Tocilizumab-induced remission of nephrotic syndrome accompanied by secondary amyloidosis and glomerulonephritis in a patient with rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune-mediated systemic disorder that primarily affects the musculoskeletal system. Patients with RA often present with kidney diseases, such as nephrotic syndrome. Causes of nephrotic syndrome include membranous nephropathy, IgA nephropathy and secondary amyloidosis. Recently, biological agents, including anti-tumor necrosis factor alpha and anti-interleukin 6 (IL-6) receptor antibodies, have been used for the treatment of RA. Anti-IL-6 receptor antibody therapy is believed to ameliorate RA-related kidney diseases, as IL-6 plays a central role in the pathogenesis of RA. We, herein, present the case of a patient with RA and related nephrotic syndrome whose proteinuria completely disappeared 1 month after tocilizumab treatment. A light microscopic examination of the pretreatment kidney biopsy specimen showed active glomerulonephritis with fibrocellular crescents and the deposition of amorphous substances stained weakly with hematoxylin-eosin and strongly with the Dylon method. Electron microscopy revealed the accumulation of microtubules ranging from 10 to 20 μm in width, primarily in the mesangial lesion. Amyloid A (AA) protein was positively stained in the mesangial area and vascular wall on immunohistochemistry. The final histologic diagnosis was RA-related glomerulonephritis and secondary AA amyloidosis. This case indicates that biological treatment targeting IL-6 is a promising therapeutic option for the treatment of kidney diseases associated with RA.

Keywords: AA amyloidosis; Glomerulonephritis; Interleukin-6; Nephrotic syndrome; Rheumatoid arthritis; Tocilizumab.

Fig. 1

Histology of the renal biopsy specimen. a A representative photomicrograph of a periodic acid–Schiff-stained section showing deposits of an amorphous substance in the mesangial lesion with endocapillary and mesangial proliferation (original magnification, ×200). b A photomicrograph of periodic acid–Schiff staining showing deposition of an amorphous substance in the vascular pole as well as mesangial hypercellularity with small crescents (original magnification, ×200). c A photomicrographs of periodic acid–methenamine silver staining showing fibrocellular crescent formation (original magnification, ×200). d A photomicrograph of Dylon staining showing the presence of amyloid fibrils in the mesangial lesion (original magnification, ×200). e A photomicrograph of immunohistochemical staining for serum amyloid A proteins. Note that amyloid A proteins were observed in the mesangial lesion and small vessel walls (original magnification, ×200)

Fig. 2

Photomicrographs of the immunofluorescence findings of the kidney specimen. C1q (1+), C3 (1+), IgG (1 +), IgA (±), IgM (1+), kappa light chain (±) and lambda light chain (1+) are positively stained in the mesangial patterns (original magnification, ×200). C complement, Ig immunoglobulin

Fig. 3

Photomicrographs of the electron microscopic findings of the kidney specimen. a A photomicrograph in low magnification (original magnification, ×5,000). b A photomicrograph in high magnification (original magnification, ×5,000). Note the presence of amyloid fibrils (10–20 μm in width) in a haphazard arrangement in the mesangial lesion

Fig. 4

Clinical course before and after tocilizumab therapy. BP blood pressure, Cr creatinine, SAA serum amyloid A, Up/Ucr urinary protein–creatinine ratio. The black bar shows the duration of hospitalization. The black arrows indicate the intravenous administration of tocilizumab every 4 weeks