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Tubulointerstitial nephritis without glomerular lesions in three patients with myeloperoxidase-ANCA-associated vasculitis

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Abstract

Background

Myeloperoxidase–antineutrophil cytoplasmic antibody (MPO–ANCA)-associated vasculitis frequently induces crescentic glomerulonephritis. However, a few cases have so far been reported to have only tubulointerstitial (TI) nephritis without any apparent glomerular lesions. We recently treated three similar cases. Therefore, their pathological features as well as clinical manifestations were studied in detail.

Methods

The pathological study was performed with immunohistochemical staining using various antibodies to the vascular endothelial cell surface markers, von Willebrand factor, type IV collagen, cytokeratin, E-cadherin, and MPO in addition to the routine histochemical examination.

Results

The study disclosed the loss of CD34 endothelial cell surface markers with and without the destruction of type IV collagen (capillary basement membrane) in the peritubular capillaries, even though the glomeruli showed good staining of these factors. Electron microscopy showed breaks in the capillary basement membrane. The loss of CD34 staining was associated with the infiltration of a few mononuclear cells and neutrophils in the lumen of peritubular capillaries and the surrounding interstitial tissues. The cytokeratin staining in the tubular epithelial cells was also diminished around these areas. Tubulitis was demonstrated with or without the destruction of the tubular basement membrane. The clinical manifestations of these three cases were only a few red blood cells and granular casts in the urinary sediment as well as slightly increased β2-microglobulin in the urine, but no proteinuria.

Conclusion

Based on these findings, the loss of CD34 vascular endothelial markers occurs in the early phase of the disease because of the MPO, which is presumed to have burst out from the infiltrated, activated neutrophils. This MPO, which releases proteolytic enzymes and radical oxygen species, acts on tissue destruction, namely the lysis of endothelial cell membranes as well as vascular basement membranes in the peritubular capillary. This mechanism eventually proceeds to the destruction of the peritubular capillary walls (vasculitis). This pathogenesis is thought to play an important role in the pathogenesis of TI nephritis, which is associated with MPO–ANCA vasculitis.

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Acknowledgments

This work was supported in part by grants (2004–2007) of the Research Committee of Refractory Vasculitis Syndrome sponsored by the Ministry of Health, Labor, and Welfare of Japan.

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Authors and Affiliations

  1. First Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan

    Kimimasa Nakabayashi, Katuko Sano, Akira Yamada, Miho Karube, Hitoshi Koji, Yoshihiro Arimura & Toshihiko Nagasawa

  2. Department of Pathology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan

    Ayumi Sumiishi & Yasunori Fujioka

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  1. Kimimasa Nakabayashi
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  2. Ayumi Sumiishi
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  9. Toshihiko Nagasawa
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Correspondence to Kimimasa Nakabayashi.

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Nakabayashi, K., Sumiishi, A., Sano, K. et al. Tubulointerstitial nephritis without glomerular lesions in three patients with myeloperoxidase-ANCA-associated vasculitis. Clin Exp Nephrol 13, 605–613 (2009). https://doi.org/10.1007/s10157-009-0200-8

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  • DOI: https://doi.org/10.1007/s10157-009-0200-8

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