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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2019  |  Volume : 30  |  Issue : 5  |  Page : 1161-1165
Monoclonal gammopathy of renal significance with light-chain deposition disease in kidney transplantation


1 Department of Internal Medicine A, Laboratory of Renal Pathology - LR00SP01, Charles Nicolle Hospital; Faculty of Medecine, University Tunis El Manar, Tunis, Tunisia
2 Department of Nephrology, Mongi Slim Hospital, La Marsa; Faculty of Medecine, University Tunis El Manar, Tunis, Tunisia

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Date of Submission15-Oct-2018
Date of Decision10-Oct-2018
Date of Acceptance18-Nov-2018
Date of Web Publication4-Nov-2019
 

   Abstract 


Light-chain deposition disease (LCDD) reoccurs almost invariably after renal transplantation, leading to early graft loss. We report a case of LCDD with monoclonal gammopathy of renal significance diagnosed in the post-transplant period in a 28-year-old male and we discuss the diagnostic and therapeutic challenges in the clinical course.

How to cite this article:
Aoudia R, Bacha MM, Ounissi M, Gaied H, Jerbi M, Abderrahim E, Abdallah TB, Goucha R. Monoclonal gammopathy of renal significance with light-chain deposition disease in kidney transplantation. Saudi J Kidney Dis Transpl 2019;30:1161-5

How to cite this URL:
Aoudia R, Bacha MM, Ounissi M, Gaied H, Jerbi M, Abderrahim E, Abdallah TB, Goucha R. Monoclonal gammopathy of renal significance with light-chain deposition disease in kidney transplantation. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Nov 23];30:1161-5. Available from: http://www.sjkdt.org/text.asp?2019/30/5/1161/270274



   Introduction Top


Monoclonal gammopathy of renal significance (MGRS) is a recently introduced clinical term aimed at identifying patients with a small B-cell clone that does not meet criteria for myeloma or lymphoma. However, it causes significant renal diseases resulting from a deposition of monoclonal immunoglobulins (MIg). MGRS is associated with a wide spectrum of glomerulopathies, classified by the type, localization, and organization of the deposited MIg.[1]

Light-chain deposition disease (LCDD) is characterized by the deposition of monoclonal, amorphous, non-Congophilic light chains in multiple organs that do not exhibit a fibrillar structure when examined on electronic microscopy.[2] Renal involvement is a constant feature which includes renal failure, hypertension, proteinuria, hematuria, or nephrotic syndrome. If not treated, most patients with kidney involvement rapidly develop an end-stage renal disease (ESRD).[3],[4] Median survival of patients with LCDD and ESRD on dialysis is four years.[5] Renal transplantation for LCDD is associated with a high risk of disease recurrence and allograft failure. Renal transplantation is not forbidden, it remains an option for a few selected patients.[6]

The aim of our work is to present a case of LCDD with MGRS diagnosed in the post-transplant period and to discuss the diagnostic and therapeutic challenges in the clinical course.


   Case Report Top


Informed consent was obtained from the patient before presenting the report.

At the age of 28, an Algerian man was diagnosed with a stage-5 chronic renal failure. Renal biopsy showed a significant fibrosis. No tissue was available for immunofluorescence (IF) study. He was treated by hemodialysis (HD) for four months, then underwent a live-related renal allograft transplantation in Jordan in August 2014. The donor was his 30-year-old brother. The posttransplant period was initially uneventful with a baseline serum creatinine of 100 μmol/L on triple drug immunosuppression (prednisone, tacrolimus and mycophenolate mofetil). In September 2015, he developed renal failure. Blood tests showed acute kidney injury with serum creatinine of 214 μmol/L. First proteinuria was negative then rapidly progressed to 2.8 g/day after two weeks. Ultrasonography showed normal-sized graft without urinary tract obstruction. An allograft biopsy was performed for the indication of graft proteinuria and a mild graft dysfunction. Light microscopy showed no evidence of rejection, but the glomeruli displayed minimal mesangial expansion with a small mesangial nodular sclerosis in one glomerulus [Figure 1]. Congo red staining was negative. The IF showed strong staining for kappa (κ) light chain in the mesangial region along the glomerular and the tubular basement membrane [Figure 2]. There was no staining for, IgG, IgA, IgM, C3, Clq and complement lambda (λ) light chain. The C4d was negative. Hence, we evoked the pathological diagnosis of LCDD. No tissue was available for electron microscopy. According to the data of the biopsy, we carried out further investigations: total protein was 49 g/L, serum albumin was 31 g/L, and gammaglobulinemia 3.5 g/L. A serum and urine electrophoresis and immunofixation isolated monoclonal kappa LC gammopathy, with serum-free kappa chains at 480 mg/L (N: 3.3–19.4) and λ at 26.6 mg/L (N: 5.71–26.3) and κ/λ ratio at 18 (N: 0.26–1.65). Serum β2 microglobulin was 10.9 mg/L (N: 1–2.5). Baseline liver tests and serum calcium were normal. Bone marrow biopsy showed 5% plasma cells and no osteolytic lesions were identified by a full skeletal survey. As bortezomib was not available, the patient had two cycles of dexa-methasone at a dose of 40 mg/day for four days.
Figure 1: First graft biopsy finding. Mild mesangial thickening (Trichrome).

