Characteristics of the main MGRS-related renal disorders with organized Ig deposits
| Disease . | Renal pathology . | Renal manifestations . | Extrarenal manifestations . | Hematologic findings . | Hematologic diagnosis . |
|---|---|---|---|---|---|
| Immunoglobulinic amyloidosis: AL amyloidosis (94%) AH/AHL amyloidosis (6%) | LM: Congo red positive glomerular (pred. mesangial), vascular +/− interstitial deposits IF (composition of deposits): AL: LC-only deposits (mostly λ) AH: HC-only deposits (mostly γ1 or γ4) with CH1 deletion AHL: monotypic LC and HC (mostly γ) deposits EM: Nonbranched, randomly arranged fibrils (7-12 nm) | CKD (median s. creat. 1.2 mg/dL) Massive proteinuria (median 5-6 g/d) Nephrotic syndrome (>60%) Hematuria/hypertension rare | Frequent: Cardiomyopathy (70%) Liver disease GI tract Peripheral neuropathy Autonomic dysfunction Carpal tunnel Soft tissues Macroglossia Periorbital hematoma | Positive serum/urine EP/IFix: 80% Abnormal sFLC level: 90% Plasma cell clone: 90% (t(11;14): 50%) Lymphocytic/LPC clone: 10% (IgM secreting) Factor X deficiency: 10% Hypocomplementemia: no | MGCS/MGRS: 80% MM: 16% WM, B-cell lymphoma: 4% |
| Immunotactoid glomerulopathy | LM: MPGN, EPGN, MGN IF: monotypic IgG (mostly IgG1κ) granular deposits in mesangium and CW EM: parallel microtubules (14-60 nm) | CKD (median s. creat 1.5 mg/dL) Heavy proteinuria (median 6 g/d) Nephrotic syndrome (~70%) Hematuria (75%-90%) Hypertension (60%-80%) | Extremely rare: Skin capillaritis Mononeuritis multiplex | Positive serum/urine EP/IFix: 50% Abnormal sFLC level: 20%-30% Plasma cell clone: 50% Lymphocytic clone: 50% Hypocomplementemia: 33% | MGRS: 50% CLL: 40%-45% B-cell lymphoma: 10% MM: 4% |
| Type 1 cryoglobulinic GN | LM: MPGN, EPGN with glomerular monocyte infiltration, frequent intracapillary immune thrombi IF: monotypic Ig (mostly IgGκ or IgMκ) granular glomerular +/− vascular deposits EM: microtubular and/or crystalline deposits (extra +/− intracellular) if IgG or IgA | CKD (median s. creat. 3 mg/dL) Heavy proteinuria (median 3 g/d) Nephrotic syndrome (40%), Hematuria/ hypertension (70%) | Frequent (60%): Pupura, skin necrosis/gangrene, livedo reticularis Raynaud phenomenon Peripheral neuropathy Arthralgias/arthritis GI tract | Positive serum/urine EP/IFix: 80% Abnormal sFLC level: 40% Plasma cell clone: 40% Lymphocytic/LPC clone: 60% Type 1 cryoglobulinemia: 60% Hypocomplementemia (mostly low C4) (60%) | MGRS: 80% CLL: 10% WM/ lymphoma: 10%-50% MM: 3%-7% |
| LC crystalline podocytopathy | LM: FSGS (60%) IF: LC-only crystals (κ 90%) EM: intracytoplasmic crystals in podocytes | CKD (median s. creat. 1.9 mg/dL) Proteinuria (median 3.4 g/d) Nephrotic syndrome (30%) | Common: LC keratopathy (25%) | Positive serum/urine EP/IFix: 100% Abnormal sFLC level: 80% Plasma cell clone: ~100% Lymphocytic clone: anecdotal | MGRS: 55% MM: 45% |
| LC proximal tubulopathy | LM: PTC swelling, dedifferentiation IF: PTC LC staining (mostly κ in crystalline variant), rarely λ (noncrystalline variant) EM: PTC LC crystals (if κ) or lysosomal inclusions | CKD (median s.creat 2 mg/dL) Proteinuria (median 1.5-2.5 g/d) Proximal tubulopathy with or without complete FS | Common: If FS: osteomalacia, stress fractures IF CSH: lungs, GI tract, cornea, bone marrow, lymph nodes, liver, spleen | Positive serum/urine PEP/IFix: ~100% Abnormal sFLC level: ~100% Plasma cell clone: 95% Lymphocytic/LPC clone: 5% | MGRS: 60%-80% MM: 15%-30% WM/ lymphoma: 3%-8% |
| Disease . | Renal pathology . | Renal manifestations . | Extrarenal manifestations . | Hematologic findings . | Hematologic diagnosis . |
|---|---|---|---|---|---|
