Home About us Current issue Ahead of Print Back issues Submission Instructions Advertise Contact Login   

Search Article 
Advanced search 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 1306 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 

Table of Contents   
Year : 2020  |  Volume : 31  |  Issue : 6  |  Page : 1399-1402
Rapidly progressive immunoglobulin M monoclonal gammopathy presenting with nephrotic syndrome and hepatic failure

Department of Internal Medicine, Division of Nephrology, Changhua Christian Hospital, Changhua, Taiwan

Click here for correspondence address and email

Date of Web Publication29-Jan-2021


We report a 73-year-old male with no relevant past medical history who presented with nephrotic syndrome and jaundice. Subsequent studies revealed immunoglobulinM (IgM) monoclonal gammopathy. Kidney biopsy revealed monoclonal Ig deposition disease and amyloidosis. Bone marrow biopsy demonstrated <10% infiltration by lymphoplasmacytic cells. However, rapidly progressive hypergammaglobulinemia of IgM and hyperbilirubinemia were noted. Despite aggressive treatment, the patient developed acute kidney injury and complications of hepatic failure. He eventually died of pneumonia, just two months after diagnosis.

How to cite this article:
Wen YK. Rapidly progressive immunoglobulin M monoclonal gammopathy presenting with nephrotic syndrome and hepatic failure. Saudi J Kidney Dis Transpl 2020;31:1399-402

How to cite this URL:
Wen YK. Rapidly progressive immunoglobulin M monoclonal gammopathy presenting with nephrotic syndrome and hepatic failure. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2021 May 15];31:1399-402. Available from: https://www.sjkdt.org/text.asp?2020/31/6/1399/308354

   Introduction Top

Immunoglobulin M (IgM) monoclonal gammopathy is a spectrum of diseases that range from asymptomatic monoclonal gammopathy of undetermined significance (MGUS) to smoldering Waldenström macro-globulinemia (WM) to symptomatic WM. Kyle et al have shown in a long-term follow-up of 213 patients with IgMMGUS that 2.8% of patients developed WM. It is estimated that the rate of progression of IgMMGUS to symptomatic WM is approximately 1.5% per year.[1] Most patients have an indolent course.

We herein report an unusual case of IgM monoclonal gammopathy of renal significance (MGRS) with a swiftly progressive course.

   Case Report Top

A 73-year-old male with no special past medical history presented with lower leg edema. Physical examinations of the chest, heart, and abdomen were unremarkable. Neither significant lymphadenopathy nor hepatosplenomegaly was present. Laboratory data included the following values: white blood cell count 3,800/mm3, hemoglobin 13.4 g/dL, platelet count 212,000/mm3, aspartate aminotransferase 57 U/L, alanine aminotransferase 32 U/L, total bilirubin 2.66 mg/dL, creatinine 0.97 mg/dL, calcium 8.7 mg/dL, glucose 85 mg/dL, albumin 2.6 g/dL, IgG 427.0 mg/dL (normal 700–1600), IgA 62.9 mg/dL (normal 70–400), and IgM 2020 mg/dL (normal 40–230). Urine sediments contained red blood cells 3.1/high-power field without casts. Urine protein-to-creatinine ratio was 2324 mg/g. Serologies for antinuclear antibody, hepatitis B, and hepatitis C were negative. Type I cryoglobulinemia was detected. Serum protein electrophoresis disclosed a monoclonal component in the gamma region, which was classified as IgM lambda. Urine immuno-fixation revealed lambda light chains. Radio-graphic imaging of the bones did not show lytic lesions. Computed tomography of the chest and abdomen did not show organo-megaly or lymphadenopathy. Kidney biopsy revealed monoclonal Ig deposition disease, in which the deposits were composed of IgM and lambda light chain [Figure 1]. Congo red stain demonstrated apple-green birefringence under polarized light [Figure 2]. Bone marrow biopsy demonstrated <10% infiltration by lymphoplasmacytic cells with immunopheno-type CD20+, CD5-, and CD23-. [Figure 3] shows the summary of the clinical course. The patient was treated with dexamethasone, cyclophosphamide, rituximab, and bortezomib. Because of increased levels of IgM (peak 4120 mg/dL) with hyperviscosity syndrome (>10.0 centipoise), plasmapheresis was instituted. However, progressive proteinuria and hyper-bilirubinemia were noted. The patient subsequently developed acute kidney injury and complications of hepatic failure. Owing to his massive ascites and altered coagulation profile, liver biopsy was contraindicated. The patient was not considered to be a suitable candidate for liver transplantation due to multiple organ failure. He eventually died of pneumonia, just two months after diagnosis.
Figure 1: Kidney biopsy showing immunoglobulin M deposition.

Click here to view
Figure 2: Congo red stain demonstrating apple- green birefringence under polarized light.

Click here to view
Figure 3: Summary of clinical course including treatment and changes of proteinuria, immunoglobulin M, creatinine, and total bilirubin levels over time.

Click here to view

The author obtained all appropriate consent forms from the patient’s relative for the publication of the case report.

