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Multiple myeloma in a kidney transplanted patient primarily diagnosed with monoclonal gammopathy of unknown significance (MGUS)-related nephropathy

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Marsela Resuli at University of Copenhagen
Marsela Resuli
Finn Thomsen Nielsen
Finn Thomsen Nielsen
Finn Thomsen Nielsen
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Peter Gimsing at Rigshospitalet
Peter Gimsing
Claus B. Andersen
Claus B. Andersen
Claus B. Andersen
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(Section Editor: G. H. Neild)
Multiple myeloma in a kidney transplanted patient primarily
diagnosed with monoclonal gammopathy of unknown significance
(MGUS)-related nephropathy
Marsela Resuli1,2, Finn Thomsen Nielsen1,2, Peter Gimsing3, Claus B. Andersen4and Martin Egfjord2
1
Department of Internal Medicine, Bornholm Hospital, Capital Region, Denmark,
2
Department of Nephrology, Rigshospitalet, University
of Copenhagen, Copenhagen, Denmark,
3
Department of Haematology, Rigshospitalet, University of Copenhagen, Copenhagen,
Denmark and
4
Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Correspondence and offprint requests to: Marsela Resuli; E-mail: marselaresuli@gmail.com
Keywords: kidney transplantation; light-chain deposition disease; monoclonal gammopathy of unknown significance; multiple myeloma
Case
A 36-year-old female was referred with renal impairment,
creatinine clearance 0.4 mL/s and proteinuria 4.7 g/day.
Physical examination was unremarkable. Biochemistry
showed normochromic normocytic anaemia, slight hypoal-
buminaemia and hypercalcaemia. Anti-neutrophil cyto-
plasmic antibodies, anti-nuclear antibodies, anti-glomerular
basement membrane, anti-phospholipid antibodies, and
viral screening were negative. IgG-kappa M-protein was
found in plasma (4.8 g/L) and urine (<0.02 g/L), while plasma
immunoglobulins and liver enzymes were normal. Bone
marrow, skeleton scintigraphy and MR scan were normal.
An ultrasound showed normal-sized kidneys. Kidney
biopsy presented focal interstitial nephritis, light grade
Fig. 1. Native kidney biopsy showing a glomerulus with a slight
homogenous thickening of capillary and arteriolar walls, minimal tubular
atrophy and a discrete interstitial fibrosis (PAS staining, magnification ×50).
Fig. 2. Eight years later: (a) Kidney-graft biopsy 4 years after
transplantation demonstrating nodular glomerular sclerosis, atrophic
tubuli and sclerotic arterioles similar to the end-stage native kidney (PAS,
magnification ×100). (b) Immunostaining was strongly positive for kappa
light chains in the expanded mesangial regions and arterioles.
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Clin Kidney J (2013) 6: 445–446
doi: 10.1093/ckj/sft060
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interstitial fibrosis but no glomerulonephritis, vasculitis or
tubular damage, and negative Congo staining (Figure 1).
The diagnoses were monoclonal gammopathy of
unknown significance (MGUS) and idiopathic interstitial
nephritis. Despite corticosteroid treatment, renal insuffi-
ciency progressed and, after 17 months, haemodialysis
was initiated.
Four years later, the patient received a kidney transplan-
tation with a standard immunosuppressive regimen: thy-
moglobulin induction, prednisolone, mycofenolat mofetil
and cyclosporine. The optimal plasma creatinine after
transplantation was 0.112 mmol/L. Unfortunately, 4 years
after transplantation renal function declined to a plasma
creatinine of 0.219 mmol/L. A kidney-graft biopsy at this
point showed global nodular glomerulosclerosis and
deposition of kappa light chains within glomeruli, vessels,
and tubular basal membranes, plus C3c in the vessels,
characteristic of light-chain deposition disease (LCDD) with
no rejection signs or amyloid deposits (Figure 2a and b).
P-IgG kappa M-protein was 0.86 g/L and Bence-Jones
proteins were present in the urine. A bone marrow re-
examination presented clonal plasma cell infiltration of
kappa type with a kappa/lambda ratio of 19.8.
Presenting M-protein, clonal bone marrow infiltration
and renal graft LCDD changes, the patient was diagnosed
with multiple myeloma [1]. Reevaluation of native kidney
biopsies revealed a weak-positive reaction for kappa light
chains in glomerular nodules, suggesting that LCDD might
have contributed to the renal insufficiency. LCDD has a
high recurrence risk and poor graft function prognosis
after kidney transplantation [2, 3]. Diagnosing LCDD might
be difficult in the early stage. Therefore, patients with a
pre-existing MGUS should be carefully evaluated and fol-
lowed prior to and after kidney transplantation [2, 3].
