Tubulointerstitial nephritis: diagnosis, treatment, and monitoring

Abstract

Tubulointerstitial nephritis (TIN) is a frequent cause of acute kidney injury (AKI) that can lead to chronic kidney disease (CKD). TIN is associated with an immune-mediated infiltration of the kidney interstitium by inflammatory cells, which may progress to fibrosis. Patients often present with nonspecific symptoms, which can lead to delayed diagnosis and treatment of the disease. Etiology can be drug-induced, infectious, idiopathic, genetic, or related to a systemic inflammatory condition such as tubulointerstitial nephritis and uveitis (TINU) syndrome, inflammatory bowel disease, or immunoglobulin G4 (IgG4)-associated immune complex multiorgan autoimmune disease (MAD). It is imperative to have a high clinical suspicion for TIN in order to remove potential offending agents and treat any associated systemic diseases. Treatment is ultimately dependent on underlying etiology. While there are no randomized controlled clinical trials to assess treatment choice and efficacy in TIN, corticosteroids have been a mainstay of therapy, and recent studies have suggested a possible role for mycophenolate mofetil. Urinary biomarkers such as alpha1- and beta2-microglobulin may help diagnose and monitor disease activity in TIN. Screening for TIN should be implemented in children with inflammatory bowel disease, uveitis, or IgG4-associated MAD.

Keywords: Acute kidney injury; Chronic kidney disease; Inflammatory bowel disease; Monitoring; TINU syndrome; Treatment; Tubulointerstitial nephritis.

Figure 1. Renal Histopathology in tubulointerstitial nephritis (TIN)

A. TIN with predominantly lymphocytic infiltrate associated with tubular damage and tubulitis (arrow). Periodic acid Schiff stain, original magnification × 400. B. Acute drug-induced tubular injury, in this case secondary to cidofovir. There is interstitial infiltrate (*), edema (#) and marked tubular regenerative changes (arrows). Glomeruli show little change. Hematoxylin and eosin stain, original magnification × 200. C. Granulomatous tubulointerstitial nephritis (arrow), in this case likely secondary to lamotrigine. Hematoxylin and eosin stain, original magnification × 200.

Figure 2. Ophthalmologic findings in tubulointerstitial nephritis with uveitis (TINU)

A. Anterior uveitis complicated by posterior (irido-lenticular) synechiae (arrows). B. Panuveitis with endothelial precipitates and chronic anterior synechiae (arrows). C. Fundus photograph of a patient with panuveitis demonstrating retinal infiltrates.