Combined immunoglobulin G kappa nephropathy: monoclonal immunoglobulin deposition disease and proximal tubulopathy: monoclonal gammopathy of renal significance or smoldering multiple myeloma? Case report and review of literature

Monoclonal gammopathies consist of a broad spectrum of diseases, ranging from asymptomatic monoclonal gammopathy of undetermined significance to multiple myeloma (MM). Multiple myeloma is a malignant plasma cell disorder and accounts for 10% of all hematological malignancies and 1% of all malignancies. Differential diagnosis may be challenging, considering the variety of clinical entities with similar behavior. About 15‑20% of MM only secretes monoclonal light chains, called light chain MM, which is associated with poorer outcome. Two intermediate concepts were recently introduced, monoclonal gammopathy of renal significance (MGRS) and a wider concept of monoclonal gammopathy of clinical significance (MGCS). The former behaves as a clonal proliferative disorder with associated nephrotoxicity, but does not have the hematological criteria for MM, while MGCS expands this concept to other organs. A subtype of MGCS is monoclonal immunoglobulin deposition disease, a multisystemic disorder characterized by light or heavy chain deposition of monoclonal immunoglobulin in various organs and encompasses three clinical entities: Light‑Chain, Light‑ and Heavy‑Chain, and Heavy‑Chain Deposition Disease (LCDD, LHCDD and HCDD, respectively). We describe an unusual case of LCDD in which MM was subsequently considered although the proposed criteria are not met. We demonstrate the variability of clinical‑pathological presentation of LCDD, requiring a rapid decision‑making, particularly in terms of kidney and survival outcomes.

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An interesting case of multiple myeloma with renal monoclonal immunoglobulin deposition disease – A case report

Clinical Queries Nephrology ◽

10.1016/j.cqn.2013.01.003 ◽

2013 ◽

Vol 2 (1) ◽

pp. 44-46

Author(s):

Sham Sunder ◽

Himanshu Verma ◽

Minakshi Bhardwaj ◽

K. Venkataramanan

Keyword(s):

Multiple Myeloma ◽

Case Report ◽

Interesting Case ◽

Monoclonal Immunoglobulin ◽

Monoclonal Immunoglobulin Deposition Disease ◽

Deposition Disease

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Monoclonal immunoglobulin–mediated kidney disease: What is beyond amyloidosis in real practice?

Journal of Onco-Nephrology ◽

10.1177/2399369319870188 ◽

2019 ◽

Vol 3 (3) ◽

pp. 105-112 ◽

Cited By ~ 1

Author(s):

Elena V Zakharova ◽

Tatyana A Makarova ◽

Ekaterina S Stolyarevich ◽

Olga A Vorobyeva

Keyword(s):

Kidney Disease ◽

B Cell ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Monoclonal Immunoglobulin ◽

