Dialysis related Amyloidosis

Self-association of wild-type β2- microglobulin (WT-β2 m) into amyloid fibrils is associated with the disorder Dialysis Related Amyloidosis (DRA). In the familial variant D76N-β2 m, the single amino acid substitution enhances the aggregation propensity of the protein dramatically and gives rise to a disorder that is independent of renal dysfunction. Numerous biophysical and structural studies on WT- and D76N-β2 m have been performed in order to better understand the structure and dynamics of the native proteins and their different potentials to aggregate into amyloid...

Dialysis-related amyloidosis (DRA), a serious complication among long-term hemodialysis patients, is caused by amyloid fibrils of β2-microglobulin (β2m). Although high serum β2m levels and a long dialysis vintage are the primary and secondary risk factors for the onset of DRA, respectively, patients with these do not always develop DRA, indicating that there are additional risk factors. To clarify these unknown factors, we investigate the effects of human sera on β2m amyloid fibril formation, revealing that sera markedly inhibit amyloid fibril formation...

INTRODUCTION: Long-term hemodialysis patients experience many hand diseases caused by dialysis-related amyloidosis (DRA), with carpal tunnel syndrome (CTS) being the most common. For the patients with arteriovenous (AV) shunt, surgical decompression remains challenging because of the contraindications of a tourniquet. A technique called wide-awake local anesthesia with no tourniquet (WALANT), in which epinephrine provides hemostasis instead of the tourniquet, can be a good option for hemodialysis patients...

BACKGROUND: Apart from ATTR amyloidosis, the epidemiology and outcomes of the most common subtypes of systemic amyloidosis in Portugal remain primarily unknown. METHODS: This retrospective cohort study evaluated patients with renal biopsy-proven amyloidosis, diagnosed from January 1978 to December 2019. Follow-up started at kidney disease presentation and ended at death or August 2020. Clinical presentation, survival, and prognostic factors were analysed. RESULTS: Of 123 patients with amyloid nephropathy, 111 had definite amyloid typing and were analysed...

Because β-2-microglobulin (β2 M) is a surface protein that is present on most nucleated cells, it plays a key role in the human immune system and the kidney glomeruli to regulate homeostasis. The primary clinical significance of β2 M is in dialysis-related amyloidosis, a complication of end-stage renal disease caused by a gradual accumulation of β2 M in the blood. Therefore, the function of β2 M in kidney-related diseases has been extensively studied to evaluate its glomerular and tubular functions. Because increased β2 M shedding due to rapid cell turnover may indicate other underlying medical conditions, the possibility to use β2 M as a versatile biomarker rose in prominence across multiple disciplines for various applications...

Dialysis-related amyloidosis (DRA) is considered an inescapable consequence of renal failure. Upon prolonged hemodialysis, it involves accumulation of toxic β2-microglobulin (β2m) amyloids in bones and joints. Current treatment methods are plagued with high cost, low specificity, and low capacity. Through our in vitro and in cellulo studies, we introduce a peptidomimetic-based approach to help develop future therapeutics against DRA. Our study reports the ability of a nontoxic, core-modified, bispidine peptidomimetic analogue "B(LVI)2 " to inhibit acid-induced amyloid fibrillation of β2m (Hβ2m)...

Dialysis-related amyloidosis (DRA) represents a group of relatively rare disorders characterized by the systemic extracellular deposition of insoluble fibrils of amyloid protein in long-term dialysis patients. We describe herein a case of relatively early DRA on the tongue of a long-term dialysis patient. A 67-year-old man with a 39-year history of dialysis was referred for diagnosis of a tongue mass. On examination, a collection of whitish-yellow papules was identified on the ventral surface of the tongue tip...

INTRODUCTION: Dialysis-related amyloidosis (DRA) caused by β2-microgloblin (B2M) fibrils is a serious complication for patients with kidney failure on long-term dialysis. Deposition of B2M amyloid fibrils is thought to be due not only to serum extracellular B2M but also to infiltrating inflammatory cells, which may have an important role in B2M amyloid deposition in osteoarticular tissues in patients with DRA. Here, we asked whether B2M amyloid fibrils activate the inflammasome and contribute to formation and deposition of amyloid fibrils in cells...

The ΔN6 truncation is the main posttranslational modification of β-microglobulin (βM) found in dialysis-related amyloid. Investigation of the interaction of wild-type (WT) βM with N-terminally truncated variants is therefore of medical relevance. However, it is unclear which residues among the six residues at the N-terminus are crucial to the interactions and the modulation of amyloid fibril propagation of βM. We herein analyzed homo- and heterotypic seeding of amyloid fibrils of WT human βM and its N-terminally-truncated variants ΔN1 to ΔN6, lacking up to six residues at the N-terminus...

