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Nephrotic syndrome secondary to proliferative glomerulonephritis with monoclonal immunoglobulin deposits of lambda light chain.

Yun S, Braunhut BL, Walker CN, Bhati W, Sussman AN, Anwer F - Case Rep Nephrol (2014)

Bottom Line: We describe a rare case of a 46-year-old woman with history of refractory nephrotic syndrome and hypertension who presented with worsening proteinuria and kidney function.Kidney biopsy demonstrated glomerular sclerotic change with lambda light chain deposits in the subendothelial space, which is consistent with proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID).The patient was treated with bortezomib and dexamethasone without clinical improvement and eventually became hemodialysis dependent.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Arizona, Tucson, AZ 85721, USA ; Department of Medicine, Arizona Health Sciences Center, 6th Floor, Room 6336, 1501 N. Campbell Avenue,Tucson, AZ 85719, USA.

ABSTRACT
We describe a rare case of a 46-year-old woman with history of refractory nephrotic syndrome and hypertension who presented with worsening proteinuria and kidney function. Work-up for both autoimmune and infectious diseases and hematologic malignancies including multiple myeloma were negative. Kidney biopsy demonstrated glomerular sclerotic change with lambda light chain deposits in the subendothelial space, which is consistent with proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID). The patient was treated with bortezomib and dexamethasone without clinical improvement and eventually became hemodialysis dependent.

No MeSH data available.


Related in: MedlinePlus

Immunofluorescence staining of kidney biopsy. Immunofluorescence staining shows trace mesangial staining for IgG (a), IgM (b), and kappa light chain (c) but 2+ mesangial and granular capillary loop staining for lambda light chain (d), confirming the diagnosis of PGNMID with monoclonal lambda light chain.
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fig3: Immunofluorescence staining of kidney biopsy. Immunofluorescence staining shows trace mesangial staining for IgG (a), IgM (b), and kappa light chain (c) but 2+ mesangial and granular capillary loop staining for lambda light chain (d), confirming the diagnosis of PGNMID with monoclonal lambda light chain.

Mentions: Vital signs revealed blood pressure of 155/83 mmHg, heart rate of 81 beats per minute, respiratory rate of 14/minute, and temperature of 37.6°C. Lung and heart exams were normal and there was no palpable cervical, supraclavicular, axillary, or inguinal lymphadenopathy. Bilateral, one plus pitting lower extremity edema was present. Laboratory exam showed serum creatinine of 1.92 (normal 0.67–1.17 mg/dL) (Figure 1), IgG of 1333 (normal 552–1631 mg/dL), elevated kappa chain of 3.67 (normal 0.33–1.94 mg/dL), and lambda chain of 2.29 (normal 0.57–2.63 mg/dL) with normal ratio of 1.62. A 24-hour urine protein excretion was 8 g (normal 80 mg), and urine and serum immunofixation demonstrated positive monoclonal-free lambda light chain. Serum IgA (201 mg/dL), IgM (102 mg/dL), C3 (152 mg/dL), and C4 (32 mg/dL) levels were within normal range. Additional rheumatologic work-up included anti-SSA, anti-SSB, anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibody (ANCA), serum cryoglobulin, hepatitis panel, and serum protein electrophoresis (SPEP), which were all negative. Renal biopsy with light microscopic examination revealed multiple globally sclerosed glomeruli and occasional glomeruli with segmental sclerosis. The glomerular capillary loops showed patchy endocapillary proliferation and mononuclear inflammatory cell infiltration. A patchy mononuclear cell infiltrate was observed with associated tubulitis (Figures 2(a) and 2(b)). Immunofluorescence (IF) examination revealed mesangial staining for IgG (trace) and IgM (trace) and glomerular capillary loops were stained positive for C3 (1 to 2+) and lambda light chain (2+) (Figures 3(a)–3(d)). Subsequent electron microscopic ultrastructural examination demonstrated scattered electron dense immune-type deposits within mesangial areas and focally within the subendothelial space. The complexes did not show any organized substructural features, and the glomerular basement membrane had markedly irregular thickness in areas involved with deposits and/or endocapillary proliferation (Figures 4(a) and 4(b)). Further work-up for multiple myeloma, including skeletal survey and bone marrow biopsy, was normal with only 5% plasma cells on bone marrow immunohistochemistry and only 0.6% CD20+ B cells on flow cytometry. Additional fluorescence in situ hybridization (FISH) analysis included 1q21 (CKS1B), 9q34 (ASS1), 11q13 (CCND1), 14q32 (IGH), 15q22 (PML), and 17p13 (TP53), which were all negative. Although the IF staining for IgG is weaker than that of previous case reports, suggesting either early stage of disease or suboptimal staining condition, the microscopic findings and laboratory results confirmed the diagnosis of proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID) with monoclonal lambda light chain.


