Monoclonal Gammopathy of Renal Significance: Clinical and Histological Efficacy of a Bortezomib-Based Regimen

Monoclonal Gammopathy of Renal Significance (MGRS) is a group of heterogeneous disorders characterized by renal dysfunction secondary to the production of a monoclonal immunoglobulin by a nonmalignant B cell or plasma cell clone. We report the clinical and histological outcomes of two patients with biopsy-proven MGRS: one patient showed membranoproliferative glomerulonephritis with monoclonal k-light chain and C3 deposits, the second patient showed immunotactoid glomerulopathy. Both patients were treated with a 9-month chemotherapy protocol including bortezomib, cyclophosphamide, and dexamethasone. Renal biospy was repeated after 1 year. The estimated glomerular filtration rate (eGFR) increased from 22.5 (baseline) to 40 ml/min per 1.73 m2 after 12 months, then to 51.5 ml/min per 1.73 m2 after 24 months; proteinuria decreased from 4.85 (baseline) to 0.17 g/day after 12 months, then to 0.14 g/day after 24 months. Repeat renal biopsies showed a dramatic improvement of the glomerular proliferative lesions and near complete disappearance of the immune deposits. A bortezomib-based treatment proved very effective and was well-tolerated in the two patients presenting with clinically and histologically aggressive MGRS.

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MO085MONOCLONAL GAMMOPATHY OF UNKNOWN SIGNIFICANCE AMONG MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab078.0021 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Marja Kovala ◽

Minna Seppala ◽

Kati Kaartinen ◽

Seppo Meri ◽

Eero Olavi Honkanen ◽

...

Keyword(s):

Membranoproliferative Glomerulonephritis ◽

Monoclonal Gammopathy ◽

Cell Clone ◽

Alternative Pathway ◽

Significant Risk ◽

Classical Pathway ◽

Unknown Significance ◽

Hematological Neoplasm ◽

The Mean ◽

Smoldering Myeloma

Abstract Background and Aims Monoclonal gammopathy is an entity where a B-cell or plasma cell clone produces monoclonal immunoglobulin. When paraproteinemia and a kidney disease is discovered without criteria for treatment of haematological malignangy, the entity is called monoclonal gammopathy of unknown significance (MGUS) or of renal significance (MGRS). It can cause variable histology, among which membranoproliferative glomerulonephritis (MPGN) has been described. Direct entrapment of paraprotein in glomeruli/tubules can be observed by immunofluorescence (IF), but IF can also be negative as paraprotein can cause complement-associated disease by acting as an activator of the classical pathway or as a dysregulator of the alternative pathway. Electron microscopy (EM) is needed to differentiate possible organized deposits. Method We investigated the prevalence, clinical parameters, histology, and the type of monoclonal gammopathy in biopsy-proven MPGN between 2006-2017. A total of 15 adult patients with a detected urine and/or serum paraprotein with concurrent biopsy-proven diagnosis were discovered among 60 patients (Figure 1). Two diagnostic biopsies were from transplants. Results MGUS was diagnosed in 15/60 (25%) of patients. Clinical variables are summarized in Table 1. The mean age at presentation was 59 years (37-79), 47-% were males. Smoldering myeloma was diagnosed in 2 (13%) patients and overt malignancy in 3 (20%) patients. Histological features are summarized in Table 2. There were 7 (47%) with dominant staining for C3 (6 with C3 glomerulonephritis, 1 Dense Deposition Disease) and 8 (53%) with dominant staining for Ig, of which 4 (31%) had mesangioproliferative, 4 (31%) membranoproliferative, 3 (23%) minimal change, 2 (15%) crescentic and 1 (8%) exudative pattern in light microscopy (LM). Seven (47%) biopsies, which did not stain for kappa or lambda light chains. The most common EM deposit location was subendothelial (69%). Conclusion MPGN was associated with a significant risk of underlying monoclonal gammopathy, as many (25%) patients were diagnosed with concurrent MGUS. When MPGN is observed, it should prompt investigations of the possible underlying monoclonal gammopathy and possibly, hematological neoplasm.

