scholarly journals Randall-Type Monoclonal Immunoglobulin Deposition Disease: New Insights into the Pathogenesis, Diagnosis and Management

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 420
Author(s):  
Camille Cohen ◽  
Florent Joly ◽  
Audrey Sibille ◽  
Vincent Javaugue ◽  
Estelle Desport ◽  
...  
Keyword(s):  
Rare Disease ◽  
Renal Involvement ◽  
Molecular Characteristics ◽  
Monoclonal Immunoglobulin ◽  
Serum Free Light Chain ◽  
Monoclonal Immunoglobulin Deposition Disease ◽  
Deposition Disease ◽  
Monoclonal Immunoglobulins

Randall-type monoclonal immunoglobulin deposition disease (MIDD) is a rare disease that belongs to the spectrum of monoclonal gammopathy of renal significance (MGRS). Renal involvement is prominent in MIDD, but extra-renal manifestations can be present and may affect global prognosis. Recent data highlighted the central role of molecular characteristics of nephrotoxic monoclonal immunoglobulins in the pathophysiology of MIDD, and the importance of serum free light chain monitoring in the diagnosis and follow-up disease. Clone-targeted therapy is required to improve the overall and renal survival, and the achievement of a rapid and deep hematological response is the goal of therapy. This review will focus on the recent progress in the pathogenesis and management of this rare disease.

scholarly journals Renal Monoclonal Immunoglobulin Deposition Disease: The Disease Spectrum

2001 ◽  
Vol 12 (7) ◽  
pp. 1482-1492 ◽  
Author(s):  
JULIE LIN ◽  
GLEN S. MARKOWITZ ◽  
ANTHONY M. VALERI ◽  
NEERAJA KAMBHAM ◽  
WILLIAM H. SHERMAN ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Heavy Chain ◽  
Renal Involvement ◽  
Prognostic Significance ◽  
Monoclonal Immunoglobulin ◽  
Cast Nephropathy ◽  
Disease Spectrum ◽  
Monoclonal Immunoglobulin Deposition Disease ◽  
Deposition Disease

Abstract. This study reports the clinicopathologic findings and outcome in 34 patients with renal monoclonal immunoglobulin deposition disease (MIDD), which included 23 light-chain DD (LCDD), 5 light- and heavy-chain DD (LHCDD), and 6 heavy-chain DD (HCDD). A total of 23 patients had pure MIDD, whereas 11 patients had LCDD with coexistent myeloma cast nephropathy (LCDD & MCN). Renal biopsy diagnosis preceded clinical evidence of dysproteinemia in 68% of all cases. By immunofluorescence, the composition of deposits included 11κ/1λ (LCDD), 3IgGκ/2IgGλ (LHCDD), 5γ/1α (HCDD), and 10κ/1λ (LCDD & MCN). Patients with pure MIDD presented with mean serum creatinine of 4.2 mg/dl, nephrotic proteinuria, and hypertension. Cases of HCDD were associated with a CH1 deletion and frequently had hypocomplementemia and a positive hepatitis C virus antibody but negative hepatitis C virus PCR. LCDD & MCN is a morphologically and clinically distinct entity from pure MIDD, presenting with higher creatinine (mean, 7.8 mg/dl;P= 0.01), greater dialysis dependence (64versus26%;P= 0.053), subnephrotic proteinuria, and less nodular glomerulopathy (18versus100%;P< 0.0001). Multiple myeloma was more frequently diagnosed in LCDD & MCN than in pure MIDD (91versus31%;P= 0.025). Renal and patient survivals were significantly worse in patients with LCDD & MCN (mean, 4 and 22 mo, respectively), compared with patients with pure MIDD (mean, 22 and 54 mo). Chemotherapy stabilized or improved renal function in 10 of 15 patients (67%) with pure MIDD who presented with creatinine of <5.0 mg/dl, emphasizing the importance of early detection. On multivariate analysis, initial creatinine was the only predictor of renal and patient survival in pure MIDD, underscoring the prognostic significance of the renal involvement.