Nephrotic syndrome secondary to proliferative glomerulonephritis with monoclonal immunoglobulin deposits of lambda light chain.

Yun S, Braunhut BL, Walker CN, Bhati W, Sussman AN, Anwer F - Case Rep Nephrol (2014)

Immunofluorescence staining of kidney biopsy. Immunofluorescence staining shows trace mesangial staining for IgG (a), IgM (b), and kappa light chain (c) but 2+ mesangial and granular capillary loop staining for lambda light chain (d), confirming the diagnosis of PGNMID with monoclonal lambda light chain.
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Related In: Results  -  Collection

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fig3: Immunofluorescence staining of kidney biopsy. Immunofluorescence staining shows trace mesangial staining for IgG (a), IgM (b), and kappa light chain (c) but 2+ mesangial and granular capillary loop staining for lambda light chain (d), confirming the diagnosis of PGNMID with monoclonal lambda light chain.
Mentions: Vital signs revealed blood pressure of 155/83 mmHg, heart rate of 81 beats per minute, respiratory rate of 14/minute, and temperature of 37.6°C. Lung and heart exams were normal and there was no palpable cervical, supraclavicular, axillary, or inguinal lymphadenopathy. Bilateral, one plus pitting lower extremity edema was present. Laboratory exam showed serum creatinine of 1.92 (normal 0.67–1.17 mg/dL) (Figure 1), IgG of 1333 (normal 552–1631 mg/dL), elevated kappa chain of 3.67 (normal 0.33–1.94 mg/dL), and lambda chain of 2.29 (normal 0.57–2.63 mg/dL) with normal ratio of 1.62. A 24-hour urine protein excretion was 8 g (normal 80 mg), and urine and serum immunofixation demonstrated positive monoclonal-free lambda light chain. Serum IgA (201 mg/dL), IgM (102 mg/dL), C3 (152 mg/dL), and C4 (32 mg/dL) levels were within normal range. Additional rheumatologic work-up included anti-SSA, anti-SSB, anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibody (ANCA), serum cryoglobulin, hepatitis panel, and serum protein electrophoresis (SPEP), which were all negative. Renal biopsy with light microscopic examination revealed multiple globally sclerosed glomeruli and occasional glomeruli with segmental sclerosis. The glomerular capillary loops showed patchy endocapillary proliferation and mononuclear inflammatory cell infiltration. A patchy mononuclear cell infiltrate was observed with associated tubulitis (Figures 2(a) and 2(b)). Immunofluorescence (IF) examination revealed mesangial staining for IgG (trace) and IgM (trace) and glomerular capillary loops were stained positive for C3 (1 to 2+) and lambda light chain (2+) (Figures 3(a)–3(d)). Subsequent electron microscopic ultrastructural examination demonstrated scattered electron dense immune-type deposits within mesangial areas and focally within the subendothelial space. The complexes did not show any organized substructural features, and the glomerular basement membrane had markedly irregular thickness in areas involved with deposits and/or endocapillary proliferation (Figures 4(a) and 4(b)). Further work-up for multiple myeloma, including skeletal survey and bone marrow biopsy, was normal with only 5% plasma cells on bone marrow immunohistochemistry and only 0.6% CD20+ B cells on flow cytometry. Additional fluorescence in situ hybridization (FISH) analysis included 1q21 (CKS1B), 9q34 (ASS1), 11q13 (CCND1), 14q32 (IGH), 15q22 (PML), and 17p13 (TP53), which were all negative. Although the IF staining for IgG is weaker than that of previous case reports, suggesting either early stage of disease or suboptimal staining condition, the microscopic findings and laboratory results confirmed the diagnosis of proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID) with monoclonal lambda light chain.

Bottom Line: We describe a rare case of a 46-year-old woman with history of refractory nephrotic syndrome and hypertension who presented with worsening proteinuria and kidney function.Kidney biopsy demonstrated glomerular sclerotic change with lambda light chain deposits in the subendothelial space, which is consistent with proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID).The patient was treated with bortezomib and dexamethasone without clinical improvement and eventually became hemodialysis dependent.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Arizona, Tucson, AZ 85721, USA ; Department of Medicine, Arizona Health Sciences Center, 6th Floor, Room 6336, 1501 N. Campbell Avenue,Tucson, AZ 85719, USA.

ABSTRACT
We describe a rare case of a 46-year-old woman with history of refractory nephrotic syndrome and hypertension who presented with worsening proteinuria and kidney function. Work-up for both autoimmune and infectious diseases and hematologic malignancies including multiple myeloma were negative. Kidney biopsy demonstrated glomerular sclerotic change with lambda light chain deposits in the subendothelial space, which is consistent with proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID). The patient was treated with bortezomib and dexamethasone without clinical improvement and eventually became hemodialysis dependent.

No MeSH data available.


Related in: MedlinePlus