| Immunoglobulinic amyloidosis: AL amyloidosis (94%) AH/AHL amyloidosis (6%) | LM: Congo red positive glomerular (pred. mesangial), vascular +/− interstitial deposits IF (composition of deposits): AL: LC-only deposits (mostly λ) AH: HC-only deposits (mostly γ1 or γ4) with CH1 deletion AHL: monotypic LC and HC (mostly γ) deposits EM: Nonbranched, randomly arranged fibrils (7-12 nm) | CKD (median s. creat. 1.2 mg/dL) Massive proteinuria (median 5-6 g/d) Nephrotic syndrome (>60%) Hematuria/hypertension rare | Frequent: Cardiomyopathy (70%) Liver disease GI tract Peripheral neuropathy Autonomic dysfunction Carpal tunnel Soft tissues Macroglossia Periorbital hematoma | Positive serum/urine EP/IFix: 80% Abnormal sFLC level: 90% Plasma cell clone: 90% (t(11;14): 50%) Lymphocytic/LPC clone: 10% (IgM secreting) Factor X deficiency: 10% Hypocomplementemia: no | MGCS/MGRS: 80% MM: 16% WM, B-cell lymphoma: 4% |
| Immunotactoid glomerulopathy | LM: MPGN, EPGN, MGN IF: monotypic IgG (mostly IgG1κ) granular deposits in mesangium and CW EM: parallel microtubules (14-60 nm) | CKD (median s. creat 1.5 mg/dL) Heavy proteinuria (median 6 g/d) Nephrotic syndrome (~70%) Hematuria (75%-90%) Hypertension (60%-80%) | Extremely rare: Skin capillaritis Mononeuritis multiplex | Positive serum/urine EP/IFix: 50% Abnormal sFLC level: 20%-30% Plasma cell clone: 50% Lymphocytic clone: 50% Hypocomplementemia: 33% | MGRS: 50% CLL: 40%-45% B-cell lymphoma: 10% MM: 4% |
| Type 1 cryoglobulinic GN | LM: MPGN, EPGN with glomerular monocyte infiltration, frequent intracapillary immune thrombi IF: monotypic Ig (mostly IgGκ or IgMκ) granular glomerular +/− vascular deposits EM: microtubular and/or crystalline deposits (extra +/− intracellular) if IgG or IgA | CKD (median s. creat. 3 mg/dL) Heavy proteinuria (median 3 g/d) Nephrotic syndrome (40%), Hematuria/ hypertension (70%) | Frequent (60%): Pupura, skin necrosis/gangrene, livedo reticularis Raynaud phenomenon Peripheral neuropathy Arthralgias/arthritis GI tract | Positive serum/urine EP/IFix: 80% Abnormal sFLC level: 40% Plasma cell clone: 40% Lymphocytic/LPC clone: 60% Type 1 cryoglobulinemia: 60% Hypocomplementemia (mostly low C4) (60%) | MGRS: 80% CLL: 10% WM/ lymphoma: 10%-50% MM: 3%-7% |
| LC crystalline podocytopathy | LM: FSGS (60%) IF: LC-only crystals (κ 90%) EM: intracytoplasmic crystals in podocytes | CKD (median s. creat. 1.9 mg/dL) Proteinuria (median 3.4 g/d) Nephrotic syndrome (30%) | Common: LC keratopathy (25%) | Positive serum/urine EP/IFix: 100% Abnormal sFLC level: 80% Plasma cell clone: ~100% Lymphocytic clone: anecdotal | MGRS: 55% MM: 45% |
| LC proximal tubulopathy | LM: PTC swelling, dedifferentiation IF: PTC LC staining (mostly κ in crystalline variant), rarely λ (noncrystalline variant) EM: PTC LC crystals (if κ) or lysosomal inclusions | CKD (median s.creat 2 mg/dL) Proteinuria (median 1.5-2.5 g/d) Proximal tubulopathy with or without complete FS | Common: If FS: osteomalacia, stress fractures IF CSH: lungs, GI tract, cornea, bone marrow, lymph nodes, liver, spleen | Positive serum/urine PEP/IFix: ~100% Abnormal sFLC level: ~100% Plasma cell clone: 95% Lymphocytic/LPC clone: 5% | MGRS: 60%-80% MM: 15%-30% WM/ lymphoma: 3%-8% |
CH1, first constant domain; CW, glomerular capillary wall; EP, electrophoresis; EPGN, endocapillary proliferative glomerulonephritis; FS, renal Fanconi syndrome; FSGS, focal segmental glomerulosclerosis; GI, gastrointestinal; GN, glomerulonephritis; IF, immunofluorescence; IFix, immunofixation; LM, light microscopy; LPC, lymphoplasmacytic; MGN; membranous glomerulopathy; MM, multiple myeloma; MPGN, membranoproliferative glomerulonephritis; PTC, proximal tubular cells; s.creat, serum creatinine; sFLC, serum free light chains; WM, Waldenström macroglobulinemia.