Proliferative glomerulonephritis with monoclonal IgM-κ deposits in chronic lymphocytic leukemia/small lymphocytic leukemia: case report and review of the literature

Oe, Yuji; Joh, Kensuke; Sato, Mitsuhiro; Taguma, Yoshio; Onishi, Yasushi; Nakayama, Keiichi I.; Sato, Toshinobu

doi:10.1007/s13730-013-0068-z

Cited by 5 publications

(5 citation statements)

References 23 publications

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“…In the remaining 70% of PGNMID cases, causative serum protein abnormalities including M-protein have not been identified. In contrast, according to Oe et al [4], of 20 patients with PGNMIMD, 8 cases were associated with MGUS; 6 with lymphoproliferative disorders, especially chronic lymphocytic leukemia; and 3 with Waldenström's macroglobulinemia. Without exception, other previous reports also indicated underling lymphoproliferative disorders in PGNMIMD [5][6][7][8][9].…”

Section: Discussionmentioning

confidence: 89%

“…PGNMID is defined as a glomerulopathy with deposition consisting of a single IgG subclass and restricted light chain, especially IgG3-κ [1]. In addition, some recent case reports have described glomerular alterations similar to PGNMID with the deposition of monoclonal IgA (PGNM IgA deposits) [11] or monoclonal IgM deposits (PGNMIMD) [4] instead of monoclonal IgG. The present case should also be categorized as PGNMIMD, because immunofluorescence analysis using cryostat sections and immunoperoxidase labeling of FFPE sections in this case exhibited specific deposition of IgM-κ chain and not IgG in glomeruli.…”

Section: Discussionmentioning

confidence: 99%

“…PGNMID differs from MIDD in that 29-65% of MIDD cases are associated with multiple myeloma, whereas PGNMID is neither associated with multiple myeloma nor the related lymphoproliferative disorders in general, even though 30% of PGNMID cases are complicated with monoclonal gammopathy of undetermined significance (MGUS) [3]. In recent years, several cases with clinical characteristics and histopathological features resembling PGNMID, as originally reported by Nasr et al [1], but involving glomerular IgM deposition rather than IgG have been described [4][5][6][7][8][9][10]. Most of these cases were associated with macroglobulinemia, MGUS, or other hematological disorders in addition to PGNMID; therefore, there are inconsistencies in the reports characterizing conditions with a similar disease background to that of PGNMID as originally described by Nasr et al but involving IgM rather than IgG. Here, we present the case of a patient who developed MPGN-like glomerular lesion with monoclonal IgM-kappa (κ) deposits and non-organized immune complex-type granular electron-dense deposits, without any underlying hematological abnormality in the range of limited clinical examination.…”

Section: Introductionmentioning

confidence: 98%

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A case report of proliferative glomerulonephritis with monoclonal immunoglobulin M-kappa deposits without associated lymphoproliferative disorder or detectable paraproteinemia

et al. 2017

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A 53-year-old man presented with proteinuria and hematuria. No significant abnormality was detected in his physical examination or laboratory tests, including evidence of paraprotein in serum and urine. Renal biopsy revealed mesangial proliferation, thickened glomerular basement membranes, and spike formation. Immunofluorescence revealed deposition of immunoglobulin (Ig) M heavy chain, kappa (κ) light chain, and complement component C3 along capillary walls in the glomeruli. Light chain staining indicated significant restriction, because only κ chain, not lambda chain, was present in glomeruli. Aggregated electron dense deposits were observed in the subepithelial area and within the lamina densa on electron-microscopic examination. Cryoglobulinemia and amyloidosis were ruled out. Clinically, steroid therapy was not initiated due to patient preference, and the only prescribed medication was an angiotensin II receptor blocker. At the approximately 3-year follow-up, estimated glomerular filtration rate had decreased very mildly. The present case demonstrates that deposition of monoclonal IgM-κ may be associated with membranoproliferative glomerulonephritis-like changes in the glomeruli. Although no underlying hematological abnormality or paraproteinemia was observed in this case within the range of limited clinical examination, the patient's condition is consistent with proliferative glomerulonephritis with monoclonal IgM deposits, similar to the recently established proliferative glomerulonephritis with monoclonal IgG deposits. Further elucidation of the pathophysiology and effective treatments of the disorder should be expected in the future through the accumulation of similar cases.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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A case report of proliferative glomerulonephritis with monoclonal immunoglobulin M-kappa deposits without associated lymphoproliferative disorder or detectable paraproteinemia

et al. 2017

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“…This has been termed “proliferative glomerulonephritis with monoclonal IgG deposits” (PGNMID) and can be mistaken as an immune-complex GN due to the fact that they both share similar histopathological findings (membranoproliferative or endocapillary proliferative GN with nonorganized granular deposits) [ 8 ]. More recently, it has been recognised that monoclonal IgM deposition may also lead to MPGN (although only two cases have been reported in association with CLL) [ 9 , 10 ], described as “proliferative glomerulonephritis with monoclonal IgM deposits” (PGNMIMD) [ 9 – 11 ].…”