   Discussion Top

We describe a patient initially presenting with nephrotic syndrome related to IgM monoclonal gammopathy in the absence of significant bone marrow lymphoplasmacytic infiltration and other characteristic features of WM that otherwise would be classified as MGRS. However, rapid disease progression to WM was identified when the patient developed hyperviscosity syndrome. To our knowledge, abrupt evolution like our case has never been reported in the literature.

Renal disease related to WM occurs infrequently. The largest series of biopsy-proven WM-related nephropathy in a cohort of 1,391 WM patients was described by Vos et al in 2016.[2] A total of 44 cases were identified. The estimated cumulative incidence of WM-related nephropathy was 5.1% at 15 years from WM diagnosis. There was a wide variation in kidney pathology, including amy-loidosis (25%), monoclonal IgM deposition disease/cryoglobulinemic glomerulonephritis (23%), lymphoplasmacytic lymphoma infiltration (18%), light-chain deposition disease (9%), cast nephropathy (9%), thrombotic microangiopathy (7%), minimal change disease (5%), membranous nephropathy (2%), and crystal-storing tubulopathy (2%).

Hepatic failure is another unique feature of our patient. Although hepatomegaly due to infiltration by lymphoplasmacytic cells is a characteristic feature of WM, it generally is not associated with severe liver damage. We suppose his hepatic failure was related to amyloidosis. Light chain amyloidosis (AL) can complicate IgMMGUS and WM. However, this is an uncommon event. IgM-related AL amyloidosis accounts for 6% of all AL amyloidosis cases and was reported in 2% of patients with IgM monoclonal gammopathy. Hepatic involvement is present in 62–90% of all AL amyloidosis cases and was reported in 14%–26% of IgM-related AL amyloidosis patients.[3] Despite the high prevalence of hepatic involvement with AL amyloidosis, clinical manifestations are generally mild. The development of acute hepatic failure from this entity is rare. Norero et al have previously published a review identifying 10 cases of acute hepatic failure associated with AL amyloidosis.[4] In all of these cases, patients initially presented with nonspecific symptoms such as jaundice, anasarca, or weight loss and subsequently developed fulminant hepatic failure over two to nine weeks from the time of initial presentation.

The therapeutic options for WM depend on the rapidity with which the symptom control is necessary. Hyperviscosity-related symptoms warrant urgent plasmapheresis. Rituximab (anti-CD20 monoclonal antibody)-based therapy is a preferred treatment option for most patients with symptomatic WM. Rituximab is generally well tolerated. However, rituximab alone is a poor choice for patients in urgent need of therapy since its median time to response is long, around three to four months or more.[5] In addition, a unique complication of rituximab therapy in WM is the IgM flare phenomenon. Bortezomib (proteasome inhibitors) is among the most effective therapies in WM, particularly when combined with steroids and rituximab, with a median time to response of 1.4 months.[6] The rapid response prompts physicians to use this combination in patients with hyperviscosity syndrome. Neuro-toxicity is the major concern with the use of bortezomib, and underlying IgM-related neuropathy may further complicate its use.

   Conclusion Top

Our case suggests that the evolution of IgMMGRS to WM could be abrupt. Disease activity should be monitored carefully. The prognosis of these patients with rapid disease progression is grave without prompt and effective chemotherapy. Since mortality usually arises from organ failure, evaluation of organ replacement therapy should be initiated promptly. Furthermore, new therapeutic approaches targeting amyloid deposit have to be developed in order to improve organ response.

Conflict of interest: None declared.

   References Top

Kyle RA, Therneau TM, Rajkumar SV, et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood 2003;102:3759-64.  Back to cited text no. 1
Vos JM, Gustine J, Rennke HG, et al. Renal disease related to Waldenström macroglobu-linaemia: Incidence, pathology and clinical outcomes. Br J Haematol 2016;175:623-30.  Back to cited text no. 2
Milani P, Merlini G. Monoclonal IgM-related AL amyloidosis. Best Pract Res Clin Haematol 2016;29:241-8.  Back to cited text no. 3
Norero B, Pérez-Ayuso RM, Duarte I, et al. Portal hypertension and acute liver failure as uncommon manifestations of primary amyloi-dosis. Ann Hepatol 2013;13:142-9.  Back to cited text no. 4
Gertz MA, Rue M, Blood E, et al. Multicenter phase 2 trial of rituximab for Waldenström macroglobulinemia (WM): An eastern cooperative oncology group study (E3A98). Leuk Lymphoma 2004;45:2047-55.  Back to cited text no. 5
Treon SP, Ioakimidis L, Soumerai JD, et al. Primary therapy of Waldenström macroglobu-linemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180. J Clin Oncol 2009;27:3830-5.  Back to cited text no. 6

Correspondence Address:
Yao-Ko Wen
Department of Internal Medicine, Division of Nephrology, Changhua Christian Hospital, Changhua
Login to access the Email id

DOI: 10.4103/1319-2442.308354

Rights and Permissions


  [Figure 1], [Figure 2], [Figure 3]


    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report
    Article Figures

 Article Access Statistics
    PDF Downloaded53    
    Comments [Add]    

Recommend this journal