A case report of paraproteinemia-associated pauci-immune glomerulonephritis – a new form of monoclonal gammopathy of renal significance?

Abstract

Background: Renal disease associated with paraproteinemias is classically predicated upon pathologic paraprotein deposition in the kidney. However, growing evidence suggests that paraproteins may be able to systemically activate complement or neutrophils to drive renal damage. This may provide an alternative pathologic mechanism for renal injury in rare cases. Case report: We report a case of a patient with crescentic pauci-immune glomerulonephritis presenting with rapidly progressive renal failure, polyarthropathy, and a purpuric rash in association with a monoclonal immunoglobulin G κ-light-chain producing multiple myeloma. Serum anti-neutrophil cytoplasmic antibodies were not detected. Kidney biopsy, including with Pronase digestion, did not reveal pathologic paraprotein deposition. Two previously published similar case reports are also discussed. Conclusion: We propose a novel pathologic mechanism involving monoclonal proteins as a trigger for pauci-immune glomerulonephritis, potentially via complement dysregulation and/or neutrophil activation. This requires further epidemiologic and mechanistic study.

A Case Report of Multiple Myeloma Associated With Myeloperoxidase and Proteinase-3 Antibodies Posing a Diagnostic Dilemma

“…He was treated with cyclophosphamide and bortezomib with resolution of his MM and improvement in renal function. 8 In the first reported case of MM with AAV, Kapoulas et al described a 72-year-old male with MM (monoclonal IgG lambda as opposed to the other case reports, which were all IgG kappa) who presented with renal failure due to AAV with positive MPO antibodies (vs negativity for all the previous case reports and MPO and PR-3 positivity for our case). The patient was treated with 7 cycles of plasma exchange, cyclophosphamide, and steroids with recovery of renal function.…”

“…Multiple myeloma has been associated with differing forms of vasculitis including ANCA-negative pauci-immune crescentic glomerulonephritis, microscopic polyangiitis with MPO-positive ANCA, and Henoch-Schonlein purpura (immunoglobulin [Ig] A-mediated vasculitis). [7][8][9][10][11] In patients with hematologic malignancies, MPO and PR-3 antibodies are not reliably indicative of vasculitis. 12 Potential mechanisms for PR-3 and MPO positivity in the absence of vasculitis include monoclonal antibody reactivity with granulocytes and/or monoclonal protein dysregulation of complement.…”

“…12 Potential mechanisms for PR-3 and MPO positivity in the absence of vasculitis include monoclonal antibody reactivity with granulocytes and/or monoclonal protein dysregulation of complement. 8,9 Further research is needed to elucidate this interaction.…”

A Case of Myeloma Kidney with Perinuclear Anti-Neutrophil Cytoplasmic Antibody and Anti-Myeloperoxidase Positivity: The Importance of Determining the True Cause of Renal Impairment

“…We present the case of a 60-year-old man who presented with clinical features and serology suggestive of AAV with anti-MPO positivity and who was subsequently found to have MM with renal involvement. Several previous cases have been reported where AAV with renal involvement and a concurrent diagnosis of MM was identified [8][9][10][11]. To our knowledge, only one previous case of MM with renal involvement with positive anti-MPO and anti-PR3 serology has been identified [12], though that case did not demonstrate a positive ANCA titre.…”

Rapidly Progressive Glomerulonephritis Secondary to Immunoglobulin M-associated Monoclonal Gammopathy of Renal Significance: A Report of a Rare Case

“…In the first of these reports, proliferative glomerulonephritis with IgG deposits and undetected kappa light chains in electrophoresis and immunofixation is described, possibly secondary to their low quantity and rapid glomerular fixation, attributed to an immune response to some self or external antigen [ 10 ]. A second case report documented a patient with renal injury, proposing paraproteinemia as a trigger for complement activation or dysregulation and neutrophil activation, leading to a pauci-immune, ANCA-negative mechanism due to the absence of renal deposits [ 11 ]. Finally, a third case of proliferative glomerulonephritis with evidence of IgG3 deposits is described, with its nephrotoxic effects attributed to its high molecular weight, positive charge, and wide complement-fixing capacity.…”