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Currently filtering by tag: MGRS

Art of Medicine: Monoclonal Gammopathies of Renal Significance

Monoclonal Gammopathies of Renal Significance
The above painting is of a bone marrow biopsy showing replacement of the hematopoietic elements with plasma cells, including atypical plasma cells (Mott cells and plasma cells with Dutcher bodies shown).  This can be seen in plasma cell myeloma. Multiple myeloma can be diagnosed with the presence of a plasma cell myeloma (>10% clonal bone marrow plasma cells), and one or more myeloma-defining events.  These include hypercalcemia, renal insufficiency, anemia, or lytic lesions within bones.   On a kidney biopsy, light chain cast nephropathy is a myeloma defining event and is a paraprotein-associated renal disease.  Other renal manifestations that can occur...

Type 1 Cryoglobulinemic Glomerulonephritis

The patient is a 75 year-old female who presents with proteinuria, a necrotic skin lesion on her lower extremity, and a creatinine of 5.5 mg/dL. Her serum complement levels (C3/C4) are low.  Serologies for ANA, dsDNA, rheumatoid factor, c-ANCA, p-ANCA, anti-GBM, and ASO are negative. Her cryoglobulins are positive. Image 1 shows hyaline thrombi and image 2 shows mild interstitial fibrosis. Images 3, 4, 5, and 6 are IgG, IgM, kappa, and lambda, respectively. This is a case of Type 1 cryoglobulinemia. Type 1 cryoglobulins are composed of a single monoclonal immunoglobulin that reversibly participates at low temperature (<37C).  Type...

Twitter Poll (July 10, 2019)

Answer: True About 5-10% of the patients with monoclonal gammopathy and findings consistent with C3GN by standard IF (on frozen tissue) will actually have a Membranoproliferative GN with masked monoclonal deposits. These patients require additional IF studies to be performed on protease-digested, paraffin-embedded tissue for identification of the monoclonal immunoglobulin in the deposits. References: Leung N, et al. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group. Nat Rev Nephrol 2019; 15(1): 45-59. Larsen CP, et al. Membranoproliferative glomerulonephritis with masked monotypic immunoglobulin deposits. Kidney Int 2015; 88(4): 867-873....

Disease Week: Monoclonal Gammopathy of Renal Significance

Disease Week: Monoclonal Gammopathy of Renal Significance   Summary: Renal disease caused by parenchymal deposition of circulating monoclonal immunoglobulins (mIg) is a well established phenomenon. Light chain cast nephropathy, light chain deposition disease and AL amyloidosis are probably the best known entities; nevertheless, the list also includes a number of less common and recently described entities, some of which are still poorly understood.  These disorders may be seen in the setting of either a B-cell or plasma cell proliferative disorder with production of a mIg. When these proliferative disorders represent an overtly malignant disease (e.g. multiple myeloma, Waldenström macroglobulinemia, high-grade...

Light Chain Cast Nephropathy

A 75-year-old female is found to have a creatinine of 4.0 mg/dL on a routine laboratory examination. At the hospital, a CT scan shows lytic lesions within the skull. A SPEP shows an IgG kappa monoclonal protein. A bone marrow biopsy shows 5% plasma cells. A kidney biopsy is requested to look for monoclonal gammopathy of renal significance. Figure 1 shows a normal glomerulus. Figure 2 shows severe interstitial fibrosis. Figures 3 & 4 show abnormal, PAS negative "stiffened" casts with cellular reaction and fracture. Figures 5 & 6 show kappa and lambda immunofluorescence, respectively. This is a case of...

AL Amyloidosis

A 70 year-old female presents with nephrotic range proteinuria and a creatinine of 1.2. She was in her normal level of health until about 6 months ago when she noticed foamy urine and swelling in her ankles. She has lost 30 lbs unintentionally during the last few months. Her cardiologist said that her proteinuria does not appear to be related to the heart. A kidney biopsy is performed. The glomerulus in figure 1 is distorted and has a “washed-out” or pale appearance on PAS stain. A silver stain shows material which is non-argyrophilic (figure 2). A Congo red stain shows...

Art of Medicine: Light Chain Proximal Tubulopathy

The painting above shows light chain proximal tubulopathy with crystals, which is one type of a monoclonal gammopathy of renal significance (MGRS).  MGRS, as defined by the International Kidney and Monoclonal Gammopathy Research Group, is a “clonal proliferative disorder that produces a nephrotoxic monoclonal immunoglobulin” (Leung N et al, 2019), and indicates end-organ damage resulting from a monoclonal gammopathy.   The most common MGRS manifestations include AL amyloidosis, monoclonal immunoglobulin deposition disease, light chain cast nephropathy, and light chain proximal tubulopathy.   In light chain proximal tubulopathy, a nephrotoxic monoclonal light chain induces acute tubular injury or proximal tubular dysfunction.  Proximal tubular...

Diagnose This (November 12, 2018)

What is your diagnosis and what do you need to prove it?           ​ ​   ​   ​ ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​   ​ ​   ​ ​   ​ ​  ...

Pushing Glass (June 22, 2018)

The patient is an 80 year-old male who presents with fatigue and a creatinine of 6.5 mg/dl. He was in his normal state of health until he and his grandchild went to the park on a hot afternoon. Subsequently, he began to feel ill and fatigued and went to see his physician. He has a past medical history significant for long-standing hypertension which is treated with a loop diuretic. Based on this history and images, what is the best diagnosis? A. Waldenstrom macroglobulinemia B. Light Chain Deposition Disease secondary to lymphoplasmacytic lymphoma C. Light Chain Deposition Disease secondary to small...

Proliferative Glomerulonephritis with Monoclonal IgG Deposits

This biopsy was performed on an 81-year-male, status post renal transplant, who presented with increased creatinine (2.3 mg/dl) and microscopic hematuria. Light microscopic examination of the biopsy shows diffuse mesangial and mild endocapillary hypercellularity with rare double contour formation of the capillary loops (Fig 1 and 2). No significant tubulointerstitial inflammation, peritubular capillaritis or endothelialitis is present, to otherwise suggest and underlying component of acute T-cell or antibody mediated rejection. Immunofluorescence (Fig 3) shows mesangial and segmental capillary loop positive staining for IgG (3+), C3 (3+), C1q (1+) and lambda light chain (3+). All other stains, including kappa light chain...