B Cell Malignancies ◽

Cast Nephropathy ◽

Monoclonal Immunoglobulin Deposition Disease ◽

Proximal Tubulopathy ◽

Light Chain Proximal Tubulopathy

Background:Monoclonal immunoglobulin–mediated kidney disease with various patterns of damage may occur in patients with B-cell malignancies and non-malignant monoclonal gammopathies, and the latter are actually merged under the umbrella of monoclonal gammopathy of renal significance. Amyloidosis is the most well-known monoclonal immunoglobulin–related kidney damage. We focused on the rarer conditions and aimed to evaluate the non-amyloid spectrum of monoclonal immunoglobulin–mediated patterns of renal damage in real clinical practice.Methods:A single-center non-interventional retrospective study included 45 patients with pathology-proven non-amyloid monoclonal immunoglobulin–mediated kidney disease, followed during 2002–2018. Disease duration, proteinuria, serum creatinine, need for dialysis at the time of kidney biopsy, clinical diagnosis, and kidney pathology findings were analyzed.Results:No significant differences in the median age, disease duration at the time of biopsy, or main clinical presentation of kidney disease were found between patients with monoclonal gammopathy of renal significance and patients with B-cell malignancies. Pathology patterns like proliferative glomerulonephritis with monoclonal immunoglobulin deposits, membranous nephropathy, C3 glomerulopathy, cryoglobulinemic glomerulonephritis, and combinations of light chain proximal tubulopathy with monoclonal immunoglobulin deposition disease, and of C3 glomerulopathy with light chain proximal tubulopathy were found in monoclonal gammopathy of renal significance setting only. In contrast, light chain proximal tubulopathy alone, anti-glomerular basement glomerulonephritis, and combinations of cast nephropathy with light chain proximal tubulopathy, and cast nephropathy with monoclonal immunoglobulin deposition disease were associated with multiple myeloma only. Monoclonal immunoglobulin deposition disease, intracapillary monoclonal immunoglobulin M deposits, and cast nephropathy alone were seen in both settings.Conclusion:The presence of monoclonal gammopathy in patients with proteinuria and/or impaired kidney function demands kidney biopsy. Neither duration of kidney disease nor its clinical presentation allows differentiating malignant and non-malignant causes of monoclonal immunoglobulin–mediated renal damage. Several pathology patterns, even cast nephropathy, can be found both in cases of monoclonal gammopathy of renal significance and in cases of B-cell malignancies. Dual patterns of damage, including combinations of organized and non-organized deposits, or organized deposits with monoclonal immunoglobulin–induced damage without monoclonal immunoglobulin deposition, constitute up to 9%, mostly in multiple myeloma cases.

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High Dose Chemotherapy and Autologous Stem Cell Transplantation with Melphalan in Patients with Monoclonal Immunoglobulin Deposition Disease Associated with Multiple Myeloma.

Blood ◽

10.1182/blood.v110.11.5113.5113 ◽

2007 ◽

Vol 110 (11) ◽

pp. 5113-5113

Author(s):

Hani Hassoun ◽

Brian T. Rafferty ◽

Carlos Flombaum ◽

Vivette D. D’Agati ◽

Virginia M. Klimek ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Kidney Transplantation ◽

Light Chain ◽

Peripheral Blood Stem Cell ◽

High Dose Chemotherapy ◽

High Dose ◽

Monoclonal Immunoglobulin ◽

Monoclonal Immunoglobulin Deposition Disease ◽

Deposition Disease

Abstract Introduction: Monoclonal immunoglobulin deposition disease (MIDD) includes several disorders that are characterized by the deposition of serum monoclonal gamma-globulins in various organs, most notably in the kidney resulting in renal dysfunction. There is no standard therapy for MIDD. We report our experience with high dose chemotherapy and autologous peripheral blood stem cell transplantation (HDC/ASCT) in patients with MIDD associated with underlying multiple myeloma (MM). Methods: We have done a retrospective analysis of patients seen at MSKCC with biopsy proven MIDD associated with MM and who underwent HDC/ASCT between 2002 and 2007. Results: Seven patients, all male with a median age of 46, had MM and MIDD. Five had Light Chain Deposition Disease (LCDD), 1 Light and Heavy Chain Deposition Disease (LHCDD), and 1 Light Chain Crystal Deposition Disease (LCCDD). All were stage IB by Durie-Salmon classification. Bone marrow plasmacytosis was a median of 21% (range 10 to 41%). Serum immunofixation showed an IgG kappa monoclonal band in only 2 patients while serum protein electrophoresis showed a monoclonal spike in only 1 of the 2. A monoclonal kappa light chain was detected by serum Free Light Chain Assay in all 7 patients. The diagnosis of MIDD was confirmed by immunofluorescence staining and electron-microscopy examination of kidney biopsy specimens in all patients. Three patients were dialysis dependent before HDC/ASCT. All patients received Melphalan 140 mg/m2 followed by peripheral blood stem cell rescue. The treatment was well tolerated with no mortality and no unexpected morbidity. This treatment modality was effective in controlling the underlying plasma cell dyscrasia and light chain production as six patients achieved complete hematologic remission (CR, by EORTC criteria) post-transplantation and remain in CR after a median follow up of 18.6 months (2.9 to 64.8 months). One patient achieved partial remission (PR). The median progression free survival has not been reached but the patient with a PR had progression of his MM and is currently receiving second-line therapy. Among the 4 patients who were dialysis independent at the time of HDC/ASCT, the renal function has improved compared to pre-HDC/ASCT in 2, remained stable in 1 (who achieved hematologic PR), and worsened in 1 leading to hemodialysis despite hematologic CR. Among the three patients who were dependent on hemodialysis at the time of HDC/ASCT, 2 have undergone kidney transplantation 14.1 and 45.7 months after HDC/ASCT and have a normal creatinine clearance 30.9 and 64.8 months after HDC/ASCT, respectively. The third patient remains in hematologic CR but has resumed peritoneal dialysis after a two-month-period of dialysis independence post-HDC/ASCT. He is currently being evaluated for kidney transplantation. Conclusions: Our results corroborate previous encouraging but limited experience with HDC/ASCT in MIDD and compare favorably with historical reports of conventional therapy in this patient population. These results also argue in favor of kidney transplantation in patients who achieve a hematologic CR after HDC/ASCT for MM associated with MIDD.