scholarly journals Randall-type monoclonal immunoglobulin deposition disease: novel insights from a nationwide cohort study

Blood ◽  
2019 ◽  
Vol 133 (6) ◽  
pp. 576-587 ◽  
Author(s):  
Florent Joly ◽  
Camille Cohen ◽  
Vincent Javaugue ◽  
Sébastien Bender ◽  
Mohamed Belmouaz ◽  
...  
Keyword(s):  
Light Chain ◽  
Interstitial Fibrosis ◽  
Rare Complication ◽  
Renal Involvement ◽  
Kidney Injury ◽  
Monoclonal Immunoglobulin ◽  
Renal Response ◽  
Monoclonal Immunoglobulin Deposition Disease ◽  
Deposition Disease ◽  
Extrarenal Manifestations

Abstract Monoclonal immunoglobulin deposition disease (MIDD) is a rare complication of B-cell clonal disorders, defined by Congo red negative–deposits of monoclonal light chain (LCDD), heavy chain (HCDD), or both (LHCDD). MIDD is a systemic disorder with prominent renal involvement, but little attention has been paid to the description of extrarenal manifestations. Moreover, mechanisms of pathogenic immunoglobulin deposition and factors associated with renal and patient survival are ill defined. We retrospectively studied a nationwide cohort of 255 patients, with biopsy-proven LCDD (n = 212) (including pure LCDD [n = 154], LCDD with cast nephropathy (CN) [n = 58]), HCDD (n = 23), or LHCDD (n = 20). Hematological diagnosis was monoclonal gammopathy of renal significance in 64% and symptomatic myeloma in 34%. Renal presentation was acute kidney injury in patients with LCCD and CN, and chronic glomerular disease in the other types, 35% of whom had symptomatic extrarenal (mostly hepatic and cardiac) involvement. Sequencing of 18 pathogenic LC showed high isoelectric point values of variable domain complementarity determining regions, possibly accounting for tissue deposition. Among 169 patients who received chemotherapy (bortezomib-based in 58%), 67% achieved serum free light chain (FLC) response, including very good partial response (VGPR) or above in 52%. Renal response occurred in 62 patients (36%), all of whom had achieved hematological response. FLC response ≥ VGPR and absence of severe interstitial fibrosis were independent predictors of renal response. This study highlights an unexpected frequency of extrarenal manifestations in MIDD. Rapid diagnosis and achievement of deep FLC response are key factors of prognosis.

scholarly journals Kidney Transplantation in Monoclonal Immunoglobulin Deposition Disease: A Report of 6 Cases

2021 ◽  
Author(s):  
Alicia Molina-Andújar ◽  
Natalia Tovar ◽  
Elena Cuadrado ◽  
Natalia Castrejón de Anta ◽  
Ignacio Revuelta ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Monoclonal Immunoglobulin ◽  
Monoclonal Immunoglobulin Deposition Disease ◽  
Deposition Disease

Monoclonal Immunoglobulin Deposition Disease

2013 ◽  
pp. 179-183
Author(s):  
Agnes B. Fogo ◽  
Arthur H. Cohen ◽  
Robert B. Colvin ◽  
J. Charles Jennette ◽  
Charles E. Alpers
Keyword(s):  
Monoclonal Immunoglobulin ◽  
Monoclonal Immunoglobulin Deposition Disease ◽  
Deposition Disease

Renal monoclonal immunoglobulin deposition disease (MIDD): the Columbia experience

2003 ◽  
pp. 130-142
Author(s):  
J. Lin ◽  
G. S. Markowitz ◽  
A. M. Valeri ◽  
N. Kambham ◽  
W. H. Sherman ◽  
...  
Keyword(s):  
Monoclonal Immunoglobulin ◽  
Monoclonal Immunoglobulin Deposition Disease ◽  
Deposition Disease

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

Blood ◽  
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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