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Figure 2: First graft biopsy finding. Positive bright staining with kappa light chain in capillary loops, mesangial areas, around the Bowman's capsule, and tubular basement membranes (Immunofluorescence).

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Because of a greater decline in his renal function (serum creatinine 897 μmol/L) a second allograft biopsy was performed two months later. All the glomeruli now showed diffuse nodular glomerulosclerosis [Figure 3]. The nodules were positive on periodic acid-Schiff s stain and were not congophilic. There were no features suggestive of rejection, and C4d staining was negative in the peritubular capillaries. There were severe fibrosis and tubular atrophy with thickening of the tubular basement membranes. IF staining showed kappa uptake in the glomerular capillary walls and mesangium along tubular basement membrane and an arterial wall staining [Figure 4], while lambda was negative. There was no deposition of any other antisera (IgG, IgM, IgA, C3, and C1q) studied.
Figure 3: Second graft biopsy finding. Diffuse glomerular sclerosis (Trichrome).

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Figure 4: Second graft biopsy finding. Positive bright staining with kappa light chain in capillary loops, mesangial areas, around the Bowman's capsule and tubular basement membranes (Immunofluorescence).

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The patient returned to Algeria where he received Bortezomib without recovering renal function and he remained on chronic HD.


   Discussion Top


Our observation shows several points of interest and raises many questions. Our patient was only 28 years old, and it has been reported that LCDD often develops in males from the 5th and 6th decades of life with age range 2494 years and one-third of cases occurring in less than 50-year-old patients.[7] The diagnosis is made after transplantation from the graftbiopsy, thanks to the systematic use of antiserums of light chains kappa and lambda. The question is whether it is recurrent or de novo LCDD? The initial nephropathy in our case was unknown. The diagnosis could not be made despite kidney biopsy. The hallmark of LCDD on renal biopsy is nodular sclerosing glomerulopathy with a variable thickening of the glomerular, tubular, and vascular basement membranes brightly eosinophilic and strongly periodic acid–Schiff-positive material. IF is characteristic and shows intense (usually kappa) diffuse linear staining of renal basement membranes throughout all the compartments of the kidney. Electron microscopy shows amorphous, nonfibrillar, finely granular, punctuate, highly electrodense deposits,[8],[9] In light microscopy, our patient showed advanced lesions. No particular nephropathy prior to transplant kidney biopsy was mentioned. Pretransplant assessment and transplantation were done in Jordan, we do not know if a monoclonal gammopathy was sought or not. However, it is difficult to think that it was de novo LCDD since clinical experiences from the few patients with LCDD who underwent transplantation showed that failure to control light-chain production resulted in rapid recurrence of the disease in the allograft. Leung et al[6] reviewed seven patients of LCDD who underwent renal transplantation. One patient had an associated multiple myeloma and received melphalan pretransplant, whereas the remaining six were hematologically classified as monoclonal gammopathy of unknown significance (MGUS) and did not receive any chemotherapy. Five of the seven patients developed a recurrence with a rapid median time of recurrence of 33.3 months (2.9–45.9 months) including four patients with MGUS. The median time to reach ESRD after recurrence was 10.9 months, and the overall median graft survival was 37.3 months. In our patient, LCDD occurred within 13 months after transplantation. Graft loss was also rapid, two months after the diagnosis of LCDD and 15 months after transplantation. Here, we emphasize the rapid progression of the disease, which impressed us on the second allograft biopsy. It showed diffuse nodular sclerosis and interstitial fibrosis and a tubular atrophy absent on the first allograft biopsy performed only two months earlier.

Treatment aims at controlling plasma cell proliferation, maintaining kidney function, and increasing survival by the use chemotherapy. There is no standard therapy because of the rare incidence of LCDD. Various treatment regimens have been used to suppress light-chain production and manage existing organ dysfunction. Melphalan combined with prednisone has been used for LCDD with or without multiple myeloma, but the response is limited.[10] There are some reports of recurrent LCDD in patients after unrelated-living-donor renal transplantation treated successfully with Bort ezomib.[1],[7],[11],[12],[13] Hence, Bortezomib can stabilize renal function in patients with LCDD. However, when substantial chronic renal damage had already occurred, as in our patient, renal dysfunction is usually progressive. Kidney transplantation should be reserved for patients, in whom the light-chain production is controlled, and long-lasting remission is documented. In case of living-donor kidney transplantation, both the donor and recipient must be thoroughly informed about the possibility of a recurrence and a potentially reduced lifespan of the allograft. Recurrence is common, and bortezomib may provide an alternative to currently available[13] treatment options in patients with LCDD recurrence after transplantation.

