https://orcid.org/0000-0003-0695-7981
Several different histopathological phenotypes of monoclonal gammopathy of renal significance (MGRS) exist, but no single patient presents with just one phenotype. Clinicians should be aware that MGRS can present as several histological phenotypes caused by monoclonal gammopathy. Findings should be confirmed with electron microscopy.
Introduction
Monoclonal gammopathy of renal significance (MGRS) is a new disease entity defined as kidney disease caused by monoclonal gammopathy in the absence of symptomatic multiple myeloma.1 MGRS is diagnosed by identifying monoclonal gammopathy-derived deposits in the renal biopsy and is classified into several phenotypes based on the morphology of the deposits.2 Many cases are diagnosed as a single phenotype, such as amyloidosis or cast nephropathy, but it is unclear whether other phenotypes overlap in the same cases.
Case presentation
A 62-year-old man presented to the nephrology clinic with a 1-month history of proteinuria and extremity oedema. The patient’s serum creatinine level was normal, and his serum albumin level was 2.1 g/dl (normal range: 4.1–5.1 g/dl). His urinary protein excretion was 7.3 g/gCr (normal range <0.3 g/gCr). Bence-Jones proteins were detected in the urine. A kidney biopsy was performed, and light microscopy revealed a membranous pattern and spicules in the glomerular basement membrane and Congo red positivity with apple-green birefringence under polarized light in some parts of the glomerular tuft (Figure 1A). Immunofluorescence microscopy revealed granular capillary loop staining with membranous patterns of immunoglobulin G and complement 3. Electron microscopy revealed randomly arranged straight fibrils with diameters of ∼10 nm (Figure 1B) and microtubules in parallel arrays with diameters of 20 nm (Figure 1C). Therefore, the patient was diagnosed with MGRS that presented as both AL amyloidosis and immunotactoid glomerulopathy (ITG). Daratumumab (1800 mg/week), bortezomib (2.1 mg/week), cyclophosphamide (500 mg/week) and dexamethasone (20 mg/week) (DCyBorD scheme) were initially administrated. The patient’s symptoms improved, and his urinary protein excretion decreased to 0.8 g/dl. No worsening of the proteinuria was observed during a 2-year follow-up period.
Histological findings of the kidney biopsy specimen. (A) Congo red staining with apple-green birefringence (red arrow) under polarized light is positive in the small blood vessels (original magnification ×200). (B, C) Electron microscopy findings reveal randomly arranged, straight fibrils (red arrow) with diameters of ∼10 nm (B, original magnification ×20 000), and microtubules (red arrows) in parallel arrays with diameters of ∼20 nm (C, original magnification ×20 000).
Discussion
The monoclonal aetiology of MGRS results in clinical and laboratory features distinct from those of other diseases. The detection of this monoclonal kidney disease is important, as conventional immunosuppression is not effective; clone-directed therapy is required. As renal lesions due to monoclonal immunoglobulins are capable of progression and result in end-stage renal disease, these lesions require therapeutic intervention even if they do not satisfy the myeloma criteria or no myeloma-defining event is observed.3 The treatment of MGRS is directed at the underlying neoplastic B-cell or plasma cell clones. Organized deposits of monoclonal immunoglobulins in MGRS can be further divided into fibrillar, microtubular or crystalline and inclusionary forms; however, to our knowledge, the possibility that these renal lesions may overlap has not been sufficiently investigated.2 Ultrastructurally, amyloid deposits appear as randomly arranged, non-branching fibrils ranging in thickness from 7 to 14 nm, whereas ITG is defined by glomerular deposition of microtubules that are usually thicker than amyloid fibrils, ranging in size from 10 to 90 nm.4 Clinicians should be aware that some patients with MGRS may have multiple phenotypes. Future case series are needed to determine whether there are differences in clinical symptoms and treatment responses due to overlapping phenotypes. Clinicians should be aware that MGRS can present as several histological phenotypes caused by monoclonal gammopathy.
Author contributions
Takeshi Kashio (Conceptualization [equal], Data curation [equal], Investigation [equal], Methodology [equal], Validation [equal], Visualization [equal], Writing—original draft [lead], Writing—review & editing [equal]), Taro Horino (Conceptualization [equal], Data curation [equal], Investigation [equal], Methodology [equal], Supervision [lead], Validation [equal], Visualization [equal], Writing—original draft [supporting], Writing—review & editing [equal]), Kenichi Yagyu (Data curation [equal], Methodology [equal], Visualization [supporting], Writing—review & editing [equal]), Yuki Osakabe (Data curation [equal], Methodology [equal], Visualization [supporting], Writing—review & editing [equal]), Satoshi Inotani (Data curation [equal], Methodology [equal], Visualization [supporting], Writing—review & editing [equal]), and Yoshio Terada (Data curation [equal], Methodology [equal], Visualization [supporting], Writing—review & editing [equal])
Funding
None.
Conflict of interest: None declared.
Informed consent
Informed consent for this report was obtained from our patient.
