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Sample records for hemolytic uremic syndrome1

  1. Hemolytic uremic syndrome.

    Science.gov (United States)

    Canpolat, Nur

    2015-06-01

    Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytopenia, and acute kidney injury. Hemolytic uremic syndrome represents a heterogeneous group of disorders with variable etiologies that result in differences in presentation, management and outcome. In recent years, better understanding of the HUS, especially those due to genetic mutations in the alternative complement pathway have provided an update on the terminology, classification, and treatment of the disease. This review will provide the updated classification of the disease and the current diagnostic and therapeutic approaches on the complement-mediated HUS in addition to STEC-HUS which is the most common cause of the HUS in childhood.

  2. Hemolytic uremic syndrome.

    Science.gov (United States)

    Webster, Kathleen; Schnitzler, Eugene

    2014-01-01

    The thrombotic microangiopathies include both hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Although debate exists as to whether these are separate entities or a spectrum of disease, both result in the clinical picture of thrombocytopenia, hemolytic anemia, and varying degrees of renal and neurologic involvement. Etiology of HUS includes diarrheal infection due to Shiga toxin-producing bacteria, complement deficiency, pneumococcal infection, and cobalamin deficiency. In disease ascribed to TTP, the main etiologic factor is deficiency of an enzyme known as a disintegrin-like and metalloprotease with thrombospondin type 1 repeats, number 13 (ADAMTS-13). The clinical manifestations may vary, but neurologic involvement can be significant, with reports of hypertensive encephalopathy, seizures, thrombosis and infarct. In nondiarrheal forms of disease, recurrence may occur and clinical diagnosis is essential in order to provide a targeted therapy for the suspected etiology. Therapies include supportive care, cobalamin supplementation, as well as plasma infusion and exchange. End stage renal disease may result and transplantation is curative for some forms of the disease. More recent research focuses on targeted immunotherapy to prevent autoantibody prevention. As of yet, there is no one cure for these potentially devastating diseases, and diagnosis and treatment selection presents a challenge to the clinician. © 2014 Elsevier B.V. All rights reserved.

  3. [Atypical hemolytic uremic syndrome].

    Science.gov (United States)

    Blasco Pelicano, Miquel; Rodríguez de Córdoba, Santiago; Campistol Plana, Josep M

    2015-11-20

    The hemolytic uremic syndrome (HUS) is a clinical entity characterized by thrombocytopenia, non-immune hemolytic anemia and renal impairment. Kidney pathology shows thrombotic microangiopathy (TMA) with endothelial cell injury leading to thrombotic occlusion of arterioles and capillaries. Traditionally, HUS was classified in 2 forms: Typical HUS, most frequently occurring in children and caused by Shiga-toxin-producing bacteria, and atypical HUS (aHUS). aHUS is associated with mutations in complement genes in 50-60% of patients and has worse prognosis, with the majority of patients developing end stage renal disease. After kidney transplantation HUS may develop as a recurrence of aHUS or as de novo disease. Over the last years, many studies have demonstrated that complement dysregulation underlies the endothelial damage that triggers the development of TMA in most of these patients. Advances in our understanding of the pathogenic mechanisms of aHUS, together with the availability of novel therapeutic options, will enable better strategies for the early diagnosis and etiological treatment, which are changing the natural history of aHUS. This review summarizes the aHUS clinical entity and describes the role of complement dysregulation in the pathogenesis of aHUS. Finally, we review the differential diagnosis and the therapeutic options available to patients with aHUS. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  4. [Hemolytic uremic syndrome in adults].

    Science.gov (United States)

    Hertig, Alexandre; Ridel, Christophe; Rondeau, Eric

    2010-07-01

    Hemolytic uremic syndrome (HUS) is related to a renal thrombotic microangiopathy, inducing hypertension and acute renal failure (ARF). Its pathogenesis involves an activation/lesion of microvascular endothelial cells, mainly in the renal vasculature, secondary to bacterial toxins, drugs, or autoantibodies. An overactivation of the complement alternate pathway secondary to a heterozygote deficiency of regulatory proteins (factor H, factor I or MCP) or to an activating mutation of factor B or C3 can also result in HUS. Less frequently, renal microthrombi are due to an acquired or a constitutional deficiency in ADAMTS-13, the protease cleaving von Wilebrand factor. Hemolytic anemia with schistocytes, thrombocytopenia without evidence of disseminated intravascular coagulation, and renal failure are consistently found. In typical HUS, a prodromal diarrhea, with blood in the stools, is observed, related to pathogenic enterobacteria, most frequently E. Coli O157:H7. HUS may also occur in the post partum period, and is then related to a factor H or factor I deficiency. HUS may also occur after various treatments such as mitomycin C, gemcitabine, ciclosporin A, or tacrolimus, and as reported more recently bevacizumab, an anti VEGF antibody. Atypical HUS are not associated with diarrhea, may be sporadic or familial, and can be related to an overactivation of the complement alternate pathway. More recently, some of them have been related to a mutation of thrombomodulin, which also regulates the alternate pathway of complement. In adults, several HUS are encountered in the course of chronic nephropathies: nephroangiosclerosis, chronic glomerulonephritis, post irradiation nephropathy, scleroderma, disseminated lupus erythematosus, antiphospholipid syndrome. Overall the prognosis of HUS has improved, with a patient survival greater than 85% at 1 year. Chronic renal failure is observed as a sequella in 20 to 65% of the cases. Plasma infusions and plasma exchanges are effective in

  5. Liver damage in the hemolytic uremic syndrome.

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    van Rhijn, A; Donckerwolcke, R A; Kuijten, R H; van der Heiden, C

    1977-06-01

    During the recovery stage of the hemolytic uremic syndrome in 2 cases an increase of serum levels of GOT, GPT, LDH, gammaGT, 5'ND and AP was noticed, without signs of a recurrence of the disease. In one patient also jaundice and hepatomegaly were found. The observations suggest a parenchymal damage of the liver.

  6. Hemolytic uremic syndrome and Clostridium difficile colitis

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    Maryam Keshtkar-Jahromi

    2012-10-01

    Full Text Available Hemolytic uremic syndrome (HUS can be associated with different infectious etiologies, but the relationship between pseudomembranous colitis and HUS was first described in the 1970s in some childhood patients. There is very limited published literature on Clostridium difficile-associated HUS. We report a case of C. difficile-related HUS in an adult patient and provide a review of the literature.

  7. Hemolytic uremic syndrome and Clostridium difficile colitis

    Science.gov (United States)

    Keshtkar-Jahromi, Maryam; Mohebtash, Mahsa

    2012-01-01

    Hemolytic uremic syndrome (HUS) can be associated with different infectious etiologies, but the relationship between pseudomembranous colitis and HUS was first described in the 1970s in some childhood patients. There is very limited published literature on Clostridium difficile-associated HUS. We report a case of C. difficile-related HUS in an adult patient and provide a review of the literature. PMID:23882375

  8. Hemolytic uremic syndrome after bone marrow transplantation

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    Arai, Ayako; Sakamaki, Hisashi; Tanikawa, Shu [Tokyo Metropolitan Komagome Hospital (Japan)] [and others

    1998-06-01

    One hundred and thirteen patients who underwent autologous or allogeneic bone marrow transplantation (BMT) were investigated for the subsequent development of hemolytic uremic syndrome (HUS). HUS developed in seven patients (four males and three females, five acute lymphocytic leukemia (ALL), one acute myelogenous leukemia, one non-Hodgkin`s lymphoma) between 36-196 days after BMT. Four patients were recipients of autologous BMT and three were those of allogeneic BMT. Six patients were preconditioned with the regimens including fractionated total body irradiation (TBI). ALL and preconditioning regimen with TBI were suspected to be the risk factors for the development of HUS. Cyclosporin A (CSP) administration was discontinued in three patients who had been given CSP for graft-versus-host disease prophylaxis. Predonisolone was given to the three patients and plasma exchange was performed in one patient. Both hemolytic anemia and thrombocytopenia were resolved in virtually all patients, while creatinine elevation has persisted along with hypertension in one patient. (author)

  9. Clinical grand rounds: atypical hemolytic uremic syndrome.

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    Hodgkins, Kavita S; Bobrowski, Amy E; Lane, Jerome C; Langman, Craig B

    2012-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare, lifethreatening, chronic, genetic disease of uncontrolled alternative pathway complement activation. The understanding of the pathophysiology and genetics of this disease has expanded over recent decades and promising new developments in the management of aHUS have emerged. Regardless of the cause of aHUS, with or without a demonstrated mutation or autoantibody, blockade of terminal complement activation through C5 is of high interest as a mechanism to ameliorate the disease. Eculizumab, an existing monoclonal antibody directed against C5 with high affinity, prevents the perpetuation of the downstream activation of the complement cascade and the damage caused by generation of the anaphylotoxin C5a and the membrane attack complex C5b-9, by blocking C5 cleavage. We report the successful use of eculizumab in a patient after kidney transplantation and discuss the disease aHUS.

  10. Hemolytic uremic syndrome associated with Acinetobacter hemolyticus.

    Science.gov (United States)

    da Silva, Paulo Sérgio Lucas; Lipinski, Rubens Wolfe

    2014-08-01

    Shiga toxin-producing Escherichia coli and Shigella dysenteriae have been associated with bloody diarrhea and hemolytic uremic syndrome (HUS) in humans. However, there have been only a couple of reports describing bloody diarrhea associated with Acinetobacter spp. and there are no reports of these bacteria causing HUS in children. Here, we report the case of a nine-month-old boy with bloody diarrhea who developed non-oliguric renal failure. The clinical and laboratory findings supported the diagnosis of Acinetobacter hemolyticus infection associated with HUS. The patient responded favorably to antibiotic therapy plus conservative treatment. In conclusion, Acinetobacter infection should be considered as a plausible cause of HUS in cases where E. coli infection is not involved. The rapid transformation ability of Acinetobacter is a matter of concern.

  11. A Case of Microangiopathic Hemolytic Anemia after Myxoma Excision and Mitral Valve Repair Presenting as Hemolytic Uremic Syndrome

    OpenAIRE

    Park, Young Joo; Kim, Sang Pil; Shin, Ho-Jin; Choi, Jung Hyun

    2016-01-01

    Microangiopathic hemolytic anemia occurs in a diverse group of disorders, including thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and prosthetic cardiac valves. Hemolytic anemia also occurs as a rare complication after mitral valve repair. In this report, we describe a case of microangiopathic hemolytic anemia following myxoma excision and mitral valve repair, which was presented as hemolytic uremic syndrome.

  12. Hemolytic uremic syndrome associated with paraquat intoxication.

    Science.gov (United States)

    Jang, Ha Nee; Bae, Eun Jin; Hwang, Kyungo; Kang, Yeojin; Yun, Seongeun; Cho, Hyun Seop; Chang, Se-Ho; Park, Dong Jun

    2014-06-01

    We report a case of a 66-year-old patient with paraquat intoxication resulting in the requirement for hemoperfusion, hemodialysis, and plasma exchange. His initial serum paraquat level was 0.24 µg/mL (0.0-0.1 µg/mL). Activated charcoal (50 g) was administered orally, and high-dose N-acetylcysteine (150 mg/kg) was administered intravenously. In addition, immediate 4 h hemoperfusion was also performed for three consecutive days after admission. Hemodialysis was started on the 4th day after admission because of uremia. On the 9th day after admission, laboratory findings demonstrated hemolytic uremic syndrome (HUS): microangiopathic hemolytic anemia (MAHA), thrombocytopenia, elevated reticulocyte count, and lactate dehydrogenase (LDH). Plasma exchange was performed three times consecutively. Anemia and thrombocytopenia were improved, and LDH was normalized after plasma exchange. Urine output increased to 2240 mL/day on the 18th day after admission, and hemodialysis was discontinued. He is currently being observed at our follow-up clinic without renal impairment or pulmonary dysfunction for 1.5 years since discharge. We should suspect paraquat-associated HUS when thrombocytopenia and anemia are maintained for a long time after paraquat intoxication.

  13. Recurrent atypical hemolytic uremic syndrome associated with factor I mutation in a living related renal transplant recipient.

    Science.gov (United States)

    Chan, Micah R; Thomas, Christie P; Torrealba, Jose R; Djamali, Arjang; Fernandez, Luis A; Nishimura, Carla J; Smith, Richard J H; Samaniego, Millie D

    2009-02-01

    Atypical hemolytic uremic syndrome, or the nondiarrheal form of hemolytic uremic syndrome, is a rare disorder typically classified as familial or sporadic. Recent literature has suggested that approximately 50% of patients have mutations in factor H (CFH), factor I (CFI), or membrane cofactor protein (encoded by CD46). Importantly, results of renal transplantation in patients with mutations in either CFH or CFI are dismal, with recurrent disease leading to graft loss in the majority of cases. We describe an adult renal transplant recipient who developed recurrent hemolytic uremic syndrome 1 month after transplantation. Bidirectional sequencing of CFH, CFI, and CD46 confirmed that the patient was heterozygous for a novel missense mutation, a substitution of a serine reside for a tyrosine residue at amino acid 369, in CFI. This report reemphasizes the importance of screening patients with atypical hemolytic uremic syndrome for mutations in these genes before renal transplantation and shows the challenges in the management of these patients.

  14. Critical appraisal of eculizumab for atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Palma, Lilian M Pereira; Langman, Craig B

    2016-01-01

    The biology of atypical hemolytic uremic syndrome has been shown to involve inability to limit activation of the alternative complement pathway, with subsequent damage to systemic endothelial beds and the vasculature, resulting in the prototypic findings of a thrombotic microangiopathy. Central to this process is the formation of the terminal membrane attack complex C5b-9. Recently, application of a monoclonal antibody that specifically binds to C5, eculizumab, became available to treat patients with atypical hemolytic uremic syndrome, replacing plasma exchange or infusion as primary therapy. This review focuses on the evidence, based on published clinical trials, case series, and case reports, on the efficacy and safety of this approach.

  15. Atypical relapse of hemolytic uremic syndrome after transplantation.

    NARCIS (Netherlands)

    Olie, K.H.; Florquin, S.; Groothoff, J.W.; Verlaak, R.; Strain, L.; Goodship, T.H.; Weening, J.J.; Davin, J.C.

    2004-01-01

    Atypical hemolytic uremic syndrome (HUS) frequently leads to end-stage renal failure and can relapse after transplantation. A 12-year-old girl presenting with familial atypical HUS with a factor H mutation was successfully transplanted 6 years after a first transplant that had failed because of imme

  16. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome.

    NARCIS (Netherlands)

    Legendre, C.M.; Licht, C.; Muus, P.; Greenbaum, L.A.; Babu, S.; Bedrosian, C.; Bingham, C.; Cohen, D.J.; Delmas, Y.; Douglas, K.; Eitner, F.; Feldkamp, T.; Fouque, D.; Furman, R.R.; Gaber, O.; Herthelius, M.; Hourmant, M.; Karpman, D.; Lebranchu, Y.; Mariat, C.; Menne, J.; Moulin, B.; Nurnberger, J.; Ogawa, M.; Remuzzi, G.; Richard, T.; Sberro-Soussan, R.; Severino, B.; Sheerin, N.S.; Trivelli, A.; Zimmerhackl, L.B.; Goodship, T.; Loirat, C.

    2013-01-01

    BACKGROUND: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. METHODS: We

  17. [Hemolytic uremic syndrome caused by enterohaemorrhagic Escherichia coli].

    Science.gov (United States)

    Ibarra, Cristina; Goldstein, Jorge; Silberstein, Claudia; Zotta, Elsa; Belardo, Marcela; Repetto, Horacio A

    2008-10-01

    Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, plaquetopenia and kidney damage. It is the leading cause of acute renal failure in pediatric age and the second for chronic renal failure. Shiga toxin-producing Escherichia coli (STEC) is the first etiologic agent of HUS being its main reservoir cattle and transmitted via contaminated food. At present, there is no specific treatment to reduce the progression of HUS. The study of the mechanisms by which STEC infects and Shiga toxin induces HUS can help to find new strategies to prevent this disease.

  18. [Hemolytic uremic syndrome. Clinical manifestations. Treatment].

    Science.gov (United States)

    Exeni, Ramón A

    2006-01-01

    Clinical manifestation are described in children with epidemic HUS. The intestinal involvement in the prodromic period, is outlined and the most common disturbances such acute renal failure, thrombocytopenia, hemolytic anemia, leucocitosis hypertension, neurological, pancreatic and cardiac manifestations are described. We discuss the acid-base and electrolyte disturbances, metabolic acidosis, hyponatremia, hyperkalemia. The etiopathogenic treatment and the control of renal sequelae are also discussed.

  19. Cardiomyopathy: a late complication of hemolytic uremic syndrome.

    Science.gov (United States)

    Walker, A M; Benson, L N; Wilson, G J; Arbus, G S

    1997-04-01

    This report describes a child who presented with classic hemolytic uremic syndrome (HUS) and 4 months later developed a life-threatening but reversible cardiomyopathy with global cardiac dysfunction and a left ventricular ejection fraction of 14%. There was no evidence of electrolyte abnormalities, anemia, hypertension, severe fluid overload, or viral infection. Endomyocardial biopsies were consistent with a dilated cardiomyopathy. This paper highlights the importance of considering the diagnosis of associated cardiomyopathy when presenting with late-onset edema following HUS.

  20. Epidemiology, clinical presentation, and pathophysiology of atypical and recurrent hemolytic uremic syndrome.

    NARCIS (Netherlands)

    Zimmerhackl, L.B.; Besbas, N.; Jungraithmayr, T.; Kar, N.C.A.J. van de; Karch, H.; Karpman, D.; Landau, D.; Loirat, C.; Proesmans, W.; Prufer, F.; Rizzoni, G.; Taylor, M.C.

    2006-01-01

    Hemolytic uremic syndrome (HUS) includes a heterogeneous group of hemolytic disorders. Among the identified causes of HUS are infections, particularly infections with Shiga toxin-producing ESCHERICHIA COLI (STEC), complement disorders, and disorders interfering with the degradation of von Willebrand

  1. Epidemiology, clinical presentation, and pathophysiology of atypical and recurrent hemolytic uremic syndrome.

    NARCIS (Netherlands)

    Zimmerhackl, L.B.; Besbas, N.; Jungraithmayr, T.; Kar, N.C.A.J. van de; Karch, H.; Karpman, D.; Landau, D.; Loirat, C.; Proesmans, W.; Prufer, F.; Rizzoni, G.; Taylor, M.C.

    2006-01-01

    Hemolytic uremic syndrome (HUS) includes a heterogeneous group of hemolytic disorders. Among the identified causes of HUS are infections, particularly infections with Shiga toxin-producing ESCHERICHIA COLI (STEC), complement disorders, and disorders interfering with the degradation of von Willebrand

  2. Atypical hemolytic uremic syndrome triggered by varicella infection

    Directory of Open Access Journals (Sweden)

    Pauline Condom

    2017-01-01

    The current case describes an aHUS associated to varicella infection as demonstrated by the simultaneous occurrence of the viral infection and aHUS manifestations. Apart from typical Hemolytic Uremic Syndrome which is triggered by bacteria mostly Shiga toxin producing Echerichia coli and Streptococcus pneumoniae or Shigella, aHUS may be linked to viral infections such as HIV, EBV and enteroviruses, but very rarely by varicella. This case highlights a possible even rare complication of varicella infection a very common childhood disease. This complication could be avoided by to anti-VZV vaccination.

  3. Atypical hemolytic uremic syndrome: A report of two cases

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    Md. Habibur Rahman

    2016-07-01

    Full Text Available Hemolytic uremic syndrome (HUS is one of the important cause of acute kidney injury in children. There is excellent outcome in patients with typical HUS but atypical HUS is associated with high mortality, risk of recurrence and may lead to end stage renal disease. We report two cases of 5 and 6 year old child having clinical & laboratory characteristics of atypical HUS. These children had a fulminant course of illness with complications involving various systems. The report provides an insight into the etio pathogenesis, diagnoses and treatment of this condition.

  4. Recurrent Hemolytic and Uremic Syndrome Induced by Escherichia Coli

    Science.gov (United States)

    Commereuc, Morgane; Weill, Francois-Xavier; Loukiadis, Estelle; Gouali, Malika; Gleizal, Audrey; Kormann, Raphaël; Ridel, Christophe; Frémeaux-Bacchi, Véronique; Rondeau, Eric; Hertig, Alexandre

    2016-01-01

    Abstract A widespread belief is that typical hemolytic and uremic syndrome (HUS) does not recur. We report the case of a patient infected twice with raw milk taken from his own cow and containing a Shiga toxin–producing Escherichia coli O174:H21 that induced recurrent HUS causing severe renal and cerebral disorders. A genomic comparison of the human and bovine Shiga toxin–producing Escherichia coli O174:H21 isolates revealed that they were identical. Typical HUS may recur. Since milk from this animal was occasionally distributed locally, thereby posing a serious threat for the whole village, this particular cow was destroyed. PMID:26735524

  5. Hemolytic uremic syndrome in Argentina: An attack scenario

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    Alcides Troncoso

    2013-08-01

    Full Text Available The recent Escherichia coli epidemic in Germany gave a lesson at an international level. There is no time to solve food security problems when an epidemic is on the way. The epidemic in Germany exposed the fissures in the control systems of the Federal Risk Evaluation Institute of this country, as well as showing the incompetency of health authorities, who had great difficulty in resolving the situation. To summarize, the possibility of prevention was confused with the utopian idea of non-occurrence. It was not less important the public’s recognition and the “awakening” of health ministers in the European Union as regards the proven fact that pathogenic and even lethal microorganisms may be present in the food we eat. Argentina has the highest incidence of hemolytic uremic syndrome in the world, and the next epidemic is likely not to occur in Germany, but in any other country, such as Argentina. In order to avoid complicity, we do not wish to remain silent about the situation in Argentina. Therefore, this is the writer’s motive for writing this article, which describes the scientific advances and the ethical pitfalls related to a disease transmitted by food, particularly hemolytic uremic syndrome, in Argentina.

  6. Hemolytic uremic syndrome in Argentina:An attack scenario

    Institute of Scientific and Technical Information of China (English)

    Alcides Troncoso

    2013-01-01

    The recent Escherichia coli epidemic in Germany gave a lesson at an international level. There is no time to solve food security problems when an epidemic is on the way. The epidemic in Germany exposed the fissures in the control systems of the Federal Risk Evaluation Institute of this country, as well as showing the incompetency of health authorities, who had great difficulty in resolving the situation. To summarize, the possibility of prevention was confused with the utopian idea of non-occurrence. It was not less important the public’s recognition and the “awakening” of health ministers in the European Union as regards the proven fact that pathogenic and even lethal microorganisms may be present in the food we eat. Argentina has the highest incidence of hemolytic uremic syndrome in the world, and the next epidemic is likely not to occur in Germany, but in any other country, such as Argentina. In order to avoid complicity, we do not wish to remain silent about the situation in Argentina. Therefore, this is the writer’s motive for writing this article, which describes the scientific advances and the ethical pitfalls related to a disease transmitted by food, particularly hemolytic uremic syndrome, in Argentina.

  7. Critical appraisal of eculizumab for atypical hemolytic uremic syndrome

    Directory of Open Access Journals (Sweden)

    Palma LMP

    2016-04-01

    Full Text Available Lilian M Pereira Palma,1 Craig B Langman2  1Pediatric Nephrology, State University of Campinas (UNICAMP, Campinas, São Paulo, Brazil; 2The Feinberg School of Medicine, Northwestern University, and the Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA Abstract: The biology of atypical hemolytic uremic syndrome has been shown to involve inability to limit activation of the alternative complement pathway, with subsequent damage to systemic endothelial beds and the vasculature, resulting in the prototypic findings of a thrombotic microangiopathy. Central to this process is the formation of the terminal membrane attack complex C5b-9. Recently, application of a monoclonal antibody that specifically binds to C5, eculizumab, became available to treat patients with atypical hemolytic uremic syndrome, replacing plasma exchange or infusion as primary therapy. This review focuses on the evidence, based on published clinical trials, case series, and case reports, on the efficacy and safety of this approach. Keywords: acute kidney injury, ESRD, thrombotic microangiopathy, kidney, alternative complement pathway, complement blockade

  8. Liver-kidney transplantation to cure atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Saland, Jeffrey M; Ruggenenti, Piero; Remuzzi, Giuseppe

    2009-05-01

    Atypical hemolytic uremic syndrome is often associated with mutations in genes encoding complement regulatory proteins and secondary disorders of complement regulation. Progression to kidney failure and recurrence with graft loss after kidney transplantation are frequent. The most common mutation is in the gene encoding complement factor H. Combined liver-kidney transplantation may correct this complement abnormality and prevent recurrence when the defect involves genes encoding circulating proteins that are synthesized in the liver, such as factor H or I. Good outcomes have been reported when surgery is associated with intensified plasma therapy. A consensus conference to establish treatment guidelines for atypical hemolytic uremic syndrome was held in Bergamo in December 2007. The recommendations in this article are the result of combined clinical experience, shared research expertise, and a review of the literature and registry information. This statement defines groups in which isolated kidney transplantation is extremely unlikely to be successful and a combined liver-kidney transplant is recommended and also defines those for whom kidney transplant remains a viable option. Although combined liver-kidney or isolated liver transplantation is the preferred therapeutic option in many cases, the gravity of risk associated with the procedure has not been eliminated completely, and assessment of risk and benefit requires careful and individual attention.

