Characteristics of MGRS-related renal disorders with nonorganized Ig deposits and without Ig deposits
| Disease . | Renal pathology . | Renal manifestations . | Extrarenal manifestations . | Hematologic findings . | Hematologic diagnosis . |
|---|---|---|---|---|---|
| MGRS-related renal disorders with nonorganized Ig deposits | |||||
| Monoclonal immunoglobulin deposition disease | LM: nodular glomerulosclerosis (2/3 of cases) with thickened TBM IF: linear deposits along GBM, TBM, and vessels LCDD: LC-only deposits (mostly κ) HCDD: HC-only deposits with CH1 deletion (mostly γ) LHCDD: deposits containing 1 LC and 1 HC lacking CH1 (mostly γ) EM: punctate linear amorphous deposits along GBM, TBM, vessels | CKD (median s.creat. 3 mg/dL) Proteinuria (median 2 g/d) Nephrotic syndrome (22%), Hematuria (60%) Hypertension (60%-80%) | Common in LCDD (35%): Cardiac disease Liver disease Peripheral neuropathy | Positive serum/urine EP/IFix: 90% Abnormal sFLC level: 99%-100% Plasma cell clone: 95%-100% Lymphocytic/LPC clone: <5% Hypocomplementemia (low C4) if HCDDγ1 or HCDDγ3 | MGRS: 65%-80% MM: 20%-35% WM/B-cell lymphoma: 2% |
| Proliferative glomerulonephritis with monoclonal immunoglobulin deposits | LM: MPGN, EPGN, MGN IF: monotypic IgG (mostly IgG3κ, rarely IgM, IgA, LC only); granular deposits in mesangium and CW EM: discontinuous nonorganized glomerular deposits | CKD (mean s.creat. 2.8 mg/dL) Heavy proteinuria (mean 6 g/d) Nephrotic syndrome (50%) Hematuria (80%) Hypertension (38%) | Absent | Positive serum/urine EP/IFix: 20%-30% Abnormal sFLC: 20% Plasma cell clone: ~10% Lymphocytic/LPC clone: ~10% Hypocomplementemia 20% Negative tests for cryoglobulins | MGRS: 95% MM: 3%-4% WM/B-cell lymphoma: 1% |
| MGRS-related renal disorders without Ig deposits | |||||
| C3GP with monoclonal gammopathy | LM: MPGN, MesPGN, EPGN IF: granular deposits of C3 only in mesangium and CW EM: C3GN: less electron dense subendothelial/subepithelial/ mesangial deposits Dense deposit disease: highly electron dense sausage-like deposits within GBM | CKD (median s.creat.1.8 mg/dL) Proteinuria (median 3 g/d) Nephrotic syndrome (43%), Hematuria (90%) | Rare: Digital ischemia | Positive serum/urine EP/IFix: 100% Abnormal sFLC level: 50%-75% Plasma cell clone: 95% Lymphocytic clone: 5% Low C3 (35%-45%) High serum C5bC9: 80% | MGRS: 80%-90% MM: 5%-15% B-cell lymphoma: 6% |
| Thrombotic microangiopathy with monoclonal gammopathy | LM and EM: GBM duplication, mesangiolysis, subendothelial widening “fluff,” thrombosis IF: no Ig deposits | CKD (median s.creat 3 mg/dL) Proteinuria (median 2-4 g/d) Hematuria (90%) | Common: MAHA (50%-90%) CNS, skin, peripheral neuropathy | Positive serum/urine EP/IFix: 100%; Abnormal sFLC level: 28% Plasma cell clone: 80% Lymphocytic/LPC clone: 20% Low C3 (33%) High serum C5bC9: 77% | MGRS: 90% POEMS syndrome: 10% MM: 5% WM/B-cell lymphoma: 5% |
| Disease . | Renal pathology . | Renal manifestations . | Extrarenal manifestations . | Hematologic findings . | Hematologic diagnosis . |
|---|---|---|---|---|---|
| MGRS-related renal disorders with nonorganized Ig deposits | |||||