We report a case of dialysis-related amyloid arthropathy in a patient with end-stage renal disease. It presented in our patient as moderately increased FDG uptake in the amyloid deposition in the periarticular tissues and eroding into adjacent bones.

INTRODUCTION: While light chain (AL) amyloidosis is more common in western countries, the most common type of amyloidosis is amyloid A (AA) amyloidosis in Eastern Mediterranean Region, including Turkey. Although worse prognosis has been attributed to the AL amyloidosis, AA amyloidosis can be related to higher mortality under renal replacement therapies. However, there are no sufficient data regarding etiology, clinical presentation, and prognostic factors of AA amyloidosis. The objective of our study is to evaluate the clinical, laboratory characteristics, and possible predictive factors related to mortality in patients with AA amyloidosis undergoing hemodialysis (HD)...

BACKGROUND AND PURPOSE: We examined whether advances in treatment strategies from older disease-modifying antirheumatic drugs (DMARDs) to new biologic agents and methotrexate improved renal complications and outcome in patients with rheumatoid arthritis (RA). METHODS: We reviewed records of 156 patients with RA who underwent kidney biopsy at our institute between January 1990 and December 2019. All patients were assigned to one of three periods: period 1, 1990-1999 (n = 48); period 2, 2000-2009(n = 57); period 3, 2010-2019 (n = 51)...

β2 -microglobulin (β2m), the light chain of the MHC-I complex, is associated with dialysis-related amyloidosis (DRA). Recently, a hereditary systemic amyloidosis was discovered, caused by a naturally occurring D76N β2m variant, which showed a structure remarkably similar to the wild-type (WT) protein, albeit with decreased thermodynamic stability and increased amyloidogenicity. Here, we investigated the role of the D76N mutation in the amyloid formation of β2m by point mutations affecting the Asp76-Lys41 ion-pair of WT β2m and the charge cluster on Asp38...

Upper extremity entrapment neuropathies are common and can cause pain, sensory loss, and muscle weakness leading to functional disability. We conducted a retrospective review from January 2007 until March 2020 of the magnetic resonance imaging (MRI) features of intrinsic and extrinsic causes of wrist, forearm, and elbow neuropathies of 637 patients who received a diagnosis of neuropathy by means of clinical and electrodiagnostic testing. We discuss cases with varying intrinsic and extrinsic nerve pathologies, including postoperative examples, affecting the median, radial, and ulnar nerve...

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Multiple myeloma accounts for 10-15% of all hematologic malignancies, and 20% of deaths related to cancers of the blood and bone marrow. Diagnosis is defined by the presence of a serum monoclonal spike (M-spike) of more than 3 g/dL or more than 10% clonal plasma cells in the bone marrow and at least one myeloma-defining event, such as hypercalcemia, anemia, bone lesions, or renal impairment. The kidney is a major target organ, and renal impairment is frequently the first manifestation of the disease. Renal damage occurs in up to 40% of patients and 10-20% will require dialysis...

BACKGROUND: Dialysis-related amyloidosis (DRA) commonly develops in patients undergoing long-term dialysis and can lead to a decline in activities of daily living and quality of life (QOL), mainly owing to orthopedic complications. METHODS: First, we determined utility scores of the EuroQol 5-Dimensions 3-Levels (EQ-5D-3L) questionnaire in 1,323 patients with DRA who had undergone dialysis for more than 10 years and compared the score between those with and without DRA...

PURPOSE AND METHOD: Patients on hemodialysis develop carpal tunnel syndrome (CTS) due to an accumulation of dialysis-related β2 microglobulin (β2m) amyloid (DRA). In Japan, dialysis technology has progressed remarkably in the past 40 years and has increased the time until patients require surgery for CTS. However, unclear is whether the time from the start of hemodialysis to the first surgery for CTS is associated with β2m clearance by the different hemodialysis techniques...

OBJECTIVES: The risk of amyloidosis during the course of AS is yet to be firmly established. We aimed to evaluate the risks, predictors and prognostic outcomes of amyloidosis among patients with AS. METHODS: A population-based cohort study was conducted comparing AS patients (n = 5911) with age-, sex- and ethnicity-matched control subjects (n = 29 007) with regard to incident cases of amyloidosis. Hazard ratios (HRs) and odds ratios (ORs) were estimated by Cox regression and logistic regression analyses, respectively...

Antineutrophil cytoplasmic autoantibody (ANCA) vasculitis has occasionally been associated with other systemic glomerulonephritis, such as anti-glomerular basement membrane disease. Here, we report the first clinical case of ANCA-associated crescentic glomerulonephritis with AL amyloidosis. An 81-years-old gentleman presented to the hospital with acute kidney injury (serum creatinine 4.7 mg/dL) on a background of chronic kidney disease and volume overload. Autoimmune serology was remarkable for p-ANCA and myeloperoxidase positivity...