Leukocyturia and hematuria enable non-invasive differentiation of Bowman's capsule rupture severity in PR3-ANCA glomerulonephritis

Background Renal involvement is a common and severe complication of anti-neutrophil cytoplasmic antibody-(ANCA)-associated vasculitis potentially resulting in pauci-immune necrotizing and crescentic ANCA glomerulonephritis (GN) with rapid deterioration of kidney function, progression to end stage kidney disease or, if left untreated, lethal exitus. Analysis of the urinary sediment routinely supports clinical management of ANCA GN, but histopathological implications of aberrancies in the urinary sediment mostly remain elusive. Therefore, we aimed to systematically assess the correlation of aberrancies in the urinary sediment and clinico-pathologic findings.Methods A total of 42 kidney biopsies with ANCA GN were retrospectively analyzed in a single-center observational study. Laboratory and histopathological parameters were systematically analyzed and correlated with findings of the urinary sediment.Results In the overall ANCA GN cohort, leukocyturia and hematuria were associated among each other, and with markers for non-selective glomerular damage, respectively. Non-invasive measurement of leukocyturia indicated focal (but not extensive) Bowman's capsule rupture (BCR) specifically in proteinase-3 (PR3)-ANCA GN, whereas hematuria correlated with extensive (but not focal) BCR. Concerning intrarenal immune cell infiltration, leukocyturia was associated with tubulointerstitial plasma cell infiltration in PR3-ANCA GN. Finally, none of these associations were detectable in myeloperoxidase-ANCA GN, implying different modes of kidney damage.Conclusion We herein expand our current knowledge by providing evidence that leukocyturia and hematuria enable non-invasive differentiation of BCR severity specifically in PR3-ANCA GN.

Automated summary

This study found that abnormalities in the urinary sediment are associated with clinical and pathological features of anti-neutrophil cytoplasmic antibody-associated vasculitis. Specifically, leukocyturia is associated with non-selective glomerular damage markers, while hematuria is correlated with the extent of Bowman's capsule rupture. In patients with PR3-ANCA, leukocyturia is also associated with tubulointerstitial plasma cell infiltration. These associations were not found in myeloperoxidase-ANCA GN, indicating different modes of kidney damage.