  9. Assesment, treatment and prevention of atypical hemolytic uremic syndrome

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    Azar Nickavar

    2013-01-01

    Full Text Available Hemolytic uremic syndrome (HUS is a heterogeneous group of hemolytic disorders. Different terminologies have been described in HUS, which are as follows: (1 D+ HUS: Presentation with a preceding diarrhea; (2 typical HUS: D+ HUS with a single and self-limited episode; (3 atypical HUS (aHUS: Indicated those with complement dysregulation; (4 recurrent HUS: Recurrent episodes of thrombocytopenia and/or microangiopathic hemolytic anemia (MAHA after improvement of hematologic abnormalities; and (5 familial HUS: Necessary to distinct synchronous outbreaks of D+ HUS in family members and asynchronous disease with an inherited risk factor. aHUS is one of the potential causes of end-stage renal disease (ESRD in children. It has a high recurrence after renal transplantation in some genetic forms. Therefore, recognition of the responsible mechanism and proper prophylactic treatment are recommended to prevent or delay the occurrence of ESRD and prolong the length of survival of the transplanted kidney. A computerized search of MEDLINE and other databases was carried out to find the latest results in pathogenesis, treatment, and prevention of aHUS.

  10. Hemolytic Uremic Syndrome-associated Encephalopathy Successfully Treated with Corticosteroids.

    Science.gov (United States)

    Hosaka, Takashi; Nakamagoe, Kiyotaka; Tamaoka, Akira

    2017-09-25

    The encephalopathy that occurs in association with hemolytic uremic syndrome (HUS), which is caused by enterohemorrhagic Escherichia coli (E. coli), has a high mortality rate and patients sometimes present sequelae. We herein describe the case of a 20-year-old woman who developed encephalopathy during the convalescent stage of HUS caused by E.coli O26. Hyperintense lesions were detected in the pons, basal ganglia, and cortex on diffusion-weighted brain MRI. From the onset of HUS encephalopathy, we treated the patient with methylprednisolone (mPSL) pulse therapy alone. Her condition improved, and she did not present sequelae. Our study shows that corticosteroids appear to be effective for the treatment of some patients with HUS encephalopathy.

  11. Hemolytic uremic syndrome: pathogenesis and update of interventions.

    Science.gov (United States)

    Palermo, Marina S; Exeni, Ramón A; Fernández, Gabriela C

    2009-08-01

    The typical form of hemolytic uremic syndrome (HUS) is the major complication of Shiga toxin-producing Escherichia coli infections. HUS is a critical health problem in Argentina since it is the main cause of acute renal failure in children and the second cause of chronic renal failure, accounting for 20% of renal transplants in children and adolescents in Argentina. Despite extensive research in the field, the mainstay of treatment for patients with HUS is supportive therapy, and there are no specific therapies preventing or ameliorating the disease course. In this review, we present the current knowledge about pathogenic mechanisms and discuss traditional and innovative therapeutic approaches, with special focus in Argentinean contribution. The hope that a better understanding of transmission dynamics and pathogenesis of this disease will produce better therapies to prevent the acute mortality and the long-term morbidity of HUS is the driving force for intensified research.

  12. Hemolytic uremic syndrome as a primary manifestation of acute human immunodeficiency virus infection.

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    Gomes, A M; Ventura, A; Almeida, C; Correia, M; Tavares, V; Mota, M; Seabra, J

    2009-05-01

    Hemolytic uremic syndrome may be associated with human immunodeficiency virus infection but it occurs in advanced stages of human immunodeficiency virus disease. As in other forms of hemolytic uremic syndrome plasmapheresis seems to be the treatment of choice. The authors present an unusual case of hemolytic uremic syndrome associated with acute human immunodeficiency virus infection in a 38 year-old black male. The patient was admitted with fever, asthenia, nausea, diarrhea, and reduced urinary output. He was found to have anemia, thrombocytopenia and severe renal failure. Hemolytic uremic syndrome was diagnosed and he was started on plasmapheresis and hemodialysis. Serological tests were consistent with acute human immunodeficiency virus infection: the enzyme linked immunosorbent assay for human immunodeficiency virus was weakly positive, Western Blot test was negative and human immunodeficiency virus RNA quantification was positive, with > 1,000,000 copies/microl. After 4 daily treatment sessions, patient's clinical condition improved and hemoglobin, platelets, lactic dehydrogenase and renal function normalized.

  13. Hemolytic Uremic Syndrome: New Developments in Pathogenesis and Treatment

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    Olivia Boyer

    2011-01-01

    Full Text Available Hemolytic uremic syndrome is defined by the characteristic triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. In children, most cases of HUS are caused by Shiga-toxin-producing bacteria, especially Escherichia coli O157:H7. Common vehicles of transmission include ground beef, unpasteurized milk, and municipal or swimming water. Shiga-toxin-associated HUS is a main cause of acute renal failure in young children. Management remains supportive as there is at present no specific therapy to ameliorate the prognosis. Immediate outcome is most often favourable but long-term renal sequelae are frequent due to nephron loss. Atypical HUS represents 5% of cases. In the past 15 years, mutations in complement regulators of the alternative pathway have been identified in almost 60% of cases, leading to excessive complement activation. The disease has a relapsing course and more than half of the patients either die or progress to end-stage renal failure. Recurrence after renal transplantation is frequent.

  14. Advanced Prostate Cancer Presenting as Hemolytic Uremic Syndrome

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    R. Ramos

    2013-01-01

    Full Text Available Introduction. Hemolytic uremic syndrome (HUS is characterized by endothelial dysfunction, consumption thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. HUS generally has a dismal prognosis, except when associated with gastroenteritis caused by verotoxin-producing bacteria. Cancer associated HUS is uncommon, and there are only scarce reports on prostate cancer presenting with HUS. Case Presentation. A 72-year-old man presented to the emergency department with oliguria, hematuria, and hematemesis. Clinical evaluation revealed acute renal failure, hemolysis, normal blood-clotting studies, and prostate-specific antigen value of 1000 ng/mL. The patient was started on hemodialysis, ultrafiltration with plasma exchange, and androgen blockade with bicalutamide and completely recovered from HUS. The authors review the 14 published cases on this association. Conclusion. The association of HUS and prostate cancer occurs more frequently in patients with high-grade, clinically advanced prostate cancer. When readily recognized and appropriately treated, HUS does not seem to worsen prognosis in prostate cancer patients.

  15. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome

    Science.gov (United States)

    Lemaire, Mathieu; Frémeaux-Bacchi, Véronique; Schaefer, Franz; Choi, Murim; Tang, Wai Ho; Le Quintrec, Moglie; Fakhouri, Fadi; Taque, Sophie; Nobili, François; Martinez, Frank; Ji, Weizhen; Overton, John D.; Mane, Shrikant M.; Nürnberg, Gudrun; Altmüller, Janine; Thiele, Holger; Morin, Denis; Deschenes, Georges; Baudouin, Véronique; Llanas, Brigitte; Collard, Laure; Majid, Mohammed A.; Simkova, Eva; Nürnberg, Peter; Rioux-Leclerc, Nathalie; Moeckel, Gilbert W.; Gubler, Marie Claire; Hwa, John; Loirat, Chantal; Lifton, Richard P.

    2013-01-01

    Pathologic thrombosis is a major cause of mortality. Hemolytic-uremic syndrome (HUS) features episodes of small vessel thrombosis resulting in microangiopathic hemolytic anemia, thrombocytopenia and renal failure1. Atypical HUS (aHUS) can result from genetic or autoimmune factors2 that lead to pathologic complement cascade activation3. By exome sequencing we identify recessive mutations in DGKE (diacylglycerol kinase epsilon) that co-segregate with aHUS in 9 unrelated kindreds, defining a distinctive Mendelian disease. Affected patients present with aHUS before age 1, have persistent hypertension, hematuria and proteinuria (sometimes nephrotic range), and develop chronic kidney disease with age. DGKE is found in endothelium, platelets, and podocytes. Arachidonic acid-containing diacylglycerols (DAG) activate protein kinase C, which promotes thrombosis. DGKE normally inactivates DAG signaling. We infer that loss of DGKE function results in a pro-thrombotic state. These findings identify a new mechanism of pathologic thrombosis and kidney failure and have immediate implications for treatment of aHUS patients. PMID:23542698

  16. Atypical relapse of hemolytic uremic syndrome after transplantation.

    Science.gov (United States)

    Olie, Karolien H; Florquin, Sandrine; Groothoff, Jaap W; Verlaak, René; Strain, Lisa; Goodship, Timothy H J; Weening, Jan J; Davin, Jean-Claude

    2004-10-01

    Atypical hemolytic uremic syndrome (HUS) frequently leads to end-stage renal failure and can relapse after transplantation. A 12-year-old girl presenting with familial atypical HUS with a factor H mutation was successfully transplanted 6 years after a first transplant that had failed because of immediate recurrent HUS. Prophylactic plasma exchange before and after transplantation was used. Two months after transplantation, concomitant with a reduction in plasma exchange frequency, the plasma creatinine increased from 70 micro mol/l to 194 micro mol/l in 2 weeks without thrombocytopenia or signs of hemolytic anemia. The patient had minimal clinical symptoms and a presumptive diagnosis of graft rejection was made. Despite treatment with six daily pulses of methylprednisolone, plasma creatinine continued to increase and a graft biopsy was therefore undertaken. This showed the typical appearance of a thrombotic microangiopathy without any evidence of rejection. Despite daily plasmapheresis and replacement of cyclosporine with tacrolimus, there was no improvement and transplant nephrectomy was undertaken. This patient demonstrates that HUS can recur in a kidney transplant without the diagnostic hematological features and emphasizes the need for early transplant biopsy in such patients showing a decline in transplant function.

  17. [Microalbuminuria in pediatric patients diagnosed with hemolytic uremic syndrome].

    Science.gov (United States)

    Cubillos C, María Paz; Del Salas, Paulina; Zambrano, Pedro O

    2015-01-01

    Hemolytic uremic syndrome (HUS) is characterized by the presence of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. It is the leading cause of acute kidney failure in children under 3 years of age. A variable number of patients develop proteinuria, hypertension, and chronic renal failure. To evaluate the renal involvement in pediatric patients diagnosed with HUS using the microalbumin/creatinine ratio. Descriptive concurrent cohort study that analyzed the presence of microalbuminuria in patients diagnosed with HUS between January 2001 and March 2012, who evolved without hypertension and normal renal function (clearance greater than 90ml/min using Schwartz formula). Demographic factors (age, sex), clinical presentation at time of diagnosis, use of antibiotics prior to admission, and need for renal replacement therapy were evaluated. Of the 24 patients studied, 54% were male. The mean age at diagnosis was two years. Peritoneal dialysis was required in 45%, and 33% developed persistent microalbuminuria. Antiproteinuric treatment was introduce in 4 patients, with good response. The mean follow-up was 6 years (range 6 months to 11 years). The serum creatinine returned to normal in all patients during follow up. The percentage of persistent microalbuminuria found in patients with a previous diagnosis of HUS was similar in our group to that described in the literature. Antiproteinuric treatment could delay kidney damage, but further multicenter prospective studies are necessary. Copyright © 2015. Publicado por Elsevier España, S.L.U.

  18. Atypical Hemolytic Uremic Syndrome Recurrence after Renal Transplantation

    Science.gov (United States)

    Bouatou, Yassine; Bacchi, Véronique Frémeaux; Villard, Jean; Moll, Solange; Martin, Pierre-Yves; Hadaya, Karine

    2015-01-01

    Abstract Risk for atypical hemolytic uremic syndrome (aHUS) recurrence after renal transplantation is low with an isolated membrane cofactor protein mutation (MCP). We report the case of a 32-year-old woman with a MCP who underwent kidney transplantation with a good evolution at 12 months. At 15 and 35 months, 2 episodes of thrombotic microangiopathy (TMA), after a miscarriage and a preeclampsia, were misinterpreted as triggered by tacrolimus. After each episode however serum creatinine returned to baseline. Five years after transplantation, she had a self-limited rhinosinusitis followed 3 weeks later by an oliguric renal failure. Her complement profile was normal. Graft biopsy showed C3 glomerulonephritis with no “humps” on electron microscopy. No significant renal function improvement followed methylprednisolone pulsing. A second biopsy showed severe acute TMA lesions with C3 glomerular deposits. Despite weekly eculizumab for 1 month, dialysis was resumed. A new workup identified the “at-risk” complement factor H haplotype. Thus, aHUS recurrence should be ruled out in aHUS patients considered at low recurrence risk when a TMA is found in graft biopsy. Prompt eculizumab therapy should be considered to avoid graft loss as aHUS recurrence can first present as a C3 glomerulonephritis. PMID:27500215

  19. Neurological involvement in a child with atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Koehl, Bérengère; Boyer, Olivia; Biebuyck-Gougé, Nathalie; Kossorotoff, Manoelle; Frémeaux-Bacchi, Véronique; Boddaert, Nathalie; Niaudet, Patrick

    2010-12-01

    We report the case of a 4-year-old boy, diagnosed with atypical hemolytic uremic syndrome (HUS) due to a hybrid factor H. He progressed to end-stage renal failure despite plasmatherapy and underwent bilateral nephrectomy because of uncontrolled hypertension. Three days after, he had partial complex seizures with normal blood pressure, normal blood count and normal magnetic resonance imaging (MRI), which recurred 1 month later. Eight months later, he had a third episode of seizures, with hemoglobin of 10 g/dl without schizocytes, low haptoglobin of 0.18 g/l, and moderate thrombocytopenia (platelets 98 × 10(9)/l). He remained hypertensive and deeply confused for 2 days. The third MRI showed bilateral symmetrical hyperintensities of the cerebral pedunculas, caudate nuclei, putamens, thalami, hippocampi, and insulae suggesting thrombotic microangiopathy secondary to a relapse of HUS rather than reversible posterior leukoencephalopathy syndrome (RPLS), usually occipital and asymmetrical. Plasmatherapy led to a complete neurological recovery within 2 days although hypertension had remained uncontrolled. The fourth MRI 10 weeks after, on maintenance plasmatherapy, was normal and clinical examination remained normal, except for high blood pressure. In conclusion, brain MRI allows differentiating thrombotic microangiopathy lesions from RPLS in atypical HUS, which is crucial since lesions may be reversible with plasmatherapy.

  20. The autoimmune disease DEAP-hemolytic uremic syndrome.

    Science.gov (United States)

    Skerka, Christine; Zipfel, Peter F; Müller, Dominik; Micklisch, Sven; Riedl, Magdalena; Zimmerhackl, Lothar-Bernd; Hofer, Johannes

    2010-09-01

    DEAP-HUS (deficiency of CFHR plasma proteins and factor H [FH] autoantibody positive hemolytic uremic syndrome [HUS]) is a new form of HUS characterized by a deletion of genes coding for FH-related proteins and the presence of autoantibodies directed to FH. These disease-associated autoantibodies inhibit FH (CFH) surface binding functions, which results in a defective regulation of the alternative pathway and damage of endothelial cells. Here we describe two representative patients with DEAP-HUS who both developed end-stage renal failure with the background of homozygous deletion of CFHR1 and CFHR3 genes and the presence of FH autoantibodies. Based on the retrospective diagnosis of DEAP-HUS 2 to 12 months after the initial clinical presentation, subsequent immunosuppressive therapy was initiated. The autoantibody titers decreased, and the complement status of the patients improved, as indicated by increased C3 levels. Thus early diagnosis of DEAP-HUS and immunosuppressive treatments are important factors to treat this particular type of HUS.

  1. Recurrence of hemolytic uremic syndrome after renal transplantation.

    Science.gov (United States)

    Seitz, B; Albano, L; Vocila, F; Mzoughi, S; Aoudia, R; Guitard, J; Ribes, D; Vachet-Copponat, H; Mourad, G; Bienaimé, F; Dahan, P; Frémeaux-Bacchi, V; Cassuto, E

    2007-10-01

    Non-Shiga toxin-associated hemolytic uremic syndrome (non-Stx-HUS) is a rare disease. The clinical outcome is often unfavorable: 50% of patients progress to end-stage renal failure. Several mutations in complement regulatory genes predispose to non-Stx-HUS. Transplantation outcomes are poor among patients with either mutation in the genes encoding complement H or I factors, with 80% graft loss due to HUS recurrence. In contrast, patients with mutation in the gene encoding MCP have no disease relapse after transplantation. There are no treatment guidelines for non-Stx-HUS recurrence. Herein we have presented 8 patients with non-Stx-HUS recurrence after transplantation during the last 10 years in the South of France. HUS recurrence, which occurred early after transplantation in all but 1 patient, was treated by plasma exchange (PE) with substitution by fresh frozen plasma (FFP). Three patients still treated with long-term plasma therapy have no recurrence at 15, 19, or 24 months. An international registry would help to define new guidelines.

  2. Peripheral gangrene in children with atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Malina, Michal; Gulati, Ashima; Bagga, Arvind; Majid, Mohammad A; Simkova, Eva; Schaefer, Franz

    2013-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy with severe clinical manifestation, frequent recurrence, and poor long-term prognosis. It is usually caused by abnormalities in complement regulation. We report 2 cases of children affected by a catastrophic extrarenal complication. A 4-year-old Indian girl developed gangrene of the finger tips 2 days after initial presentation of aHUS. Factor H autoantibodies were identified. Renal function continued to decline despite daily plasma exchanges, and she was started on peritoneal dialysis 5 days after admission. The distal tips of the left hand remained gangrenous with a line of demarcation. Three weeks later, she did not return for follow-up and died at home because of dialysis-related complications. An Arabic girl developed end-stage renal disease due to aHUS in the fourth month after birth. A de novo activating C3 mutation was found. At age 9 months, she suddenly developed ischemic changes in fingers of both hands and several toes. The lesions progressed, and several finger tips became gangrenous despite intense plasma exchange therapy. The decision was made to administer complement blocking therapy with the C5 antibody eculizumab. All nonnecrotic digits rapidly regained perfusion. The 3 already gangrenous fingers healed with loss of the end phalanges. During maintenance, eculizumab aHUS activity subsided completely and some late recovery of renal function was observed. aHUS may present by thrombotic macroangiopathy of small peripheral arteries. Eculizumab appears effective in preserving tissue viability if administered before gangrene occurs and should be considered as first-line rescue therapy in such cases.

  3. Shigatoxin-associated hemolytic uremic syndrome: current molecular mechanisms and future therapies

    Directory of Open Access Journals (Sweden)

    Keir LS

    2012-07-01

    Full Text Available Lindsay S Keir,1 Stephen D Marks,2 Jon Jin Kim21Academic Renal Unit, University of Bristol, Bristol; 2Department of Paediatric Nephrology, Great Ormond Street Hospital NHS Foundation Trust, London, United KingdomAbstract: Hemolytic uremic syndrome is the leading cause of acute kidney injury in childhood. Ninety percent of cases are secondary to gastrointestinal infection with shigatoxin-producing bacteria. In this review, we discuss the molecular mechanisms of shigatoxin leading to hemolytic uremic syndrome and the emerging role of the complement system and vascular endothelial growth factor in its pathogenesis. We also review the evidence for treatment options to date, in particular antibiotics, plasma exchange, and immunoadsorption, and link this to the molecular pathology. Finally, we discuss future avenues of treatment, including shigatoxin-binding agents and complement inhibitors, such as eculizumab.Keywords: hemolytic uremic syndrome, shigatoxin, diarrhea, Escherichia coli, complement, alternative pathway, eculizumab

  4. Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany

    DEFF Research Database (Denmark)

    Rasko, David A; Webster, Dale R; Sahl, Jason W

    2011-01-01

    A large outbreak of diarrhea and the hemolytic-uremic syndrome caused by an unusual serotype of Shiga-toxin-producing Escherichia coli (O104:H4) began in Germany in May 2011. As of July 22, a large number of cases of diarrhea caused by Shiga-toxin-producing E. coli have been reported--3167 without...... the hemolytic-uremic syndrome (16 deaths) and 908 with the hemolytic-uremic syndrome (34 deaths)--indicating that this strain is notably more virulent than most of the Shiga-toxin-producing E. coli strains. Preliminary genetic characterization of the outbreak strain suggested that, unlike most of these strains......, it should be classified within the enteroaggregative pathotype of E. coli....

  5. A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders.

    NARCIS (Netherlands)

    Besbas, N.; Karpman, D.; Landau, D.; Loirat, C.; Proesmans, W.; Remuzzi, G.; Rizzoni, G.; Taylor, C.M.; Kar, N.C.A.J. van de; Zimmerhackl, L.B.

    2006-01-01

    The diagnostic terms hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are based on historical and overlapping clinical descriptions. Advances in understanding some of the causes of the syndrome now permit many patients to be classified according to etiology. The increase

  6. Eculizumab safely reverses neurologic impairment and eliminates need for dialysis in severe atypical hemolytic uremic syndrome

    Directory of Open Access Journals (Sweden)

    Ohanian M

    2011-05-01

    Full Text Available Maro Ohanian, Christian Cable, Kathleen HalkaDepartment of Hematology and Oncology, Scott and White Healthcare, The Texas A&M Health Science Center College of Medicine, Temple, TX, USAAbstract: This case report describes how eculizumab reversed neurologic impairment and improved renal damage in severe atypical hemolytic uremic syndrome. A 50-year-old female, after presenting with diarrhea and abdominal pain, developed pancolitis, acute renal failure, and thrombocytopenia. The patient underwent total abdominal colectomy. Pathology confirmed ischemic colitis with scattered mesenteric microthrombi. Due to mental and respiratory decline, she remained intubated. Continuous venovenous hemodialysis was initiated. Renal failure, neurologic changes, hemolysis, thrombotic microangiopathy, and low complement levels all suggested atypical hemolytic uremic syndrome. Eculizumab 900 mg was administered intravenously on hospital day 6 and continued weekly for four doses followed by maintenance therapy. She recovered neurologically and renally after the third dose, and hematologically by the sixth dose. Her recovery has been sustained on long-term eculizumab treatment. In severe atypical hemolytic uremic syndrome, eculizumab safely reverses neurologic impairment and eliminates the need for dialysis. The optimal duration of treatment with eculizumab remains to be determined.Keywords: eculizumab, thrombotic microangiopathy, atypical hemolytic uremic syndrome

  7. DIARRHEA, UROSEPSIS AND HEMOLYTIC UREMIC SYNDROME CAUSED BY THE SAME HETEROPATHOGENIC ESCHERICHIA COLI STRAIN

    NARCIS (Netherlands)

    Ang, C. Wim; Bouts, Antonia H. M.; Rossen, John W. A.; Van der Kuip, Martijn; Van Heerde, Marc; Bokenkamp, Arend

    2016-01-01

    We describe an 8-month-old girl with diarrhea, urosepsis and hemolytic uremic syndrome caused by Escherichia coli. Typing of cultured E. coli strains from urine and blood revealed the presence of virulence factors from multiple pathotypes of E. coli. This case exemplifies the genome plasticity of E.

  8. Detection of apoptosis in kidney biopsies of patients with D+ hemolytic uremic syndrome.

    NARCIS (Netherlands)

    Loo, D.M.W.M. te; Monnens, L.A.H.; Heuvel, L.P.W.J. van den; Gubler, M.C.; Kockx, M.M.

    2001-01-01

    In this study we have investigated the presence of apoptotic cells in renal biopsy material of seven patients with hemolytic uremic syndrome (HUS) by using an improved and stringent terminal deoxynucleotidyl nick-end labeling (TUNEL) technique. Renal biopsy material was taken in the second or third

  9. The fibrinolytic system in the hemolytic uremic syndrome: In vivo and in vitro studies

    NARCIS (Netherlands)

    Kar, N.C.A.J. van de; Hinsbergh, V.W.M. van; Brommer, E.J.P.; Monnens, L.A.H.

    1994-01-01

    Fibrinolytic parameters and von Willebrand factor (vWF) antigen were measured in the plasma of 10 patients with hemolytic uremic syndrome (HUS). Samples were taken at presentation and again 2 wk later, before and after infusion of 1-desamino-8-arginine vasopressin. Compared with the plasma values of

  10. Vero cytotoxin binding to polymorphonuclear leukocytes among households with children with hemolytic uremic syndrome.

    NARCIS (Netherlands)

    Loo, D.M.W.M. te; Heuvelink, A.E.; Boer, E. de; Nauta, J.; Walle, J. van der; Schröder, C.H.; Hinsbergh, V.W.H. van; Chart, H.; Kar, N.C.A.J. van de; Heuvel, L.P.W.J. van den

    2001-01-01

    Hemolytic uremic syndrome (HUS), the leading cause of acute renal failure in childhood, can be caused by different serotypes of vero cytotoxin (VT; i.e., Shiga toxin)-producing Escherichia coli (VTEC). Recently, VT was shown to bind to polymorphonuclear leukocytes (PMNL) in the systemic circulation

  11. Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome

    NARCIS (Netherlands)

    Volokhina, E.B.; Kar, N.C.A.J. van de; Bergseth, G.; Velden, T.J.A.M. van der; Westra, D.; Wetzels, J.F.M.; Heuvel, L.P.W.J. van den; Mollnes, T.E.