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A case of nephrotic syndrome secondary to HIV immune complex kidney disease

Journal of Nephropathology ◽

10.34172/jnp.2021.09 ◽

2020 ◽

Vol 10 (1) ◽

pp. e09-e09

Author(s):

Michael Edwards ◽

Patrick Linden ◽

Anindya Banerjee

Keyword(s):

Immune Complex ◽

Membranoproliferative Glomerulonephritis ◽

Diabetes Mellitus Type 2 ◽

Filtration Rate ◽

Complex Disease ◽

Estimated Glomerular Filtration Rate ◽

Treatment Options ◽

Hiv Positive ◽

Immune Complex Disease

HIV immune complex disease of the kidney (HIVICK) is a rare but increasingly well-recognised cause of renal dysfunction and proteinuria in HIV-positive patients. A 56-year-old man with known HIV, diabetes mellitus type 2, liver cirrhosis and previous Hepatitis C virus (HCV) presented with a labile estimated glomerular filtration rate and significant proteinuria. Electron microscopy from a renal biopsy identified capillary wall deposition for IgG, IgM, Kappa, Lambda and focal C1q consistent with membranoproliferative glomerulonephritis (MPGN) and associated immune complex disease. A second opinion of the images confirmed the diagnosis of HIVICK. The increased recognition of HIVICK in HIV patients should prompt further research into the causes and treatment options available.

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Monoclonal gammapathy of renal significance (MGRS) at the current state: terminology, diagnosis and treatment

Terapevticheskii arkhiv ◽

10.26442/00403660.2020.06.000666 ◽

2020 ◽

Vol 92 (6) ◽

pp. 15-22

Author(s):

Lidia V. Lysenko (Kozlovskaya) ◽

Vilen V. Rameev ◽

Tatyana V. Androsova

Keyword(s):

Monoclonal Gammopathy ◽

Multidisciplinary Approach ◽

Cell Clone ◽

Current Treatment ◽

Al Amyloidosis ◽

Monoclonal Immunoglobulin ◽

Current State ◽

Monoclonal Gammapathy ◽

Amyloid Nephropathy

In this article we discussed the current state of monoclonal gammapathy of renal significance (Monoclonal Gammopathy of Renal Significance MGRS) and revealed problems of B-cell clone secreting nephrotoxic monoclonal immunoglobulin identification. We followed 276 patients with monoclonal gammapathy including patients with non-amyloid nephropathy. The majority of patients had systemic AL-amyloidosis. We established better survival of the treated patients with systemic AL-amyloidosis in comparison with retrospective untreated cohort. We considered current treatment of patients with non-amyloid nephropathy and focused on the crucial role of multidisciplinary approach in management of these patients.

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Association between the Delta Estimated Glomerular Filtration Rate and the Prevalence of Monoclonal Gammopathy of Undetermined Significance in Korean Males

BioMed Research International ◽

10.1155/2014/356080 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5

Author(s):

Tae-Dong Jeong ◽

Woochang Lee ◽

Sail Chun ◽

Won-Ki Min

Keyword(s):

Glomerular Filtration Rate ◽

Serum Creatinine ◽

Glomerular Filtration ◽

Monoclonal Gammopathy ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Age Group ◽

Creatinine Concentration ◽

Serum Free Light Chain ◽

Undetermined Significance

Background. We investigated the association between the reduction in the estimated glomerular filtration rate (eGFR) and the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in Korean males.Methods. We enrolled 723 healthy Korean males. Serum creatinine concentration, serum electrophoresis, serum immunofixation, and the serum free light chain assay were performed. We calculated delta eGFR per year (ΔeGFR/yr). The prevalence of MGUS was compared based on the ΔeGFR/yr and age group.Results. Thirteen (1.8%) of 723 participants exhibited the monoclonal band on serum immunofixation. Prevalence of MGUS by age group was 0.00% (0/172 for 40 years), 1.63% (6/367 for 60 years), and 3.80% (7/184 for >60 years). The median decrease in ΔeGFR/yr was 5.3%. The prevalence of MGUS in participants in their 50s with >5.3% decline in ΔeGFR/yr was significantly higher than those with <5.3% decrease in ΔeGFR/yr (3.16% versus 0.00%;P=0.049). The prevalence of MGUS in participants in their 50s with >5.3% decrease in ΔeGFR/yr was similar to that of healthy males in their 60s.Conclusion. Using the rate of reduction in ΔeGFR/yr in healthy Korean males who had their serum creatinine level checked regularly may increase the MGUS detection rate in clinical practice.

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