Tubulointerstitial nephritis in antineutrophil cytoplasmic antibody-associated vasculitis with monoclonal gammopathy

Abstract

Isolated tubulointerstitial nephritis (TIN) without glomerular crescent formation is a rare manifestation of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Some patients with monoclonal gammopathy of undetermined significance present with renal complications due to serum monoclonal protein. Here, we present a case of TIN presumably attributable to AAV with monoclonal gammopathy. Laboratory data revealed acute kidney injury, elevated C-reactive protein (CRP) and ANCA titers, and elevated tubular injury markers. Renal biopsy revealed TIN with no apparent glomerular lesion. The findings of peritubular capillaritis and tubulitis indicated that AAV had contributed to the development of TIN. However, in situ hybridization for free light chains revealed kappa light chain restriction, indicating that the involvement of monoclonal gammopathy in the pathogenesis of TIN remains possible. The patient also developed ophthalmic neuropathy, probably caused by AAV. Oral prednisone (0.6 mg/kg/day) administration improved both the ocular symptoms and the laboratory parameters. Our case demonstrated that the concurrence of AAV and monoclonal gammopathy could pose a diagnostic dilemma in distinguishing the cause of TIN. Besides, some reports suggest an association between AAV and monoclonal gammopathy, although direct evidence is lacking. Further research is needed to establish this association.

Keywords: ANCA-associated vasculitis (AAV); Antineutrophil cytoplasmic antibody (ANCA); Monoclonal gammopathy; Peritubular capillaritis (PTCitis); Tubulointerstitial nephritis (TIN).

Fig. 1

Photomicrographs of renal biopsy. A Peritubular capillaritis. Infiltration of neutrophils in the capillary lumen and the surrounding area is observed (A: periodic acid–Schiff staining ×400). B Infiltration of neutrophils inside the tubule is also detected (periodic acid–Schiff staining ×400, black arrows). Some tubules show necrotic debris with neutrophils inside the tubular lumen (periodic acid–Schiff staining ×400, black arrowheads). C High magnification of the renal interstitium shows mononuclear cell infiltration, although plasma cells are also remarkable (hematoxylin and eosin staining ×400). D Glomeruli are almost normal, except for neutrophil infiltration into the capillary loops and vascular pole (periodic acid–Schiff staining ×400, black arrowheads)

Fig. 2

A Immunohistochemistry for CD31 showed loss of peritubular capillaries (black arrows). B With mononuclear cell infiltration in the renal interstitium. Mouse monoclonal anti-human CD31 antibody (Dako, Agilent Pathology Solutions, Santa Clara, CA, USA) was used. (A CD31 ×400, B hematoxylin and eosin staining ×400). C, D MPO (myeloperoxidase) immunostaining. C Although some cells exist on the normal glomerulus, most of the MPO-positive cells are mainly detected on the renal interstitium (×200). D MPO-positive cells also exist in the lumens of tubules and the peritubular area (×400)

Fig. 3

A, B Immunostaining for free light chains (FLCs). A Kappa light chain staining. (×400). B Lambda light chain staining (×400). C, D In situ hybridization (ISH) for FLCs. C ISH reveals positive kappa light chain plasma cell infiltration in the renal interstitium (×200). D Few lambda positive cells are detected (×200)

Fig. 4

A, B Electron microscopy. A No electron dense-deposits are found in glomerular basement membranes (×10,000). B No electron dense-deposits are found in tubular basement membranes. Neither tubular crystals nor phagolysosomes are observed in tubular epithelial cells (×1000). C IgG4 immunostaining. Few IgG4 positive cells are detected (×400)

Fig. 5

Clinical course. Changes in the serum level of Cr, CRP, MPO-ANCA titer, urine level of β2M and FLC ratio. Note that after oral corticosteroid administration, MPO-ANCA titers decreased to undetected levels, and his ocular symptoms completely resolved. Cr creatinine, CRP C-reactive protein, MPO-ANCA myeloperoxidase anti-neutrophil cytoplasmic antibody, urine β2M urine β2 microglobulin, FLC ratio free light chain ratio