    2015-01-01

    Complement C5 inhibitor eculizumab treatment in atypical hemolytic uremic syndrome is effective, but associated with high costs. Complement inhibition monitoring in these patients has not been standardized. In this study we evaluated novel functional assays for application in routine follow-up. We d

  12. Novel sequence variation affects GPIb α in post-diarrheal hemolytic uremic syndrome

    NARCIS (Netherlands)

    Volokina, E.; Jakobi, A.J.; Urbanus, R.T; Huizinga, E.G.; Sluiter, H.; Middel, C.; Westra, D.; van Heerde, W.L.; van de Kar, N.; van den Heuvel, L.

    2014-01-01

    Background: Hemolytic uremic syndrome (HUS) is one of the major causes of renal failure in children. In most cases the disease is caused by infection with Shiga toxin- producing Escherichia coli (STEC) and preceded by diarrhea. Only in 15% of cases STEC infection leads to HUS. Genetic predisposition

  13. Eculizumab as rescue therapy for atypical hemolytic uremic syndrome with normal platelet count.

    NARCIS (Netherlands)

    Dorresteijn, E.M.; Kar, N.C.A.J. van de; Cransberg, K.

    2012-01-01

    BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) in childhood is a rare disease with frequent progression to end-stage renal disease and a high recurrence after kidney transplantation. Eculizumab, a humanized monoclonal antibody that binds to complement protein C5, may be beneficial in the trea

  14. Hemolytic uremic syndrome due to Capnocytophaga canimorsus bacteremia after a dog bite

    NARCIS (Netherlands)

    Tobe, TJM; Franssen, CFM; Zijlstra, JG; de Jong, PE; Stegeman, CA

    1999-01-01

    The hemolytic uremic syndrome (HUS) is known to have several causes, including infectious diseases, drugs, pregnancy, and malignant disease. We report a patient who developed acute renal failure attributable to HUS in the course of Capnocytophaga canimorsus bacteremia. Acute tubular necrosis as well

  15. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome.

    NARCIS (Netherlands)

    Ariceta, G.; Besbas, N.; Johnson, S.; Karpman, D.; Landau, D.; Licht, C.; Loirat, C.; Pecoraro, C.; Taylor, C.M.; Kar, N.C.A.J. van de; Walle, J. van de; Zimmerhackl, L.B.

    2009-01-01

    This guideline for the investigation and initial treatment of atypical hemolytic uremic syndrome (HUS) is intended to offer an approach based on opinion, as evidence is lacking. It builds on the current ability to identify the etiology of specific diagnostic sub-groups of HUS. HUS in children is mos

  16. Eculizumab as rescue therapy for atypical hemolytic uremic syndrome with normal platelet count

    NARCIS (Netherlands)

    E.M. Dorresteijn (Eiske); N.C. van de Kar (Nicole); K. Cransberg (Karlien)

    2012-01-01

    textabstractBackground Atypical hemolytic uremic syndrome (aHUS) in childhood is a rare disease with frequent progression to end-stage renal disease and a high recurrence after kidney transplantation. Eculizumab, a humanized monoclonal antibody that binds to complement protein C5, may be beneficial

  17. Decrease of thrombomodulin contributes to the procoagulant state of endothelium in hemolytic uremic syndrome.

    NARCIS (Netherlands)

    Fernandez, G.C.; Loo, D.M.W.M. te; Velden, T.J.A.M. van der; Heuvel, L.P.W.J. van den; Palermo, M.S.; Monnens, L.L.

    2003-01-01

    The typical form of hemolytic uremic syndrome (D+HUS) is a thrombotic microangiopathy that causes acute renal failure in children. The etiology of this disease is a toxin called Shiga-like toxin (Stx), present in certain strains of gram-negative bacteria. Vascular endothelial cell (EC) injury appear

  18. A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders.

    NARCIS (Netherlands)

    Besbas, N.; Karpman, D.; Landau, D.; Loirat, C.; Proesmans, W.; Remuzzi, G.; Rizzoni, G.; Taylor, C.M.; Kar, N.C.A.J. van de; Zimmerhackl, L.B.

    2006-01-01

    The diagnostic terms hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are based on historical and overlapping clinical descriptions. Advances in understanding some of the causes of the syndrome now permit many patients to be classified according to etiology. The

  19. Hemolytic uremic syndrome due to Capnocytophaga canimorsus bacteremia after a dog bite

    NARCIS (Netherlands)

    Tobe, TJM; Franssen, CFM; Zijlstra, JG; de Jong, PE; Stegeman, CA

    The hemolytic uremic syndrome (HUS) is known to have several causes, including infectious diseases, drugs, pregnancy, and malignant disease. We report a patient who developed acute renal failure attributable to HUS in the course of Capnocytophaga canimorsus bacteremia. Acute tubular necrosis as well

  20. Diarrhea, Urosepsis and Hemolytic Uremic Syndrome Caused by the Same Heteropathogenic Escherichia coli Strain.

    Science.gov (United States)

    Ang, C Wim; Bouts, Antonia H M; Rossen, John W A; Van der Kuip, Martijn; Van Heerde, Marc; Bökenkamp, Arend

    2016-09-01

    We describe an 8-month-old girl with diarrhea, urosepsis and hemolytic uremic syndrome caused by Escherichia coli. Typing of cultured E. coli strains from urine and blood revealed the presence of virulence factors from multiple pathotypes of E. coli. This case exemplifies the genome plasticity of E. coli and the resulting heteropathogenic strains.

  1. A case of severe preeclampsia diagnosed as post-partum hemolytic uremic syndrome

    Institute of Scientific and Technical Information of China (English)

    WANG Yong-qing; WANG Jing; JIANG Yuan-hui; YE Rong-hua; ZHAO Yang-yu

    2012-01-01

    Post-partum hemolytic uremic syndrome (PHUS) is a severe thrombotic microangiopathy clinically characterized by hemolytic anemia,renal dysfunction,and low platelets after birth with rapid progression and poor prognosis.Here,we reported a rare case of severe preeclampsia diagnosed as hemolytic uremic syndrome after birth.The patient was diagnosed with PHUS and underwent intermittent plasma exchange with supportive treatment including glucocorticoid injections and transfusion of suspended red blood cells.After these treatments,the patient experienced no apparent remission and chronic renal dysfunction occurred on her.PHUS is a severe emergency with acute onset,rapid progress,and poor prognosis.Early detection,diagnosis,and treatment can significantly improve the prognosis.

  2. How atypical can Atypical Hemolytic Uremic Syndrome be?

    Science.gov (United States)

    Sajan, Thomas; Vinay, Srinivasa; Sonu, Nigam; Alan, Parnham

    2014-04-01

    A 24-year-old man with diarrhea found to have acute renal failure with microangiopathic hemolytic anemia (MAHA). A diagnosis of hemolytic uraemic syndrome (HUS) was made. He was initiated on plasma exchange and hemodialysis. On day 6, he was started on eculizumab. His renal functions progressively improved. His main complication during eculizumab therapy was hypertension-related posterior reversible encephalopathy syndrome.

  3. Atypical hemolytic-uremic syndrome: a case report and literature review.

    Science.gov (United States)

    Rafiq, Arsalan; Tariq, Hassan; Abbas, Naeem; Shenoy, Roopalekha

    2015-02-24

    Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by hemolysis, thrombocytopenia, and renal dysfunction. It is a disease related to genetic mutations in the alternative complement pathway and has a distinct pathophysiology but is difficult to differentiate from other thrombotic microangiopathies. We present a case of a 59-year-old female patient who presented with accelerated hypertension, acute renal failure, hemolysis, and encephalopathy. She was managed with antihypertensive medication, but her encephalopathy did not improve. Evaluation resulted in our impression of the disease being atypical hemolytic-uremic syndrome. The patient continued to be managed with good blood pressure control and later was started on eculizumab, but evaluation of response to therapy was hindered by the patient's non-compliance with therapy and follow-up appointments. We have a very limited understanding of the genetics and epidemiology of atypical HUS, and the overlapping clinical features sometimes delay diagnosis and initiation of appropriate treatment of this rare disease.

  4. [Successful treatment of enterohemorrhagic Escherichia coli O111-induced hemolytic-uremic syndrome and acute encephalopathy].

    Science.gov (United States)

    Mizuno, Hideki; Minouchi, Keiji; Aoyama, Shou; Hinoue, Yoshinobu

    2015-07-01

    We report a case of a woman in her twenties with enterohemorrhagic Escherichia coli O111-induced hemolytic-uremic syndrome who developed acute encephalopathy on day 5 of admission. She recovered after treatment with steroid pulse therapy, plasmapheresis, and recombinant thrombomodulin, without any adverse sequelae. We report this interesting case and provide a summary of the recent outbreak of enterohemorrhagic Escherichia coli O111.

  5. A patient with Crohn's disease who presented with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome.

    Science.gov (United States)

    Unverdi, Selman; Ceri, Mevlut; Öztürk, Mehmet Akif; Akbal, Erdem; Ensari, Arzu; Yılmaz, Rahmi; Kocak, Erdem; Inal, Salih; Koklu, Seyfettin; Duranay, Murat

    2011-01-01

    Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) is characterized with fever, purpura, anemia due to microangiopathic hemolysis, thrombocytopenia, kidney damage, and neurologic symptoms. The development of TTP/HUS during the course of inflammatory bowel diseases was rarely reported. However, coexistence of TTP/HUS and Crohn's disease in the same patient has not been reported previously. We herein present a case of TTP/HUS who presented with Crohn's disease. He responded to cyclosporine treatment.

  6. Shiga Toxin–Producing Escherichia coli Infections Associated with Hemolytic Uremic Syndrome, Italy, 1988–2000

    Science.gov (United States)

    Caprioli, Alfredo; Minelli, Fabio; Gianviti, Alessandra; De Petris, Laura; Edefonti, Alberto; Montini, Giovanni; Ferretti, Alfonso; De Palo, Tommaso; Gaido, Maurizio; Rizzoni, Gianfranco

    2003-01-01

    The mean annual incidence of hemolytic uremic syndrome in persons <15 years of age in Italy from 1988 to 2000 was 0.28 per 100,000 population. Laboratory investigations showed that Shiga toxin–producing Escherichia coli (STEC) infection occurred in 73.1% of patients. STEC O157 was the most common serotype, but a considerable number of cases were from infections by non-O157 STEC. PMID:12533290

  7. Shiga toxin-producing Escherichia coli infections associated with hemolytic uremic syndrome, Italy, 1988-2000.

    Science.gov (United States)

    Tozzi, Alberto E; Caprioli, Alfredo; Minelli, Fabio; Gianviti, Alessandra; De Petris, Laura; Edefonti, Alberto; Montini, Giovanni; Ferretti, Alfonso; De Palo, Tommaso; Gaido, Maurizio; Rizzoni, Gianfranco

    2003-01-01

    The mean annual incidence of hemolytic uremic syndrome in persons

  8. [Atypic hemolytic uremic syndrome taken for Goodpasture's syndrome: A case report].

    Science.gov (United States)

    Bourgault, Marie; Sarret, Damien; Isnard, Pierre; Rabant, Marion; Labaye, Jacques

    2015-12-01

    We report the case of a patient suffering from atypical hemolytic uremic syndrome with inaugural intra-alveolar hemorrhage. Clinical features and detection of circulating anti-glomerular basal membrane antibodies first raise the possibility of a Goodpasture syndrome. Renal biopsy allows to correct the diagnosis. Partial remission is obtained thanks to specific care and eculizumab infusions. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  9. Posterior reversible encephalopathy and cerebral vasoconstriction in a patient with hemolytic uremic syndrome.

    Science.gov (United States)

    Agarwal, Rajkumar; Davis, Cresha; Altinok, Deniz; Serajee, Fatema J

    2014-05-01

    We report a patient with hemolytic uremic syndrome who presented with radiological manifestations suggestive of posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome. A 13-year-old girl presented with fever and bloody diarrhea and progressed to develop hemolytic uremic syndrome. She subsequently developed encephalopathy, aphasia, and right-sided weakness. Brain magnetic resonance imaging showed presence of vasogenic edema in the left frontal lobe, in addition to T2 and fluid-attenuated inversion recovery changes in white matter bilaterally, compatible with posterior reversible encephalopathy syndrome. Magnetic resonance angiography showed beading of the cerebral vessels. Neurological deficits reversed 8 days after symptom onset, with resolution of the beading pattern on follow-up magnetic resonance angiography after 3 weeks, suggesting reversible cerebral vasoconstriction syndrome. Both posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome may represent manifestations of similar underlying pathophysiologic mechanisms. Recognition of the co-existence of these processes in patients with hemolytic uremic syndrome may aid in judicious management of these patients and avoidance of inappropriate therapeutic interventions. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Association of verotoxin-producing E. coli and verotoxin with hemolytic uremic syndrome.

    Science.gov (United States)

    Arbus, G S

    1997-03-01

    It has been over 10 years since we first showed an association [1] between classical hemolytic uremic syndrome (hemolytic anemia, thrombocytopenia, and uremia, following a diarrheal prodome) and certain E. coli [1] capable of producing a toxin, initially called verotoxin (VT) because of its cytopathic effect on Vero cells [2] and later Shiga-like toxin (SLT) because of the toxin's close biological and structural similarity to Shiga toxin. Although we initially reported that 75% of children with idiopathic hemolytic uremic syndrome (HUS) [1] had evidence of a verotoxin-producing E. coli (VTEC) [1], a later study showed that over a seven year period (1980-86), of 86 children seen with HUS, 91% had a classical presentation and 88% of these had evidence of a VTEC infection [3]. This paper traces the path of the incriminating organisms (VTEC) from the time of ingestion, up to and including internalization of the toxin into a target cell; in vitro experiments demonstrating the effect of toxin on endothelial cells are included. It is hoped that we might gain a clearer insight into factors that might predispose an individual to contracting HUS. Once a better understanding of the pathogenesis of VTEC associated HUS is known, areas for therapeutic intervention might be realized.

  11. Dangerous drug interactions leading to hemolytic uremic syndrome following lung transplantation

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    Parissis Haralabos

    2010-09-01

    Full Text Available Abstract Background To report our experience of a rather uncommon drug interaction, resulting in hemolytic uremic syndrome (HUS. Methods Two consecutive cases of hemolytic uremic syndrome were diagnosed in our service. In both patients the use of macrolides in patients taking Tacrolimus, resulted in high levels of Tacrolimus. Results The first patient was a 48 years old female with Bilateral emphysema. She underwent Single Sequential Lung Transplantation. She developed reperfusion injury requiring prolonged stay. Tacrolimus introduced (Day 51. The patient remained well up till 5 months later; Erythromycin commenced for chest infection. High Tacrolimus levels and a clinical diagnosis of HUS were made. She was treated with plasmapheresis successfully. The second case was a 57 years old female with Emphysema & A1 Antithrypsin deficiency. She underwent Right Single Lung Transplantation. A2 rejection with mild Obliterative Bronchiolitis diagnosed 1 year later and she switched to Tacrolimus. She was admitted to her local Hospital two and a half years later with right middle lobe consolidation. The patient commenced on amoxicillin and clarithromycin. Worsening renal indices, high Tacrolimus levels, hemolytic anemia & low Platelets were detected. HUS diagnosed & treated with plasmapheresis. Conclusions There are 21 cases of HUS following lung transplantation in the literature that may have been induced by high tacrolimus levels. Macrolides in patients taking Cyclosporin or Tacrolimus lead to high levels. Mechanism of action could be glomeruloconstrictor effect with reduced GFR increased production of Endothelin-1 and increased Platelet aggregation.

  12. MRI findings of hemolytic uremic syndrome with encephalopathy: widespread symmetrical distribution.

    Science.gov (United States)

    Nakamura, Hiroshi; Takaba, Hitonori; Inoue, Takeshi; Saku, Yoshisuke; Saito, Fumihiko; Ibayashi, Setsuro; Fujishima, Masatoshi

    2003-01-01

    The authors report the magnetic resonance imaging (MRI) findings in a 22-year-old woman with hemolytic uremic syndrome and encephalopathy secondary to verotoxin-producing Escherichia coli. Multiple lesions in the midbrain, cerebellum, occipital lobe, and basal ganglia showed high signal intensity on T2-weighted images with widespread symmetrical distribution. Most of these findings showed remarkable reduction on MRI images obtained 70 days after the onset. It is suggested that edema induced by local breakdown of blood-brain barrier might play an important role in the patient.

  13. An adult case of combined encephalopathy and hemolytic uremic syndrome caused by Escherichia coli O157.

    Science.gov (United States)

    Yoshimitsu, Masashi; Hayashi, Nobuaki; Kaneko, Yoshibumi; Doyama, Hisashi

    2011-01-01

    We report a 28-year-old woman with O157 enterohemorrhagic colitis-associated hemolytic uremic syndrome in whom seizures and transient hemiparesis developed on the 12th day after admission to hospital. Her subsequent recovery was characterized by improvements in renal function and platelet count. The patient recovered after treatment with steroid pulse and plasma exchange therapy, without any sequelae. As there have been few reports on the onset of encephalopathy in adults, we report this interesting case, with reference to the literature for possible effective treatment.

  14. Long-term neurological sequelae of hemolytic-uremic syndrome: a preliminary report.

    Science.gov (United States)

    Qamar, I U; Ohali, M; MacGregor, D L; Wasson, C; Krekewich, K; Marcovitch, S; Arbus, G S

    1996-08-01

    Seven patients with hemolytic-uremic syndrome who had major neurological symptoms during the acute illness were neurologically and cognitively evaluated prospectively several years after recovery from the illness. Four patients showed evidence of subtle neurological sequelae, including posturing, clumsiness, poor fine-motor coordination, hyperactivity, and distractibility. Psychoeducational evaluation of all seven subjects revealed mean scores within the average range in cognitive abilities, academic achievement, single word receptive vocabulary, visual/motor planning, overall adaptive functioning, and hyperactivity. The lapse of time (minimum of 7 years) between the acute illness and the psychometric evaluation could have been responsible for our normal results.

  15. Moyamoya vasculopathy in a child after hemolytic uremic syndrome: a possible etiopathogenesis.

    Science.gov (United States)

    Singla, M; John, E; Hidalgo, G; Grewal, D; Macmillan, C

    2008-04-01

    Moyamoya disease is a cerebral vasculopathy of unknown etiology frequently seen in the Asian population. We report a case of moyamoya vasculopathy in an African-American child who had renal failure followed by cerebral ischemia. Our patient presented with hemolytic uremic syndrome (HUS) and renal failure, and later developed seizures. We believe that in this patient HUS led to the pathogenesis of moyamoya disease. We suggest that patients with HUS who develop any neurological symptoms should be investigated for moyamoya vasculopathy for early diagnosis and treatment.

  16. Severe pneumococcal hemolytic uremic syndrome in an 8-month-old girl

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    Tahar Gargah

    2012-01-01

    Full Text Available The hemolytic uremic syndrome (HUS, characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure, represents one of the major causes of acute renal failure in infancy and childhood. The typical form occurring after an episode of diarrhea caused by Escherichia coli is the most frequent in children. Other microorganisms also may be responsible for HUS, such as Streptococcus pneumoniae, which causes more severe forms of the disease. We report an 8-month-old girl who presented with pneumonia and subsequently developed HUS. Renal biopsy showed characteristic lesion of thrombotic microangiopathy and extensive cortical necrosis. She was managed with peritoneal dialysis but did not improve and developed severe sepsis due to staphylococcal peritonitis, resulting in the death of the patient. Streptococcus pneumoniae-induced HUS is uncommon, but results in severe disease in the young. There is a high risk of these patients developing end-stage kidney disease in the long term.

  17. Severe transient ADAMTS13 deficiency in pneumococcal-associated hemolytic uremic syndrome.

    Science.gov (United States)

    Pelras, Sybille; Delmas, Yahsou; Lamireau, Delphine; Villega, Frédéric; Nolent, Paul; Ryman, Anne; Llanas, Brigitte; Brissaud, Olivier; Harambat, Jérôme

    2011-04-01

    Thrombotic microangiopathies comprise different entities, including hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and several other conditions. TTP is characterized by hemolytic anemia, thrombocytopenia, and multiorgan failure. TTP is the result of severe von Willebrand factor multimer cleaving protease (ADAMTS13) deficiency that is either inherited or the result of acquired autoantibodies. We report a critically ill 2-year-old girl with invasive pneumococcal disease associated HUS (p-HUS) whose condition was complicated by severe ADAMTS13 deficiency, without detectable inhibitor, in a context of multiple organ failure. The patient recovered with supportive treatment, and ADAMTS13 activity normalized without plasmatherapy. Severe ADAMTS13 deficiency appears to be a manifestation of transient endothelial cell injury in the context of severe sepsis, including invasive p-HUS. The choice of appropriate therapy should not be based on this finding.

  18. [A case of hemolytic uremic syndrome after adjuvant chemotherapy with gemcitabine in a patient with pancreatic cancer].

    Science.gov (United States)

    Wato, Masaki; Inaba, Tomoki; Ishikawa, Hisashi; Ishikawa, Shigenao; Baba, Nobuyuki; Miyoshi, Masatsugu; Senoh, Tomonori; Nagano, Takuya; Takaguchi, Koichi; Watanabe, Seishiro; Kawai, Kozo

    2010-10-01

    A 63-year-old man with Stage IVa pancreas tail cancer was admitted for a distal pancreatectomy and splenectomy; adjuvant chemotherapy with gemcitabine was also administered. The chemotherapy was terminated after 16 courses due to hemolytic anemia, thrombocytopenia and renal dysfunction. Plasma exchange was performed; however the patient's renal function was diminished, requiring chronic hemodialysis. Physicians should be cautious of hemolytic uremic syndrome as a possible adverse reaction to gemcitabine and be aware that tests are needed for its early detection.

  19. Direct evidence of complement activation in HELLP syndrome: A link to atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Vaught, Arthur J; Gavriilaki, Eleni; Hueppchen, Nancy; Blakemore, Karin; Yuan, Xuan; Seifert, Sara M; York, Sarah; Brodsky, Robert A

    2016-05-01

    HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) is a severe variant of pre-eclampsia whose pathogenesis remains unclear. Recent evidence and clinical similarities suggest a link to atypical hemolytic uremic syndrome, a disease of excessive activation of the alternative complement pathway effectively treated with a complement inhibitor, eculizumab. Therefore, we used a functional complement assay, the modified Ham test, to analyze sera of women with classic or atypical HELLP syndrome, pre-eclampsia with severe features, normal pregnancies, and healthy nonpregnant women. Sera were also evaluated using levels of the terminal product of complement activation (C5b-9). We tested the in vitro ability of eculizumab to inhibit complement activation in HELLP serum. Increased complement activation was observed in participants with classic or atypical HELLP compared with those with normal pregnancies and nonpregnant controls. Mixing HELLP serum with eculizumab-containing serum resulted in a significant decrease in cell killing compared with HELLP serum alone. We found that HELLP syndrome is associated with increased complement activation as assessed with the modified Ham test. This assay may aid in the diagnosis of HELLP syndrome and could confirm that its pathophysiology is related to that of atypical hemolytic uremic syndrome.

  20. Hemolytic-uremic syndrome associated with enterohemorrhagic Escherichia coli O26:H infection and consumption of unpasteurized cow's milk

    NARCIS (Netherlands)

    Allerberger, Franz; Friedrich, Alexander W; Grif, Katharina; Dierich, Manfred P; Dornbusch, Hans-Jürgen; Mache, Cristoph J; Nachbaur, Edith; Freilinger, Michael; Rieck, Petra; Wagner, Martin; Caprioli, Alfredo; Karch, Helge; Zimmerhackl, Lothar B

    2003-01-01

    BACKGROUND: Enterohemorrhagic Escherichia coli (EHEC) O26 has emerged as a significant cause of hemolytic-uremic syndrome (HUS). The source and the vehicle of contamination with EHEC O26 are not often identified. We report two Austrian cases of HUS due to E. coli O26:H- affecting an 11-month-old boy

  1. Hemolytic-uremic syndrome associated with enterohemorrhagic Escherichia coli O26:H infection and consumption of unpasteurized cow's milk

    NARCIS (Netherlands)

    Allerberger, Franz; Friedrich, Alexander W; Grif, Katharina; Dierich, Manfred P; Dornbusch, Hans-Jürgen; Mache, Cristoph J; Nachbaur, Edith; Freilinger, Michael; Rieck, Petra; Wagner, Martin; Caprioli, Alfredo; Karch, Helge; Zimmerhackl, Lothar B

    BACKGROUND: Enterohemorrhagic Escherichia coli (EHEC) O26 has emerged as a significant cause of hemolytic-uremic syndrome (HUS). The source and the vehicle of contamination with EHEC O26 are not often identified. We report two Austrian cases of HUS due to E. coli O26:H- affecting an 11-month-old boy

  2. Hemolytic-uremic syndrome associated with enterohemorrhagic Escherichia coli O26:H infection and consumption of unpasteurized cow's milk

    NARCIS (Netherlands)

    Allerberger, Franz; Friedrich, Alexander W; Grif, Katharina; Dierich, Manfred P; Dornbusch, Hans-Jürgen; Mache, Cristoph J; Nachbaur, Edith; Freilinger, Michael; Rieck, Petra; Wagner, Martin; Caprioli, Alfredo; Karch, Helge; Zimmerhackl, Lothar B

    2003-01-01

    BACKGROUND: Enterohemorrhagic Escherichia coli (EHEC) O26 has emerged as a significant cause of hemolytic-uremic syndrome (HUS). The source and the vehicle of contamination with EHEC O26 are not often identified. We report two Austrian cases of HUS due to E. coli O26:H- affecting an 11-month-old boy

  3. Complement factor H-associated atypical hemolytic uremic syndrome in monozygotic twins: Concordant presentation, discordant response to treatment

    NARCIS (Netherlands)

    J.C. Davin; K.H. Olie; R. Verlaak; F. Horuz; S. Florquin; J.J. Weening; J.W. Groothoff; L. Strain; T.H.J. Goodship

    2006-01-01

    Hemolytic uremic syndrome not associated with diarrhea (diarrhea negative, atypical) is less common than the diarrhea-positive typical form, but frequently results In end-stage renal failure. Although there are anecdotal cases of successful treatment with fresh frozen plasma alone, the value of this

  4. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies

    NARCIS (Netherlands)

    Licht, C.; Greenbaum, L.A.; Muus, P.; Babu, S.; Bedrosian, C.L.; Cohen, D.J.; Delmas, Y.; Douglas, K.; Furman, R.R.; Gaber, O.A.; Goodship, T.; Herthelius, M.; Hourmant, M.; Legendre, C.M.; Remuzzi, G.; Sheerin, N.; Trivelli, A.; Loirat, C.

