Renal Disorders Associated with Waldenström Macroglobulinaemia, IgM MGUS and IgM-Producing B-Cell Lymphoproliferative Disorders
Abstract
:1. Introduction
2. Investigating Renal Impairment in a Patient with WM or IgM MGUS
3. Patients with Symptomatic WM with a Significant Tumour Burden and Renal Impairment
4. Patients with Suspected Renal Amyloidosis
5. Patients with a Non-Amyloid form of MGRS and Serum Monoclonal IgM
6. Cryoglobulinaemic Glomerulopathy
7. Light-Chain Deposition Disease (LCDD)
8. Rarer MGRS
9. Other Renal Pathologies with Less Clear Relationships to WM and IgM MGUS
10. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Disease/Renal Lesion | Clinical Symptoms | Renal Histology |
---|---|---|
Amyloidosis (AL, AH and AHL) | Renal: Proteinuria, low serum albumin, oedema and reduced eGFR Cardiac: Restrictive cardiomyopathy, shortness of breath, raised cardiac bio-markers Peripheral and/or autonomic neuropathy Easy bruising (peri orbital) and soft tissue infiltration (macroglossia, muscle stiffness and jaw claudication) | Organised fibrillar deposits LM and Congo red-positive deposits IF and IHC-positive deposits for kappa or lambda EM: randomly oriented fibrils (7–14 nm) |
Cryoglobulinaemia/ Cryoglobulinaemic glomerulonephropathy | Renal: Isolated proteinuria or haematuria, and occasionally, nephrotic syndrome Cutaneous disease: Digital ischemia, Livedo reticularis and skin necrosis, erythematous macules and purpuric papules in lower limbs, and Reynaud’s phenomena Other manifestations: Peripheral neuropathy Hyperviscosity symptoms (blurred vision, headache, vertigo, nystagmus, confusion, stroke and coma) Arthralgia, fatigue and myalgia Pulmonary involvement: small airways disease, dyspnoea, cough and pleurisy Lymphadenopathy and splenomegaly Vasculitis of most internal organs possible | Organized microtubular or crystal deposits LM: membranoproliferative or endocapillary proliferative GN with monocyte infiltration and often immune thrombi IF: monotypic Ig granular deposits in glomeruli and vessels EM: microtubular extracellular electron-dense deposits and occasional intracellular crystals |
Monoclonal immunoglobulin deposition disease (MIDD) LCDD, LHCDD and HCDD | Predominantly renal-limited (nephrotic syndrome and common hypertension) Cardiac involvement, cardiomyopathy and heart failure symptoms (rare) Liver involvement Peripheral nerve involvement possible | Non-organised deposits LM: nodular glomerulosclerosis (67% of cases) and thickened TBM IF: linear deposits along GBM, TBM and vessels EM: punctate electron-dense deposits along GBM, TBM and vessels |
Immunotactoid glomerulonephritis | Renal isolated disease Proteinuria seen in 100% Haematuria is common Reduced eGFR in 50% of cases Low complements may be seen | Organised non-fibrillar deposits LM: atypical membranous, membranoproliferative, mesangial or endocapillary proliferative GN IF: monotypic IgG granular deposits in mesangium and GBM EM: glomerular microtubular deposits (14–60 nm) in parallel arrangement |
Proliferative glomerulonephritis with monoclonal Ig deposits (PGNMID) | Renal isolated disease Nephrotic syndrome (50%) Haematuria (70%) Reduced eGFR (70%) | Non-organised deposits LM: membranoproliferative, endocapillary proliferative or membranous GN IF: monotypic Ig (mostly IgG3κ) granular deposits in mesangium and GBM EM: electron-dense deposits in glomeruli |
Light-chain Proximal Tubulopathy | Renal isolated disease Fanconi syndrome, hypophosphataemia, renal glucosuria and/or aminoaciduria Muscle weakness, increased urine output and thirst | Organized crystals or inclusions LM: proximal tubular swelling IF: proximal tubular staining with κ (in crystalline variant) or λ (mostly in non-crystalline variant) EM: proximal tubular LC crystals or lysosomal inclusions |
Fibrillary GN with monoclonal gammopathy | Renal isolated disease Proteinuria is common, and nephrotic syndrome is reported in 70% Haematuria is common Reduced eGFR in 50% of cases Low complements may be seen | Organised fibrillar deposits LM: MPGN, diffuse proliferative, mesangial proliferative or diffuse sclerosis IF: Smudged deposits; stain for IgG, C3, κ, or λ, and DNAJB9 EM: Randomly arranged fibrils (12–24 nm) |
C3 glomerulopathy with monoclonal gammopathy | Renal isolated disease Hypertension Proteinuria Declining renal function Low complements in some patients | Non-organised deposits LM: membranoproliferative, mesangioproliferative or endocapillary proliferative GN IF: C3 granular deposits in mesangium and GBM (with paucity of Ig deposits) EM: ill-defined electron-dense deposits in C3GN and intramembranous and mesangial highly electron-dense deposits in dense-deposit disease |
Thrombotic microangiopathy (TMA) | Unexplained anaemia and thrombocytopenia Hypertension, possibly severe | Light and electron microscopy: GBM duplication, mesangiolysis, subendothelial “fluff,” and thrombosis IF: no Ig deposits |
Membranous nephropathy | Renal isolated disease Nephrotic syndrome is common Proteinuria is the predominant feature | LM: diffuse thickening of the GBM. “Spikes” of GBM extending among immune deposits may be seen on silver stain EM: subepithelial electron-dense deposits; effacement of foot processes and expansion of the GBM with deposition of extracellular matrix. IF: diffuse granular pattern of immunoglobulin (Ig) G and C3 staining along the GBM |
Minimal change nephropathy | Renal isolated disease Nephrotic syndrome with rapid onset | LM: glomeruli appear normal EM: diffuse effacement of epithelial foot processes IF: no complement or immunoglobulin deposits |
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Pratt, G.; Giles, H.V.; Pinney, J.H. Renal Disorders Associated with Waldenström Macroglobulinaemia, IgM MGUS and IgM-Producing B-Cell Lymphoproliferative Disorders. Hemato 2023, 4, 184-195. https://doi.org/10.3390/hemato4020015
Pratt G, Giles HV, Pinney JH. Renal Disorders Associated with Waldenström Macroglobulinaemia, IgM MGUS and IgM-Producing B-Cell Lymphoproliferative Disorders. Hemato. 2023; 4(2):184-195. https://doi.org/10.3390/hemato4020015
Chicago/Turabian StylePratt, Guy, Hannah V. Giles, and Jennifer H. Pinney. 2023. "Renal Disorders Associated with Waldenström Macroglobulinaemia, IgM MGUS and IgM-Producing B-Cell Lymphoproliferative Disorders" Hemato 4, no. 2: 184-195. https://doi.org/10.3390/hemato4020015