Rapid Deterioration of the Renal Function Caused by the Coexistence of Intratubular Amyloidosis and Myeloma Cast Nephropathy

Kato, Hideki; Fujigaki, Yoshihide; Asakawa, Shinichiro; Yamaguchi, Yutaka; Uozaki, Hiroshi; Komatsuda, Atsushi; Nagata, Michio; Uchida, Shunya

doi:10.2169/internalmedicine.54.5174

Cited by 9 publications

(16 citation statements)

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“…5,6 Purely intratubular amyloid is viewed as an unusual variant of light chain cast nephropathy with no clinical significance and, accordingly, 'does not merit the diagnosis of renal amyloidosis since the amyloid is exclusively intratubular and not deposited in the renal parenchyma'. 7 However, the literature on this point only relies upon case reports 5,[8][9][10][11][12][13] and old clinicopathological studies, 6,[14][15][16][17][18][19] which did not properly assess the clinical significance of intratubular amyloid, especially its relationship with the occurrence of systemic light chain amyloidosis in extrarenal sites. Thus, we designed this retrospective study to evaluate the frequency of intratubular amyloid in light chain cast nephropathy biopsy specimens seen at a single academic institution, and to assess whether intratubular amyloid was associated with extrarenal systemic light chain amyloidosis.…”

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Intratubular amyloid in light chain cast nephropathy is a risk factor for systemic light chain amyloidosis

et al. 2018

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Light chain cast nephropathy is the most common form of kidney disease in patients with multiple myeloma. Light chain casts may occasionally show amyloid staining properties, that is, green birefringence after Congo red staining. The frequency and clinical significance of this intratubular amyloid are poorly understood. Here, we retrospectively assessed the clinicopathological features of 60 patients with histologically proven light chain cast nephropathy with a specific emphasis on intratubular amyloid, especially, its association with extrarenal systemic light chain amyloidosis. We found intratubular amyloid in 17 cases (17/60, 28%) and it was more frequent in patients with λ light chain gammopathy (13/17 in the 'intratubular amyloid' group vs 19/43 in the 'no intratubular amyloid' group, P=0.02). Pathological examination of extrarenal specimens showed that intratubular amyloid was significantly associated with the occurrence of systemic light chain amyloidosis (5/13 in the 'intratubular amyloid' group vs 0/30 in the 'no intratubular amyloid' group, P=0.001). Our results indicate that first, intratubular amyloid is not a rare finding in kidney biopsies of patients with light chain cast nephropathy, and, second, it reflects an amyloidogenic capacity of light chains that can manifest as systemic light chain amyloidosis. Thus, intratubular amyloid should be systematically screened for in kidney biopsies from patients with light chain cast nephropathy and, if detected, should prompt a work-up for associated systemic light chain amyloidosis.

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Intratubular amyloid in light chain cast nephropathy is a risk factor for systemic light chain amyloidosis

et al. 2018

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“…From 1962 to 1980, LCACs were found in approximately 55 autopsy patients with MM, and in about 2/3 of these patients, amyloid casts were diagnosed only by methyl violet staining and/or thiocyanin T staining [7][8][9][10][11][12]. From 1980 to 2020, only 25 patients with LCACs caused by MM were identified (renal biopsy in 24 cases and autopsy in 1 case), and the diagnosis of amyloid casts in these patients was based on Congo red staining and/or electron microscopy [6,[13][14][15][16][17][18][19][20][21] (Table 1). In addition, in three other papers the authors mentioned that they also observed LCACs in some patients with renal damage caused by MM, but they did not provide a detailed description [22][23][24].…”

Section: Discussionmentioning

confidence: 99%

“…Under polarized light microscopy, ordinary light microscopy and fluorescence microscopy, Congo red staining exhibits apple green double refraction, brick red and bright red, respectively [19]. In addition to the abovementioned typical pattern, the amyloid deposits also have other distribution forms in the cast, such as lamination form, which can present as two or more layers, and sometimes in a tree-ring shape [6-10, 12, 19-21], and homogeneous form, which is composed of clumped homogeneous deposits distributed in the whole cast [6,12,17,19]. Electron microscopy shows numerous randomly arranged unbranched fibrils with a diameter of 8-12 nm in the amyloid structures of the casts [6, 13, 15-17, 19, 21].…”