    2015-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characterized by platelet activation, hemolysis and thrombotic microangiopathy (TMA) leading to renal and other end-organ damage. We originally conducted two phase 2 studies (26 weeks and 1 year) evaluating eculiz

  5. Concurrent presentation of hemolytic uremic syndrome in two adult siblings : effects of plasma therapy on hemolysis and renal function

    NARCIS (Netherlands)

    von Gameren, I I; Rensma, P L; Zijlstra, J G; de Wolf, J; de Jong, Paul

    1994-01-01

    We describe 2 sisters who presented with the hemolytic uremic syndrome (HUS) almost simultaneously. In both patients an upper airway infection with Haemophilus influenzae immediately preceding HUS may have been the environmental trigger. Fresh plasma infusion had only minor therapeutic effects but p

  6. Hemolytic-uremic syndrome in a postpartum mare concurrent with encephalopathy in the neonatal foal.

    Science.gov (United States)

    Dickinson, Charles E; Gould, Daniel H; Davidson, Ann H; Avery, Paul R; Legare, Marie E; Hyatt, Doreene R; DebRoy, Chitrita

    2008-03-01

    A postpartum mare and foal were presented for evaluation of fever and lethargy in the mare. The mare was diagnosed with endometritis and initially responded well to treatment. On the second day of hospitalization, the mare developed renal insufficiency characterized by oliguria, azotemia, hemolysis, and thrombocytopenia. Concurrently, the foal developed rapidly progressive central nervous system signs culminating in refractory seizures. Both animals failed to respond to treatment and were euthanized. Thrombotic microangiopathy involving glomeruli was evident on microscopic examination of the mare's kidneys. Microscopic evidence of brain edema was the principal postmortem finding in the foal. No specific etiology was confirmed in either case. Notably, Escherichia coli 0103:H2 was isolated from the mare's uterus and the gastrointestinal tracts of both animals. To the authors' knowledge, this is the first report in which an organism implicated as a cause of hemolytic-uremic syndrome was isolated from an animal with clinical signs and postmortem findings consistent with the disease.

  7. Role of Polymorphonuclear Leukocytes in the Pathophysiology of Typical Hemolytic Uremic Syndrome

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    Ramón A. Exeni

    2007-01-01

    Full Text Available Thrombotic microangiopathy and acute renal failure are cardinal features of post-diarrheal hemolytic uremic syndrome (HUS. These conditions are related to endothelial and epithelial cell damage induced by Shiga toxin (Stx, through an interaction with its globotriaosylceramide (Gb3 receptor. Although, Stx is the main pathogenic factor and necessary for HUS development, clinical and experimental evidence suggest that the inflammatory response is able to potentiate Stx toxicity. Lipopolysaccharides (LPS and neutrophils (PMN represent two central components of inflammation during a Gram-negative infection. In this regard, patients with high peripheral PMN counts at presentation have a poor prognosis. In the present review, we discuss the contribution of experimental models and patient's studies in an attempt to elucidate the pathogenic mechanisms of HUS.

  8. Role of polymorphonuclear leukocytes in the pathophysiology of typical hemolytic uremic syndrome.

    Science.gov (United States)

    Exeni, Ramón A; Fernández, Gabriela C; Palermo, Marina S

    2007-08-10

    Thrombotic microangiopathy and acute renal failure are cardinal features of post-diarrheal hemolytic uremic syndrome (HUS). These conditions are related to endothelial and epithelial cell damage induced by Shiga toxin (Stx), through an interaction with its globotriaosylceramide (Gb3) receptor. Although, Stx is the main pathogenic factor and necessary for HUS development, clinical and experimental evidence suggest that the inflammatory response is able to potentiate Stx toxicity. Lipopolysaccharides (LPS) and neutrophils (PMN) represent two central components of inflammation during a Gram-negative infection. In this regard, patients with high peripheral PMN counts at presentation have a poor prognosis. In the present review, we discuss the contribution of experimental models and patient's studies in an attempt to elucidate the pathogenic mechanisms of HUS.

  9. Prevalence and clinical course of typical hemolytic uremic syndrome among sibling.

    Science.gov (United States)

    Eymann, Alfredo; Coccia, Paula; Raddavero, Claudia; Lafi, Gabriela; Ferraris, Verónica; Ramírez, José; Ferraris, Jorge

    2016-12-01

    Hemolytic uremic syndrome (HUS) isaninfectious disease caused by Shiga toxin-producing Escherichia coli. The objective of this study was to assess the risk of transmission and clinical course between siblings with typical HUS. Medical records of children with typical HUS between 1997 and 2012 were reviewed. Sibling pairs were established as inclusion criteria. A severity score was defined. A total of 133 patients with HUS were recorded; 40 had siblings and 4 progressed to HUS (10%). The mean age of the 4 sibling pairs was 29.3 months old (SD ± 11.5); 5 (62.5%) were girls. The mean time between each case was 5.7 days (SD ± 3). HUS was more severe in the siblings who became infected in the second place. The risk of HUS transmission between siblings was 10%, and the clinical course of the second sibling was less favorable.

  10. Incomplete hemolytic-uremic syndrome in Argentinean children with bloody diarrhea.

    Science.gov (United States)

    López, E L; Contrini, M M; Devoto, S; de Rosa, M F; Graña, M G; Aversa, L; Gómez, H F; Genero, M H; Cleary, T G

    1995-09-01

    Argentina has an exceptionally high frequency of hemolytic-uremic syndrome (HUS). We sought to define prospectively the role of verocytotoxins (Shiga-like toxins [SLTs]) in 254 Argentinean children with grossly bloody diarrhea during spring and summer. Free fecal SLTs (I/II) and/or DNA probe-positive isolates were found in 99 (39%) of the children. During the follow-up period, HUS developed in 6 patients (4 with evidence of recent SLT infection based on stool studies); another 14 patients had some, but not all, of the abnormalities seen in typical HUS. The development of HUS or incomplete HUS in these children was significantly associated with recent SLT-Escherichia coli infection (p = 0.024). The high incidence of SLT-associated bloody diarrhea in Argentina explains, at least partially, the unusually high frequency of HUS. Our data indicate that incomplete forms of HUS may be common in patients with SLT-associated bloody diarrhea.

  11. Campylobacter-Associated Hemolytic Uremic Syndrome Associated with Pulmonary-Renal Syndrome.

    Science.gov (United States)

    Bowen, Emily Elizabeth; Hangartner, Robert; Macdougall, Iain

    2016-03-01

    Common causes of pulmonary-renal syndrome include anti-glomerular basement membrane (anti-GBM) disease anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis, and systemic lupus erythematosus. We describe a case of life-threatening pulmonary hemorrhage associated with Campylobacter hemolytic uremic syndrome (HUS), which we believe is a new disease entity. We hypothesize that the cause of this pulmonary-renal syndrome was an immunological reaction to Campylobacter; and that the initiation of high-dose steroids was responsible for the rapid reversal of the patient's pulmonary and renal impairment. The aim of this article is to raise awareness of this unusual cause of a pulmonary-renal syndrome, guiding physicians to recognize it as a potential complication, and to consider high-dose steroids in managing the condition.

  12. Case report of atypical hemolytic uremic syndrome with retinal arterial and venous occlusion treated with eculizumab

    Directory of Open Access Journals (Sweden)

    Greenwood GT

    2015-10-01

    Full Text Available Gregory T Greenwood Nephrology Associates, PLLC, Winston-Salem, NC, USA Abstract: Atypical hemolytic uremic syndrome (aHUS is a rare disease caused by chronic, uncontrolled activation of the alternative complement pathway, leading to thrombotic microangiopathy. Renal impairment and progression to end-stage renal disease are common in untreated patients with aHUS, and extrarenal manifestations are being increasingly characterized in the literature. Ocular involvement remains rare in aHUS. This report describes a patient with aHUS with bilateral central retinal artery and vein occlusion, vitreous hemorrhage, and blindness in addition to renal impairment. The patient’s hematologic and renal parameters and ocular manifestation improved following initiation of eculizumab therapy. Keywords: acute kidney injury, complement, dialysis, plasma exchange, thrombotic microangiopathy

  13. Involvement of the fractalkine pathway in the pathogenesis of childhood hemolytic uremic syndrome.

    Science.gov (United States)

    Ramos, María Victoria; Fernández, Gabriela C; Patey, Natasha; Schierloh, Pablo; Exeni, Ramón; Grimoldi, Irene; Vallejo, Graciela; Elías-Costa, Christian; Del Carmen Sasiain, Maria; Trachtman, Howard; Combadière, Christophe; Proulx, François; Palermo, Marina S

    2007-03-15

    Thrombotic microangiopathy and acute renal failure are cardinal features of postdiarrheal hemolytic uremic syndrome (HUS). These conditions are related to endothelial and epithelial cell damage induced by Shiga toxin (Stx) through the interaction with its globotriaosyl ceramide receptor. However, inflammatory processes contribute to the pathogenesis of HUS by sensitizing cells to Stx fractalkine (FKN), a CX(3)C transmembrane chemokine expressed on epithelial and endothelial cells upon activation, is involved in the selective migration and adhesion of specific leukocyte subsets to tissues. Here, we demonstrated a selective depletion of circulating mononuclear leukocytes expressing the receptor for FKN (CX(3)CR1) in patients with HUS. We found a unique phenotype in children with HUS distinct from that seen in healthy, uremic, or infected controls, in which monocytes lost CX(3)CR1, down-modulated CD62L, and increased CD16. In addition, the CD56(dim) natural killer (NK) subpopulation was decreased, leading to an altered peripheral CD56(dim)/CD56(bright) ratio from 10.0 to 4.5. It is noteworthy that a negative correlation existed between the percentage of circulating CX(3)CR1(+) leukocytes and the severity of renal failure. Finally, CX(3)CR1(+) leukocytes were observed in renal biopsies from patients with HUS. We suggest that the interaction of CX(3)CR1(+) cells with FKN present on activated endothelial cells may contribute to renal injury in HUS.

  14. Impaired neutrophils in children with the typical form of hemolytic uremic syndrome.

    Science.gov (United States)

    Fernández, Gabriela C; Gómez, Sonia A; Rubel, Carolina J; Bentancor, Leticia V; Barrionuevo, Paula; Alduncín, Marta; Grimoldi, Irene; Exeni, Ramón; Isturiz, Martín A; Palermo, Marina S

    2005-09-01

    Experimental and clinical evidence suggest that activated neutrophils (PMN) could contribute to endothelial damage in Hemolytic Uremic Syndrome (D+HUS). Additionally, while PMN-activating cytokines and PMN-derived products have been found in D+HUS sera, we have demonstrated phenotypic alterations in D+HUS PMN compatible with a deactivation state. Here, we investigated whether D+HUS PMN were actually hyporesponsive, and explored some of the mechanisms probably involved in their derangement. Twenty-two D+HUS children were bled in the acute period, and blood samples from healthy, acute uremic and neutrophilic children were obtained as controls. We evaluated degranulation markers in response to cytokines, intracellular granule content, and reactive oxygen species (ROS) generation in circulating D+HUS and control PMN. The influence of D+HUS-derived plasma and the direct effects of Stx in vitro were evaluated on healthy donors' PMN. We found that D+HUS PMN presented reduced degranulatory capacity in response to cytokines and intracellular granule content, and decreased ROS generation. D+HUS plasma or Stx did not affect the phenotype and function of healthy donors' PMN. These results suggest that upon hospitalization D+HUS PMN are functionally impaired and show features of previous degranulation, indicating a preceding process of activation with release of ROS and proteases involved in endothelial damage.

  15. Renal recovery with eculizumab in atypical hemolytic uremic syndrome following prolonged dialysis.

    Science.gov (United States)

    Povey, Hannah; Vundru, Rahul; Junglee, Naushad; Jibani, Mahdi

    2014-11-01

    Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA) which encompasses hemolytic anemia, thrombocytopenia, and organ impairment. Around 10% of cases are atypical HUS (aHUS), a rare disease with poor outcomes caused by uncontrolled activation of the alternative complement pathway. This case describes a young woman with clinical manifestations compatible with TMA during childhood and adolescence who was formally diagnosed with aHUS at the age of 21. She was managed with intensive plasma exchange and hemodialysis, which failed to improve her severe acute kidney injury and other hematological manifestations of aHUS. This was further compounded by several episodes of flash pulmonary edema and the posterior reversible encephalopathy syndrome (PRES). Treatment with the monoclonal anti-C5 inhibitor, eculizumab, improved all hematological parameters with almost full renal recovery following 3.5 months of dialysis. So far, long-term use of eculizumab (> 11 months) continues to be effective and without complication. Our case illustrates the difficulty but importance of early consideration of aHUS in patients presenting with TMA. More importantly, we highlight that near-normal renal recovery may be attained with eculizumab in adults even after a long dependence on dialysis - an observation that has not been reported in the literature so far.

  16. Eculizumab Therapy Leads to Rapid Resolution of Thrombocytopenia in Atypical Hemolytic Uremic Syndrome

    Directory of Open Access Journals (Sweden)

    Han-Mou Tsai

    2014-01-01

    Full Text Available Eculizumab is highly effective in controlling complement activation in patients with the atypical hemolytic uremic syndrome (aHUS. However, the course of responses to the treatment is not well understood. We reviewed the responses to eculizumab therapy for aHUS. The results show that, in patients with aHUS, eculizumab therapy, when not accompanied with concurrent plasma exchange therapy, led to steady increase in the platelet count and improvement in extra-renal complications within 3 days. By day 7, the platelet count was normal in 15 of 17 cases. The resolution of hemolytic anemia and improvement in renal function were less predictable and were not apparent for weeks to months in two patients. The swift response in the platelet counts was only observed in one of five cases who received concurrent plasma exchange therapy and was not observed in a case of TMA due to gemcitabine/carboplatin. In summary, eculizumab leads to rapid increase in the platelet counts and resolution of extrarenal symptoms in patients with aHUS. Concurrent plasma exchange greatly impedes the response of aHUS to eculizumab therapy. Eculizumab is ineffective for gemcitabine/carboplatin associated TMA.

  17. Low levels of serum erythropoietin in children with endemic hemolytic uremic syndrome.

    Science.gov (United States)

    Exeni, R; Donato, H; Rendo, P; Antonuccio, M; Rapetti, M C; Grimoldi, I; Exeni, A; de Galvagni, A; Trepacka, E; Amore, A

    1998-04-01

    Serum erythropoietin (EPO) levels were measured in ten previously non-transfused children with hemolytic uremic syndrome (HUS). Complete blood cell count, serum EPO, and renal function tests were carried out upon admission and weekly thereafter. Blood samples were obtained: (1) prior to the first transfusion; (2) after the first transfusion but before recovery from renal failure; (3) during the recovery stage. All patients required transfusions (mean 1.8+/-0.8 per child). Absolute values of EPO correlated positively with the hematocrit during the three stages (r = 0.53, 0.36, and 0.12, respectively) which is opposite to expected results. The observed EPO logarithm/predicted EPO logarithm upon admission was low (0.70+/-0.08), falling further during stage 2 (0.57+/-0.03), but increasing thereafter (0.78+/-0.07) without reaching normal values. The reticulocyte production rate followed a parallel course (0.74+/-0.14, 0.54+/-0.11, and 0.60+/-0.10, respectively). On comparing the observed serum EPO levels with those expected, 9 of 11 pre-transfusion samples showed low values; in stage 2, all samples were below normal; in the recovery phase most (77.8%) were still low. Our results show an inadequate EPO synthesis in children with HUS, which could play an important pathogenic role, since it aggravates the severity of the existing hemolytic anemia; the secondary inhibitory effect of repeated transfusions exacerbates this inadequate synthesis.

  18. Induction of Neutrophil Extracellular Traps in Shiga Toxin-Associated Hemolytic Uremic Syndrome.

    Science.gov (United States)

    Ramos, Maria Victoria; Mejias, Maria Pilar; Sabbione, Florencia; Fernandez-Brando, Romina Jimena; Santiago, Adriana Patricia; Amaral, Maria Marta; Exeni, Ramon; Trevani, Analia Silvina; Palermo, Marina Sandra

    2016-01-01

    Hemolytic uremic syndrome (HUS), a vascular disease characterized by hemolytic anemia, thrombocytopenia, and acute renal failure, is caused by enterohemorrhagic Shiga toxin (Stx)-producing bacteria, which mainly affect children. Besides Stx, the inflammatory response mediated by neutrophils (PMN) is essential to HUS evolution. PMN can release neutrophil extracellular traps (NET) composed of DNA, histones, and other proteins. Since NET are involved in infectious and inflammatory diseases, the aim of this work was to investigate the contribution of NET to HUS. Plasma from HUS patients contained increased levels of circulating free-DNA and nucleosomes in comparison to plasma from healthy children. Neutrophils from HUS patients exhibited a greater capacity to undergo spontaneous NETosis. NET activated human glomerular endothelial cells, stimulating secretion of the proinflammatory cytokines IL-6 and IL-8. Stx induced PMN activation as judged by its ability to trigger reactive oxygen species production, increase CD11b and CD66b expression, and induce NETosis in PMN from healthy donors. During HUS, NET can contribute to the inflammatory response and thrombosis in the microvasculature and thus to renal failure. Intervention strategies to inhibit inflammatory mechanisms mediated by PMN, such as NETosis, could have a potential therapeutic impact towards amelioration of the severity of HUS.

  19. Acute Systolic Heart Failure Associated with Complement-Mediated Hemolytic Uremic Syndrome

    Directory of Open Access Journals (Sweden)

    John L. Vaughn

    2015-01-01

    Full Text Available Complement-mediated hemolytic uremic syndrome (otherwise known as atypical HUS is a rare disorder of uncontrolled complement activation that may be associated with heart failure. We report the case of a 49-year-old female with no history of heart disease who presented with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Given her normal ADAMSTS13 activity, evidence of increased complement activation, and renal biopsy showing evidence of thrombotic microangiopathy, she was diagnosed with complement-mediated HUS. She subsequently developed acute hypoxemic respiratory failure secondary to pulmonary edema requiring intubation and mechanical ventilation. A transthoracic echocardiogram showed evidence of a Takotsubo cardiomyopathy with an estimated left ventricular ejection fraction of 20%, though ischemic cardiomyopathy could not be ruled out. Treatment was initiated with eculizumab. After several failed attempts at extubation, she eventually underwent tracheotomy. She also required hemodialysis to improve her uremia and hypervolemia. After seven weeks of hospitalization and five doses of eculizumab, her renal function and respiratory status improved, and she was discharged in stable condition on room air and independent of hemodialysis. Our case illustrates a rare association between acute systolic heart failure and complement-mediated HUS and highlights the potential of eculizumab in stabilizing even the most critically-ill patients with complement-mediated disease.

  20. Familial Atypical Hemolytic Uremic Syndrome: A Review of Its Genetic and Clinical Aspects

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    Fengxiao Bu

    2012-01-01

    Full Text Available Atypical hemolytic uremic syndrome (aHUS is a rare renal disease (two per one million in the USA characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Both sporadic (80% of cases and familial (20% of cases forms are recognized. The study of familial aHUS has implicated genetic variation in multiple genes in the complement system in disease pathogenesis, helping to define the mechanism whereby complement dysregulation at the cell surface level leads to both sporadic and familial disease. This understanding has culminated in the use of Eculizumab as first-line therapy in disease treatment, significantly changing the care and prognosis of affected patients. However, even with this bright outlook, major challenges remain to understand the complexity of aHUS at the genetic level. It is possible that a more detailed picture of aHUS can be translated to an improved understanding of disease penetrance, which is highly variable, and response to therapy, both in the short and long terms.

  1. Atypical hemolytic uremic syndrome secondary to lupus nephritis, responsive to eculizumab

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    Alexander G. Raufi

    2016-09-01

    Full Text Available Among the spectrum of disease manifestations associated with systemic lupus erythematosus, lupus nephritis is particularly concerning due to the potential for renal failure. This autoimmune attack may not, however, be limited to the kidney and is increasingly being recognized as a trigger for atypical Hemolytic Uremic Syndrome (aHUS. Atypical HUS falls under the spectrum of the thrombotic microangiopathies (TMAs – a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ damage. Although plasma exchange is considered first-line therapy for thrombotic thrombocytopenic purpura – a TMA classically associated with autoimmune depletion of ADAMTS-13 – aHUS demonstrates less reliable responsiveness to this modality. Instead, use of the late complement inhibitor Eculizumab has emerged as an effective modality for the management of such patients. Diagnosis of aHUS, however, is largely clinically based, relying heavily upon a multidisciplinary approach. Herein we present the case of a patient with atypical HUS successfully treated with Eculizumab in the setting of Class IV-G (A lupus nephritis and hypocomplementemia.

  2. Postoperative Atypical Hemolytic Uremic Syndrome Associated with Complement C3 Mutation

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    Eiji Matsukuma

    2014-01-01

    Full Text Available Atypical hemolytic uremic syndrome (aHUS can be distinguished from typical or Shiga-like toxin-induced HUS. The clinical outcome is unfavorable; up to 50% of affected patients progress to end-stage renal failure and 25% die during the acute phase. Multiple conditions have been associated with aHUS, including infections, drugs, autoimmune conditions, transplantation, pregnancy, and metabolic conditions. aHUS in the nontransplant postsurgical period, however, is rare. An 8-month-old boy underwent surgical repair of tetralogy of Fallot. Neurological disturbances, acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia developed 25 days later, and aHUS was diagnosed. Further evaluation revealed that his complement factor H (CFH level was normal and that anti-FH antibodies were not detected in his plasma. Sequencing of his CFH, complement factor I, membrane cofactor protein, complement factor B, and thrombomodulin genes was normal. His ADAMTS-13 (a disintegrin-like and metalloprotease with thrombospondin-1 repeats 13 activity was also normal. However, he had a potentially causative mutation (R425C in complement component C3. Restriction fragment length polymorphism analysis revealed that his father and aunt also had this mutation; however, they had no symptoms of aHUS. We herein report a case of aHUS that developed after cardiovascular surgery and was caused by a complement C3 mutation.

  3. Atypical Hemolytic Uremic Syndrome Secondary to Lupus Nephritis, Responsive to Eculizumab

    Science.gov (United States)

    Raufi, Alexander G.; Scott, Shruti; Darwish, Omar; Harley, Kevin; Kahlon, Kanwarpal; Desai, Sheetal; Lu, Yuxin; Tran, Minh-Ha

    2016-01-01

    Among the spectrum of disease manifestations associated with systemic lupus erythematosus, lupus nephritis is particularly concerning due to the potential for renal failure. This autoimmune attack may not, however, be limited to the kidney and is increasingly being recognized as a trigger for atypical Hemolytic Uremic Syndrome (aHUS). Atypical HUS falls under the spectrum of the thrombotic microangiopathies (TMAs) – a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ damage. Although plasma exchange is considered first-line therapy for thrombotic thrombocytopenic purpura – a TMA classically associated with autoimmune depletion of ADAMTS-13 – aHUS demonstrates less reliable responsiveness to this modality. Instead, use of the late complement inhibitor Eculizumab has emerged as an effective modality for the management of such patients. Diagnosis of aHUS, however, is largely clinically based, relying heavily upon a multidisciplinary approach. Herein we present the case of a patient with atypical HUS successfully treated with Eculizumab in the setting of Class IV-G (A) lupus nephritis and hypocomplementemia.

  4. Successful Colectomy for Hemorrhagic Colitis with Hemolytic Uremic Syndrome and Acute Encephalopathy due to Escherichia coli O157 Infection.

    Science.gov (United States)

    Tominaga, Tetsuro; Oikawa, Masahiro; Takeshita, Hiroaki; Kunizaki, Masaki; Tou, Kazuo; Abo, Takafumi; Hidaka, Shigekazu; Nanashima, Atsushi; Sawai, Terumitsu; Nagayasu, Takeshi

    2014-01-01

    An 81-year-old man was admitted to a primary care hospital due to bloody diarrhea. The findings of abdominal computed tomography indicated ischemic colitis, so conservative therapy was started. On the 4th hospital day, the patient was transferred to our hospital because of renal dysfunction. Physical examination showed clouding of consciousness and abdominal distention. Abdominal computed tomography revealed massive ascites and thickening of the whole colonic wall. With a diagnosis of acute abdomen, an emergent laparotomy was performed. Extended right hemicolectomy was performed because of severe ischemic change and necrosis of the right side of the colon. In the stool culture before the operation, Escherichia coli O157 and verotoxin were found, so this case was diagnosed as hemorrhagic colitis with hemolytic uremic syndrome and acute encephalopathy due to Escherichia coli O157 infection. Postoperatively, the hemolytic uremic syndrome and acute encephalopathy were prolonged. However, with intensive care, the patient recovered and was discharged on the 33rd postoperative day.