This case emphasizes the importance of identifying a kidney disease before transplantation, especially in young patients and potential recurrent nephropathies. When MGRS is diagnosed in the pre-transplant period, the paraprotein secreting clone can be optimally treated. Atfer transplantation, allo-graft biopsy is an essential tool to understand graft abnormalities and consequently ensure the follow-up of renal transplant patients. A proper histological analysis of all transplant biopsies, including light microscopy, immunohistochemistry and if possible electronic microscopy is essential to diagnose MGRS-related kidney diseases. Post-transplant management of recurrent LCDD is challenging. Larger prospective studies are needed to make strong recommendations regarding transplantation for this population of patients who appear to be at a high risk of a recurrence of the disease.

Conflict of interest: None declared.



 
   References Top

1.
Nambirajan A, Bhowmik D, Singh G, Agarwal SK, Dinda AK. Monoclonal gammopathy of renal significance with light-chain deposition disease diagnosed postrenal transplant: A diagnostic and therapeutic challenge. Transpl Int .2015:28:375-9.  Back to cited text no. 1
    
2.
Touchard G, Bauwens M, Preud’homme JL. Glomerulopathies in monoclonal dysglobulinemias. Rev Prat 1991:41:2459-63.  Back to cited text no. 2
    
3.
Confalonieri R, Barbiano di Belgiojoso G, Banfi G, et al. Light chain nephropathy: Histological and clinical aspects in 15 cases. Nephrol Dial Transplant 1988:3:150-6.  Back to cited text no. 3
    
4.
Kijner CH, Yousem SA. Systemic light chain deposition disease presenting as multiple pulmonary nodules. A case report and review of the literature. Am J Surg Pathol 1988:12: 405-13.  Back to cited text no. 4
    
5.
Montseny JJ, Kleinknecht D, Meyrier A, et al. Long-term outcome according to renal histological lesions in 118 patients with monoclonal gammopathies. Nephrol Dial Transplant 1998: 13:1438-45.  Back to cited text no. 5
    
6.
Leung N, Lager DJ, Gertz MA, et al. Long-term outcome of renal transplantation in light-chain deposition disease. Am J Kidney Dis 2004:43:147-53.  Back to cited text no. 6
    
7.
Nasr SH, Valeri AM, Cornell LD, et al. Renal monoclonal immunoglobulin deposition disease: A report of 64 patients from a single institution. Clin J Am Soc Nephrol 2012:7:231-9.  Back to cited text no. 7
    
8.
Lin J, Markowitz GS, Valeri AM, et al. Renal monoclonal immunoglobulin deposition disease: The disease spectrum. J Am Soc Nephrol 2001:12:1482-92.  Back to cited text no. 8
    
9.
Taneda S, Honda K, Horita S, et al. Light chain deposition disease after renal transplan? tation. Am J Kidney Dis 2008:52:621-5.  Back to cited text no. 9
    
10.
Ronco PM, Alyanakian MA, Mougenot B, Aucouturier P. Light chain deposition disease: A model of glomerulosclerosis defined at the molecular level. J Am Soc Nephrol 2001:12: 1558-65.  Back to cited text no. 10
    
11.
Kuppachi S, Holanda D, Thomas CP. Light chain deposition disease after kidney transplantation with long graft survival: Case report. Transplant Proc 2016:48:255-8.  Back to cited text no. 11
    
12.
Kaposztas Z, Kahan BD, Katz SM, Van Buren CT, Cherem L. Bortezomib successfully reverses early recurrence of light-chain deposition disease in a renal allograft: A case report. Transplant Proc 2009:41:4407-10.  Back to cited text no. 12
    
13.
Moiz A, Javed T, Garces J, Staffeld-Coit C, Paueksakon P. Late recurrence of light chain deposition disease after kidney transplantation treated with bortezomib: A case report. Ochsner J 2014:14:445-9.  Back to cited text no. 13
    

Top
Correspondence Address:
Raja Aoudia
Department of Internal Medicine A, Laboratory of Renal Pathology - LR00SP01, Charles Nicolle Hospital, Tunis
Tunisia
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DOI: 10.4103/1319-2442.270274

PMID: 31696857

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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    Abstract
   Introduction
   Case Report
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    References
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