| Monoclonal immunoglobulin deposition disease | LM: nodular glomerulosclerosis (2/3 of cases) with thickened TBM IF: linear deposits along GBM, TBM, and vessels LCDD: LC-only deposits (mostly κ) HCDD: HC-only deposits with CH1 deletion (mostly γ) LHCDD: deposits containing 1 LC and 1 HC lacking CH1 (mostly γ) EM: punctate linear amorphous deposits along GBM, TBM, vessels | CKD (median s.creat. 3 mg/dL) Proteinuria (median 2 g/d) Nephrotic syndrome (22%), Hematuria (60%) Hypertension (60%-80%) | Common in LCDD (35%): Cardiac disease Liver disease Peripheral neuropathy | Positive serum/urine EP/IFix: 90% Abnormal sFLC level: 99%-100% Plasma cell clone: 95%-100% Lymphocytic/LPC clone: <5% Hypocomplementemia (low C4) if HCDDγ1 or HCDDγ3 | MGRS: 65%-80% MM: 20%-35% WM/B-cell lymphoma: 2% |
| Proliferative glomerulonephritis with monoclonal immunoglobulin deposits | LM: MPGN, EPGN, MGN IF: monotypic IgG (mostly IgG3κ, rarely IgM, IgA, LC only); granular deposits in mesangium and CW EM: discontinuous nonorganized glomerular deposits | CKD (mean s.creat. 2.8 mg/dL) Heavy proteinuria (mean 6 g/d) Nephrotic syndrome (50%) Hematuria (80%) Hypertension (38%) | Absent | Positive serum/urine EP/IFix: 20%-30% Abnormal sFLC: 20% Plasma cell clone: ~10% Lymphocytic/LPC clone: ~10% Hypocomplementemia 20% Negative tests for cryoglobulins | MGRS: 95% MM: 3%-4% WM/B-cell lymphoma: 1% |
| MGRS-related renal disorders without Ig deposits | |||||
| C3GP with monoclonal gammopathy | LM: MPGN, MesPGN, EPGN IF: granular deposits of C3 only in mesangium and CW EM: C3GN: less electron dense subendothelial/subepithelial/ mesangial deposits Dense deposit disease: highly electron dense sausage-like deposits within GBM | CKD (median s.creat.1.8 mg/dL) Proteinuria (median 3 g/d) Nephrotic syndrome (43%), Hematuria (90%) | Rare: Digital ischemia | Positive serum/urine EP/IFix: 100% Abnormal sFLC level: 50%-75% Plasma cell clone: 95% Lymphocytic clone: 5% Low C3 (35%-45%) High serum C5bC9: 80% | MGRS: 80%-90% MM: 5%-15% B-cell lymphoma: 6% |
| Thrombotic microangiopathy with monoclonal gammopathy | LM and EM: GBM duplication, mesangiolysis, subendothelial widening “fluff,” thrombosis IF: no Ig deposits | CKD (median s.creat 3 mg/dL) Proteinuria (median 2-4 g/d) Hematuria (90%) | Common: MAHA (50%-90%) CNS, skin, peripheral neuropathy | Positive serum/urine EP/IFix: 100%; Abnormal sFLC level: 28% Plasma cell clone: 80% Lymphocytic/LPC clone: 20% Low C3 (33%) High serum C5bC9: 77% | MGRS: 90% POEMS syndrome: 10% MM: 5% WM/B-cell lymphoma: 5% |
CH1, first constant domain; CNS, central nervous system; CW, glomerular capillary wall; EP, electrophoresis; EPGN, endocapillary proliferative glomerulonephritis; GBM, glomerular basement membrane; IF, immunofluorescence; IFix, immunofixation; LM, light microscopy; LPC, lymphoplasmacytic; MAHA, microangiopathic hemolytic anemia; MGN; membranous glomerulopathy; MesPGN, mesangial proliferative glomerulonephritis; MM, multiple myeloma; MPGN, membranoproliferative glomerulonephritis; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes; s.creat, serum creatinine; sFLC, serum free light chains; TBM, tubular basement membrane; WM, Waldenström macroglobulinemia.