Section: Discussionmentioning

confidence: 99%

“…The casts appear red with hematoxylin-eosin (HE) staining, polychromatic with Masson trichrome staining, and light or negative with periodic acid-Schiff (PAS) staining and periodic acid silver methenamine (PASM) staining. Immunofluorescence (IF) or immunohistochemical examination reveals that the light chain protein in casts is monoclonal light chain λ or κ [3,5,6]. However, in rare cases of MM, some casts with unusual shapes can also be seen, including light chain amyloid casts (LCAC) and light chain crystal casts (LCCC), can also be seen.…”

Section: Introductionmentioning

confidence: 99%

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Two kinds of rare light chain cast nephropathy caused by multiple myeloma: case reports and literature review

Sun

Dong

et al. 2021

BMC Nephrol

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Background Light chain cast nephropathy (LCCN) is the most common renal disease caused by multiple myeloma (MM). In addition to ordinary light chain protein casts, there are a few rare casts with unique shapes, including light chain amyloid casts (LCAC) and light chain crystal casts (LCCC). Case presentations Here, we report two patients. Patient 1 is a 72-year-old man who was clinically diagnosed with MM and acute kidney injury (AKI). Pathological examination of a renal biopsy revealed that there were many amyloid casts in the distal tubules that had a lightly-stained central area and a deeply-stained burr-like edge. The marginal zone of the cast was positive for Congo red staining and contained numerous amyloid fibers, as observed by electron microscopy. No systemic amyloidosis was found. The patient received 4 courses of bortezomib-based chemotherapy, and then, his MM achieved partial remission. Patient 2 is a 57-year-old man who was also clinically diagnosed with MM and AKI. Pathological examination of a renal biopsy showed that there were many crystalline casts in the distal tubules that were fully or partially composed of crystals with different shapes, including rhomboid, needle, triangle, rectangle and other geometric shapes. Congo red staining was negative. Crystals were also detected in the urine of this patient. After 9 courses of treatment with a bortezomib-based regimen, his MM obtained complete remission and his renal function returned to normal. Conclusions LCAC and LCCC nephropathy caused by MM are two rare types of LCCN, and both have their own unique morphological manifestations. LCAC nephropathy may not be accompanied by systemic amyloidosis. The diagnosis of these two unique LCCNs must rely on renal biopsy pathology, and the discovery of urine crystals is of great significance for indicating LCCC nephropathy.

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“…Myeloma nephropathy is relatively common complications in patients with MM. Generally, the majority of severe renal injuries in patients with multiple myeloma are associated with immunoglobulin (Ig) free light chains (FLCs) [9,10]. Substantial FLCs (nephrotoxic proteins) accumulated in the proximal tubular epithelium are responsible for most tubulointerstitial injuries.…”

Section: The Relationship Between Cystatin C and Myeloma Nephropathymentioning

confidence: 99%

The role of cystatin C as a proteasome inhibitor in multiple myeloma

Jiang

Zhang

et al. 2020

Hematology

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Objectives: Bone destruction and renal impairment are two frequent complications of multiple myeloma (MM). Cystatin C, an extracellular cysteine proteinase inhibitor, is encoded by the housekeeping gene CST3 and associated with human tumors. The role of cystatin C in multiple myeloma has been revealed recently. The purpose of this study was to explore the role of cystatin C as a proteasome inhibitor in multiple myeloma. Methods: A comprehensive literature review was conducted through Pubmed to summarize the published evidence on cystatin C in multiple myeloma. English literature sources since 1999 were searched, using the terms cystatin C, multiple myeloma. Results: cystatin C is a sensitive indicator for the diagnosis of myeloma nephropathy and has a dual role in myeloma bone disease. Also, cystatin C reflects tumor burden and is strongly associated with prognosis in patients with multiple myeloma. Conclusion: Cystatin C have great diagnostic and prognostic value in multiple myeloma. It can provide a new treatment direction for MM by designing and searching for antagonists of cystatin C or cysteine protease agonists using cystatin C as a therapeutic target.

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Rapid Deterioration of the Renal Function Caused by the Coexistence of Intratubular Amyloidosis and Myeloma Cast Nephropathy

Cited by 9 publications

References 15 publications

Intratubular amyloid in light chain cast nephropathy is a risk factor for systemic light chain amyloidosis

Intratubular amyloid in light chain cast nephropathy is a risk factor for systemic light chain amyloidosis

Two kinds of rare light chain cast nephropathy caused by multiple myeloma: case reports and literature review

The role of cystatin C as a proteasome inhibitor in multiple myeloma

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