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Dialysis related Amyloidosis

Periyasamy Muthukumar, Jeyachandran Dhanapriya, Natarajan Gopalakrishnan, Thanigachalam Dineshkumar, Ramanathan Sakthirajan, T Balasubramaniyan
The most common causes of renal disease in rheumatoid arthritis (RA) are glomerulonephritis (GN), amyloidosis, tubulo-interstitial nephritis, and drug toxicity. Our aim was to evaluate the clinicopathologic correlation of renal lesions and to assess the course and prognosis of renal disease in patients with RA. We conducted a prospective observational study in all adult patients with RA between July 2010 and June 2015. The total number of patients studied was 90, with a female:male ratio of 2.3:1. Mean follow-up duration was 30 ± 6...
January 2017: Saudi Journal of Kidney Diseases and Transplantation
R Scarpioni, M Ricardi, V Albertazzi, S De Amicis, F Rastelli, L Zerbini
Amyloidosis refers to the extracellular tissue deposition of fibrils composed of low-molecular-weight subunits of a variety of proteins. These deposits may result in a wide range of clinical manifestations depending upon their type, location, and the amount of deposition. Dialysis-related amyloidosis is a serious complication of long-term dialysis therapy and is characterized by the deposition of amyloid fibrils, principally composed of β2 microglobulins (β2M), in the osteoarticular structures and viscera...
2016: International Journal of Nephrology and Renovascular Disease
Tadashi Tomo
BACKGROUND: Biocompatibility and the efficiency of solute removal are important considerations in blood purification therapy. Improvement of biocompatibility is expected to lead to the prevention of dialysis-related complications (e.g. amyloidosis, arteriosclerosis, and malnutrition) and to the delay of disease progression by alleviating microinflammation. SUMMARY: The biocompatibility of dialyzers is greatly influenced by the interaction between blood and the treatment materials, in which the chemical and physical characteristics of membrane materials play important roles...
2017: Contributions to Nephrology
T Sahutoglu, K Atay, Y Caliskan, E Kara, H Yazici, A Turkmen
BACKGROUND: Amyloid A (AA) amyloidosis is a multisystemic, progressive, and severe disease. Renal involvement is a prominent feature of the disease, and the outcome of patients on dialysis is poor. We aimed to analyze the outcomes of kidney transplantation in patients with AA amyloidosis in comparison with chronic glomerulonephritis (CGN). METHODS: Charts of patients who underwent kidney transplantation between 1988 and 2012 were reviewed; 41 patients with AA amyloidosis were identified, and 41 age- and sex-matched control patients with chronic CGN were included...
July 2016: Transplantation Proceedings
Tatsuya Seki, Atsuo Hattori, Toshihito Yoshida
We report a case of hemodynamic deterioration after aortic valve replacement in a patient with mixed systemic amyloidosis. A 77-year-old male with severe aortic valve stenosis and 19 years hemodialysis underwent aortic valve replacement. Postoperatively, the patient died of hemodynamic deterioration. Autopsy findings showed massive, whole-body edema and mixed systemic amyloidosis (dialysis-related and AA amyloidosis). Clinical and autopsy findings implied that hemodynamic deterioration was caused by increased vascular permeability...
August 4, 2016: General Thoracic and Cardiovascular Surgery
Dominic Narang, Anubhuti Singh, Hema M Swasthi, Samrat Mukhopadhyay
Misfolding and amyloid aggregation of human β2-microglobulin (β2m) have been linked to dialysis-related amyloidosis. Previous studies have shown that in the presence of different salt concentrations and at pH 2.5, β2m assembles into aggregates with distinct morphologies. However, the structural and mechanistic details of the aggregation of β2m, giving rise to different morphologies, are poorly understood. In this work, we have extensively characterized the salt-induced oligomers of the acid-unfolded state of β2m using an array of biophysical tools including steady-state and time-resolved fluorescence, circular dichroism, dynamic light scattering, and atomic force microscopy imaging...
August 18, 2016: Journal of Physical Chemistry. B
Kristine D Schandorff, Iben M Miller, Dorrit Krustrup, Gregor B E Jemec, Peter Marckmann
Rheumatic disease is the dominant cause of amyloid A (AA) amyloidosis, but other chronic inflammatory diseases may have similar consequences. Hidradenitis suppurativa (HS) is a relatively common, but little known skin disease characterized by chronic inflammation. Here we present a case of chronic HS leading to biopsy-verified severe renal AA amyloidosis and dialysis dependency.
