American Journal of Kidney Diseases
Volume 52, Issue 3 , Pages 621-625, September 2008

Light Chain Deposition Disease After Renal Transplantation

  • Sekiko Taneda, MD

      Affiliations

    • Department of Pathology, Kidney Center, Tokyo Women's Medical University, Tokyo
    • Corresponding Author InformationAddress correspondence to Sekiko Taneda, MD, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
    • ,
  • Kazuho Honda, MD

      Affiliations

    • Department of Pathology, Kidney Center, Tokyo Women's Medical University, Tokyo
    • ,
  • Shigeru Horita, MS

      Affiliations

    • Department of Pathology, Kidney Center, Tokyo Women's Medical University, Tokyo
    • ,
  • Ichiro Koyama, MD

      Affiliations

    • Department of Surgery, Kidney Center, Tokyo Women's Medical University, Tokyo
    • ,
  • Satoshi Teraoka, MD

      Affiliations

    • Department of Surgery, Kidney Center, Tokyo Women's Medical University, Tokyo
    • ,
  • Hideaki Oda, MD

      Affiliations

    • Department of Pathology, Kidney Center, Tokyo Women's Medical University, Tokyo
    • ,
  • Yutaka Yamaguchi, MD

      Affiliations

    • Department of Pathology, Kashiwa Hospital, Jikei University, Chiba, Japan

Received 10 September 2007; accepted 13 February 2008. published online 16 June 2008.

Article Outline

Index Words: light chain deposition disease, transplantation, tubular basement membrane, retrospective, serial biopsies

 

Light chain deposition disease (LCDD) is characterized by the deposition of κ or λ immunoglobulin light chains in many organs, including the kidney.1, 2 The disease frequently is associated with multiple myeloma or other lymphoplasmacytic proliferative disorders, although a significant number of patients with LCDD show no evidence of bone marrow abnormalities.3 LCDD frequently has been reported to recur after renal transplantation, inevitably followed by graft failure.3 Multiple myeloma also has been considered a major cause of light chain deposition in renal allografts and to show a high rate of recurrence.4, 5

The most characteristic feature of LCDD is nodular glomerulopathy resembling diabetic glomerulosclerosis. The mesangial nodules are composed of extracellular matrix proteins admixed with the monoclonal light chain deposits. Glomerular basement membranes (GBMs), tubular basement membranes (TBMs), and vessel walls are variably thickened as a consequence of subendothelial light chain deposition. Clinically, various degrees of proteinuria and renal insufficiency are common manifestations,2 and rapid deterioration in kidney function can occur as a consequence of disease progression.

We report a case of LCDD progression more than 4 years after renal transplantation, with a retrospective analysis of serial biopsy specimens that showed gradual progression of κ light chain deposition in the renal allograft.

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Case Report 

Clinical History 

A 61-year-old man received an HLA-identical, blood group type ABO–compatible renal transplant from his sister. The cause of his renal failure was unknown. Cyclosporine, mycophenolate mofetil, and methylprednisolone were administered as immunosuppressive therapy. A small amount of proteinuria, ± to + by dipstick (∼0.5 g/d), had been found 3 days after the transplantation (Fig 1). Renal biopsy was performed on postoperative days 18 and 43 because of a slight increase in serum creatinine level and showed no evidence of rejection and unremarkable glomerular changes (Fig 1). Two years later, serum creatinine level increased to 3 mg/dL (265 μmol/L; estimated glomerular filtration rate, 15.84 mL/min/1.73 m2 [0.26 mL/s/1.73 m2]), and renal biopsy was performed again on postoperative day 774. It showed very mild tubulointerstitial rejection without apparent glomerular changes. Although methylprednisolone therapy had been continued and the patient was additionally administered intravenous 15-deoxyspergualin (total, 1,750 mg), serum creatinine level remained high, and another renal biopsy was performed on postoperative day 913. The biopsy specimen showed chronic allograft nephropathy without apparent glomerular changes. To prevent further deterioration of graft function, cyclosporine therapy was replaced with tacrolimus, and the doses of mycophenolate mofetil and methylprednisolone were increased. However, despite these dose adjustments, kidney function gradually deteriorated. The final biopsy on postoperative day 1,543, when serum creatinine and blood urea nitrogen levels had increased to 6.0 mg/dL (530 μmol/L; estimated glomerular filtration rate, 7.12 mL/min/1.73 m2 [0.12 mL/s/1.73 m2]) and 90 mg/dL (32 mmol/L) accompanied by slight proteinuria, respectively.