  5. Acute encephalopathy associated with hemolytic uremic syndrome caused by Escherichia coli O157: H7 and rotavirus infection.

    Science.gov (United States)

    Imataka, G; Wake, K; Suzuki, M; Yamanouchi, H; Arisaka, O

    2015-05-01

    We reported a case of a 22-months child with hemolytic uremic syndrome associated with encephalopathy. As the cause of this case, the involvements of verotoxin 1 and 2 caused by O157: the H7 strain of the enterohemorrhagic Escherichia coli and rotavirus were presumed. We administered brain hypothermic therapy and steroid pulse therapy in the intensive care unit, but we were not able to save his life and the child died on the 6th day from the onset.

  6. Acute Renal Replacement Therapy in Children with Diarrhea-Associated Hemolytic Uremic Syndrome: A Single Center 16 Years of Experience

    OpenAIRE

    Silviu Grisaru; Morgunov, Melissa A.; Samuel, Susan M.; Julian P Midgley; Wade, Andrew W; Tee, James B.; Hamiwka, Lorraine A.

    2011-01-01

    Acute kidney injury (AKI) is becoming more prevalent among hospitalized children, its etiologies are shifting, and new treatment modalities are evolving; however, diarrhea-associated hemolytic uremic syndrome (D+HUS) remains the most common primary disease causing AKI in young children. Little has been published about acute renal replacement therapy (ARRT) and its challenges in this population. We describe our single center's experience managing 134 pediatric patients with D+HUS out of whom 5...

  7. [Diabetes mellitus as a rare complication of hemolytic uremic syndrome--case report].

    Science.gov (United States)

    Rogowska-Kalisz, Anna; Tkaczyk, Marcin; Szałapska-Zawodniak, Małgorzata

    2010-01-01

    A 4-year-old girl was hospitalized in a local hospital with bloody diarrhoea, vomitus and abdominal pain. Because of acute abdominal symptoms she underwent appendectomy after which convulsions and acute respiratory distress were noticed. The child was transferred to the intensive care unit. During the examination she was unconscious, pale, oedematous with scattered ecchymoses, severe hypertension and urine output diminished to several ml per day. Routine blood tests showed microangiopathic anaemia, thrombocytopenia (52000/ul.) and uremia. Proteinuria and hematuria were revealed on urine examination. Among coagulation parameters kaolin-kefalin time (69 s) and D-dimers (2000-4000/ul.) were abnormal. On the strength of history, clinical and laboratory investigation the diagnosis of D-positive hemolytic uremic syndrome was established. Controlled artificial respiration (for 10 weeks), total parenteral alimentation (TPN), antihypertensive treatment and diuretics (furosemide, dopamine) were introduced. Daily temporary access hemodialyses were performed for 4 weeks. Subsequently peritoneal dialysis was started for 2 weeks. Despite the appropriate TPN glucose blood levels were unexpectedly high from first days from admission (200-330 mg%). Intensive intravenous insulin therapy was performed for 50 days. The child was discharged after 72 days with moderate renal function impairment (blood urea-53 mg%, creatinine-1,2 mg%), mild hypertension and proteinuria. Additional factor prone to thrombotic events was the 4G/4G genotype responsible for increased PAI-1 blood concentration, which may result in intensified fibrinolysis inhibition. Diabetes mellitus as a rare immunological complication of haemolytic uremic syndrome was suspected on the following evidence: positive anti-GAD antibodies (ELISA), elevated levels of glycosylated haemoglobin A1c, three-fold reduction of blood C-peptide concentration, negative family history for diabetes. After 12 y of follow up glucose and C

  8. Treatment and outcome of Shiga-toxin-associated hemolytic uremic syndrome (HUS).

    Science.gov (United States)

    Scheiring, Johanna; Andreoli, Sharon P; Zimmerhackl, Lothar Bernd

    2008-10-01

    Hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure in childhood and the reason for chronic renal replacement therapy. It leads to significant morbidity and mortality during the acute phase. In addition to acute morbidity and mortality, long-term renal and extrarenal complications can occur in a substantial number of children years after the acute episode of HUS. The most common infectious agents causing HUS are enterohemorrhagic Escherichia coli (EHEC)-producing Shiga toxin (and belonging to the serotype O157:H7) and several non-O157:H7 serotypes. D(+) HUS is an acute disease characterized by prodromal diarrhea followed by acute renal failure. The classic clinical features of HUS include the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. HUS mortality is reported to be between 3% and 5%, and death due to HUS is nearly always associated with severe extrarenal disease, including severe central nervous system (CNS) involvement. Approximately two thirds of children with HUS require dialysis therapy, and about one third have milder renal involvement without the need for dialysis therapy. General management of acute renal failure includes appropriate fluid and electrolyte management, antihypertensive therapy if necessary, and initiation of renal replacement therapy when appropriate. The prognosis of HUS depends on several contributing factors. In general "classic" HUS, induced by EHEC, has an overall better outcome. Totally different is the prognosis in patients with atypical and particularly recurrent HUS. However, patients with severe disease should be screened for genetic disorders of the complement system or other underlying diseases.

  9. Is therapeutic plasma exchange indicated for patients with gemcitabine-induced hemolytic uremic syndrome?

    Science.gov (United States)

    Gore, Ethan McCaleb; Jones, Benjamin Scott; Marques, Marisa B

    2009-01-01

    Atypical hemolytic uremic syndrome (aHUS) has been described as an uncommon complication of gemcitabine. In this review, we discuss the diagnosis of gemcitabine-induced aHUS (GiHUS) and the published experience with therapeutic plasma exchange (TPE). To illustrate GiHUS, we present a patient who developed hypertension and peripheral edema while receiving gemcitabine and subsequently was found to have thrombocytopenia, hemolytic anemia, renal failure, and normal ADAMTS-13 activity. Although laboratory parameters improved on suspending gemcitabine, they worsened after reinstitution of the drug. Thrombocytopenia and hemolysis ceased once the drug was permanently discontinued without therapeutic plasma exchange (TPE). The pathological characteristics of GiHUS suggest damage of the glomeruli endothelial lining, leading to occlusion by fibrin-rich thrombi. Among 26 patients described in the literature not treated with TPE, 56% recovered from GiHUS, whereas only 30% of 18 patients treated with TPE did. The difference in recovery rate may have been confounded by the severity of GiHUS as suggested by the rate of dialysis in each group: 10/26 (38%) patients who did not receive TPE were dialyzed compared with 11/18 (61%) of those who had plasma exchange. Thus, although the currently available evidence is not decisive for use or non use of TPE, we suggest that the most important therapeutic intervention in GiHUS is discontinuation of the drug. Apheresis medicine specialists should be aware of this specific type of aHUS and provide treatment advice based on the currently available evidence.

  10. Shiga toxin-associated hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: distinct mechanisms of pathogenesis.

    Science.gov (United States)

    Tarr, Phillip I

    2009-02-01

    The hemolytic uremic syndrome (HUS) of childhood is, in its most common form, a non-immune microangiopathic hemolytic anemia. HUS typically follows an enteric infection with a Shiga toxin-producing Escherichia coli, usually belonging to serotype O157:H7. The antecedent infection is almost always manifested as non-bloody diarrhea. In about 80% of cases, the diarrhea becomes bloody between one and five days after the onset of diarrhea. The courses of acute gastrointestinal infections, and of HUS, in adults and children are similar. There are no convincing data that this easily recognizable form of microangiopathy is related to any inborn or acquired deficiency of ADAMTS13, and plasma therapies are not justified on either theoretical or empirical grounds. Similarly, there are no realistic animal data to support use of plasma exchange or infusion in children or adults with, or at risk for, HUS secondary to gastrointestinal infection with E. coli O157:H7. Best clinical practices involve rapid and accurate clinical and microbiological identification of infected patients, volume expansion, and support of the intestinal and extraintestinal complications that can ensue during acute enteric infection and associated HUS. Clinical clues include a sequence of events where the stool becomes bloody after a several-day interval of bloody diarrhea, considerable abdominal pain, five or more stools in the 24 h before presentation, pain on defection, and absence of fever at the time of presentation. Diagnosis should rely primarily on sorbitol MacConkey agar culture. Shiga toxin testing should not be used as the only screen to identify infected patients.

  11. Atypical hemolytic uremic syndrome: update on the complement system and what is new.

    Science.gov (United States)

    Hirt-Minkowski, Patricia; Dickenmann, Michael; Schifferli, Jürg A

    2010-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare disease of microangiopathic hemolytic anemia, thrombocytopenia, and predominant renal impairment. It is characterized by the absence of Shiga toxin-producing bacteria as a triggering factor. During the last decade, aHUS has been demonstrated to be a disorder of the complement alternative pathway dysregulation, as there is a growing list of mutations and polymorphisms in the genes encoding the complement regulatory proteins that alone or in combination may lead to aHUS. Approximately 60% of aHUS patients have so-called 'loss-of-function' mutations in the genes encoding the complement regulatory proteins, which normally protect host cells from complement activation: complement factor H (CFH), factor I (CFI) and membrane cofactor protein (MCP or CD46), or have 'gain-of-function' mutations in the genes encoding the complement factor B or C3. In addition, approximately 10% of aHUS patients have a functional CFH deficiency due to anti-CFH antibodies. Recent advances in understanding the pathogenesis of aHUS have led to a revised classification of the syndrome. Normal plasma levels of CFH and CFI do not preclude the presence of a mutation in these genes. Further, genotype-phenotype correlations of aHUS have clinical significance in predicting renal recovery and transplant outcome. Therefore, it is important to make a comprehensive analysis and perform genetic screening of the complement system in patients with aHUS to allow a more precise approach, especially before transplantation. This may also provide opportunities for more specific treatments in the near future, as complement inhibition could represent a therapeutic target in these patients who have a considerably poor prognosis in terms of both mortality and progression to end-stage renal disease and a great risk of disease recurrence after transplantation.

  12. Atypical hemolytic uremic syndrome diagnosed four years after ABO-incompatible kidney transplantation.

    Science.gov (United States)

    Kawaguchi, Keiko; Kawanishi, Kunio; Sato, Masayo; Itabashi, Mitsuyo; Fujii, Akiko; Kanetsuna, Yukiko; Huchinoue, Shouhei; Ohashi, Ryuji; Koike, Junki; Honda, Kazuho; Nagashima, Yoji; Nitta, Kosaku

    2015-07-01

    Atypical hemolytic uremic syndrome (aHUS) in allograft kidney transplantation is caused by various factors including rejection, infection, and immunosuppressive drugs. We present a case of a 32 year old woman with aHUS four years after an ABO-incompatible kidney transplantation from a living relative. The primary cause of end-stage renal disease was unknown; however, IgA nephropathy (IgAN) was suspected from her clinical course. She underwent pre-emptive kidney transplantation from her 60 year old mother. The allograft preserved good renal function [serum creatinine (sCr) level 110-130 μmol/L] until a sudden attack of abdominal pain four years after transplant, with acute renal failure (sCr level, 385.3 μmol/L), decreasing platelet count, and hemolytic anemia with schizocytes. On allograft biopsy, there was thrombotic microangiopathy in the glomeruli, with a cellular crescent formation and mesangial IgA and C3 deposition. Microvascular inflammation, such as glomerulitis, peritubular capillaritis, and arteriole endarteritis were also detected. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) did not decrease and Shiga toxin was not detected. Donor-specific antibodies or autoantibodies, including anti-neutrophil cytoplasmic antibody and anti-glomerular basement membrane (anti-GBM) antibody, were negative. The patient was diagnosed with aHUS and received three sessions of plasmapheresis and methylprednisolone pulse therapy, followed by oral methylprednisolone (0.25-0.5 mg/kg) instead of tacrolimus. She temporarily required hemodialysis (sCr level, 658.3 μmol/L). Thereafter, her sCr level improved to 284.5 μmol/L without dialysis therapy. This case is clinically considered as aHUS after kidney transplantation, associated with various factors, including rejection, glomerulonephritis, and toxicity from drugs such as tacrolimus.

  13. [Perioperative evaluation of cerebral hemodynamics by transcranial Doppler ultrasonography in patient with hemolytic uremic syndrome].

    Science.gov (United States)

    Nishikawa, M; Hayashi, T; Yoshitomi, T; Inoue, T; Ichiyama, T; Furukawa, S

    2000-11-01

    Major central nervous system (CNS) complications such as seizures and coma, occur in about 30% of children with hemolytic uremic syndrome (HUS). Serious CNS involvement is associated with an increased mortality. The purpose of this study was to evaluate intracranial hemodynamics in HUS encephalopathy. We measured mean blood flow velocity and pulsatility index (PI) of the middle cerebral artery (MCA) with transcranial Doppler (TCD) in a two year-old girl with acute encephalopathy, and compared them to those in a one year-old girl with febrile convulsion incidentally complicating HUS (a disease control). In the patient with HUS encephalopathy TCD demonstrated abnormally low PI of 0.58, while the magnetic resonance imaging (MRI) and single-photon emission-computed tomography (SPECT) reveal no abnormal findings in the acute stage. The abnormal TCD findings disappeared with her recovery. In the HUS patient with febrile convulsion alone, TCD demonstrated normal maximal flow velocity and PI. Thus TCD may be useful in evaluating intracranial hemodynamics in HUS encephalopathy in the absence of MRI and SPECT abnormalities at the early stage of illness.

  14. Posterior Reversible Encephalopathy Syndrome in Henoch-Schonlein Purpura and Hemolytic Uremic Syndrome.

    Science.gov (United States)

    Fidan, Kibriya; Kandur, Yasar; Ucar, Murat; Gucuyener, Kivilcim; Soylemezoglu, Oguz

    2016-07-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological syndrome, composed of symptoms such as headache, seizures, visual disturbances, lethargy, confusion, stupor, focal neurologic findings and radiological findings of bilateral gray and white matter abnormalities suggestive of edema in the posterior regions of the cerebral hemispheres. PRES is associated with significant morbidity and mortality if it is not expeditiously recognized. Magnetic resonance image (MRI) represents the most sensitive imaging technique for recognizing PRES. PRES has been seen in various clinical settings including renal disorders such as acute glomerulonephritis, lupus nephritis, nephrotic syndrome, and drug usage such as calcineurin inhibitors. We aimed to present two study cases for such clinical setting. In this report, we present two patients with PRES in whom the primary diagnosis was hemolytic uremic syndrome (HUS) and Henoch-Schonlein purpura (HSP). Both of them were treated with anticonvulsant and proper antihypertensive drugs. A repeated MRI scan of the head, an ophthalmologic assessment, and a follow-up electroencephalogram produced normal results with no sequelae. Early recognition of PRES as a complication during different diseases and therapies in childhood may facilitate the appropriate treatment, so that intensive treatment should be performed as soon as possible to avoid neurological sequelae.

  15. Risk factors for neurological complications in complete hemolytic uremic syndrome caused by Escherichia coli O157.

    Science.gov (United States)

    Yamamoto, Takehisa; Satomura, Kenichi; Okada, Shintaro; Ozono, Keiichi

    2009-04-01

    The aim of the present study was to investigate the predictive parameters for encephalopathy in complete hemolytic uremic syndrome (HUS) in a large outbreak of O157: H7 infection in 1996. A total of 182 inpatients, 71 of whom had complete HUS, including 12 patients with neurological complications, and 46 colitis patients were studied. Presenting signs and symptoms (n = 115) and laboratory data (n = 69) were analyzed using monovariate and multivariate analysis. After adjusting for age and gender, logistic regression showed that presenting symptoms such as bloody diarrhea (odds ratio [OR] = 7.39), proteinuria (OR = 6.16), hematuria (OR = 8.31), oliguria (OR = 17.4) and a pale face (OR = 10.7) were useful for predicting complete HUS. Also, increased white blood cell counts >12,000 microL/mL (OR = 10.0) and C-reactive protein >1.5 mg/dL (OR = 7.39) at the onset of infection, were useful as predictive laboratory parameters. To predict neurological complications in complete HUS patients, the average daily increase of lactate dehydrase >1200 IU/L per day (OR = 26.3) and creatinine >0.5 mg/dL per day (OR = 12) were found to be useful on multivariate logistic regression. There are useful predictive clinical factors for neurological complications in complete HUS.

  16. Differential expression of function-related antigens on blood monocytes in children with hemolytic uremic syndrome.

    Science.gov (United States)

    Fernández, Gabriela C; Ramos, María V; Gómez, Sonia A; Dran, Graciela I; Exeni, Ramón; Alduncín, Marta; Grimoldi, Irene; Vallejo, Graciela; Elías-Costa, Christian; Isturiz, Martín A; Palermo, Marina S

    2005-10-01

    Monocytes (Mo) mediate central functions in inflammation and immunity. Different subpopulations of Mo with distinct phenotype and functional properties have been described. Here, we investigate the phenotype and function of peripheral Mo from children with hemolytic uremic syndrome (HUS). For this purpose, blood samples from patients in the acute period of HUS (HUS AP) were obtained on admission before dialysis and/or transfusion. The Mo phenotypic characterization was performed on whole blood by flow cytometry, and markers associated to biological functions were selected: CD14 accounting for lipopolysaccharide (LPS) responsiveness, CD11b for adhesion, Fc receptor for immunoglobulin G type I (FcgammaRI)/CD64 for phagocytosis and cytotoxicity, and human leukocyte antigen (HLA)-DR for antigen presentation. Some of these functions were also determined. Moreover, the percentage of CD14+ CD16+ Mo was evaluated. We found that the entire HUS AP Mo population exhibited reduced CD14, CD64, and CD11b expression and decreased LPS-induced tumor necrosis factor production and Fcgamma-dependent cytotoxicity. HUS AP showed an increased percentage of CD14+ CD16+ Mo with higher CD16 and lower CD14 levels compared with the same subset from healthy children. Moreover, the CD14++ CD16- Mo subpopulation of HUS AP had a decreased HLA-DR expression, which correlated with severity. In conclusion, the Mo population from HUS AP patients presents phenotypic and functional alterations. The contribution to the pathogenesis and the possible scenarios that led to these changes are discussed.

  17. Eculizumab in neonatal hemolytic uremic syndrome with homozygous factor H deficiency.

    Science.gov (United States)

    Michaux, Katell; Bacchetta, Justine; Javouhey, Etienne; Cochat, Pierre; Frémaux-Bacchi, Véronique; Sellier-Leclerc, Anne-Laure

    2014-12-01

    Neonatal atypical hemolytic uremic syndrome (aHUS) is a rare but severe disease that is mainly due to methylmalonic aciduria or genetic complement abnormalities. Traditional management of aHUS includes plasma infusion/exchange, but in small or unstable infants, plasma exchange can be challenging because of high extracorporeal volume and difficulty to obtain an adequate venous access. The C5 complement blocker eculizumab has become a cornerstone of first-line management of aHUS due to complement deregulation in older patients. However, little data are available on its use in neonatal aHUS. We report on an 11-day-old neonate with severe aHUS (myocardial impairment, respiratory failure, acute kidney disease requiring hemodiafiltration) due to homozygous factor-H deficiency. She received early treatment with eculizumab as first-line therapy and completely recovered within 5 days. A second dose of eculizumab was administered 7 days after the first infusion, followed by a dose every 2 weeks for 2 months and then every 3 weeks, at the same dosage (300 mg). With more than 24 months of follow-up, renal function remains normal. We report on the long-term efficacy and safety of eculizumab as first-line therapy in neonatal aHUS. However its use still requires optimization in terms of indications and administration (frequency, dosage).

  18. Shiga Toxins and the Pathophysiology of Hemolytic Uremic Syndrome in Humans and Animals

    Directory of Open Access Journals (Sweden)

    Deborah J. Stearns-Kurosawa

    2012-11-01

    Full Text Available Food-borne diseases are estimated at 76 million illnesses and 5000 deaths every year in the United States with the greatest burden on young children, the elderly and immunocompromised populations. The impact of efficient food distribution systems and a truly global food supply ensures that outbreaks, previously sporadic and contained locally, are far more widespread and emerging pathogens have far more frequent infection opportunities. Enterohemorrhagic E. coli is an emerging food- and water-borne pathogen family whose Shiga-like toxins induce painful hemorrhagic colitis with potentially lethal complications of hemolytic uremic syndrome (HUS. The clinical manifestations of Shiga toxin-induced HUS overlap with other related syndromes yet molecular mechanisms differ considerably. As discussed herein, understanding these differences and the novel properties of the toxins is imperative for clinical management decisions, design of appropriate animal models, and choices of adjunctive therapeutics. The emergence of new strains with rapidly aggressive virulence makes clinical and research initiatives in this field a high public health priority.

  19. Shiga Toxins and the Pathophysiology of Hemolytic Uremic Syndrome in Humans and Animals

    Science.gov (United States)

    Mayer, Chad L.; Leibowitz, Caitlin S.; Kurosawa, Shinichiro; Stearns-Kurosawa, Deborah J.

    2012-01-01

    Food-borne diseases are estimated at 76 million illnesses and 5000 deaths every year in the United States with the greatest burden on young children, the elderly and immunocompromised populations. The impact of efficient food distribution systems and a truly global food supply ensures that outbreaks, previously sporadic and contained locally, are far more widespread and emerging pathogens have far more frequent infection opportunities. Enterohemorrhagic E. coli is an emerging food- and water-borne pathogen family whose Shiga-like toxins induce painful hemorrhagic colitis with potentially lethal complications of hemolytic uremic syndrome (HUS). The clinical manifestations of Shiga toxin-induced HUS overlap with other related syndromes yet molecular mechanisms differ considerably. As discussed herein, understanding these differences and the novel properties of the toxins is imperative for clinical management decisions, design of appropriate animal models, and choices of adjunctive therapeutics. The emergence of new strains with rapidly aggressive virulence makes clinical and research initiatives in this field a high public health priority. PMID:23202315

  20. Clostridium sordellii as a Cause of Fatal Septic Shock in a Child with Hemolytic Uremic Syndrome

    Directory of Open Access Journals (Sweden)

    Rebekah Beyers

    2014-01-01

    Full Text Available Clostridium sordellii is a toxin producing ubiquitous gram-positive anaerobe, mainly associated with trauma, soft tissue skin infections, and gynecologic infection. We report a unique case of a new strain of Clostridium sordellii (not present in the Center for Disease Control (CDC database infection induced toxic shock syndrome in a previously healthy two-year-old male with colitis-related hemolytic uremic syndrome (HUS. The patient presented with dehydration, vomiting, and bloody diarrhea. He was transferred to the pediatric critical care unit (PICU for initiation of peritoneal dialysis (PD. Due to increased edema and intolerance of PD, he was transitioned to hemodialysis through a femoral vascular catheter. He subsequently developed severe septic shock with persistent leukocytosis and hypotension, resulting in subsequent death. Stool culture confirmed Shiga toxin producing Escherichia coli 0157:H7. A blood culture was positively identified for Clostridium sordellii. Clostridium sordelli is rarely reported in children; to our knowledge this is the first case described in a pediatric patient with HUS.

  1. Complement Factor B Mutations in Atypical Hemolytic Uremic Syndrome—Disease-Relevant or Benign?

    Science.gov (United States)

    Marinozzi, Maria Chiara; Vergoz, Laura; Rybkine, Tania; Ngo, Stephanie; Bettoni, Serena; Pashov, Anastas; Cayla, Mathieu; Tabarin, Fanny; Jablonski, Mathieu; Hue, Christophe; Smith, Richard J.; Noris, Marina; Halbwachs-Mecarelli, Lise; Donadelli, Roberta; Fremeaux-Bacchi, Veronique

    2014-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a genetic ultrarare renal disease associated with overactivation of the alternative pathway of complement. Four gain-of-function mutations that form a hyperactive or deregulated C3 convertase have been identified in Factor B (FB) ligand binding sites. Here, we studied the functional consequences of 10 FB genetic changes recently identified from different aHUS cohorts. Using several tests for alternative C3 and C5 convertase formation and regulation, we identified two gain-of-function and potentially disease-relevant mutations that formed either an overactive convertase (M433I) or a convertase resistant to decay by FH (K298Q). One mutation (R178Q) produced a partially cleaved protein with no ligand binding or functional activity. Seven genetic changes led to near-normal or only slightly reduced ligand binding and functional activity compared with the most common polymorphism at position 7, R7. Notably, none of the algorithms used to predict the disease relevance of FB mutations agreed completely with the experimental data, suggesting that in silico approaches should be undertaken with caution. These data, combined with previously published results, suggest that 9 of 15 FB genetic changes identified in patients with aHUS are unrelated to disease pathogenesis. This study highlights that functional assessment of identified nucleotide changes in FB is mandatory to confirm disease association. PMID:24652797

  2. Relapsing or refractory idiopathic thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: the role of rituximab.

    Science.gov (United States)

    Caramazza, Domenica; Quintini, Gerlando; Abbene, Ignazio; Malato, Alessandra; Saccullo, Giorgia; Lo Coco, Lucio; Di Trapani, Rosa; Palazzolo, Roberto; Barone, Rita; Mazzola, Giuseppina; Rizzo, Sergio; Ragonese, Paolo; Aridon, Paolo; Abbadessa, Vincenzo; Siragusa, Sergio

    2010-12-01

    Idiopathic thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is a rare disease responsive to treatment with plasma exchange (PE) but with a high percentage of relapse or refractory patients. A severe deficiency of ADAMTS-13 (<5% of normal activity), congenital or caused by an autoantibody, may be specific for TTP and it has been proposed that severe ADAMTS-13 deficiency now defines TTP. B cells play a key role in both the development and the perpetuation of autoimmunity, suggesting that B-cell depletion could be a valuable treatment approach for patients with idiopathic TTP-HUS. This review of the literature focuses on the role of rituximab, a chimeric monoclonal antibody directed against CD20 antigen expressed by B lymphocytes, in patients with relapsing or refractory TTP-HUS with or without ADAMTS-13 deficiency, suggesting that rituximab may produce clinical remission in a significant proportion of patients. Rituximab therapy reduces plasma requirement and avoids complications related to salvage-immunosuppressive therapy. In conclusion, rituximab provides an effective, well-tolerated, and safe treatment option for patients with idiopathic TTP-HUS, thus giving an alternative approach to the current treatment based on PE.

