Natural history and outcome of light chain deposition disease

Sayed, Rabya; Wechalekar, Ashutosh; Gilbertson, Janet A.; Bass, Paul; Mahmood, Shameem; Sachchithanantham, Sajitha; Fontana, Marianna; Patel, Ketna; Whelan, Carol; Lachmann, HJ; Hawkins, Philip N.; Gillmore, Julian D.

doi:10.1182/blood-2015-07-658872

Cited by 113 publications

(146 citation statements)

References 24 publications

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“…Fortunately, the hematologic response can be improved by the addition of autologous stem cell transplant. Achievement of VGPR in monoclonal Ig deposition disease similarly has been found to improve renal and patient survival (21,42,74,89). Kidney transplant has been successfully performed in patients with hematologic complete response without recurrence.…”

Section: Managementmentioning

confidence: 99%

“…Bortezomib seems to be the most effective agent in monoclonal Ig deposition disease (21,42,74,89). In one study, immunomodulatory drugs represented by thalidomide and lenalidomide were found to be less effective in achieving VGPR or better responses (21). Fortunately, the hematologic response can be improved by the addition of autologous stem cell transplant.…”

Section: Managementmentioning

confidence: 99%

“…The median age of these patients is between 56 and 64 years old. Nearly two thirds are men (19,21,42). Median Scr ranges from 2.2 to 3.8 mg/dl.…”

Section: Monoclonal Ig Deposition Diseasementioning

confidence: 99%

“…Patients with complete response are less likely to have recurrence after kidney transplant (88). Bortezomib seems to be the most effective agent in monoclonal Ig deposition disease (21,42,74,89). In one study, immunomodulatory drugs represented by thalidomide and lenalidomide were found to be less effective in achieving VGPR or better responses (21).…”

Section: Managementmentioning

confidence: 99%

“…The renal histology, however, remains useful for predicting the natural history, clinical features, and recurrence after kidney transplantation. One should not forget about extrarenal involvement in patients with AL amyloidosis and monoclonal Ig deposition disease (17,21,42). Patients with severe heart involvement may need to have modified chemotherapy, aggressive fluid management, and care for CKD (77)(78)(79).…”

Section: Managementmentioning

confidence: 99%

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Dysproteinemias and Glomerular Disease

Leung

Drosou

Nasr

2017

CJASN

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Dysproteinemia is characterized by the overproduction of an Ig by clonal expansion of cells from the B cell lineage. The resultant monoclonal protein can be composed of the entire Ig or its components. Monoclonal proteins are increasingly recognized as a contributor to kidney disease. They can cause injury in all areas of the kidney, including the glomerular, tubular, and vascular compartments. In the glomerulus, the major mechanism of injury is deposition. Examples of this include Ig amyloidosis, monoclonal Ig deposition disease, immunotactoid glomerulopathy, and cryoglobulinemic GN specifically from types 1 and 2 cryoglobulins. Mechanisms that do not involve Ig deposition include the activation of the complement system, which causes complement deposition in C3 glomerulopathy, and cytokines/growth factors as seen in thrombotic microangiopathy and precipitation, which is involved with cryoglobulinemia. It is important to recognize that nephrotoxic monoclonal proteins can be produced by clones from any of the B cell lineages and that a malignant state is not required for the development of kidney disease. The nephrotoxic clones that do not meet requirement for a malignant condition are now called monoclonal gammopathy of renal significance. Whether it is a malignancy or monoclonal gammopathy of renal significance, preservation of renal function requires substantial reduction of the monoclonal protein. With better understanding of the pathogenesis, clone-directed strategies, such as rituximab against CD20 expressing B cell and bortezomib against plasma cell clones, have been used in the treatment of these diseases. These clone-directed therapies been found to be more effective than immunosuppressive regimens used in nonmonoclonal protein-related kidney diseases.

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Section: Managementmentioning

confidence: 99%

Section: Managementmentioning

confidence: 99%

“…The median age of these patients is between 56 and 64 years old. Nearly two thirds are men (19,21,42). Median Scr ranges from 2.2 to 3.8 mg/dl.…”

Section: Monoclonal Ig Deposition Diseasementioning

confidence: 99%

Section: Managementmentioning

confidence: 99%

Section: Managementmentioning

confidence: 99%

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Dysproteinemias and Glomerular Disease

Leung

Drosou

Nasr

2017

CJASN

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Paraprotein‐associated Kidney Disorders

Javaugue

Bridoux

Leung

2022

Evidence‐Based Nephrology

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Outcomes of patients with renal monoclonal immunoglobulin deposition disease

et al. 2016

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Recent reports suggest that deep hematologic responses to chemotherapy are associated with improved renal outcomes in monoclonal immunoglobulin deposition disease (MIDD). Here we describe the long term outcomes and identify prognostic factors after first line treatment of the largest reported series of patients with MIDD. Between March 1992 and December 2014, 88 patients with MIDD were seen at Mayo Clinic, MN. Renal responses were defined using criteria used for light chain amyloidosis (AL) or those used by the IMWG. Sixty-one (69%) patients had a GFR < 30 mL/min/1.73 m and 16 (18%) were on renal replacement therapy at diagnosis. The interval between albuminuria or elevation in creatinine and MIDD diagnosis was 12 months suggesting a delay in diagnosis. Thirty-seven patients (42%) had at least a hematologic CR/VGPR. Fifty-three (60%) received an autologous stem cell transplant (ASCT) or proteasome inhibitor (PI)-based treatments. Patients receiving ASCT or PI-based therapies were more likely to achieve at least a hematologic CR/VGPR compared to those receiving other therapies: 66% vs 2%, p < 0.0001. Patients that achieved a hematologic CR were more likely to achieve a renal response (53% vs 24%, p = 0.001). Five year overall and renal survival for the entire cohort was 67% and 57%, respectively. In multivariate analyses, a baseline GFR < 20 mL/min/1.73 m and a renal response (using AL or IMWG criteria) were independently predictive of progression to dialysis. This study confirms that deep hematologic responses, best achieved with ASCT or PI-based therapies, are a prerequisite to achieving renal responses. Am. J. Hematol. 91:1123-1128, 2016. © 2016 Wiley Periodicals, Inc.

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Natural history and outcome of light chain deposition disease

Abstract: Key Points Deep clonal responses to chemotherapy are associated with improved renal and overall outcomes in patients with light chain deposition disease. Deep clonal responses should be targeted, even in patients with advanced chronic kidney disease from light chain deposition disease.

Cited by 113 publications

References 24 publications

Dysproteinemias and Glomerular Disease

Dysproteinemias and Glomerular Disease

Paraprotein‐associated Kidney Disorders

Outcomes of patients with renal monoclonal immunoglobulin deposition disease

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