Tubulointerstitial diseases: an updated framework for diverse and emerging entities

Area of Science:

• Nephrology
• Pathology
• Immunology

Background:

• Tubulointerstitial diseases (TIN) are a diverse group of kidney disorders lacking specific classification.
• Advances in personalized medicine necessitate greater diagnostic precision for TIN.
• Existing classifications struggle with overlapping histopathologic and immunophenotypic patterns.

Purpose of the Study:

• To provide an updated etiologic framework for tubulointerstitial nephritis/nephropathy (TIN) and tubular injury.
• To highlight recently identified TIN entities and their diagnostic evolution.
• To discuss the role of emerging technologies in refining TIN classification and diagnosis.

Main Methods:

• Literature review of tubulointerstitial diseases.
• Synthesis of current understanding of TIN etiology and classification.
• Discussion of novel TIN entities and future diagnostic approaches.

Main Results:

• An updated etiologic framework for TIN is proposed with eight categories: drug effect, autoimmune/immune-mediated, infection-associated, hereditary/genetic, toxic/metabolic, monoclonal protein-associated, mimics of TIN, and idiopathic/other.
• Recently described TIN entities, including immune checkpoint inhibitor-associated TIN, IgG4-related TIN, IgM plasma cell TIN, and VEXAS syndrome, are highlighted.
• The evolution of IgG4-related TIN serves as a model for recognizing new TIN entities.

Conclusions:

• Greater diagnostic precision in TIN is achievable and essential for personalized nephrology.
• Emerging technologies like digital pathology and AI hold promise for refining TIN classification and diagnostics.
• Collaborative efforts are vital to translate advancements into clinical practice for improved patient outcomes.