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Monoclonal gammopathy of renal significance: A novel combination of C3 glomerulopathy and light-chain proximal tubulopathy

Journal of Onco-Nephrology ◽

10.1177/2399369320916467 ◽

2020 ◽

Vol 4 (1-2) ◽

pp. 59-63 ◽

Cited By ~ 1

Author(s):

Elena V Zakharova ◽

Tatyana A Makarova ◽

Ekaterina S Stolyarevich ◽

Olga A Vorobyeva ◽

Irina G Rekhtina

Keyword(s):

Serum Creatinine ◽

Light Chain ◽

Immunoglobulin G ◽

Monoclonal Gammopathy ◽

Plasma Cells ◽

Bence Jones Protein ◽

Monoclonal Immunoglobulin ◽

Monoclonal Gammopathies ◽

Proximal Tubulopathy ◽

Light Chain Proximal Tubulopathy

Introduction: According to the recent International Kidney and Monoclonal Gammopathy Research Group Consensus report, the spectrum of monoclonal gammopathies of renal significance merges more than 12 conditions; and combinations of various patterns of monoclonal gammopathies of renal significance–associated kidney damage have already been described. We present a case of a previously unreported combination of C3 glomerulopathy and light-chain proximal tubulopathy. Case description: A 53-year-old Caucasian man presented with general weakness. Three years prior, a check-up revealed proteinuria and microhematuria, later accompanied by arterial hypertension, elevated serum creatinine, and a low serum C3 levels. On admission, his creatinine was 1.5 mg/dL; his protein excretion was 1900 mg/24 h with microhematuria at 150 hpf. His serum C3 was 79 mg/dL with a normal C4 level. Serum protein electrophoresis revealed an M-spike, immunochemistry confirmed monoclonal immunoglobulin G kappa secretion of 920 mg/dL, and traces of Bence–Jones protein kappa in his urine. A kidney biopsy showed mesangial hypercellularity with diffuse fine granular C3 mesangial expression and tubular atrophy with diffuse coarse granular kappa light-chain tubular epithelial cytoplasmic expression. Computed tomography did not reveal any destructive lesions. A bone marrow smear showed 5% plasma cells, and bone marrow cell flow cytometry demonstrated 87.4% of plasma cells with an aberrant phenotype. The patient was diagnosed with an monoclonal gammopathy of renal significance and administered bortezomib–cyclophosphamide–dexamethasone. After four courses, his monoclonal immunoglobulin G kappa secretion halved, but his serum creatinine and proteinuria remained almost unchanged. Chemotherapy was switched to lenalidomide–dexamethasone, and after five courses his immunoglobulin G kappa secretion decreased to traces, Bence–Jones protein was not observed and his urinalysis, serum creatinine, and C3 levels were detected as normal. Conclusion: The combination of kidney damage patterns, one of which was directly and the other indirectly associated with monoclonal gammopathy, complements the monoclonal gammopathies of renal significance spectrum. Chemotherapy led to a very good partial response and kidney function recovery.

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