Inflammation in Early Kidney Allograft Surveillance Biopsies With and Without Associated Tubulointerstitial Chronic Damage as a Predictor of Fibrosis Progression and Development of De Novo Donor Specific Antibodies

In Brief Background Interstitial fibrosis and tubular atrophy (IFTA) associated with interstitial inflammation in nonscarred areas (IFTA+i) is associated with poorer graft outcome than inflammation without IFTA or IFTA without inflammation. Methods We evaluated if histological categories at week 6 could predict the development of interstitial fibrosis and de novo donor specific anti-HLA antibodies (dnDSA) at 1 year. Biopsies were classified according to Banff criteria as normal (i+t≤1 and ci+ct≤1), inflammation (i+t≥2 and ci+ct≤1), IFTA (i+t≤1 and ci+ct≥2) or IFTA+i (i+t≥2 and ci+ct≥2). Results We analyzed 598 standard immunological risk recipients. The histological diagnosis at 6 weeks was: normal (n = 206), inflammation (n = 29), IFTA (n = 255), and IFTA+i (n = 108). Moderate/severe interstitial fibrosis (ci≥2) at 1 year was observed in 4.2% of patients with prior (6 weeks) normal histology, in 3.4% with inflammation, in 13.8% with IFTA, and in 24.5% with IFTA+i (P = 0.0001). Fifty-three recipients (8.9%) had dnDSA at 1 year. Independent predictors of development of dnDSA at 1 year were: HLA-DR mismatches (odds ratio [OR], 1.95; 95% confidence interval [95% CI], 1.09-3.49), the presence of inflammation (OR, 5.49; 95% CI, 1.67-18.03) or IFTA+i (OR, 4.09; 95% CI, 1.67-10.0) in the 6-week surveillance biopsy. Conclusions Early subclinical inflammation in surveillance biopsies with or without tubulointerstitial chronic lesions is associated with an increased risk of dnDSA development. Retrospective sequential histological analysis suggests that subclinical inflammation in surveillance kidney biopsies with or without tubulo-interstitial chronic lesions at 6 weeks is associated with an increased risk of de novo donor specific anti-HLA antibody development at 1 year.