Early and Late Microvascular Inflammation Have Differing Etiological Causes and Clinical Expression.

Area of Science:

• Nephrology
• Transplantation Immunology
• Pathology

Background:

• Microvascular inflammation (MVI) is a key feature of antibody-mediated rejection (AMR) in kidney transplants.
• The impact of posttransplant time on the clinicopathological presentation of MVI is not well understood.

Purpose of the Study:

• To investigate how the timing of microvascular inflammation (MVI ≥ 2) influences its clinicopathological characteristics and impact on kidney transplant outcomes.
• To identify risk factors and consequences associated with early versus late MVI in kidney allografts.

Main Methods:

• Retrospective analysis of 3398 kidney transplant biopsies, with 202 cases of MVI ≥ 2 identified.
• Biopsies were dichotomized based on the median incidence time of 9 months post-transplant.
• Comparison of clinicopathological features, risk factors, and graft survival between early and late MVI groups and controls.

Main Results:

• MVI ≥ 2 occurred in 12.4% of kidney transplants and was associated with higher failure rates.
• Early MVI (before 9 months) was linked to delayed graft function, prior AMR, and donor-specific antibodies (DSAs), often presenting as AMR or cellular rejection with good outcomes.
• Late MVI (after 9 months) was associated with factors like nonadherence, underimmunosuppression, and AMR, showing worse interstitial fibrosis, tubular atrophy, C4d deposition, and poorer graft survival.

Conclusions:

• The temporal changes in MVI expression are driven by distinct mechanisms, including underimmunosuppression and AMR-related microvascular injury.
• These time-dependent differences in MVI significantly affect kidney allograft function and long-term survival.
• Addressing nonadherence and optimizing immunosuppression are crucial for managing late MVI and improving transplant outcomes.