The monoclonal gammopathies of renal significance (MGRS) are paraprotein-mediated diseases of the kidney in patients who do not meet criteria for multiple myeloma or systemic lymphoma. The diagnosis requires a kidney biopsy, and management is geared toward detection and treatment of the underlying plasma or B cell clone that is producing the pathogenic paraprotein. This approach is extrapolated from well-studied paraprotein-mediated diseases such as multiple myeloma and AL amyloidosis. In this review, we aim to demystify the workup and treatment of the MGRS disorders.
BridouxFLeungNHutchisonCAet al.International Kidney and Monoclonal Gammopathy Research Group. Diagnosis of monoclonal gammopathy of renal significance. Kidney Int2015; 87(4): 698–711
2.
CookLMacdonaldDHManagement of paraproteinaemia. Postgrad Med J2007; 83(978): 217–223
3.
HutchisonCAHardingSHewinsPet al.Quantitative assessment of serum and urinary polyclonal free light chains in patients with chronic kidney disease. Clin J Am Soc Nephrol2008; 3(6): 1684–1690
4.
MagnanoLFernández de LarreaCElenaMet al.Prognostic impact of serum heavy/light chain pairs in patients with monoclonal gammopathy of undetermined significance and smoldering myeloma: long-term results from a single institution. Clin Lymphoma Myeloma Leuk2016; 16(6): e71–e77
5.
Ramirez-AlvaradoMBarnidgeDRMurrayDLet al.Assessment of renal response with urinary exosomes in patients with AL amyloidosis: a proof of concept. Am J Hematol2017; 92(6): 536–541
6.
KyleRATherneauTMRajkumarSVet al.Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med2006; 354(13): 1362–1369
7.
LandgrenOGridleyGTuressonIet al.Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States. Blood2006; 107(3): 904–906
8.
KyleRADurieBGRajkumarSVet al.International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia2010; 24(6): 1121–1127
9.
BridouxFJavaugueVBenderSet al.Unravelling the immunopathological mechanisms of heavy chain deposition disease with implications for clinical management. Kidney Int2017; 91(2): 423–434
10.
BonaudABenderSTouchardGet al.A mouse model recapitulating human monoclonal heavy chain deposition disease evidences the relevance of proteasome inhibitor therapy. Blood2015; 126(6): 757–765
11.
PalladiniGDispenzieriAGertzMAet al.New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol2012; 30(36): 4541–4549
12.
DebiecHHanoyMFrancoisAet al.Recurrent membranous nephropathy in an allograft caused by IgG3κ targeting the PLA2 receptor. J Am Soc Nephrol2012; 23(12): 1949–1954
13.
NasrSHCollinsABAlexanderMPet al.The clinicopathologic characteristics and outcome of atypical anti-glomerular basement membrane nephritis. Kidney Int2016; 89(4): 897–908
14.
NasrSHSethiSCornellLDet al.Proliferative glomerulonephritis with monoclonal IgG deposits recurs in the allograft. Clin J Am Soc Nephrol2011; 6(1): 122–132
15.
NasrSHValeriAMCornellLDet al.Renal monoclonal immunoglobulin deposition disease: a report of 64 patients from a single institution. Clin J Am Soc Nephrol2012; 7(2): 231–239
16.
PozziCDAmicoMFogazziGBet al.Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors. Am J Kidney Dis2003; 42(6): 1154–1163
17.
CohenCRoyerBJavaugueVet al.Bortezomib produces high hematological response rates with prolonged renal survival in monoclonal immunoglobulin deposition disease. Kidney Int2015; 88(5): 1135–1143
18.
LinJMarkowitzGSValeriAMet al.Renal monoclonal immunoglobulin deposition disease: the disease spectrum. J Am Soc Nephrol2001; 12(7): 1482–1492
19.
BhutaniGNasrSHSaidSMet al.Hematologic characteristics of proliferative glomerulonephritides with nonorganized monoclonal immunoglobulin deposits. Mayo Clin Proc2015; 90(5): 587–596
20.
FermandJPBridouxFKyleRAet al.International Kidney and Monoclonal Gammopathy Research Group. How I treat monoclonal gammopathy of renal significance (MGRS). Blood2013; 122(22): 3583–3590
21.
DittusCUwumugambiNSunFSloanJMSanchorawalaVThe effect of bone marrow plasma cell burden on survival in patients with light chain amyloidosis undergoing high-dose melphalan and autologous stem cell transplantation. Biol Blood Marrow Transplant2016; 22(9): 1729–1732
22.
HoganJJWeissBMBridging the divide: an onco-nephrologic approach to the monoclonal gammopathies of renal significance. Clin J Am Soc Nephrol2016; 11(9): 1681–1691
23.
PalladiniGHegenbartUMilaniPet al.A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood2014; 124(15): 2325–2332
24.
KourelisTVNasrSHDispenzieriAet al.Outcomes of patients with renal monoclonal immunoglobulin deposition disease. Am J Hematol2016; 91(11): 1123–1128
25.
ZiogasDCKastritisETerposEet al.Hematologic and renal improvement of monoclonal immunoglobulin deposition disease after treatment with bortezomib-based regimens. Leuk Lymphoma2017; 58(8): 1832–1839
26.
EdwardsCVGouldJLangerALet al.Interim analysis of the phase 1a/b study of chimeric fibril-reactive monoclonal antibody 11-1F4 in patients with AL amyloidosis. Amyloid2017; 24(Supp 1): 58–59
27.
GertzMALandauHComenzoRLet al.First-in-human Phase I/II study of NEOD001 in patients with light chain amyloidosis and persistent organ dysfunction. J Clin Oncol2016; 34(10): 1097–1103
28.
YingWZAllenCECurtisLMAaronKJSandersPWMechanism and prevention of acute kidney injury from cast nephropathy in a rodent model. J Clin Invest2012; 122(5): 1777–1785
29.
DimopoulosMASonneveldPLeungNet al.International Myeloma Working Group recommendations for the diagnosis and management of myeloma-related renal impairment. J Clin Oncol2016; 34(13): 1544–1557
