Acute renal injury in ANCA-associated glomerulonephritis: etiology related to acute tubulointerstitial injury versus glomerular injury

Acute kidney injury (AKI) is common in anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA GN). Although ANCA GN has crescents in 90% of cases, the crescentic form occurs in only 20 to 30%, so it is challenging to attribute acute kidney injury (AKI) solely to the glomerular component. In contrast, IgA nephropathy (IgAN), while also frequently demonstrating crescent formation, is associated with a notably lower incidence and severity of AKI compared to ANCA GN. This discrepancy suggests that acute tubulointerstitial injury may constitute a more prominent-and previously underrecognized-contributor to AKI in ANCA GN. This study aimed to compare tubulointerstitial injury between ANCA GN and IgAN after matching for glomerular injury, and to assess its impact on AKI in ANCA GN. Propensity score matching were used to compare 48 ANCA GN patients and 48 IgAN patients, matched for age, sex, and glomerular injury parameters. We compared the disparities in tubulointerstitial injury in the renal pathology of ANCA GN and IgAN and analyzed the influence of tubulointerstitial injury on AKI in ANCA GN. ANCA GN had more severe acute tubulointerstitial injury, alongside higher serum creatinine (<i>p</i> = 0.048) and AKI incidence (31.3% vs 4.2%, <i>p</i> < 0.001) than IgAN. In patients with ANCA GN, whether the influence of glomerular injury is corrected, patients with interstitial cell infiltration > 25% exhibit higher levels of serum creatinine. Acute tubulointerstitial injury is a major contributor to AKI in ANCA GN, independent of glomerular injury, highlighting its clinical significance in the acute disease phase.