*Purpose: We aimed to identify clinical, serological and histopathological predictors of graft loss in kidney transplant recipients who underwent clinically indicated graft biopsies for worsening kidney function and/or proteinuria. We especially aimed to investigate the effect of interstitial inflammation on allograft outcome.

*Methods: We retrospectively evaluated 516 patients who underwent kidney transplant biopsy between January 2009 and January 2018. Acute and chronic allograft injury scores of Banff classification were used. We sub grouped the patients with chronic allograft injury score (ci+ct+cv) ≥ 3 or < 3 and sub grouped per interstitial inflammation (i score=0 and > 0) and compared to biopsies with both ci+ct+cv and i=0. Anti-HLA antibodies were studied using Luminex SAB at the time of the biopsy

*Results: Transplant kidneys biopsies are done at a median 12.5 months after kidney transplantation. The histopathological diagnosis were as following: acute antibody-mediated rejection (AMR) (6%), acute T-cell mediated rejection (9.3%), chronic AMR (6.7%), transplant glomerulopathy without donor-specific antibody (DSA) (10.2%), recurrent/de novo glomerular disease (10.8%), BKV nephropathy (2.5%), and the rest 54.2% had other diagnosis (normal, acute tubular necrosis, or non-specific interstitial fibrosis/tubular atrophy). During a median follow up of 59.3 months after kidney biopsy, 36 %recipients lost their graft. In univariate analysis, the following factors were significant for graft loss: Black race (p=0.005), previous rejection (p<0.0001), DSA at the time of biopsy (p=0.014), DSA-B (p=0.0017), DSA-C (p=0.016), DSA-DQ (p=0.0021), DSA-DR (p=0.039), ci+ct+cv ≥ 3 (p=0.0485), ci+ct+cv ≥ 3 with interstitial inflammation > 0 ( p<0.0001), microvascular inflammation (p=0.0052), C4d positivity ( p=0.008), serum creatinine at time of the biopsy (p<0.0001), and spot urine protein/creatinine ( <0.0001). In the multivariate analysis ci+ct+cv < 3 with i>0 has the highest hazard ratio followed by ci+ct+cv ≥ 3 with i>0, ci+ct+cv ≥ 3 with i=0, black race, serum creatinine, and spot urine protein/creatinine

*Conclusions: Interstitial inflammation on top of chronic allograft injury is the best predictor for allograft loss after clinically indicated kidney biopsy regardless of the severity of chronic allograft injury score. We suggest that Interstitial inflammation on top of chronic allograft injury should be validated and recognized in the future revision of Banff classification

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