  3. Federal Clinical Guidelines on Rendering Help to Children with Hemolytic Uremic Syndrome

    Directory of Open Access Journals (Sweden)

    A. N. Tsygin

    2015-01-01

    Full Text Available The hemolytic uremic syndrome (HUS is a serious therapeutic problem in pediatrics and pediatric nephrology. HUS is one of the leading causes of acute renal failure with the potential of transforming into terminal chronic renal failure at various periods from the disease onset. The typical form of HUS with a diarrheal prodrome associated with Shiga toxin (STEC is the most common form. Despite this fact, it requires careful confirmation of infectious etiology to exclude atypical HUS and HUS associated with pneumococcal infection in time. In respect of STEC-HUS it is recommended to conduct adequate symptomatic therapy with a timely dialysis connection if needed. The prognosis here will depend on the anuretic period duration and on the related central nervous system injuries. Atypical HUS is often based on genetic mutations leading to the complement cascade disfunction with uncontrolled activation of the alternative pathway. The overall prognosis for this prone to recurrence form is unfavourable, however, it is recommended to conduct aeculizumabum treatment which will block the terminal components of the complement cascade.

  4. Blood pressure in the long-term follow-up of children with hemolytic uremic syndrome.

    Science.gov (United States)

    De Petris, Laura; Gianviti, Alessandra; Giordano, Ugo; Calzolari, Armando; Tozzi, Alberto E; Rizzoni, Gianfranco

    2004-11-01

    The hemolytic uremic syndrome (HUS) is the most common cause of acute renal failure (ARF) in young children. Most patients recover from the acute phase of the illness but they may develop arterial hypertension(AH) after many years, even in the absence of signs of renal impairment during short-term follow-up. In this study, we performed casual blood pressure (BP) measurement, 24-h blood pressure monitoring (ABPM), and a Bruce walking treadmill study (ET) in 24 children (aged 5-15 years, 13 males, 11 females) with a history of HUS and normal renal function during follow-up (median 5.8 years, range 1.8-12.4 years). There were 22 children(91%) with prodromal diarrhea associated with HUS and 20 (83%) underwent dialysis during the acute illness. All children had normal casual BP measurement. Of 13 children (54%) with normal ABPM, 5 patients (38%) had an abnormal BP response during the ET study. There were 4 (58%) of the 7 patients with AH by ABPM (29%)and an abnormal BP response during ET. These findings suggest that ET could be a useful means of identifying children with a history of HUS that could be at risk of future AH even if they had normal renal function, casual BP, and ABPM during long-term follow-up. These results should be confirmed with a large prospective clinical study.

  5. Risk factors for poor renal prognosis in children with hemolytic uremic syndrome.

    Science.gov (United States)

    Gianviti, Alessandra; Tozzi, Alberto E; De Petris, Laura; Caprioli, Alfredo; Ravà, Lucilla; Edefonti, Alberto; Ardissino, Gianluigi; Montini, Giovanni; Zacchello, Graziella; Ferretti, Alfonso; Pecoraro, Carmine; De Palo, Tommaso; Caringella, Angela; Gaido, Maurizio; Coppo, Rosanna; Perfumo, Francesco; Miglietti, Nunzia; Ratsche, Ilse; Penza, Rosa; Capasso, Giovambattista; Maringhini, Silvio; Li Volti, Salvatore; Setzu, Carmen; Pennesi, Marco; Bettinelli, Alberto; Peratoner, Leopoldo; Pela, Ivana; Salvaggio, Elio; Lama, Giuliana; Maffei, Salvatore; Rizzoni, Gianfranco

    2003-12-01

    Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D(-)STEC(- )recovered normal renal function compared with 65%-76% of D(+)STEC(+), D(+)STEC(-) and D(-)STEC(+ )patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D(-) but STEC(+) patients have a significantly better prognosis.

  6. Role of non-polio enterovirus infection in pediatric hemolytic uremic syndrome.

    Science.gov (United States)

    De Petris, Laura; Gianviti, Alessandra; Caione, Daniela; Innocenzi, Daniele; Edefonti, Alberto; Montini, Giovanni; De Palo, Tommaso; Tozzi, Alberto Eugenio; Caprioli, Alfredo; Rizzoni, Gianfranco

    2002-10-01

    Verocytotoxin-producing Escherichia coli(VTEC) infections cause most cases of hemolytic uremic syndrome (HUS); 10-30% of patients, however, are negative for VTEC infection. The etiology of HUS in VTEC-negative cases remains poorly understood. Before the association between VTEC infection and HUS was recognized, sporadic cases of HUS with enterovirus infection were reported in the literature. Since May 1988, most cases of HUS in Italy have been reported to the Italian surveillance system, and in 73% of these, evidence of VTEC infection was demonstrated. The aim of this study was to determine whether the frequency of enteroviral infections was different in the acute phase of VTEC-positive and VTEC-negative HUS. Eighty-nine patients were investigated for enteroviral infection, of whom 58 were VTEC positive and 31 VTEC negative. Two serum samples from each patient were examined for seroconversion to enterovirus (coxsackie, echovirus, and picornavirus) by a complement fixation test. Serological evidence of acute infection with non-polio enterovirus was found in 33 patients (37%) [20/58 (34.5%) VTEC positive and 13/31 (41.9%) VTEC negative]. There was no statistically significant difference between the two groups. These results demonstrate that there are no significant differences for enteroviral infection in VTEC-positive and VTEC-negative patients and, therefore, enteroviral infections should not be considered a cause of HUS in VTEC-negative children.

  7. Late Onset Cobalamin Disorder and Hemolytic Uremic Syndrome: A Rare Cause of Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Gianluigi Ardissino

    2017-01-01

    Full Text Available Hemolytic uremic syndrome (HUS is an unrare and severe thrombotic microangiopathy (TMA caused by several pathogenetic mechanisms among which Shiga toxin-producing Escherichia coli infections and complement dysregulation are the most common. However, very rarely and particularly in neonates and infants, disorders of cobalamin metabolism (CblC can present with or be complicated by TMA. Herein we describe a case of atypical HUS (aHUS related to CblC disease which first presented in a previously healthy boy at age of 13.6 years. The clinical picture was initially dominated by nephrotic range proteinuria and severe hypertension followed by renal failure. The specific treatment with high dose of hydroxycobalamin rapidly obtained the remission of TMA and the complete recovery of renal function. We conclude that plasma homocysteine and methionine determinations together with urine organic acid analysis should be included in the diagnostic work-up of any patient with TMA and/or nephrotic syndrome regardless of age.

  8. Cytokine profiles of patients with enterohemorrhagic Escherichia coli O111-induced hemolytic-uremic syndrome.

    Science.gov (United States)

    Shimizu, Masaki; Kuroda, Mondo; Sakashita, Natsumi; Konishi, Michio; Kaneda, Hisashi; Igarashi, Noboru; Yamahana, Junya; Taneichi, Hiromichi; Kanegane, Hirokazu; Ito, Mika; Saito, Shigeru; Ohta, Kazuhide; Taniguchi, Takumi; Furuichi, Kengo; Wada, Takashi; Nakagawa, Masaru; Yokoyama, Hitoshi; Yachie, Akihiro

    2012-12-01

    Proinflammatory cytokines are related to the pathogenesis of enterohemorrhagic Escherichia coli (EHEC) infection and hemolytic-uremic syndrome (HUS). We assessed the kinetics of the release of cytokines such as neopterin, interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α and the soluble forms of type I and II TNF receptors during EHEC O111-induced HUS (EHEC O111/HUS). Fourteen patients with EHEC O111/HUS were enrolled in this study. Serum concentrations of all cytokines other than TNF-α were significantly elevated in patients with severe HUS compared with those in patients with mild HUS. Although serum concentrations of TNF-α were not significantly higher in patients with severe HUS, most patients with acute encephalopathy showed elevated TNF-α levels. Serum concentrations of these cytokines rapidly and markedly increased, and massive hypercytokinaemia developed 1 day before the diagnosis of HUS in patients with severe HUS. Changes in the number of white blood cells and concentration of serum lactate dehydrogenase were significantly larger between the onset of hemorrhagic colitis and the time of the diagnosis of HUS in patients with severe HUS compared with those in patients with mild HUS. Proinflammatory cytokines play an important role in the pathogenesis of EHEC infection and development of severe complications, including HUS and encephalopathy. Monitoring the cytokine profile may be useful for assessing disease activity of EHEC O111 infections.

  9. Interventions for preventing diarrhea-associated hemolytic uremic syndrome: systematic review.

    Science.gov (United States)

    Thomas, Diana E; Elliott, Elizabeth J

    2013-09-03

    Hemolytic Uremic Syndrome (HUS) may follow infection with Shiga-toxin-producing organisms, principally E. coli O157: H7 (STEC), causing high morbidity and mortality. Our aim was to identify interventions to prevent diarrhea-associated HUS. Systematic search of the literature for relevant systematic reviews (SRs), randomised controlled trials (RCTs) and public health guidelines. Of 1097 animal and 762 human studies, 18 animal studies (2 SRs, 2 reviews, plus 14 RCTs) and 6 human studies (3 SRs, plus 3 RCTs) met inclusion criteria. E. coli O157: H7 Type III secreted protein vaccination decreased fecal E. coli O157 shedding in cattle (P = 0.002). E. coli O157: H7 siderophore receptor and porin proteins (SRP) vaccines reduced fecal shedding in cows (OR 0.42 (95% CI 0.25 to 0.73) and increased anti-E. coli 0157: H7 SRP antibodies in their calves (P improved farm hygiene (P diarrhea, HUS rates were similar in children treated with Trimethoprim-sulfamethoxazole and controls (RR 0.57; 95% CI 0.11 to 2.81). In another RCT, HUS rates were similar in children receiving Synsorb-Pk and placebo (RR 0.93; 95% CI 0.39 to 2.22). In one SR, hand washing reduced diarrhea by 39% in institutions (IRR 0.61; 95% CI 0.40 to 0.92) and 32% in community settings (IRR 0.68; 95% CI 0.52 to 0.90) compared to controls. Guidelines contained recommendations to prevent STEC transmission from animals and environments to humans, including appropriate food preparation, personal hygiene, community education, and control of environmental contamination, food and water quality. Animal carriage of STEC is decreased by vaccination and improved farm practices. Treatment of STEC diarrhea with antibiotics and toxin-binders did not prevent HUS. Public health interventions are the key to preventing STEC-associated diarrhea and HUS.

  10. Effect of diet, enalapril, or losartan in post-diarrheal hemolytic uremic syndrome nephropathy.

    Science.gov (United States)

    Caletti, Maria Gracia; Missoni, Mabel; Vezzani, Clarisa; Grignoli, María; Piantanida, Juan Jose; Repetto, Horacio A; Exeni, Ramon; Rasse, Stella Maris

    2011-08-01

    Proteinuria is the main indicator of renal disease progression in many chronic conditions. There is currently little information available on the efficacy, safety, and individual tolerance of patients with post-diarrheal hemolytic uremic syndrome (D+ HUS) nephropathy to therapies involving diet, enalapril, or losartan. A multicenter, double-blind, randomized controlled trail was conducted to evaluate the effect of a normosodic-normoproteic diet (Phase I) and the effect of normosodic-normoproteic diet plus enalapril (0.18-0.27 mg/kg/day) or losartan (0.89-1.34 mg/kg/day) (Phase II) on children with D+ HUS, normal renal function, and persistent, mild (5.1-49.9 mg/kg/day) proteinuria. Dietary intervention reduced the mean protein intake from 3.4 to 2.2 mg/kg/day. Of 137 children, proteinuria normalized in 91 (66.4 %) within 23-45 days; the remaining 46 patients were randomized to diet plus placebo (group 1, n = 16), plus losartan (group 2, n = 16), or enalapril (group 3, n = 14). In groups 1, 2, and 3, proteinuria was reduced by 30.0, 82.0, and 66.3%, respectively, and normalized in six (37.5%), three (81.3%), and 11 (78.6%) patients, respectively (χ(2)= 8.9, p = 0.015). These results suggest that: (1) a normosodic-normoproteic diet can normalize proteinuria in the majority of children with D+ HUS with mild sequelae, (2) the addition of enalapril or losartan to such dietary restrictions of protein further reduces proteinuria, and (3) these therapeutic interventions are safe and well tolerated. Whether these short-term effects can be extended to the long-term remains to be demonstrated.

  11. Atypical Hemolytic Uremic Syndrome post Kidney Transplantation: Two Case Reports and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Sami eAlasfar

    2014-12-01

    Full Text Available Atypical hemolytic uremic syndrome (aHUS is a rare disorder characterized by over-activation and dysregulation of the alternative complement pathway. Its estimated prevalence is 1-2 per million. The disease is characterized by thrombotic microangiopathy, which causes anemia, thrombocytopenia, and acute renal failure. aHUS has more severe course compared to typical (Infection-induced HUS and is frequently characterized by relapses that leads to end stage renal disease (ESRD. For a long time, kidney transplantation for these patients was contraindicated because of high rate of recurrence and subsequent renal graft loss. The post-kidney transplantation recurrence rate largely depends on the pathogenetic mechanisms involved. However, over the past several years, advancements in the understanding and therapeutics of aHUS have allowed successful kidney transplantation in these patients. Eculizumab, which is a complement C5 antibody that inhibits complement factor 5a (C5a and subsequent formation of the membrane attack complex, has been used in prevention and treatment of post-transplant aHUS recurrence. In this paper, we present two new cases of aHUS patients who underwent successful kidney transplantation in our center with the use of prophylactic and maintenance eculizumab therapy that have not been published before. The purpose of reporting these two cases is to emphasize the importance of using eculizumab as a prophylactic therapy to prevent aHUS recurrence post transplant in high-risk patients. We will also review the current understanding of the genetics of aHUS, the pathogenesis of its recurrence after kidney transplantation, and strategies for prevention and treatment of post-transplant aHUS recurrence.

  12. A Case Report and Literature Review of Eculizumab Withdrawal in Atypical Hemolytic-Uremic Syndrome

    Science.gov (United States)

    Quiroga, Borja; de Lorenzo, Alberto; Vega, Cristina; de Alvaro, Fernando

    2016-01-01

    Patient: Female, 37 Final Diagnosis: SHUa Symptoms: Abdominal discomfort • nausea • weakness Medication: — Clinical Procedure: — Specialty: Nephrology Objective: Unusual clinical course Background: Recent advances in the treatment of atypical hemolytic-uremic syndrome (aHUS) have resulted to better long-term survival rates for patients with this life-threatening disease. However, many questions remain such as whether or not long-term treatment is necessary in some patients and what are the risks of prolonged therapy. Case Report: Here, we discuss the case of a 37-year-old woman with CFH and CD46 genetic abnormalities who developed aHUS with severe renal failure. She was successfully treated with three doses of rituximab and a three month treatment with eculizumab. After eculizumab withdrawal, symptoms of thrombotic micro-angiopathy (TMA) recurred, therefore eculizumab treatment was restarted. The patient exhibited normal renal function and no symptoms of aHUS at one-year follow-up with further eculizumab treatment. Conclusions: This case highlights the clinical challenges of the diagnosis and management of patient with aHUS with complement-mediated TMA involvement. Attention was paid to the consequences of the treatment withdrawal. Exact information regarding genetic abnormalities and renal function associated with aHUS, as well as estimations of the relapse risk and monitoring of complement tests may provide insights into the efficacy of aHUS treatment, which will enable the prediction of therapeutic responses and testing of new treatment options. Improvements in our understanding of aHUS and its causes may facilitate the identification of patients in whom anti-complement therapies can be withdrawn without risk. PMID:27974740

  13. Hemolytic uremic syndrome in children:some predictive findings on the disease outcome

    Institute of Scientific and Technical Information of China (English)

    Banihashemi Kambiz; Naeeni KMohammad; Yasseri Mehdi; Ghasemi Saeed; Abutalebi Roba-beh; Pourkhani Maryam

    2008-01-01

    Objective:To decrease or delay the major un-wanted clinical consequences to improve the quality of life in the involved patients.Methods:A retrospective case series study has been made on the forty five pediatric pa-tients admitted to nephrology department of Ali-Asghar Hospital during a period of nearly 10 years.The pa-tients have been divided into two groups of good and poor prognoses according to their clinical outcomes.The routine laboratory records and clinical manifestations extracted and statistically analyzed as independent varia-bles both by univariate and multivariate methods.Results:Forty three patients have been managed successful-ly with only two deaths occurred.According to clinical findings,nineteen patients were classified as poor prog-nosis and the rest were categorized as good prognosis.Multivariate statistical analyses showed that lesser age at the time of admission (age 15 000,P<0.226)were well-interrelated to ominous clinical consequences like convulsion,coma and peritonitis and statistically different between the two groups of patients.Conclusion:Despite the importance of predictive var-iables in the course of Hemolytic uremic syndrome(HUS)in children and their critical influence on the clinical outcome,many aspects of these parameters have been remained to be elucidated comprehensively.Our study showed that simultaneous low age of child at the time of admission with simultaneous high WBC count will re-sult in the poorer prognoses of the patients.This may warn the clinicians to provide more supportive cares for this group of patients.

  14. Adjustment of Eculizumab Dosage Pattern in Patients with Atypical Hemolytic Uremic Syndrome with Suboptimal Response to Standard Treatment Pattern

    Science.gov (United States)

    Peralta Roselló, Carmen; Baltar Martín, José María; Castillo Eraso, Lorena; de Álvaro Moreno, Fernando; Martínez Vea, Alberto; Visus-Fernández de Manzanos, María Teresa

    2016-01-01

    In patients with atypical hemolytic uremic syndrome (aHUS), complement blocking by eculizumab rapidly halts the process of thrombotic microangiopathy and it is associated with clear long-term hematologic and renal improvements. Eculizumab treatment consists of a 4-week initial phase with weekly IV administration of 900 mg doses, followed by a maintenance phase with a 1,200 mg dose in the fifth week and every 14 ± 2 days thereafter. We present three patients with aHUS and suboptimal response to eculizumab treatment at the usual administration dosage who showed hematologic and renal improvements after an adjustment in the eculizumab treatment protocol. PMID:28025630

  15. Renoscintigraphy in assessment of renal lesions in children after hemolytic-uremic syndrome; Renoscyntygrafia w ocenie skutkow uszkodzenia nerek u dzieci po przebytym zespole hemolityczno-mocznicowym

    Energy Technology Data Exchange (ETDEWEB)

    Lass, P.; Marczak, E.; Romanowicz, G. [Akademia Medyczna, Gdansk (Poland); and others

    1994-12-31

    The aim of the study was to assess the role of renoscintigraphic examination in monitoring of patients after the hemolytic-uremic syndrome. 27 children mean 9 years the hemolytic-uremic syndrome underwent the complex of biochemical, ultrasound and renoscintigraphic examinations. The abnormal renoscintigraphic was seen in 85.1% of children, while the alternative test described the renal lesion in 29-66%. Renoscintigraphic examination seems to be the most sensitive in monitoring of remote sequel in patients after HUS. Those patients should undergone long-lasting observation, for the sake of possibility of development of renal insufficiency. (author). 14 refs.

  16. Successful Colectomy for Hemorrhagic Colitis with Hemolytic Uremic Syndrome and Acute Encephalopathy due to Escherichia coli O157 Infection

    Directory of Open Access Journals (Sweden)

    Tetsuro Tominaga

    2014-03-01

    Full Text Available An 81-year-old man was admitted to a primary care hospital due to bloody diarrhea. The findings of abdominal computed tomography indicated ischemic colitis, so conservative therapy was started. On the 4th hospital day, the patient was transferred to our hospital because of renal dysfunction. Physical examination showed clouding of consciousness and abdominal distention. Abdominal computed tomography revealed massive ascites and thickening of the whole colonic wall. With a diagnosis of acute abdomen, an emergent laparotomy was performed. Extended right hemicolectomy was performed because of severe ischemic change and necrosis of the right side of the colon. In the stool culture before the operation, Escherichia coli O157 and verotoxin were found, so this case was diagnosed as hemorrhagic colitis with hemolytic uremic syndrome and acute encephalopathy due to Escherichia coli O157 infection. Postoperatively, the hemolytic uremic syndrome and acute encephalopathy were prolonged. However, with intensive care, the patient recovered and was discharged on the 33rd postoperative day.

  17. Protection from hemolytic uremic syndrome by eyedrop vaccination with modified enterohemorrhagic E. coli outer membrane vesicles.

    Directory of Open Access Journals (Sweden)

    Kyoung Sub Choi

    Full Text Available We investigated whether eyedrop vaccination using modified outer membrane vesicles (mOMVs is effective for protecting against hemolytic uremic syndrome (HUS caused by enterohemorrhagic E. coli (EHEC O157:H7 infection. Modified OMVs and waaJ-mOMVs were prepared from cultures of MsbB- and Shiga toxin A subunit (STxA-deficient EHEC O157:H7 bacteria with or without an additional waaJ mutation. BALB/c mice were immunized by eyedrop mOMVs, waaJ-mOMVs, and mOMVs plus polymyxin B (PMB. Mice were boosted at 2 weeks, and challenged peritoneally with wild-type OMVs (wtOMVs at 4 weeks. As parameters for evaluation of the OMV-mediated immune protection, serum and mucosal immunoglobulins, body weight change and blood urea nitrogen (BUN/Creatinin (Cr were tested, as well as histopathology of renal tissue. In order to confirm the safety of mOMVs for eyedrop use, body weight and ocular histopathological changes were monitored in mice. Modified OMVs having penta-acylated lipid A moiety did not contain STxA subunit proteins but retained non-toxic Shiga toxin B (STxB subunit. Removal of the polymeric O-antigen of O157 LPS was confirmed in waaJ-mOMVs. The mice group vaccinated with mOMVs elicited greater humoral and mucosal immune responses than did the waaJ-mOMVs and PBS-treated groups. Eyedrop vaccination of mOMVs plus PMB reduced the level of humoral and mucosal immune responses, suggesting that intact O157 LPS antigen can be a critical component for enhancing the immunogenicity of the mOMVs. After challenge, mice vaccinated with mOMVs were protected from a lethal dose of wtOMVs administered intraperitoneally, conversely mice in the PBS control group were not. Collectively, for the first time, EHEC O157-derived mOMV eyedrop vaccine was experimentally evaluated as an efficient and safe means of vaccine development against EHEC O157:H7 infection-associated HUS.

  18. Tumor necrosis factor and interleukin-1 induce expression of the verocytotoxin receptor globotriaosylceramide on human endothelial cells: Implications for the pathogenesis of the hemolytic uremic syndrome

    NARCIS (Netherlands)

    Kar, N.C.A.J. van de; Monnens, L.A.H.; Karmali, M.A.; Hinsbergh, V.W.M. van

    1992-01-01

    The epidemic form of the hemolytic uremic syndrome (HUS), beginning with an acute gastroenteritis, has been associated with a verocytotoxin-producing Escherichia coli infection. The endothelial cell is believed to play an important role in the pathogenesis of HUS. Endothelial cell damage by

  19. CONCURRENT PRESENTATION OF HEMOLYTIC-UREMIC SYNDROME IN 2 ADULT SIBLINGS - EFFECTS OF PLASMA THERAPY ON HEMOLYSIS AND RENAL-FUNCTION

    NARCIS (Netherlands)

    VONGAMEREN, [No Value; RENSMA, PL; ZIJLSTRA, JG; DEWOLF, J; DEJONG, PE

    1994-01-01

    We describe 2 sisters who presented with the hemolytic uremic syndrome (HUS) almost simultaneously In both patients an upper airway infection with Haemophilus influenzae immediately preceding HUS may have been the environmental trigger. Fresh plasma infusion had only minor therapeutic effects but pl

  20. Comparison of Multilocus Variable-Number Tandem-Repeat Analysis and Multilocus Sequence Typing for Differentiation of Hemolytic-Uremic Syndrome-Associated Escherichia coli (HUSEC) Collection Strains▿

    OpenAIRE

    2011-01-01

    Multilocus variable-number tandem-repeat analysis (MLVA) was compared to multilocus sequence typing (MLST) to differentiate hemolytic uremic syndrome-associated enterohemorrhagic Escherichia coli strains. Although MLVA—like MLST—was highly discriminatory (index of diversity, 0.988 versus 0.984), a low level of concordance demonstrated the limited ability of MLVA to reflect long-term evolutionary events.