Conflict of interest statement. None declared.
References
1. International Myeloma Working Group. Criteria for the classifi-
cation of monoclonal gammopathies, multiple myeloma and
related disorders: a report of the International Myeloma
Working Group. Br J Haematol 2003; 121: 749–757
2. Ponticelli C, Moroni G, Glassock R. Recurrence of secondary glo-
merular disease after renal transplantation. Clin J Am Soc
Nephrol 2011; 6: 1214–1221
3. Leung N, Lager DJ, Gertz MA et al. Long-term outcome of renal
transplantation in light chain deposition disease. Am J Kidney
Dis 2004; 43: 147–153
Received for publication: 10.4.13; Accepted in revised form: 3.5.13
446 M. Resuli et al.
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Recurrence of Secondary Glomerular Disease after Renal Transplantation
Article
Full-text available
  • May 2011
  • CLIN J AM SOC NEPHRO
The risk of a posttransplant recurrence of secondary glomerulonephritis (GN) is quite variable. Histologic recurrence is frequent in lupus nephritis, but the lesions are rarely severe and usually do not impair the long-term graft outcome. Patients with Henoch-Schonlein nephritis have graft survival similar to that of other renal diseases, although recurrent Henoch-Schonlein nephritis with extensive crescents has a poor prognosis. Amyloid light-chain amyloidosis recurs frequently in renal allografts but it rarely causes graft failure. Amyloidosis secondary to chronic inflammation may also recur, but this is extremely rare in patients with Behcet's disease or in those with familial Mediterranean fever, when the latter are treated with colchicine. Double organ transplantation (liver/kidney; heart/kidney), chemotherapy, and autologous stem cell transplantation may be considered in particular cases of amyloidosis, such as hereditary amyloidosis or multiple myeloma. There is little experience with renal transplantation in light-chain deposition disease, fibrillary/immunotactoid GN, or mixed cryoglobulinemic nephritis but successful cases have been reported. Diabetic nephropathy often recurs but usually only after many years. Recurrence in patients with small vessel vasculitis is unpredictable but can cause graft failure. However, in spite of recurrence, patient and graft survival rates are similar in patients with small vessel vasculitis compared with those with other renal diseases. Many secondary forms of GN no longer represent a potential contraindication to renal transplantation. The main issues in transplantation of patients with secondary GN are the infectious, cardiovascular, or hepatic complications associated with the original disease or its treatment.
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Criteria for the classification monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group The International Myeloma Working Group Br J Haematol 2003 121 749 57 10.1046/j.1365-2141.2003.04355.x 12780789
Article
The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/1 and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is ≥ 30 g/1 and/or bone marrow clonal cells ≥ 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTL Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (± recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.
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Long-Term Outcome of Renal Transplantation in Light-Chain Deposition Disease
Article
  • Feb 2004
  • AM J KIDNEY DIS
Light-chain deposition disease (LCDD) is a monoclonal gammopathy characterized by nonamyloid deposition of light chain in various organs. A small number of kidney transplantations have been performed on LCDD patients in whom end-stage renal disease (ESRD) developed. The authors retrospectively reviewed the clinical and histologic findings and outcome of 7 patients with LCDD who underwent kidney transplantation at our institution. Renal insufficiency, hypertension, and proteinuria were present in all 7 patients. Proteinuria level was greater than 3.5 g/24 h in 3 patients. Three patients had microscopic hematuria. Monoclonal protein was detected in the serum in 3 patients, urine in 5, and was undetectable in 2. Median age at presentation was 42.7 (range, 33 to 58) years. The most common renal biopsy findings were mesangial expansion, mesangial nodules, tubular basement membrane thickening, and tubular atrophy. Kappa light chain was detected in all 7 renal biopsy results. Five patients were on dialysis before transplantation. LCDD recurred after a median of 33.3 (range, 2 to 45) months in 5 of the 7 patients. One patient remains on dialysis, whereas the other 4 have died. One patient died of progression of multiple myeloma 3 months after kidney transplantation without evidence of recurrence. Only 1 patient remains recurrence free after 13 years with normal renal allograft function. Although long-term benefits are occasionally seen, renal allograft survival is reduced significantly in LCDD patients. Kidney transplantation should not be an option for LCDD patients unless measures have been taken to reduce light chain production.
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