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  • Figure 1. 

    Clinical course of the patient. Abbreviations: CsA, cyclosporine A; FK, tacrolimus; MMF, mycophenolate mofetil; MP, methylprednisolone; DSG, 15-deoxyspergualin; sCr, serum creatinine; U-P, urinary-protein; Bx, graft biopsy; Tx, transplantation; AZP, azathioprine; HD, hemodialysis; Ccr, creatinine clearance.

Kidney Biopsy Diagnosis 

Light microscopic examination of the final biopsy specimen showed diffuse interstitial fibrosis with tubular atrophy, with no evidence of rejection (Fig 2A). One third of glomeruli were globally sclerotic, and residual glomeruli showed widening of the mesangial area with sclerosis (Fig 2B). The basement membrane of Bowman's capsule, TBM, and vessel walls were thickened and tortuous. Arteriolar hyalinosis was severe. Direct immunofluorescence examination showed diffuse linear deposition of κ light chains along the GBM, mesangial area, TBM, and Bowman's capsule (Fig 2C). However, staining for λ light chain was negative (Fig 2D), as well as immunoglobulin G, immunoglobulin M, and immunoglobulin A. Congo red staining for amyloid was negative. Electron microscopy showed band-like subendothelial electron-dense deposits along the GBM (Fig 2E). Electron-dense deposits were also present along the TBM (Fig 2F) and Bowman's capsule and showed deposition of granular to powdery electron-dense material. Pathological changes were mostly consistent with the diagnosis of LCDD.

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  • Figure 2. 

    (A-F) Pathological findings of the graft biopsy performed on day 1,540. (A) Light microscopy shows diffuse interstitial fibrosis with tubular atrophy without evidence of rejection. Tubular basement membranes (TBMs) were thickened and tortuous (periodic acid–Schiff; original magnification ×200). (B) Glomeruli show typical nodular lesions resembling those in diabetic glomerulosclerosis. The basement membrane of Bowman's capsule and proximal and distal tubules were irregularly thickened. Severe arteriolar hyalinosis was noted (periodic acid-silver methenamine; original magnification ×400). (C) Immunofluorescence study shows intense κ staining in the nodular glomerular lesions, glomerular capillaries, tubules, Bowman's capsule, and small-vessel walls (original magnification ×400). (D) Immunofluorescence study shows negative staining for λ light chains (original magnification ×400). (E, F) Electron microscopy shows fine granular electron-dense deposits along the (E) glomerular basement membrane and (F) TBM (original magnification: [E] ×6,000; [F] ×7,000). (F inset). Electron-dense material along the TBM shows a granular to powdery appearance (original magnification ×10,000).

Retrospective Study of Serial Biopsy Specimens 

Staining for κ light chains was negative in the biopsy specimens from day 43 (Fig 3E). In biopsy specimens obtained on day 774, weak immunofluorescence staining for κ light chain was detected along the GBM, TBM, and Bowman's capsule basement membrane (Fig 3I), which had become more intense in the biopsy specimens obtained on day 913 (Fig 3M). Electron microscopy showed no deposits in the GBM or TBM on day 0 (Fig 3B and C) or 43 (Fig 3F and G). In the biopsy performed on day 774, electron-dense deposits were detected along the GBM and TBM, but the deposits were very fine and powdery, without continuity (Fig 3J and K). However, the deposits had become more apparent in the biopsy specimen from day 913 (Fig 3N and O). The intensity of κ light chain deposition was proportional to the amount of the electron-dense deposits.

