J Korean Soc Transplant.  2018 Sep;32(3):57-62. 10.4285/jkstn.2018.32.3.57.

Bortezomib Treatment for Refractory Antibody-Mediated Rejection Superimposed with BK Virus-Associated Nephropathy during the Progression of Recurrent C3 Glomerulonephritis

• Do W
• Lee JH
• Kim KJ
• Han MH
• Jung HY
• Choi JY
• Park SH
• Kim YL
• Kim CD
• Cho JH
• Yang Y
• Kim M
• Hwang I
• Kim KY
• Yim T
• Kim YJ

• KMID: 2421281
• DOI: http://doi.org/10.4285/jkstn.2018.32.3.57

Abstract

A 38-year-old man, who underwent a second kidney transplantation (KT), was admitted because of antibody-mediated rejection (AMR) complicated by BK virus-associated nephropathy (BKVAN). He was placed on hemodialysis at the age of 24 years because of membranoproliferative glomerulonephritis. At the age of 28 years, he underwent a living donor KT from his father; however, 1 year after the transplantation, he developed a recurrence of the primary glomerular disease, resulting in graft failure 2 years after the first KT. Ten years later, he received a deceased-donor kidney with a B-cell-positive-cross-match. He received 600 mg of rituximab before the KT with three cycles of plasmapheresis and immunoglobulin (0.5 g/kg) therapy after KT. During the follow-up, the first and second allograft biopsies at 4 and 10 months after KT revealed AMR with a recurrence of primary glomerular disease that was reclassified as C3 glomerulonephritis (C3GN). He received a steroid pulse, rituximab, plasmapheresis, and immunoglobulin therapies. The third allograft biopsy demonstrated that the BKVAN was complicated with AMR and C3GN. As the azotemia did not improve after repeated conventional therapies for AMR, one cycle of bortezomib (1.3 mg/m²Ã—4 doses) was administered. The allograft function stabilized, and BK viremia became undetectable after 6 months. The present case suggests that bortezomib therapy may be applicable to patients with refractory AMR, even in cases complicated with BKVAN.

Keyword

Graft rejection; BK virus; Bortezomib; Kidney transplantation

MeSH Terms

Adult
Allografts
Azotemia
Biopsy
BK Virus
Bortezomib*
Fathers
Follow-Up Studies
Glomerulonephritis*
Glomerulonephritis, Membranoproliferative
Graft Rejection
Humans
Immunization, Passive
Immunoglobulins
Kidney
Kidney Transplantation
Living Donors
Plasmapheresis
Recurrence
Renal Dialysis
Rituximab
Transplants
Viremia
Bortezomib
Immunoglobulins
Rituximab

Figure

• 

  Fig. 1 The second biopsy showing peritubular capillaritis (A, Periodic acid–Schiff, ×400) and focal proliferative glomerulitis with leukocytes infiltration. Only C3 is positive at the glomerular mesangium and capillary wall (B, immunofluorescence, ×200). Electron dense deposits with humplike appearance can be observed at the mesangium and subepithelium (C, electron microscopy, ×5,000). Leukocytes can be seen in the capillary lumen.

• 

  Fig. 2 The third biopsy showing proliferative glomerulitis with crescent formation. The interstitium is infiltrated by a large amount of lymphocytes (Periodic acid–Schiff, ×200). The immunohistochemical staining for BK virus shows SV 40 antibody-positive enlarged tubular epithelial cells (inset, ×200).

• 

  Fig. 3 Hospital progression. As the creatinine level of the patient increased to 3.58 mg/dL after repeated conventional treatments, he received one cycle of bortezomib injection (1.3 mg/m2×4 doses). Thereafter, the allograft function stabilized for 6 months. Abbreviations: PP, plasma pheresis; IVIG, intravenous immunoglobulin; Bx., biopsy; POD, post-operation day.

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