Section: Discussionmentioning

confidence: 99%

Multiple Faces of Chronic Lymphocytic Leukaemia: A Patient with Renal, Cardiac, and Skeletal Complications

Htet

Gómez

Ali

et al. 2019

Case Reports in Nephrology

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We describe a patient who had chronic lymphocytic leukaemia (CLL) Binet stage A at presentation with further evidence of disease at multiple sites but who initially required no treatment. However, several years later, her peripheral blood lymphocyte count started to increase, and soon after that she suffered an acute myocardial infarct (in the absence of coronary atheroma) together with proteinuric renal failure due to membranoproliferative glomerulonephritis. Her renal function improved markedly following anti-CLL chemotherapy. We postulate that her cardiac and renal disease were both complications of her CLL. In patients with CLL who develop new clinical signs or symptoms (even if apparently unrelated), consideration should be given as to whether these may be disease complications as this may serve as an indication to commence anti-CLL therapy; close liaison between different specialties is vital.

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“…Otherwise, anti-nuclear antibodies, anti-double-stranded DNA, anti-histone antibodies, anti-neutrophil cytoplasmic antibodies, anti-glomerular basement membrane antibodies, hepatitis B and C serologies, HIV, and syphilis serologies were negative and hemoglobin A1c was 5.5%. A renal biopsy was pursued due to high clinical suspicion for MPGN given low complements and high rheumatoid factor titers that was felt to represent cryoglobulinemia, which has been described in CLL [ 2 , 23 , 24 ]. Other considerations in the differential prior to biopsy included lymphoid invasion of the renal parenchyma, amyloidosis [ 3 , 4 ] or light-chain nephropathy [ 25 ].…”

Section: Case Presentationmentioning

confidence: 99%

A case report of pre-eclampsia-like endothelial injury in the kidney of an 85-year-old man treated with ibrutinib

Ambruso

Oto

et al. 2022

BMC Nephrol

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Background Glomerular endotheliosis is the pathognomonic glomerular lesion in pre-eclampsia that has also been described in those taking tyrosine kinase inhibitors for cancer treatment. Ibrutinib is a Bruton’s tyrosine kinase inhibitor used to treat chronic lymphocytic leukemia (CLL). We report the first known case of glomerular endotheliosis on kidney biopsy in a patient on ibrutinib monotherapy. Case presentation The patient presented with acute on chronic kidney disease, proteinuria, low C3 and C4 and a high rheumatoid factor titer. A kidney biopsy was performed to confirm a preliminary diagnosis of membranoproliferative glomerulonephritis (MPGN), the most common glomerular disease in patients with CLL. Unexpectedly, the kidney biopsy showed pre-eclampsia-like lesions on light and electron microscopy: occlusion of glomerular peripheral capillary lumens by swollen reactive endothelial cells. Findings of glomerulonephritis were not seen, and there were no specific glomerular immune deposits by immunofluorescence or electron microscopy. Conclusions CLL is known to cause glomerular lesions, mainly MPGN. There is increasing evidence that ibrutinib, a major treatment for CLL, can cause kidney disease, but the precise pathology is not characterized. We present a patient with CLL on ibrutinib with signs of glomerular endotheliosis. Based on the absence of CLL-induced kidney pathologies typically seen on the kidney biopsy and the non-selectivity of ibrutinib, we attributed the glomerular endotheliosis to ibrutinib. In pre-eclampsia, increased soluble fms-like tyrosine kinase 1 (sFlt1) levels induce endothelial dysfunction by decreasing vascular endothelial growth factor (VEGF). Ibrutinib has been demonstrated to have non-selective tyrosine kinase inhibition, including inhibition of VEGF receptor (VEGFR) and epidermal growth factor receptor (EGFR). VEGFR and EGFR inhibitors have recently been described in the literature to cause hypertension, proteinuria, and glomerular endotheliosis. Kidney biopsy should be performed in CLL patients on ibrutinib that present with acute kidney injury (AKI) or proteinuria to determine whether the clinical picture is attributable to the disease itself or a complication of the therapy.

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Proliferative glomerulonephritis with monoclonal IgM-κ deposits in chronic lymphocytic leukemia/small lymphocytic leukemia: case report and review of the literature

Cited by 5 publications

References 23 publications

A case report of proliferative glomerulonephritis with monoclonal immunoglobulin M-kappa deposits without associated lymphoproliferative disorder or detectable paraproteinemia

A case report of proliferative glomerulonephritis with monoclonal immunoglobulin M-kappa deposits without associated lymphoproliferative disorder or detectable paraproteinemia

Multiple Faces of Chronic Lymphocytic Leukaemia: A Patient with Renal, Cardiac, and Skeletal Complications

A case report of pre-eclampsia-like endothelial injury in the kidney of an 85-year-old man treated with ibrutinib

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