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  • Figure 3. 

    Serial changes in (A, D, H, L) glomerular histological characteristics, (E, I, M) immunofluorescent staining for κ light chains, and electron microscopy of the (B, F, J, N) glomerular and (C, G, K, O) tubular basement membranes. (A-C) Day 0, (D-G) day 43 (biopsy [Bx] 3), (H-K) day 774 (Bx 4), and (L-O) day 913 (Bx 5). Immunofluorescent staining was not performed in the 0-hour biopsy because frozen sections were not obtained.

Clinical Follow-up 

The patient needed to be started on hemodialysis therapy again 5 days after the final biopsy. Serum and urine immunoelectrophoresis showed neither the M spike nor Bence-Jones proteins. However, immunofixation electrophoresis of urine showed the κ type of Bence-Jones protein. Bone marrow biopsy showed a moderately hypocellular bone marrow with small collections of atypical plasmacytoid cells. The myelogram showed an increase in percentage of plasma cells (11.6%). Flow cytometric analysis of bone marrow specimens showed monoclonality of the plasmacytoid fraction gated by CD38 for cytoplasmic κ chain (86.4%).

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Discussion 

LCDD in renal allografts is uncommon and in general is associated in most patients with recurrent myeloma, rather than as a de novo disease.6, 7 Recurrence of LCDD in renal allografts has been reported to occur at an incidence of more than 50% within 4 years of renal transplantation and frequently is associated with graft failure.8, 9, 10 Conversely, de novo multiple myeloma or LCDD arising in a renal allograft is very rare, and only a few cases have been reported7, 8, 9 despite the high frequency of monoclonal gammopathy in transplant recipients.11 In the native kidney, LCDD is associated with various degrees of renal insufficiency in most patients, and rapid deterioration of kidney function could also occur during the advanced stage of the disease.12 However, acute renal failure could be present at the time of diagnosis in approximately 30% of patients with LCDD.13

Other paraprotein-related kidney diseases, including heavy chain deposition disease,14 cryoglobulinemia,15 immunotactoid glomerulopathy,16, 17, 18, 19 and amyloidosis16, 17, 18, 19 also have been reported after renal transplantation. One transplant patient with heavy chain deposition disease developed recurrent disease approximately 1.5 years after transplantation.14 Cryoglobulinemic nephropathy may develop either de novo or as recurrent cryoglobulinemic nephropathy in patients with active hepatitis.15 Although recurrent immunotactoid glomerulopathy after renal transplantation has been reported to occur in approximately half the cases, graft function has been reported to remain adequate after 5 to 11 years of follow-up in most cases.16, 17, 18, 19 Several cases of de novo immunotactoid glomerulopathy in renal allografts have been reported.16, 20, 21 However, the recurrence rate of amyloidosis after renal transplantation has been reported to be 10% to 20% for AL amyloidosis22, 23 and 4% for AA amyloidosis,24 and the graft loss rate from recurrent amyloidosis was only 3%.22

The accumulated experiences of LCDD in renal transplantation suggest that transplantation is not a valid option for patients with LCDD because of the high frequency of recurrence and progression to graft failure. However, in some recipients in whom the original kidney disease remains uncertain, such as in this case, recurrent LCDD can be a possible reason for graft dysfunction. Immunohistochemical analysis for light chains and careful electron microscopic observation to identify inconspicuous light chain deposition can be helpful for the diagnosis of LCDD, which should prompt further examination to detect an underlying plasma cell disorder in the course of patient management.

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Acknowledgements 

We gratefully acknowledge the technical assistance of Hideki Nakayama and Mayuko Ohno.

Support: None.

Financial Disclosure: None.

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References 

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 Originally published online as doi:10.1053/j.ajkd.2008.02.370 on June 12, 2008.

PII: S0272-6386(08)00770-1

doi:10.1053/j.ajkd.2008.02.370

American Journal of Kidney Diseases
Volume 52, Issue 3 , Pages 621-625, September 2008

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