  1. Posttransplantation cytomegalovirus-induced recurrence of atypical hemolytic uremic syndrome associated with a factor H mutation: successful treatment with intensive plasma exchanges and ganciclovir.

    NARCIS (Netherlands)

    Olie, K.H.; Goodship, T.H.; Verlaak, R.; Florquin, S.; Groothoff, J.W.; Strain, L.; Weening, J.J.; Davin, J.C.

    2005-01-01

    Atypical hemolytic uremic syndrome (HUS) can recur after renal transplantation and often leads to graft loss. In some series of familial HUS, the risk of early graft loss due to recurrence of HUS approaches 100% despite any therapy. This led some authors to claim that kidney transplantation is contr

  2. Escherichia coli O-157-induced hemolytic uremic syndrome: Usefulness of SCWP score for the prediction of neurological complication.

    Science.gov (United States)

    Teramoto, Takahide; Fukao, Toshiyuki; Hirayama, Kouichiro; Asano, Tsutomu; Aoki, Yusuke; Kondo, Naomi

    2009-02-01

    Hemolytic uremic syndrome (HUS) is commonly caused by hemorrhagic colitis with Shiga toxin-producing Escherichia coli O-157. Central nervous system (CNS) involvements, including seizures, encephalopathy and brain infarction, are serious complications, but there are no useful scores for the prediction of CNS complications. Routine laboratory data at onset of HUS were re-evaluated in 14 patients to find useful parameters for the prediction of CNS complication. Serum sodium and total protein were significantly lower and C-reactive protein (CRP) and white blood cell counts were significantly higher in patients with CNS complications than in patients without. A cumulated score, SCWP score (sodium, CRP, white blood cell count, and total protein) discriminated better between patients with/without CNS complications than individual values. SCWP score would be useful for prediction of CNS complications.

  3. Serum ferritin as an indicator of the development of encephalopathy in enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome.

    Science.gov (United States)

    Shimizu, Masaki; Inoue, Natsumi; Kuroda, Mondo; Irabu, Hitoshi; Takakura, Maiko; Kaneda, Hisashi; Sugimoto, Naotoshi; Ohta, Kazuhide; Yachie, Akihiro

    2017-03-10

    To investigate the diagnostic value of serum ferritin levels as a marker of disease activity and the development of encephalopathy in hemolytic uremic syndrome (HUS) induced by enterohemorrhagic Escherichia coli. Twenty patients with HUS were studied. Serum ferritin levels were compared with clinical features and serum soluble tumor necrosis factor receptor (sTNFR) I and sTNFRII levels. Serum sTNFRI and sTNFRII levels were quantified by enzyme-linked immunosorbent assays. Serum ferritin levels were significantly elevated at the time of the diagnosis of HUS. Serum ferritin levels were significantly elevated in patients with encephalopathy compared to patients without encephalopathy. HUS patients with serum ferritin levels of >687.5 ng/ml were at high risk of encephalopathy. Serum ferritin levels were significantly positively correlated with serum sTNFRI and sTNFRII levels. Serum ferritin levels are a promising indicator of the development of encephalopathy in HUS.

  4. Gemcitabine-induced hemolytic uremic syndrome mimicking scleroderma renal crisis presenting with Raynaud's phenomenon, positive antinuclear antibodies and hypertensive emergency.

    Science.gov (United States)

    Yamada, Yuichiro; Suzuki, Keisuke; Nobata, Hironobu; Kawai, Hirohisa; Wakamatsu, Ryo; Miura, Naoto; Banno, Shogo; Imai, Hirokazu

    2014-01-01

    A 58-year-old woman who received gemcitabine for advanced gallbladder cancer developed an impaired renal function, thrombocytopenia, Raynaud's phenomenon, digital ischemic changes, a high antinuclear antibody titer and hypertensive emergency that mimicked a scleroderma renal crisis. A kidney biopsy specimen demonstrated onion-skin lesions in the arterioles and small arteries along with ischemic changes in the glomeruli, compatible with a diagnosis of hypertensive emergency (malignant hypertension). The intravenous administration of a calcium channel blocker, the oral administration of an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker and the transfusion of fresh frozen plasma were effective for treating the thrombocytopenia and progressive kidney dysfunction. Gemcitabine induces hemolytic uremic syndrome with accelerated hypertension and Raynaud's phenomenon, mimicking scleroderma renal crisis.

  5. Successful isolated liver transplantation in a child with atypical hemolytic uremic syndrome and a mutation in complement factor H.

    Science.gov (United States)

    Haller, W; Milford, D V; Goodship, T H J; Sharif, K; Mirza, D F; McKiernan, P J

    2010-09-01

    A male infant was diagnosed with atypical hemolytic uremic syndrome (aHUS) at the age of 5.5 months. Sequencing of the gene (CFH) encoding complement factor H revealed a heterozygous mutation (c.3644G>A, p.Arg1215Gln). Despite maintenance plasmapheresis he developed recurrent episodes of aHUS and vascular access complications while maintaining stable renal function. At the age of 5 years he received an isolated split liver graft following a previously established protocol using pretransplant plasma exchange (PE) and intratransplant plasma infusion. Graft function, renal function and disease remission are preserved 2 years after transplantation. Preemptive liver transplantation prior to the development of end stage renal disease is a valuable option in the management of aHUS associated with CFH mutations.

  6. Adjustment of Eculizumab Dosage Pattern in Patients with Atypical Hemolytic Uremic Syndrome with Suboptimal Response to Standard Treatment Pattern

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    Camino García Monteavaro

    2016-01-01

    Full Text Available In patients with atypical hemolytic uremic syndrome (aHUS, complement blocking by eculizumab rapidly halts the process of thrombotic microangiopathy and it is associated with clear long-term hematologic and renal improvements. Eculizumab treatment consists of a 4-week initial phase with weekly IV administration of 900 mg doses, followed by a maintenance phase with a 1,200 mg dose in the fifth week and every 14±2 days thereafter. We present three patients with aHUS and suboptimal response to eculizumab treatment at the usual administration dosage who showed hematologic and renal improvements after an adjustment in the eculizumab treatment protocol.

  7. Eculizumab for atypical hemolytic-uremic syndrome in India: First report from India and the challenges faced

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    Sethi, S. K.; Rohatgi, S.; Dragon-Durey, M. A.; Raghunathan, V.; Dhaliwal, M.; Rawat, A.; Jha, P.; Bansal, S. B.; Raina, R.; Kher, V.

    2017-01-01

    Much progress has been made in understanding the pathophysiology and treatment of atypical hemolytic uremic syndrome (aHUS). Plasma therapy is the mainstay of treatment for aHUS. The availability of the first effective anti-complement therapeutic agent, eculizumab, has dramatically changed the outlook of this disease. However, its use in clinical practice raises important questions, such as who should receive the drug, when to start such therapy, and is it safe to stop treatment once the disease is controlled. We describe here for the 1st time in India, use of eculizumab in a 12-year-old boy with aHUS. We also describe in this report challenges faced in procuring the drug, and an ideal, evidence-based method of treating aHUS in children. PMID:28182046

  8. Idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in a 17-year-old woman: a case report

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    Patschan Daniel

    2011-12-01

    Full Text Available Abstract Introduction Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome is a life-threatening condition with various etiopathogeneses. Without therapy approximately 90% of all patients die from the disease. Case presentation We report the case of a 17-year-old Caucasian woman with widespread hematomas and headache. Due to hemolytic anemia, thrombocytopenia, and schistocytosis, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected and plasma exchange therapy was initiated immediately. Since her thrombocyte level did not increase during the first week of therapy, plasma treatment had to be intensified to a twice-daily schedule. Further diagnostics showed markedly reduced activities of both ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 - also known as von Willebrand factor-cleaving protease and factor H. Test results for antibodies against both proteins were positive. While plasma exchange therapy was continued, rituximab was given once weekly for four consecutive weeks. After the last dose, thrombocytes and activities of ADAMTS-13 and factor H increased into the normal range. Our patient improved and was discharged from the hospital. Conclusions Since no clinical symptoms/laboratory findings indicated a malignant or specific autoimmune-mediated disorder, the diagnosis made was thrombotic thrombocytopenic purpura-hemolytic uremic syndrome due to idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency.

  9. Hemolytic uremic syndrome with ischemic glomerulonephropathy and obliterative vasculopathy in a systemic sclerosis patient treated with cyclosporine-A.

    Science.gov (United States)

    Chen, Wei-Sheng; Young, An-Hang; Wang, Hon-Pin; Huang, De-Feng

    2009-05-01

    Hemolytic uremic syndrome (HUS) is not a commonly reported complication in post-transplantation patients treated with cyclosporine-A (CSA), and is extremely rare in systemic sclerosis (SSc) patients treated with this drug. CSA may contribute to the development of chronic ischemic glomerulonephropathy and vasculopathy, features not easily distinguished from SSc-related nephropathy. Here, we describe a 41-year-old Chinese man with diffuse-type SSc treated with CSA who developed thrombocytopenia, acute renal failure and hemolytic anemia and was diagnosed with HUS. Renal function and thrombocytopenia improved gradually after intensive treatment of plasma exchange (PE) and high-dose steroid therapy. After PE, renal biopsy showed ischemic glomerulonephropathy and obliterative vasculopathy. This case illustrates that PE can improve the hematological disorders and characteristic renal changes of HUS in SSc patients treated with CSA. However, this therapy may not be effective in normalizing serum creatinine level in SSc patients once CSA has triggered the normal kidney to develop glomerulonephropathy and vasculopathy with ischemic and sclerotic changes.

  10. Catastrophic relapse of Evans syndrome five years after allogeneic BMT notwithstanding full donor chimerism. Terminal hemolytic-uremic syndrome.

    Science.gov (United States)

    Marmont, A M; Gualandi, F; Occhini, D; Morandi, F; Ferretti, E; Pezzolo, A; Strada, P; Ravetti, J L; Pistoia, V; Falanga, A; Bacigalupo, A

    2006-09-01

    A patient with severe Evans syndrome received an allo-BMT from his HLA-identical sister on November, 2000. Full marrow and blood donor chimerism were achieved only after 5 donor lymphocyte infusions (DLI), and coincided with complete clinical remission and disappearence of auto-antibodies. Five years later, hemolytic anemia recurred with rapid increase of serum bilirubin to over 50 mg%: he responded to combined therapy, but died on day +17 from admission of an acute hemolytic uremic syndrome (HUS). All circulating blood cells, including erythrocytes, were 100% donor. Ex vivo cultured and expanded T and B cells from the peripheral blood were also 100% donor. The supernatants from B cell cultures, containing either IgM or IgG, did not react with a panel of erythrocytes. Thus in this typical autoimmune disease with a predominant B cell pathogenesis the donor immune system resulted "innocent of autoimmunity". The persistence of long-lived recipient autoreactive plasma-cell lines in survival niches, still producing autoantibodies, may be hypothesized for this and similar cases. The postulated graft-versus-autoimmunity (GVA) effect was apparently not sufficient to eradicate autoimmunity in this patient.

  11. Pulse cyclophosphamide therapy and clinical remission in atypical hemolytic uremic syndrome with anti-complement factor H autoantibodies.

    Science.gov (United States)

    Boyer, Olivia; Balzamo, Eve; Charbit, Marina; Biebuyck-Gougé, Nathalie; Salomon, Rémi; Dragon-Durey, Marie-Agnès; Frémeaux-Bacchi, Véronique; Niaudet, Patrick

    2010-05-01

    We report 3 children with atypical hemolytic uremic syndrome associated with anti-complement factor H (CFH) autoantibodies who presented with sustained remission with low antibody titers and normal kidney function after plasma exchanges (PEs) and cyclophosphamide pulses. The 3 children initially presented with acute vomiting, fatigue, gross hematuria, hypertension, hemolytic anemia, thrombocytopenia, nephrotic syndrome, and acute kidney injury. C3 levels were normal in patients 1 and 3 and low in patient 2 (0.376 mg/mL [0.376 g/L]). CFH antibody titers were increased (15,000 to > 32,000 arbitrary units [AU]). Patient 1, an 11-year-old boy, was treated with 12 PEs, leading to a decrease in CFH antibody titer (to 800 AU). A first relapse 1 month later was treated with 6 PEs and 4 rituximab infusions. A second relapse 3 months later required 5 PEs, and the patient received oral steroids (0.5 mg/d/kg body weight) and 5 cyclophosphamide pulses (1 g/1.73 m(2)), leading to sustained remission with normal kidney function (estimated glomerular filtration rate [eGFR], 120 mL/min/1.73 m(2) [2.0 mL/s/1.73 m(2)]) and a stable decrease in CFH antibody titer (to 2,000 AU) 3 years later. Patient 2, a 5-year-old boy, required dialysis therapy for 2 weeks. He received 3 plasma infusions without remission. Six PEs associated with 2 cyclophosphamide pulses (0.5 g/1.73 m(2)) and steroids (1 mg/d/kg body weight) led to rapid remission, with eGFR of 107 mL/min/1.73 m(2) [1.78 mL/s/1.73 m(2)] and a prolonged decrease in CFH antibody titer after 15 months (1,300 AU). Patient 3, a 16-month-old boy, was treated with oral steroids (1 mg/d/kg body weight), 2 PEs, and 2 cyclophosphamide pulses (0.5 g/1.73 m(2)), resulting in a stable decrease in CFH antibody titer to 276 AU. Kidney function quickly normalized (eGFR, 110 mL/min/1.73 m(2) [1.83 mL/s/1.73 m(2)]) and has remained normal after 14 months. All 3 patients show a homozygous deletion mutation of the CFHR1 and CFHR3 genes

  12. Eculizumab: safety and efficacy after 17 months of treatment in a renal transplant patient with recurrent atypical hemolytic-uremic syndrome: case report.

    Science.gov (United States)

    Châtelet, V; Lobbedez, T; Frémeaux-Bacchi, V; Ficheux, M; Ryckelynck, J Ph; Hurault de Ligny, B

    2010-12-01

    In a recent study, eculizumab, a humanized monoclonal antibody which targets complement factor C5, appeared to resolve hemolysis and thrombocytopenia leading to recovery of renal function in a transplant patient during an episode of an atypical hemolytic uremic syndrome. We report the efficacy of eculizumab in a patient who presented with a recurrence of atypical hemolytic syndrome at 3 years after renal transplantation. After 17 months of eculizumab treatment, and without concomitant plasma therapy, renal function was maintained, the need for blood transfusions reduced, and acute thrombotic microangiopathy and hemolysis controlled. These data suggested that eculizumab should be considered to be a permanent treatment for this patient.

  13. Mild encephalitis/encephalopathy with reversible splenial and cerebellar lesions (MERS type II) in a patient with hemolytic uremic syndrome (HUS).

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    Gawlitza, Matthias; Hoffmann, Karl-Titus; Lobsien, Donald

    2015-01-01

    The typical form of mild encephalitis/encephalopathy with a reversible splenial lesion— called MERS type I—is characterized by a singular, reversible lesion in the midline of the splenium. Very rarely, additional lesions with similar signal characteristics can occur in other brain areas, which is then referred to as MERS type II. We present the case of a patient with a reversible splenial lesion and concomitant reversible cerebellar lesions within the scope of an atypical hemolytic uremic syndrome (HUS).

  14. Shiga toxins present in the gut and in the polymorphonuclear leukocytes circulating in the blood of children with hemolytic-uremic syndrome.

    Science.gov (United States)

    Brigotti, Maurizio; Caprioli, Alfredo; Tozzi, Alberto E; Tazzari, Pier Luigi; Ricci, Francesca; Conte, Roberto; Carnicelli, Domenica; Procaccino, Maria Antonietta; Minelli, Fabio; Ferretti, Alfonso V S; Paglialonga, Fabio; Edefonti, Alberto; Rizzoni, Gianfranco

    2006-02-01

    Hemolytic-uremic syndrome, the main cause of acute renal failure in early childhood, is caused primarily by intestinal infections from some Escherichia coli strains that produce Shiga toxins. The toxins released in the gut are targeted to renal endothelium after binding to polymorphonuclear leukocytes. The presence of Shiga toxins in the feces and the circulating neutrophils of 20 children with hemolytic uremic syndrome was evaluated by the Vero cell cytotoxicity assay and flow cytometric analysis, respectively. The latter showed the presence of Shiga toxins on the polymorphonuclear leukocytes of 13 patients, 5 of whom had no other microbiologic or serologic evidence of infection by Shiga toxin-producing Escherichia coli. A positive relationship was observed between the amounts of Shiga toxins released in the intestinal lumen and those released in the bloodstream. The toxins were detectable on the neutrophils for a median period of 5 days after they were no longer detectable in stools. This investigation confirms that the immunodetection of Shiga toxins on neutrophils is a valuable tool for laboratory diagnosis of Shiga toxin-producing Escherichia coli infection in hemolytic-uremic syndrome and provides clues for further studies on the role of neutrophils in the pathogenesis of this syndrome.

  15. Shiga Toxins Present in the Gut and in the Polymorphonuclear Leukocytes Circulating in the Blood of Children with Hemolytic-Uremic Syndrome†

    Science.gov (United States)

    Brigotti, Maurizio; Caprioli, Alfredo; Tozzi, Alberto E.; Tazzari, Pier Luigi; Ricci, Francesca; Conte, Roberto; Carnicelli, Domenica; Procaccino, Maria Antonietta; Minelli, Fabio; Ferretti, Alfonso V. S.; Paglialonga, Fabio; Edefonti, Alberto; Rizzoni, Gianfranco

    2006-01-01

    Hemolytic-uremic syndrome, the main cause of acute renal failure in early childhood, is caused primarily by intestinal infections from some Escherichia coli strains that produce Shiga toxins. The toxins released in the gut are targeted to renal endothelium after binding to polymorphonuclear leukocytes. The presence of Shiga toxins in the feces and the circulating neutrophils of 20 children with hemolytic uremic syndrome was evaluated by the Vero cell cytotoxicity assay and flow cytometric analysis, respectively. The latter showed the presence of Shiga toxins on the polymorphonuclear leukocytes of 13 patients, 5 of whom had no other microbiologic or serologic evidence of infection by Shiga toxin-producing Escherichia coli. A positive relationship was observed between the amounts of Shiga toxins released in the intestinal lumen and those released in the bloodstream. The toxins were detectable on the neutrophils for a median period of 5 days after they were no longer detectable in stools. This investigation confirms that the immunodetection of Shiga toxins on neutrophils is a valuable tool for laboratory diagnosis of Shiga toxin-producing Escherichia coli infection in hemolytic-uremic syndrome and provides clues for further studies on the role of neutrophils in the pathogenesis of this syndrome. PMID:16455876

  16. Angiopoietin-1 and -2 as markers for disease severity in hemolytic uremic syndrome induced by enterohemorrhagic Escherichia coli.

    Science.gov (United States)

    Shimizu, Masaki; Inoue, Natsumi; Kuroda, Mondo; Mizuta, Mao; Sugimoto, Naotoshi; Kaneda, Hisashi; Ohta, Kazuhide; Yachie, Akihiro

    2017-02-01

    Angiopoietin (Ang)-1 and -2 play important roles in maintaining vascular homeostasis. This study aimed to assess the roles of angiopoietin (Ang)-1 and -2 and to investigate the clinical significance of their serum levels in patients with hemolytic uremic syndrome (HUS) induced by enterohemorrhagic Escherichia coli (EHEC). Twenty patients with HUS and 15 healthy controls were studied. Serum Ang-1 and Ang-2 levels were quantified using enzyme-linked immunosorbent assay. The results were compared with the clinical features of HUS. During the HUS phase, serum Ang-1 levels were significantly decreased, whereas serum Ang-2 levels and the Ang-2/Ang-1 ratio were significantly elevated. Compared with patients without encephalopathy, serum Ang-2 levels and Ang-2/Ang-1 ratio were significantly elevated in patients with encephalopathy. Patients with HUS and serum Ang-2 levels of >7061 pg/mL or Ang2/Ang1 ratios of >2.29 were at high risk of encephalopathy. Serum Ang-1 levels were significantly decreased in patients in the pre-HUS phase compared with those in healthy controls. Disruption of homeostasis of vascular endothelial function by Ang-1 and -2 may be closely associated with the development of HUS. Serum Ang-1 and -2 levels and the Ang-2/Ang-1 ratio may be promising indicators of disease activity in HUS and the development of encephalopathy.

  17. Encephalopathy, disseminated intravascular coagulation, and hemolytic-uremic syndrome after infection with enterohemorrhagic Escherichia coli O111.

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    Matano, Sadaya; Inamura, Katsuhisa; Konishi, Michio; Okumura, Toshiya; Kawai, Hiroshi; Okamura, Toshiyuki; Takata, Yoshiko; Yamada, Keiko; Obata, Misato; Nagata, Hajime; Muramoto, Yoshiko; Sugimoto, Tatsuho

    2012-08-01

    An outbreak of enterohemorrhagic Escherichia coli (EHEC) occurred in Toyama and other prefectures in Japan during 2011. Some patients, including adults, showed complications such as encephalopathy, disseminated intravascular coagulation, and hemolytic-uremic syndrome, and the disease course was extremely aggressive. This report describes the clinical features of four patients infected with Escherichia coli (E. coli) O111 who developed very severe to fatal complications. The initial symptoms in all patients included abdominal pain, diarrhea, and bloody stools, and neurological abnormalities started to appear from 1 to 3 days after admission. Vomiting and pyrexia developed in three patients. Leukocyte counts, lactate dehydrogenase (LDH), and fibrin/fibrinogen degradation products were elevated, and thrombocytopenia was evident. Extremely elevated LDH and severe thrombocytopenia were characteristic at the time encephalopathy became apparent. All patients received oral fosfomycin, intravenous antibiotics, and anticoagulant therapy, three received gamma globulin, plasma exchange, and blood transfusion, and two received steroids and dialysis. Three patients required mechanical ventilation, and two adult patients died. E. coli O111 positive for Shiga toxin 2 was detected in stool culture in two patients, and serological tests for E. coli O111 were positive in the other two patients. In conclusion, EHEC O111 can cause severe illness in children and adults, and the prognosis becomes poorer as the severity of complications increases. Close monitoring including platelet counts and LDH are useful. Once these clinical parameters change, intensive treatment should be provided to prevent the development of severe complications.

  18. Soluble tumor necrosis factor receptor 1 and tissue inhibitor of metalloproteinase-1 in hemolytic uremic syndrome with encephalopathy.

    Science.gov (United States)

    Shiraishi, Masahiro; Ichiyama, Takashi; Matsushige, Takeshi; Iwaki, Takuma; Iyoda, Kuniaki; Fukuda, Ken; Makata, Haruyuki; Matsubara, Tomoyo; Furukawa, Susumu

    2008-05-30

    Enterohemorrhagic Escherichia coli (EHEC) induces hemorrhagic colitis and hemolytic uremic syndrome (HUS). Morbidity and mortality are increased in HUS patients with neurologic complications. To determine the pathogenesis of the central nervous system (CNS) involvement in HUS by EHEC, we determined the serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 (sTNFR1), IL-10, interferon-gamma (IFN-gamma), IL-2, IL-4, soluble E-selectin (sE-selectin), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) during the acute stage in children with HUS with or without CNS involvement. Serum concentrations of IL-6, IL-10, sTNFR1, sE-selectin, MMP-9, and TIMP-1, but not TNF-alpha, IFN-gamma, IL-2, or IL-4, were significantly higher in patients with HUS with encephalopathy compared with controls. Serum IL-6, sTNFR1 and TIMP-1 concentrations were significantly higher in patients with HUS with encephalopathy compared with those with HUS without encephalopathy (P=0.031, P=0.005, and P=0.007, respectively) and those with acute colitis without HUS (P=0.011, Pencephalopathy. Our preliminary study suggests that serum IL-6, sTNFR1 and TIMP-1 levels, particularly sTNFR1 and TIMP-1, are important for predicting neurological complications in patients with HUS.

  19. Acute Renal Replacement Therapy in Children with Diarrhea-Associated Hemolytic Uremic Syndrome: A Single Center 16 Years of Experience

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    Silviu Grisaru

    2011-01-01

    Full Text Available Acute kidney injury (AKI is becoming more prevalent among hospitalized children, its etiologies are shifting, and new treatment modalities are evolving; however, diarrhea-associated hemolytic uremic syndrome (D+HUS remains the most common primary disease causing AKI in young children. Little has been published about acute renal replacement therapy (ARRT and its challenges in this population. We describe our single center's experience managing 134 pediatric patients with D+HUS out of whom 58 (43% required ARRT over the past 16 years. In our cohort, all but one patient were started on peritoneal dialysis (PD. Most patients, 47 (81%, received acute PD on a pediatric inpatient ward. The most common recorded complications in our cohort were peritoneal fluid leaks 13 (22%, peritonitis 11 (20%, and catheter malfunction 5 (9%. Nine patients (16% needed surgical revision of their PD catheters. There were no bleeding events related to PD despite a mean platelets count of 40.9 (±23.5 × 103/mm3 and rare use of platelets infusions. Despite its methodological limitations, this paper adds to the limited body of evidence supporting the use of acute PD as the primary ARRT modality in children with D+HUS.