July 2016: Clinical Nephrology
Junichi Hoshino, Masahiro Kawada, Aya Imafuku, Koki Mise, Keiichi Sumida, Rikako Hiramatsu, Eiko Hasegawa, Noriko Hayami, Masayuki Yamanouchi, Tatsuya Suwabe, Naoki Sawa, Yoshifumi Ubara, Kenmei Takaichi
BACKGROUND: The ongoing effort to prevent dialysis-related amyloidosis (DRA) has been hampered by lack of any way to measure DRA's severity. Yet, such measurement is essential for assessing the effect of DRA treatment. Accordingly, we developed a scoring system focused on the physical manifestations of DRA. METHODS: Forty-four patients on maintenance hemodialysis with DRA, and 96 without it, were enrolled. The SF-36v2 Health Survey ascertained whether patients experienced general bodily pain and/or physical dysfunction with any attendant specific pain (dysfunction)...
June 23, 2016: Clinical and Experimental Nephrology
Dominic Narang, Anubhuti Singh, Samrat Mukhopadhyay
Amyloid fibril formation by human β2-microglobulin (β2m) is associated with dialysis-related amyloidosis. In order to understand the mechanism of protein misfolding, it is important to characterize the nature and properties of various intermediates formed during protein unfolding. In this work, we studied the effect of pH change on the unfolding of β2m using a range of spectroscopic readouts. In order to investigate the local structural changes, we created single tryptophan (W60 and W95) mutants of β2m...
January 2017: European Biophysics Journal: EBJ
Daniel Fonseca, Samuel Gilberto, Cristina Ribeiro-Silva, Raquel Ribeiro, Inês Batista Guinote, Susana Saraiva, Ricardo A Gomes, Élia Mateus, Ana Viana, Eduardo Barroso, Ana Ponces Freire, Patrick Freire, Carlos Cordeiro, Gonçalo da Costa
Transthyretin amyloidosis (ATTR) belongs to a class of disorders caused by protein misfolding and aggregation. ATTR is a disabling disorder of autosomal dominant trait, where transthyretin (TTR) forms amyloid deposits in different organs, causing dysfunction of the peripheral nervous system. We previously discovered that amyloid fibrils from ATTR patients are glycated by methylglyoxal. Even though no consensus has been reached about the actual role of methylglyoxal-derived advanced glycation end-products in amyloid diseases, evidence collected so far points to a role for protein glycation in conformational abnormalities, being ubiquitously found in amyloid deposits in Alzheimer's disease, dialysis-related amyloidosis and Parkinson's diseases...
July 15, 2016: Biochemical Journal
Carlo Camilloni, Benedetta Maria Sala, Pietro Sormanni, Riccardo Porcari, Alessandra Corazza, Matteo De Rosa, Stefano Zanini, Alberto Barbiroli, Gennaro Esposito, Martino Bolognesi, Vittorio Bellotti, Michele Vendruscolo, Stefano Ricagno
A wide range of human diseases is associated with mutations that, destabilizing proteins native state, promote their aggregation. However, the mechanisms leading from folded to aggregated states are still incompletely understood. To investigate these mechanisms, we used a combination of NMR spectroscopy and molecular dynamics simulations to compare the native state dynamics of Beta-2 microglobulin (β2m), whose aggregation is associated with dialysis-related amyloidosis, and its aggregation-resistant mutant W60G...
2016: Scientific Reports
P Chandrasekaran, R Rajasekaran
Beta-2 microglobulin (β2m) is an amyloidogenic protein belongs to the immunoglobulin superfamily, responsible for the dialysis-related amyloidosis (DRA). Misfolding of β2m is a prerequisite to the formation of systemic amyloidosis that has an effect on the structure and function of the affected organ. The aim of our present study is to intensively explore the structural characterization of amyloid aggregation propensity of recently identified natural mutation D76N by applying the classical molecular dynamics (MD) approach...
March 2016: Molecular BioSystems
Nelson Leung, Shaji K Kumar, Siobhan V Glavey, Angela Dispenzieri, Martha Q Lacy, Francis K Buadi, Suzanne R Hayman, David Dingli, Prashant Kapoor, Steven R Zeldenrust, Stephen J Russell, John A Lust, William J Hogan, S Vincent Rajkumar, Dennis A Gastineau, Taxiarchis V Kourelis, Yi Lin, Wilson I Gonsalves, Ronald S Go, Morie A Gertz
BACKGROUND: Acute renal failure requiring dialysis is associated with high mortality during autologous stem cell transplantation (ASCT). This study examined the association between acute renal failure and mortality in immunoglobulin light chain (AL) amyloidosis during ASCT. METHODS: Between 1996 and 2010, 408 ASCT patients were evaluated. Data were collected from electronic medical records. RESULTS: Dialysis was performed on 72 (17.6%) patients...
August 2016: Nephrology, Dialysis, Transplantation
Yukio Ando
In neurological disorder related amyloidosis, several therapies have been developed in the recent decade. In AL and AA amyloidosis, novel chemotherapy and IL6 receptor antibody have been found to be effective, respectively. In addition to these amyloidosis, in transthyretin (TTR) related familial amyloidotic polyneuropathy (FAP), liver transplantation, tertial structure stabilizing drugs, and gene silencing drugs have been developing now. As neurological disorder related amyloidosis, systemic amyloidosis, such as AL amyloidosis, AA amyloidosis, dialysis related amyloidosis, FAP, senile systemic amyloidosis, and brain localized amyloidosis, such as Alzheimer's disease, and prion disease are listed...
