Dialysis amyloidosis

Amyloid formation due to protein misfolding has gained significant attention due to its association with neurodegenerative diseases. α-Synuclein (α-syn) is one such protein that undergoes a profound conformational switch to form higher order cross-β-sheet structures, resulting in amyloid formation, which is linked to the pathophysiology of Parkinson's disease (PD). The present status of research on α-syn aggregation and PD reveals that the disease progression may be linked with many other diseases, such as kidney-related disorders...

ALECT2 systemic amyloidosis is associated with deposition of the leukocyte cell-derived chemotaxin-2 (LECT2) protein in the form of fibrils. In ALECT2 amyloidosis, ALECT2 fibrils deposit in the glomerulus, resulting in renal failure. Patients lack effective treatment options outside of renal transplant or dialysis. The structure of globular LECT2 has been determined but structures of ALECT2 amyloid fibrils remain unknown. Using single-particle cryo-EM, we find that recombinant human LECT2 forms robust twisting fibrils with canonical amyloid features...

Beta-2 microglobulin (B2M) is an immune system protein that is found on the surface of all nucleated human cells. B2M is naturally shed from cell surfaces into the plasma, followed by renal excretion. In patients with impaired renal function, B2M will accumulate in organs and tissues leading to significantly reduced life expectancy and quality of life. While current hemodialysis methods have been successful in managing electrolyte as well as small and large molecule disturbances arising in chronic renal failure, they have shown only modest success in managing plasma levels of B2M and similar sized proteins, while sparing important proteins such as albumin...

BACKGROUND: Using technetium (Tc)-labelled pyrophosphate (PYP) cardiac scintigraphy, a non-invasive diagnosis of transthyretin amyloid (ATTR) cardiomyopathy can be made without histopathological confirmation. In patients suspected of ATTR cardiomyopathy, however, atypical presentations may necessitate further investigation. CASE SUMMARY: A 30-year-old man with hypertension and end-stage renal disease on peritoneal dialysis presented with progressive exertional dyspnoea...

Chronic expanding hematoma (CEH) is a rare anatomical condition that gradually expands due to trauma or surgery. We report the case of a 56-year-old woman who developed CEH 25 years after metal-on-polyethylene total hip arthroplasty. She presented with swelling and radiating pain in the right inguinal region. Tocilizumab was administered for treating rheumatoid arthritis and renal amyloid A amyloidosis. Diagnostic imaging and partial resection revealed a soft tissue mass and a CEH, respectively. The symptoms recurred 6 months later; dialysis was initiated, and the CEH was resected under general anesthesia, leading to improvement...

The accumulation of β2-microglobulin due to long-term hemodialysis is known as dialysis-related amyloidosis, a rare phenomenon that manifests as a subcutaneous mass. Subcutaneous β2-microglobulin amyloidomas are predominantly located on the buttocks. Owing to the load-bearing properties of this location and proximity to the anus, amyloidomas on the buttocks may be prone to pressure ulcers and infection. This report presents two cases of long-term hemodialysis patients who required surgical treatment for infected ulcers caused by buttock amyloidomas...

BACKGROUND: Cardiac amyloidosis is caused by the deposition of misfolded proteins in the myocardium. The majority of cases of cardiac amyloidosis is caused by misfolded transthyretin or light chain proteins. In this case report, we discuss a case of a rare form of cardiac amyloidosis related to beta 2-microglobulin (B2M) in a patient not on dialysis. CASE SUMMARY: A 63-year-old man was referred for workup of possible cardiac amyloidosis. Serum and urine immunofixation electrophoresis demonstrated no monoclonal bands, and the serum kappa/lambda light chain ratio was normal, excluding light chain amyloidosis...

A 74-year-old woman with a 34-year history of hemodialysis presented with an intermittent fever, which later coincided with recurrent bilateral shoulder and hip joint pain. Imaging studies suggested amyloid arthropathy, which was histologically confirmed by a synovial biopsy. Increasing β2 -microglobulin clearance during dialysis alone attenuated the intermittent fever and joint pain, but the symptoms did not disappear until the administration of prednisolone 10 mg/day. Reported cases of dialysis-related amyloidosis with a fever imply that changing to blood purification methods with high β2 -microglobulin clearance is crucial for controlling the condition long-term, whereas concurrent use of anti-inflammatory agents promptly alleviates the symptoms...

Systemic mastocytosis (SM) is a disorder of excessive mast cell accumulation in tissues due to a somatic gain-of-function mutation, commonly in the KIT gene, which prevents apoptosis of mast cells. Whereas bone marrow, skin, lymph nodes, spleen and gastrointestinal tract are commonly involved, kidneys are rarely involved directly by SM. However, there are increasing reports of indirect kidney involvement in patients with SM. Novel anti-neoplastic agents to treat advanced forms of SM include non-specific tyrosine kinase inhibitors, which are reported to be associated with kidney dysfunction in some patients...

INTRODUCTION AND OBJECTIVE: Amyloidoses are a heterogeneous group of disorders resulting from deposition of amyloid fibrils into extracellular tissues. While the kidneys are one of the most frequent sites of amyloid deposition, amyloid deposits can also affect a wide range of organ systems, including the heart, liver, gastrointestinal tract, and peripheral nerves. The prognosis of amyloidosis, especially with cardiac involvement, remains poor; however, a collaborative approach applying new tools for diagnosis and management may improve outcomes...

