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Monoclonal Gammopathy of Undetermined Significance (MGUS) is a premalignant condition characterized by the presence of monoclonal immunoglobulins in the serum at concentrations less than 30 g/L and fewer than 10% plasma cells in the bone marrow, in patients with no discernible organ damage attributable (1).
MGRS encompasses all clonal B-cell precursor or plasma cell disorders that secrete a nephrotoxic monoclonal paraprotein. Typically, patients present with progressive deterioration of renal function and proteinuria, with diagnosis confirmed through biopsy, demonstrating immunoglobulin deposits in the renal parenchyma.
The most serious complication of MGRS is end-stage renal disease, occurring in up to 22% of patients, with an approximate median of 30.3 months. Here, we present a case of MGRS presenting as RPGN (2).
Results
A 69-year-old female, with a medical history of hypertension, diabetes mellitus and stage 3B chronic kidney disease who frequently sought emergency care due to a clinical picture characterized by a dyspnea and progressive edema in the lower limbs.
During hospital admissions from April to July, there was evidence of progressive deterioration in renal function, the development of nephrotic-range proteinuria, and anemia, all associated with difficulty in controlling blood pressure. Investigations were conducted for secondary hypertension, renal artery Doppler, aldosterone levels, and plasma renin activity, all of which returned normal results. Due to the chronological and clinical criteria for rapidly progressive glomerulonephritis, further investigation was decided upon.
All tests for infectious and autoimmune etiologies returned negative result. The protein electrophoresis showed a polyclonal gamma peak. However, immunofixation revealed a monoclonal peak of IgM heavy chains and lambda light chains with normal serum immunoglobulin levels; urine immunofixation showed the elimination of both kappa and lambda chains, both free and bound, all with the appearance of a paraprotein.
In light of these findings, a bone marrow biopsy was conducted, which did not reveal clonal plasma cells, effectively ruling out multiple myeloma, Waldenström's macroglobulinemia, and marginal zone lymphoma as potential causes. As a result, it was concluded that the patient likely had a monoclonal gammopathy of renal significance. With this presumptive diagnosis, a renal biopsy was performed, confirming our suspicions as it identified fibrocellular crescents and deposits of IgM heavy chains and lambda light chains within the renal tissue.
Pulse therapy with 500 mg of methylprednisolone over a 72-hour period was administered, but unfortunately, it did not yield any improvement. The hematology department considered initiating a VCD (Bortezomib, Dexamethasone, Cyclophosphamide) regimen. Subsequently, the patient's renal function began to show signs of improvement.
We report a case of a patient with histological evidence consistent with immunoglobulin M - associated Monoclonal Gammopathy of Renal Significance (MGRS) presenting as rapidly progressive glomerulonephritis. To our knowledge, there have been no reported cases with similar presentations. While there are three documented cases of paraproteinemia leading to the development of MGRS, the etiology in those cases was either pauci-immune or associated with IgG deposits (3–5).
References
1. Lomas OC, Mouhieddine TH, Tahri S, Ghobrial IM. Monoclonal gammopathy of undetermined significance (MGUS)—not so asymptomatic after all. Vol. 12, Cancers. MDPI AG; 2020. p. 1–16.
2. Leung N, Bridoux F, Batuman V, Chaidos A, Cockwell P, D’Agati VD, et al. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group. Vol. 15, Nature Reviews Nephrology. Nature Publishing Group; 2019. p. 45–59.
3. James T, Afrouzian M, Truong L, Aleter O, Badalamenti J, Kassem H. Proliferative glomerulonephritis with monoclonal IgG deposits: a unique case with a clinical course of over 46 years. BMC Nephrol. 2023 Dec 1;24(1).
4. Fatima R, Jha R, Gowrishankar S, Narayen G, Rao BS. Proliferative glomerulonephritis associated with monoclonal immune deposits: A case report and review of literature. Vol. 24, Indian Journal of Nephrology. Wolters Kluwer Medknow Publications; 2014. p. 376–9.
5. Rope R, Kambham N, Arora N. A case report of paraproteinemia-associated pauci-immune glomerulonephritis – a new form of monoclonal gammopathy of renal significance? Clin Nephrol. 2017 Aug 17; 48-53.