Clinicopathologic Spectrum of Renal Lesions Following Anti-TNF- Inhibitor Therapy: A Single Center Experience

Background Anti-TNF alpha inhibitors, as biological agents, are used in autoimmune inflammatory states, rheumatoid arthritis (RA), psoriatic arthritis (PA), and Crohn disease. They can induce autoimmune serologic responses and clinical disorders, including systemic vasculitis and lupus-like diseases, affecting the kidney. Methods Retrospective analysis of clinicopathologic features of kidney disease after anti-TNF alpha therapy (treatment group) from our renal biopsy files from 2000 to 2018 is conducted and compared with 106 patients without therapy (control group). Results Forty-eight patients using anti-TNF alpha agents had renal biopsies: RA in 30, PA six, Crohn disease six, RA and PA one, RA and Crohn disease one, and others four. Twenty received etanercept, 15 adalimumab, eight infliximab, and five two forms of agents manifesting new-onset nephritic syndrome or CKD, 17 with AKI and 16 nephrotic syndrome, with recent ANCA and/or lupus serology. The renal lesions were crescentic GN in eight, pauciimmune-type in five, and ANCA1 in five. Lupus or lupus-like nephritis was seen in six: International Society of Nephrology/Renal Pathology Society 2018 class II-2, classV-2, class III1V-1, and class wIV1V-1, and concurrent fibrillary GN, scleroderma/thromboticmicroangiopathy (TMA), and amyloidosis in three. Renal lesions unrelated to anti-TNF alpha therapy or underlying autoimmune disease were noted in 23 patients (e.g., diabetic nephropathy, interstitial nephritis, acute tubular injury, infection-related GN); immunoglobulin A nephropathy, renal sarcoidosis, and amyloid A amyloidosis were noted in five patients. TMA was recognized in five patients, one associated with scleroderma and one anti-phospholipid antibodies, and two had nephrotic syndrome secondary to podocytopathy. The control group was similar with higher number of immune-mediated GN, interstitial nephritis, and amyloidosis. Conclusion: The renal lesions during anti-TNF alpha therapy have an autoimmune basis such as ANCA and lupus or lupus-like disease, correlated with new-onset serology, while others were similar to those observed in the control group. Renal biopsy findings integrated with clinical features and therapy can identify the underlying pathophysiologic process for appropriate management.