Inflammation in early kidney allograft surveillance biopsies and its relationship with de novo donor specific antibodies

Interstitial fibrosis and tubular atrophy (IFTA) associated with interstitial inflammation in non scarred areas (IFTA+i) is associated with poorer graft outcome than inflammation without IFTA or IFTA without inflammation. 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 one 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). 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 (OR 1.95, 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. This research has been accepted and published in Transplantation. © 2017 Lippincott, Williams & Wilkin

One‐year protocol biopsies from ABO

INTRODUCTION: Early acute antibody-mediated rejection (ABMR) occurs more frequently in ABO-incompatible (ABOi) than in ABO-compatible (ABOc) kidney transplantation. This could lead to increased inflammation/scarring in the ABOi grafts. Protocol biopsy data in ABOi kidney recipients are scarce. METHODS: A single-center retrospective matched cohort study was conducted. Eighty adult living donor (LD) renal transplant recipients without HLA donor-specific antibodies (DSA) transplanted between 2009 and 2012 were included; 20 ABOi and 60 ABOc controls matched for donor age and transplantation year. Protocol biopsies at one yr were scored according to the Banff classification. Three sums of scores were constructed: tubulointerstitial inflammation (t + i = 0 vs. >0), microvascular inflammation (g + ptc = 0 vs. >0), scarring/hyalinosis (ci + ct + cv + ah ≤ 1 vs. >1. Scores and presence of subclinical rejection (SCR) at one yr were compared. RESULTS: Protocol biopsy findings at one yr in the ABOi vs. ABOc matched control group were not statistically different: (t + i) > 0, 30% vs. 20%; (g + ptc) > 0, 5% vs. 8%; (ci + ct + cv + ah) > 1, 85% vs. 60%, respectively. No transplant glomerulopathy occurred. SCR rate at one yr was 30% vs. 18%, subclinical ABMR 5% vs. 7% (all with de novo HLA DSA). CONCLUSION: One-year protocol biopsies of ABOi and ABOc LD recipients do not differ in chronic changes, inflammation, or SCRs

One-year protocol biopsies from ABO-incompatible renal allografts compared with a matched cohort of ABO-compatible allografts

Abstract: Introduction: Early acute antibody-mediated rejection (ABMR) occurs more frequently in ABO-incompatible (ABOi) than in ABO-compatible (ABOc) kidney transplantation. This could lead to increased inflammation/scarring in the ABOi grafts. Protocol biopsy data in ABOi kidney recipients are scarce. Methods: A single-center retrospective matched cohort study was conducted. Eighty adult living donor (LD) renal transplant recipients without HLA donor-specific antibodies (DSA) transplanted between 2009 and 2012 were included; 20 ABOi and 60 ABOc controls matched for donor age and transplantation year. Protocol biopsies at one yr were scored according to the Banff classification. Three sums of scores were constructed: tubulointerstitial inflammation (t + i = 0 vs. >0), microvascular inflammation (g + ptc = 0 vs. >0), scarring/hyalinosis (ci + ct + cv + ah ≤ 1 vs. >1. Scores and presence of subclinical rejection (SCR) at one yr were compared. Results: Protocol biopsy findings at one yr in the ABOi vs. ABOc matched control group were not statistically different: (t + i) > 0, 30% vs. 20%; (g + ptc) > 0, 5% vs. 8%; (ci + ct + cv + ah) > 1, 85% vs. 60%, respectively. No transplant glomerulopathy occurred. SCR rate at one yr was 30% vs. 18%, subclinical ABMR 5% vs. 7% (all with de novo HLA DSA). Conclusion: One-year protocol biopsies of ABOi and ABOc LD recipients do not differ in chronic changes, inflammation, or SCRs

Tacrolimus and mycophenolate regimen and subclinical tubulo-interstitial inflammation in low immunological risk renal transplants

The aim was to evaluate the relationship between maintenance immunosuppression, subclinical tubulo-interstital inflammation and interstitial fibrosis/tubular atrophy (IF/TA) in surveillance biopsies performed in low immunological risk renal transplants at two transplant centers. The Barcelona cohort consisted of 109 early and 66 late biopsies in patients receiving high tacrolimus (TAC-C0 target at 1-year 6-10 ng/mL) and reduced MMF dose (500 mg bid at 1-year). The Oslo cohort consisted of 262 early and 237 late biopsies performed in patients treated with low TAC-C0 (target 3-7 ng/mL) and standard MMF dose (750 mg bid). Subclinical inflammation, adjusted for confounders, was associated with low TAC-C0 in the early (OR: 0.75, 95%CI: 0.61-0.92; p=0.006) and late biopsies (OR: 0.69, 95%CI: 0.50-0.95; p=0.023) from Barcelona. In the Oslo cohort, it was associated with low MMF in early biopsies (OR: 0.90, 95%CI: 0.83-0.98; p=0.0101) and with low TAC-C0 in late biopsies (OR: 0.77, 95%CI: 0.61-0.97; p=0.0286). MMF dose was significantly reduced in Oslo between early and late biopsies. IF/TA was not associated with TAC-C0 or MMF dose in the multivariate analysis. Our data suggest that in TAC and MMF based regimens, TAC-C0 levels are associated with subclinical inflammation in patients receiving reduced MMF dose. This research has been accepted and published in Transplant International. © 2017 Wile