9.6% vs 27.1%; p<0.001) and Banff inflammation scores including glomerulitis and peritubular capillaritis were lower on surveillance biopsies at 1, 5 and 10 years. In contrast, chronic Banff scores (interstitial fibrosis, arteriolar hyalinosis, mesangial expansion, etc.) were similar in prevalence and severity on surveillance biopsies at 1, 5 and 10 years. CONCLUSIONS HLA-ID LDKTx have less inflammation and less transplant glomerulopathy, but most chronic histologic changes were similar to less-well matched LDKTx. We conclude that these types of chronic changes are not associated with HLA mismatches and may be due to non-immunologic causes (hypertension, obesity, etc.) suggesting that new management approaches to prevent these lesions may be needed.