Recognition that allograft microvascular inflammation can occur in the absence of circulating donor-specific anti-HLA antibodies (DSAs) led to the inclusion of two new categories in the diagnostic framework of the 2022 Banff Classification of Renal Allograft Pathology: ‘microvascular inflammation or injury (MVI), DSA-negative, and C4d-negative’, which includes cases of allograft rejection with no evidence of an antibody-mediated response; and ‘probable antibody-mediated rejection’, which includes DSA-positive cases with mild microvascular inflammation but without C4d deposition. New findings presented at ASN Kidney Week 2024 and published in the New England Journal of Medicine provide insights into the clinical importance of these new phenotypes. “Our study revealed distinct phenotypes of microvascular inflammation, each associated with a varying risk of disease progression and long-term graft failure,” explains researcher Alexandre Loupy. “It highlights the importance of clinically recognizing these phenotypes to standardize renal diagnostics and improve patient risk stratification and treatment.”

Assessment of long-term graft outcomes revealed that despite similar clinical features at presentation, kidney transplant recipients with evidence of microvascular inflammation according to the 2022 Banff classification had a higher risk of alloimmune-mediated disease progression and worse long-term graft survival than patients with nonrejection-related diagnoses. Specifically, patients with a diagnosis classified as MVI, DSA-negative, and C4d-negative or probable antibody-mediated rejection had a higher cumulative incidence of antibody-mediated rejection compared with patients without a diagnosis of microvascular inflammation over a median of 5-years follow-up but a lower cumulative incidence compared with patients with active antibody-mediated rejection. Likewise, the risk of development or progression of transplant glomerulopathy was similar between the two microvascular inflammation phenotypes but lower than that of patients with active antibody-mediated rejection.