Spontaneous quadriceps tendon rupture is very rare. Its occurrence is usually linked to an underlying disease that weakens the tendons causing them to rupture. Here, we report the case of a 44-year-old patient undergoing long-term hemodialysis who had spontaneous bilateral quadriceps tendon rupture. We present the clinical presentation and the management of this injury.

Gastrointestinal amyloidosis can be primary, more associated with monoclonal plasma cell dyscrasia, or secondary, usually secondary to a tissue-destructive, chronic inflammatory process (such as inflammatory bowel disease, for example) and long-term dialysis. The rare presentation of severe acute liver failure in systemic amyloidosis can make this diagnosis/ management more difficult. Hepatomegaly with signs of diffuse infiltrative disease and periportal involvement associated with thoracic and other abdominal radiological findings in the appropriate clinical context may constitute a diagnostic imaging clue in this challenge...

A man in his 20s initiated intermittent peritoneal dialysis in the late 1960s. He subsequently transitioned to hemodialysis and survived for more than 50 years, spanning low-flux and high-flux hemodialysis eras. He underwent surgery for cervical and lumbar spinal canal stenosis after 30 and 35 years, respectively, and both surgeries revealed similar degrees of severe amyloid deposition. At autopsy, significant improvement was seen in lumbar amyloid deposition. During the previous 25 years, serum β2 microglobulin levels had decreased from 40 mg/L and been maintained at 20 mg/L...

β2 -microglobulin (β2 m) and its truncated variant ΔΝ6 are co-deposited in amyloid fibrils in the joints, causing the disorder dialysis-related amyloidosis (DRA). Point mutations of β2 m result in diseases with distinct pathologies. β2 m-D76N causes a rare systemic amyloidosis with protein deposited in the viscera in the absence of renal failure, whilst β2 m-V27M is associated with renal failure, with amyloid deposits forming predominantly in the tongue. Here we use cryoEM to determine the structures of fibrils formed from these variants under identical conditions in vitro...

BACKGROUND: Light-chain deposition disease (LCDD) is a systemic disorder characterized by non-amyloidotic light-chain deposition in various organs with Bence-Jones type monoclonal gammopathy. Although known as monoclonal gammopathy of renal significance, it may involve interstitial tissue of various organs, and in rare cases, proceeds to organ failure. We present a case of cardiac LCDD in a patient initially suspected of dialysis-associated cardiomyopathy. CASE SUMMARY: A 65-year-old man with end-stage renal disease requiring haemodialysis presented with fatigue, anorexia, and shortness of breath...

ALECT2 is a type of systemic amyloidosis caused by deposition of the leukocyte cell-derived chemotaxin-2 (LECT2) protein in the form of fibrils. In ALECT2, LECT2 fibril deposits can be found in the glomerulus, resulting in renal failure. Affected patients lack effective treatment options outside of renal transplant or dialysis. While the structure of LECT2 in its globular form has been determined by X-ray crystallography, structures of LECT2 amyloid fibrils remain unknown. Using single particle cryo-EM, we now find that human LECT2 forms robust twisting fibrils with canonical amyloid features...

AA amyloidosis is secondary to the deposit of excess insoluble Serum Amyloid A (SAA) protein fibrils. AA amyloidosis complicates chronic inflammatory diseases, especially chronic inflammatory rheumatisms such as rheumatoid arthritis and spondyloarthritis; chronic infections such as tuberculosis, bronchectasia, chronic inflammatory bowel diseases such as Crohn's disease; and auto-inflammatory diseases including familial Mediterranean fever. This work consists of the French guidelines for the diagnosis workup and treatment of AA amyloidosis...

The objectives of this study were to investigate the clinical biological and histological renal involvement secondary to familial Mediterranean fever (FMF), the epidemiological data, genetics of our patients and their evolution under treatment. We prospectively studied 58 Algerian patients admitted in our nephrology department from January 2012 to January 2021. The diagnosis of nephropathy was suspected clinically and biologically and confirmed histologically. All our patients were tested for MEFV mutations...

BACKGROUND: The nephrotoxicity of bortezomib, a proteasome inhibitor, has not yet been concluded, although tumor lysis syndrome (TLS) associated with multiple myeloma (MM) has increased after introduction of the drug. This study compared the incidence and risk factors of acute kidney injury (AKI) and TLS in patients with MM after bortezomib-based chemotherapy to investigate drug-related nephrotoxicity. METHODS: From 2006 to 2017, 276 patients who underwent a first cycle of bortezomib-based chemotherapy for MM were identified in a single tertiary hospital...

BACKGROUND: Cardiac and neurological involvements are the main clinical features of hereditary transthyretin (ATTRv) amyloidosis. Few data are available about ATTRv amyloid nephropathy (ATTRvN). METHODS: We retrospectively included 30 patients with biopsy-proven ATTRvN [V30M (26/30) including two domino liver recipients, S77Y (2/30), V122I (1/30) and S50R (1/30) variants] from two French reference centers. We described the pathological features by comparing amyloid deposits distribution to patients with AL or AA amyloidosis, and sought to determine clinicopathological correlation with known disease-modifying factors such as TTR variant, gender and age at diagnosis...