The Pathophysiology and Impact of Inflammation in Nonscarred Renal Interstitium: The Banff i Lesion
| Autor: | Anita Achan, Jeremy R. Chapman, Brian J. Nankivell, Raghwa Sharma, Meena Shingde, Chow H. P'Ng, Jasveen Renthawa, Seethalakshmi Viswanathan |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Graft Rejection Male medicine.medical_specialty Time Factors viruses Biopsy T-Lymphocytes 030230 surgery Kidney Gastroenterology Risk Assessment Lesion 03 medical and health sciences 0302 clinical medicine Fibrosis Predictive Value of Tests Risk Factors Internal medicine medicine Humans Arteritis Longitudinal Studies Pathological Acute tubular necrosis Subclinical infection Transplantation Immunity Cellular Nephritis medicine.diagnostic_test business.industry Graft Survival Middle Aged medicine.disease Kidney Transplantation Pathophysiology Phenotype Treatment Outcome 030211 gastroenterology & hepatology Female medicine.symptom Atrophy business Immunosuppressive Agents |
| Zdroj: | Transplantation. 104(4) |
| ISSN: | 1534-6080 |
| Popis: | BACKGROUND Interstitial inflammation (i-INT) is the driver of T-cell-mediated rejection. Its causes, pathophysiology, kinetics, and outcomes are poorly documented. METHODS The role of i-INT was evaluated in 2055 biopsies from 775 renal transplant recipients. RESULTS i-INT was present in 374 (18.2% prevalence) from acute and subclinical rejection (67.4%); interstitial fibrosis and tubular atrophy (14.4%); BK virus nephropathy (BKVAN) 9.9%; and acute tubular necrosis (ATN with i-INT) in 5.9% of cases. i-INT was predicted by prior T-cell-mediated rejection and BKVAN, human leukocyte antigen mismatch, cyclosporine therapy, and indication biopsy for dysfunction. It correlated with tubulitis, arteritis, and antibody markers within concurrent histology (P < 0.001). After treatment, renal functional recovery was best with histological ATN, milder i-INT, and early posttransplant biopsy times. The initial histological improvement of inflammation depended on baseline i-INT severity. Complete resolution to Banff i0 was predicted by early biopsy time, antilymphocyte therapy, recipient age, and medication compliance (all P < 0.001). Clearance i-INT was followed by delayed resolution of tubulitis (P < 0.001). i-INT was associated with histological ATN, renal dysfunction, and increased incident fibrosis on sequential pathology. Progressive fibrosis following related-rejection i-INT was dependent on tubulitis using multivariable analysis. In contrast, fibrogenesis after BKVAN or ATN was unrelated to inflammation. i-INT cases were followed by recurrent rejection in 35.3%, increased graft loss, and greater patient mortality. Multiple complementary outcome analyses determined the optimal lower diagnostic threshold for inflammation was Banff i1 score. CONCLUSIONS i-INT is a heterogeneous pathological phenotype that results in adverse functional and structural outcomes, for which active and robust therapy should be considered. |
| Databáze: | OpenAIRE |
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