2015: Rinshō Shinkeigaku, Clinical Neurology
Tadakazu Okoshi, Itaru Yamaguchi, Daisaku Ozawa, Kazuhiro Hasegawa, Hironobu Naiki
Dialysis-related amyloidosis is a major complication in long-term hemodialysis patients. In dialysis-related amyloidosis, β2-microglobulin (β2-m) amyloid fibrils deposit in the osteoarticular tissue, leading to carpal tunnel syndrome and destructive arthropathy with cystic bone lesions, but the mechanism by which these amyloid fibrils destruct bone and joint tissue is not fully understood. In this study, we assessed the cytotoxic effect of β2-m amyloid fibrils on the cultured rabbit synovial fibroblasts...
2015: PloS One
Masatomo So, Akira Ishii, Yasuko Hata, Hisashi Yagi, Hironobu Naiki, Yuji Goto
Although various natural and synthetic compounds have been shown to accelerate or inhibit the formation of amyloid fibrils, the mechanisms by which they achieve these adverse effects in a concentration-dependent manner currently remain unclear. Sodium dodecyl sulfate (SDS), one of the compounds that has adverse effects on fibrillation, is the most intensively studied. Here we examined the effects of a series of detergents including SDS on the amyloid fibrillation of β2-microglobulin at pH 7.0, a protein responsible for dialysis-related amyloidosis...
September 15, 2015: Langmuir: the ACS Journal of Surfaces and Colloids
Junichi Hoshino, Kunihiro Yamagata, Shinichi Nishi, Shigeru Nakai, Ikuto Masakane, Kunitoshi Iseki, Yoshiharu Tsubakihara
BACKGROUND: Although dialysis technology greatly improved in recent years, it remained unclear whether those improvements helped decrease the incidence of dialysis-related amyloidosis (DRA). Accordingly, we retrospectively compared the incidence of first-time carpal tunnel surgery (CTS)-as proxy for DRA onset-in two cohorts of chronic hemodialysis patients, with the second cohort studied after dialysis methods (especially dialyzate quality control) had greatly improved. METHODS: We used the 1998 and 2010 Japan Renal Data Registries to compare crude risk of first-time CTS the following year...
April 2016: Nephrology, Dialysis, Transplantation
Masayuki Adachi, Masatomo So, Kazumasa Sakurai, József Kardos, Yuji Goto
Although amyloid fibrils and amorphous aggregates are two types of aggregates formed by denatured proteins, their relationship currently remains unclear. We used β2-microglobulin (β2m), a protein responsible for dialysis-related amyloidosis, to clarify the mechanism by which proteins form either amyloid fibrils or amorphous aggregates. When ultrasonication was used to accelerate the spontaneous fibrillation of β2m at pH 2.0, the effects observed depended on ultrasonic power; although stronger ultrasonic power effectively accelerated fibrillation, excessively strong ultrasonic power decreased the amount of fibrils formed, as monitored by thioflavin T fluorescence...
July 17, 2015: Journal of Biological Chemistry
Hidekazu Sugiura, Kayu Nakayama, Takashi Takei, Ken Tsuchiya, Kosaku Nitta
Dialysis-related amyloidosis (DRA) is one of the most important complications in long-term dialysis patients. Pulmonary involvement in patients with DRA has been rarely described, and lung radiographic findings have not yet been reported. The most common chronic lung disease process in chronic dialysis patients is interstitial fibrosis. This is the first case report of DRA presenting in the lung in a manner resembling interstitial pneumonia. This case study suggests that interstitial pneumonia as a result of DRA should be considered when dyspnoea and reticular opacity of the lung are observed in patients undergoing long-term dialysis...
February 2011: NDT Plus
Noriko Hayami, Junichi Hoshino, Tastuya Suwabe, Keiichi Sumida, Koki Mise, Satoshi Hamanoue, Naoki Sawa, Izuru Kitajima, Yutaka Hirota, Kenichi Oohashi, Takeshi Fujii, Itsuko Okuda, Kenmei Takaichi, Yoshifumi Ubara
Destructive spondyloarthropathy (DSA) is the most serious spinal complication of dialysis-related amyloidosis in patients on long-term hemodialysis (HD), but we could not find any information about DSA in patients on peritoneal dialysis (PD) for over 10 years. We retrospectively evaluated factors contributing to DSA in HD and PD patients. Sixty-seven patients on dialysis for 10 to 19 years were compared between a PD group (n = 23) or a HD group (n = 44). In the PD group, nine patients (39%) developed DSA...
August 2015: Therapeutic Apheresis and Dialysis
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