  20. The functional state of neutrophils correlates with the severity of renal dysfunction in children with hemolytic uremic syndrome.

    Science.gov (United States)

    Fernandez, Gabriela C; Gomez, Sonia A; Ramos, Maria V; Bentancor, Leticia V; Fernandez-Brando, Romina J; Landoni, Veronica I; Lopez, Laura; Ramirez, Flavia; Diaz, Mario; Alduncin, Marta; Grimoldi, Irene; Exeni, Ramon; Isturiz, Martin A; Palermo, Marina S

    2007-01-01

    Hemolytic Uremic Syndrome (HUS) is the main cause of acute renal failure in children. The high percentage of patients who develop long-term sequelae constitutes an important medical concern. The identification of parameters that correlate with the degree of renal failure may be useful to plan the best treatment soon after hospitalization. Here, we investigated the functional state of neutrophils (PMN) from HUS patients on admission, before dialysis and/or transfusion, in relation to the severity of renal impairment reached during the acute period (AP). We found that all PMN activation parameters measured in severe cases of HUS (HUS AP3) were statistically lower comparing to children with mild cases of HUS (HUS AP1). As HUS PMN phenotype and dysfunction is compatible with that of cells undergoing cell death, we also studied spontaneous apoptosis. Not only were HUS PMN not apoptotic, but HUS AP3 PMN showed an increased survival. Almost all phenotypic and functional parameters measured on PMN correlated with severity. Our results revealed a marked deactivation of PMN in severe cases of HUS, and suggest that studying the functional state of PMN could be of prognostic value.

  1. Unusual Manifestation of Severe Conjugated Hyperbilirubinemia in an Infant with Streptococcus pneumoniae-associated Hemolytic Uremic Syndrome

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    Jung-Pin Chen

    2007-01-01

    Full Text Available Streptococcus pneumoniae is an uncommon etiologic organism in children with hemolytic uremic syndrome (HUS. Historically, severe S. pneumoniae-associated HUS usually has a poor clinical outcome. The clinical manifestations of marked jaundice and hepatic dysfunction in this form of HUS are extremely rare. We report a 10-month-old female infant with S. pneumoniae-associated HUS who had the unusual manifestation of severely elevated conjugated bilirubin and hepatic transaminases. Screening for viral hepatitis was negative, and evidence of biliary obstruction and hepatotoxic drug exposure was also absent. The patient was treated with antihypertensive agents for 2.5 months and required peritoneal dialysis for a period of 26 days. Hepatic function returned to normal on the 8th day of hospitalization. Renal function was mildly impaired at 1-year follow-up. Our report suggests that severe conjugated hyperbilirubinemia is a rare manifestation of S. pneumoniae-associated HUS in children. It is important for pediatricians that pneumococcal infection with severe hematologic and renal disorders should be investigated for evidence of S. pneumoniae-associated HUS. [J Formos Med Assoc 2007;106(2 Suppl:S17-S22

  2. Association among Complement Factor H Autoantibodies, Deletions of CFHR, and the Risk of Atypical Hemolytic Uremic Syndrome.

    Science.gov (United States)

    Jiang, Hong; Fan, Meng-Nan; Yang, Min; Lu, Chao; Zhang, Ming; Liu, Xiao-Hong; Ma, Le

    2016-12-05

    To evaluate the association among complement factor H-related (CFHRs) gene deficiency, complement factor H (CFH) autoantibodies, and atypical hemolytic uremic syndrome (aHUS) susceptibility. EMBASE, PubMed, and the ISI Web of Science databases were searched for all eligible studies on the relationship among CFHRs deficiency, anti-FH autoantibodies, and aHUS risk. Eight case-control studies with 927 cases and 1182 controls were included in this study. CFHR1 deficiency was significantly associated with an increased risk of aHUS (odds ratio (OR) = 3.61, 95% confidence interval (95% CI), 1.96, 6.63, p < 0.001), while no association was demonstrated in individuals with only CFHR1/R3 deficiency (OR = 1.32, 95% CI, 0.50, 3.50, p = 0.56). Moreover, a more significant correlation was observed in people with both FH-anti autoantibodies and CFHR1 deficiency (OR = 11.75, 95% CI, 4.53, 30.44, p < 0.001) in contrast to those with only CFHR1 deficiency. In addition, the results were essentially consistent among subgroups stratified by study quality, ethnicity, and gene detection methods. The present meta-analysis indicated that CFHR1 deletion was significantly associated with the risk of aHUS, particularly when combined with anti-FH autoantibodies, indicating that potential interactions among CFHR1 deficiency and anti-FH autoantibodies might impact the risk of aHUS.

  3. Bacterial genetic determinants of non-O157 STEC outbreaks and hemolytic-uremic syndrome after infection.

    Science.gov (United States)

    Wickham, Mark E; Lupp, Claudia; Mascarenhas, Mariola; Vazquez, Alejandra; Coombes, Brian K; Brown, Nat F; Coburn, Bryan A; Deng, Wanyin; Puente, Jose L; Karmali, Mohamed A; Finlay, B Brett

    2006-09-15

    Although O157:H7 Shiga toxin-producing Escherichia coli (STEC) are the predominant cause of hemolytic-uremic syndrome (HUS) in the world, non-O157:H7 serotypes are a medically important cause of HUS that are underdetected by current diagnostic approaches. Because Shiga toxin is necessary but not sufficient to cause HUS, identifying the virulence determinants that predict severe disease after non-O157 STEC infection is of paramount importance. Disease caused by O157:H7 STEC has been associated with a 26-gene pathogenicity island known as O island (OI) 122. To assess the public-health significance of this pathogenicity island, we examined the association between OI122 genes and outbreaks and HUS after non-O157 STEC infection. We found that a subset of OI122 genes is independently associated with outbreaks and HUS after infection with non-O157 STEC. The presence of multiple virulence genes in non-O157 serotypes strengthened this association, which suggests that the additive effects of a variable repertoire of virulence genes contribute to disease severity. In vivo, Citrobacter rodentium mutants lacking outbreak- and HUS-associated genes were deficient for virulence in mice; in particular, nleB mutant bacteria were unable to cause mortality in mice. The present study shows that virulence genes associated epidemiologically with outbreaks and HUS after non-O157 STEC infection are pivotal to the initiation, progression, and outcome of in vivo disease.

  4. Shiga toxin activates complement and binds factor H: evidence for an active role of complement in hemolytic uremic syndrome.

    Science.gov (United States)

    Orth, Dorothea; Khan, Abdul Basit; Naim, Asma; Grif, Katharina; Brockmeyer, Jens; Karch, Helge; Joannidis, Michael; Clark, Simon J; Day, Anthony J; Fidanzi, Sonja; Stoiber, Heribert; Dierich, Manfred P; Zimmerhackl, Lothar B; Würzner, Reinhard

    2009-05-15

    Infections with enterohemorrhagic Escherichia coli (EHEC) are a major cause of hemolytic uremic syndrome (HUS). Shiga toxins (Stxs), especially Stx2, are believed to represent major virulence factors of EHEC, contributing to HUS pathogenesis. Beside EHEC-associated HUS, there are hereditary atypical forms of HUS, which are mostly caused by mutations of complement regulators. The aim of the present study was to investigate whether or not complement is also involved in the pathogenesis of EHEC-induced typical HUS, by being activated either directly or indirectly by involvement of its inhibitors. Purified Stx2 markedly activated complement via the alternative pathway and was found to bind to factor H (FH), however, only when it was active. No apparent cleavage or destruction of FH was visible, and cofactor activity in fluid phase was unaffected, but clearly delayed for surface-attached FH, where it is essential for host cell protection. Binding studies using FH constructs revealed that Stx2 binds to short consensus repeats (SCRs) 6-8 and SCRs18-20, but not to SCRs16-17, i.e., to regions involved in the surface recognition function of FH. In conclusion, complement, and in particular FH, not only plays an important role in atypical HUS, but most probably also in EHEC-induced HUS.

  5. Characterization of a New DGKE Intronic Mutation in Genetically Unsolved Cases of Familial Atypical Hemolytic Uremic Syndrome

    Science.gov (United States)

    Mele, Caterina; Lemaire, Mathieu; Iatropoulos, Paraskevas; Piras, Rossella; Bresin, Elena; Bettoni, Serena; Bick, David; Helbling, Daniel; Veith, Regan; Valoti, Elisabetta; Donadelli, Roberta; Murer, Luisa; Neunhäuserer, Maria; Breno, Matteo; Frémeaux-Bacchi, Véronique; Lifton, Richard; Noris, Marina

    2015-01-01

    Background and objectives Genetic and acquired abnormalities causing dysregulation of the complement alternative pathway contribute to atypical hemolytic uremic syndrome (aHUS), a rare disorder characterized by thrombocytopenia, nonimmune microangiopathic hemolytic anemia, and acute kidney failure. However, in a substantial proportion of patients the disease-associated alterations are still unknown. Design, setting, participants, & measurements Whole-exome and whole-genome sequencing were performed in two unrelated families with infantile recessive aHUS. Sequencing of cDNA from affected individuals was used to test for the presence of aberrant mRNA species. Expression of mutant diacylglycerol kinase epsilon (DGKE) protein was evaluated with western blotting. Results Whole-exome sequencing analysis with conventional variant filtering parameters did not reveal any obvious candidate mutation in the first family. The report of aHUS-associated mutations in DGKE, encoding DGKE, led to re-examination of the noncoding DGKE variants obtained from next-generation sequencing, allowing identification of a novel intronic DGKE mutation (c.888+40A>G) that segregated with disease. Sequencing of cDNA from affected individuals revealed aberrant forms of DGKE mRNA predicted to cause profound abnormalities in the protein catalytic site. By whole-genome sequencing, the same mutation was found in compound heterozygosity with a second nonsense DGKE mutation in all affected siblings of another unrelated family. Homozygous and compound heterozygous patients presented similar clinical features, including aHUS presentation in the first year of life, multiple relapsing episodes, and proteinuria, which are prototypical of DGKE-associated aHUS. Conclusions This is the first report of a mutation located beyond the exon-intron boundaries in aHUS. Intronic mutations such as these are underreported because conventional filtering parameters used to process next-generation sequencing data routinely

  6. Serum tau protein as a marker of disease activity in enterohemorrhagic Escherichia coli O111-induced hemolytic uremic syndrome.

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    Kuroda, Mondo; Shimizu, Masaki; Inoue, Natsumi; Ikeno, Iku; Nakagawa, Hiroyasu; Yokoi, Ayano; Niida, Yo; Konishi, Michio; Kaneda, Hisashi; Igarashi, Noboru; Yamahana, Junya; Taneichi, Hiromichi; Kanegane, Hirokazu; Ito, Mika; Saito, Shigeru; Furuichi, Kengo; Wada, Takashi; Nakagawa, Masaru; Yokoyama, Hitoshi; Yachie, Akihiro

    2015-01-01

    Tau protein levels in cerebrospinal fluid (CSF) and serum are elevated in patients with various central nervous system diseases. We investigated whether serum tau protein levels are useful for predicting and assessing disease activity of acute encephalopathy (AE) in enterohemorrhagic Escherichia coli (EHEC) O111-induced hemolytic uremic syndrome (HUS; EHEC encephalopathy). Serum samples were obtained from 14 patients with EHEC O111/HUS, 20 patients with non-EHEC-related AE, and 20 age- and sex-matched healthy controls. CSF samples were obtained from 2 patients with EHEC encephalopathy and 20 patients with non-EHEC-related AE. Tau protein levels and levels of several proinflammatory cytokines were quantified by enzyme-linked immunosorbent assays. Results were compared with the clinical features of EHEC encephalopathy, including magnetic resonance image (MRI) findings. Serum tau levels in patients with EHEC encephalopathy were significantly elevated compared with those in patients with EHEC O111/HUS without encephalopathy, patients with non-EHEC-related AE, and healthy controls. The ratio of CSF tau levels to serum tau levels was >1.0 in all patients with non-EHEC-related AE but encephalopathy. Serum tau protein levels increased rapidly and markedly in patients with severe EHEC 0111/HUS and encephalopathy when HUS occurred, but were not elevated in mild patients, even in the HUS phase. Furthermore, changes in serum tau protein levels in patients with EHEC encephalopathy were consistent with abnormalities on brain MRI and were positively correlated with proinflammatory cytokine levels. Our results indicate that serum tau protein might be useful to predict and assess disease activity of EHEC encephalopathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Function of von Willebrand factor in children with diarrhea-associated hemolytic-uremic syndrome (D+ HUS).

    Science.gov (United States)

    Sutor, A H; Thomas, K B; Prüfer, F H; Grohmann, A; Brandis, M; Zimmerhackl, L B

    2001-06-01

    Reports on von Willebrand factor (vWF) in hemolytic-uremic syndrome (HUS) are not unequivocal. Because of potential pathogenic implications, we examined the ability of vWF to bind to collagen in vitro, which reflects its function. Plasma vWF antigen (vWF:Ag) and collagen-binding activity (vWF:CBA) were measured by enzyme-linked immunosorbent assay in children with (1) diarrhea-associated (D+) HUS (n = 27), (2) chronic renal insufficiency (CRI) (n = 8), (3) gastroenteritis (GE) not associated with HUS (n = 15), (4) immune thrombocytopenia (ITP) (n = 40) and from controls (n = 35). Structural vWF was evaluated by multimer analysis. Children with D+ HUS had vWF:Ag of 2.53 and vWF:CBA of 1.98 U/mL. The corresponding values for patients with ITP were 1.35 and 1.82 U/mL, with CRI 1.55 and 1.55 U/mL, and with GE 1.68 and 2.10 U/mL; all values were higher than in controls (1.04 and 1.16 U/mL). The mean ratio of vWF:CBA to vWF:Ag ratio in controls was 1.13; only children with HUS had a dysfunctional vWF, as indicated by a low ratio of 0.78; the ratio was elevated in children with ITP (1.36) and GE (1.27) and was normal in those with CRI (1.06). No ultralarge molecular multimers of vWF were detected in any group, including HUS. The very high concentration of plasma vWF:Ag in HUS probably reflects endothelial cell damage or irritation. In contrast to all other groups, only children with HUS had a dysfunctional vWF, caused either by a primary (due to enterohemorrhagic Escherichia coli) or secondary (due to consumption of functionally active vWF) process. This abnormality was not obvious as structural anomaly by multimer analysis.

  8. Fatal case of hemolytic-uremic syndrome in an adult due to a rare serogroup O91 Entero hemorrhagic Escherichia coli associated with a Clostridium difficile infection. More than meets the eye

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    Thomas Guillard

    2015-08-01

    Full Text Available Hemolytic-uremic syndrome due to enterohemorrhagic Escherichia coli, belonging to serogroup O91 has rarely been described. We report here a case of post-diarrheal HUS due to EHEC O91 in an elderly patient for whom diagnosis was delayed given a previously diagnosed C. difficile infection. This case highlights the usefulness of Shiga-toxin detection.

  9. Hemolytic-uremic syndrome with acute encephalopathy in a pregnant woman infected with epidemic enterohemorrhagic Escherichia coli: characteristic brain images and cytokine profiles.

    Science.gov (United States)

    Ito, M; Shiozaki, A; Shimizu, M; Saito, S

    2015-05-01

    A food-poisoning outbreak due to enterohemorrhagic Escherichia coli (EHEC) occurred in Toyama, Japan. The case of a 26-year-old pregnant woman with hemolytic-uremic syndrome who developed acute encephalopathy due to EHEC infection after eating raw meat is presented herein. On day 2 following admission, a cesarean section was performed because of a non-reassuring fetal status. Fecal bacterial culture confirmed an O111/O157 superinfection. Intensive care therapies including continuous hemodiafiltration and plasma exchange were performed. After the operation, the patient developed encephalopathy for which steroid pulse therapy was added. Her condition improved gradually and she was discharged 55 days after delivery. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. [Predictive indicators for progression to severe complications(hemolytic-uremic syndrome and encephalopathy) and their prevention in enterohemorrhagic Escherichia coli infection].

    Science.gov (United States)

    Joh, K

    1997-03-01

    The treatment of infection with enterohemorrhagic Escherichia coli(EHEC) aims for early prediction and prevention of severe complications such as hemolytic-uremic syndrome, encephalopathy and/or thrombotic thrombocytopenic purpura. Factors related to the complications are divided into three categories; risk factors or predisposition, predictors, and indicators of severity and outcome. Risk factors for complications include two extreme ages, infection with verotoxin 2 producing E. coli, positive stool culture for EHEC, use of antimotility drug, use of trimethoprim-sulfamethoxazole. Predictors for complications include severe abdominal pain and bloody diarrhea development of high fever, change of consciousness, urinal protein and/or occult blood, abrupt increase of white blood cell count, urinal NAG, alpha 1 microglobulin, beta 2 microglobulin, low osmolar urine, high thrombomodulin level, marked thickening of intestinal wall, increased brightness of kidney in ultrasound sonography. No preventive treatment for these complications is proven except SYNSORB-pk which is expected to effectively aborb verotoxin in the intestine.

  11. [Update on the treatment of endemic hemolytic uremic syndrome. Pathogenesis and treatment of the most severe systemic complication of infections by Shiga toxin-producing Escherichia coli].

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    Fernández-Brando, Romina J; Bentancor, Leticia V; Mejías, María Pilar; Panek, Analía C; Cabrera, Gabriel G; Exeni, Ramón A; Palermo, Marina S

    2011-01-01

    The typical form of hemolytic uremic syndrome (HUS) is the major complication of Shiga toxin-producing Escherichia coli (STEC) infections. HUS is a critical health problem in Argentina since it is the main cause of acute renal failure in children and the second cause of chronic renal failure, giving account for 20% of renal transplants in children and adolescents in our country. In spite of the extensive research in the field, the mainstay of treatment for patients with HUS is supportive therapy, and there are no specific therapies preventing or ameliorating the disease course. In this review, we present the current knowledge about pathogenic mechanisms and discuss traditional and innovative therapeutic approaches, with special focus in national status and contributions made by Argentinean groups.

  12. [Fenotypic and genotypic characterization of Shiga toxin-producing Escherichia coli O111 strain isolated from patient with hemolytic-uremic syndrome].

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    Januszkiewicz, Aleksandra; Podsiadły, Edyta; Szych, Jolanta; Semkowicz-Chmielewska, Anna; Demkow, Urszula; Pierzchlewicz, Anna; Rastawicki, Waldemar

    2010-01-01

    Shiga toxin-producing E. coli O157 and non-O157 are important emergance pathogens that can cause diarrhea and hemorrhagic colitis with life-threatening complications, such as hemolytic uremic syndrome (HUS). A few cases of EHEC infections are documented per year in Poland. Among them only one patient with EHEC O157 infection developed HUS. We characterized the first VTEC non-O157 strain isolated from child with HUS in Poland. The VTEC O111 strain produced Stx2 which was cytotoxic for Vero cell. Using DNA microarray analysis we have found set of virulence genes in VTEC O111 strain as: stx2A, stx2B, ehly, eae, tir tccP espA, espJ, cif nleA, nleB, lpfA, iha, efa1, cba. The strain was fenotypic resistant to streptomycin, tetracyclin and sulphonamides (strA, tetA, sul2 genes were detected).

  13. [Verotoxin as a major laboratory criterion for Escherichia coli O157-induced enteric infection complicated by hemolytic uremic syndrome in infants in the Omsk region].

    Science.gov (United States)

    Dolgikh, T I; Kaftyreva, L A; Voĭtovich, M A; Podkolzin, A T; Galileĭskaia, S B; Lazareva, L I

    2010-08-01

    The paper presents the results of etiological interpretation of the outbreak of Escherichia coli O157-induced enteric infection complicated by hemolytic uremic syndrome in Omsk in spring 2009. Seventeen infants aged 5 months to 2.5 years were examined; of them 9 patients were on hemodialysis. The diagnosis was verified in 7 children, by isolating verotoxin after fecal enrichment on the concentrating nutrient RIDA Enrichment Bouillon medium containing bile salts and mitomycin C, E. coli O157:H7 cultures on the sorbitol medium and/or by identifying E. coli O157 DNA. Six (4 having verotoxin) infants were found to have rotavirus and noro-virus antigens or DNA/RNA, which may make a contribution into the development of mixed infection and increase the risk of complications.

  14. The Shiga toxin genotype rather than the amount of Shiga toxin or the cytotoxicity of Shiga toxin in vitro correlates with the appearance of the hemolytic uremic syndrome.

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    Orth, Dorothea; Grif, Katharina; Khan, Abdul B; Naim, Asma; Dierich, Manfred P; Würzner, Reinhard

    2007-11-01

    Shiga toxins (Stx) are believed to play a key role in the pathogenesis of diseases caused by Stx-producing Escherichia coli (STEC), including the potentially life-threatening hemolytic uremic syndrome (HUS). In this study, 201 STEC strains collected from patients and environmental sources were investigated with regard to the stx genotypes and pathogenicity. The stx(2) and stx(2c) alleles were associated with high virulence and the ability to cause HUS, whereas stx(2d), stx(2e,)stx(1), and stx(1c) occurred in milder or asymptomatic infections. Quantification of Stx using an enzyme immunoassay and the Vero cell cytotoxicity assay showed no significant differences between the strains associated with HUS and those causing milder diseases. We hypothesize that the stx genotype and perhaps other yet unknown virulence factors rather than the amount of Stx or the in vitro cytotoxicity correlate with the development of HUS.

  15. Chemiluminescence determination of antioxidant property of Zizyphus mistol and Prosopis alba during oxidative stress generated in blood by Hemolytic Uremic Syndrome-producing Escherichia coli.

    Science.gov (United States)

    Albrecht, Claudia; Pellarin, María G; Baronetti, José; Rojas, María J; Albesa, Inés; Eraso, Alberto J

    2011-01-01

    This study was undertaken to elucidate the antioxidant effect of Zizyphus mistol and Prosopis alba, with the hypothesis that these fruits can counteract the induction of reactive oxygen species (ROS) caused by toxins produced by Escherichia coli. In the search of nutrients effective against the Hemolytic Uremic Syndrome (HUS), we detected by chemiluminescence a protective role of both plants, due to their natural antioxidants significantly decreasing the levels of ROS induced by toxins from E. coli in blood. The ferric reducing antioxidant power (FRAP) was found to be higher in Z. mistol than in P. alba. The chemical analyses of the phenols and flavonoids present in the fruit extracts indicated that the FRAP correlated with the amount of phenolic compounds, but not with the flavonoids analyzed. Both fruits studied reduce the induction of ROS, and in this way help to prevent the development of complications related to oxidative stress generated in the blood of patients with HUS.

  16. Circulating microRNAs in patients with Shiga-Toxin-producing E. coli O104:H4 induced hemolytic uremic syndrome.

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    Johan M Lorenzen

    Full Text Available BACKGROUND: In early May 2011, an outbreak of hemorrhagic colitis associated with hemolytic-uremic syndrome (HUS first developed in Northern Germany and spread to 15 other countries in Europe. The outbreak-strain O104:H4, which combined virulence factors of typical enteroaggregative and Shiga-Toxin-producing E. coli was associated with an unusual high rate of hemolytic uremic syndrome. Also an unexpected high rate of coma and seizures leading to mechanical ventilation and ICU treatment was observed. MicroRNAs are small ribonucleotides orchestrating gene expression. We tested whether circulating microRNAs in serum of HUS patients during the 2011 epidemics are altered in this patient cohort and related to clinical manifestations. METHODOLOGY/PRINCIPAL FINDINGS: We profiled microRNAs using RNA isolated from serum of patients and healthy age-matched controls. The results were validated in 38 patients at baseline, 29 patients during follow-up and 21 age-matched healthy controls by miRNA-specific quantitative RT-PCR. Circulating levels of miR-24, miR-126 were increased in HUS patients versus controls. There was no association between these microRNAs and renal function or the need for renal replacement therapy. In contrast, levels of miR-126 were associated with neurological symptoms at baseline and during follow-up. In addition, miR-126 (on admission and miR-24 (on admission and during follow-up were associated with platelet count. CONCLUSIONS/SIGNIFICANCE: Circulating microRNAs are strongly altered in this patient cohort and associated with neurological symptoms as well as platelet count.

  17. Distinct Renal Pathology and a Chemotactic Phenotype after Enterohemorrhagic Escherichia coli Shiga Toxins in Non-Human Primate Models of Hemolytic Uremic Syndrome

    Science.gov (United States)

    Stearns-Kurosawa, Deborah J.; Oh, Sun-Young; Cherla, Rama P.; Lee, Moo-Seung; Tesh, Vernon L.; Papin, James; Henderson, Joel; Kurosawa, Shinichiro

    2014-01-01

    Enterohemorrhagic Escherichia coli cause approximately 1.5 million infections globally with 176,000 cases occurring in the United States annually from ingesting contaminated food, most frequently E. coli O157:H7 in ground beef or fresh produce. In severe cases, the painful prodromal hemorrhagic colitis is complicated by potentially lethal hemolytic uremic syndrome (HUS), particularly in children. Bacterial Shiga-like toxins (Stx1, Stx2) are primarily responsible for HUS and the kidney and neurologic damage that ensue. Small animal models are hampered by the inability to reproduce HUS with thrombotic microangiopathy, hemolytic anemia, and acute kidney injury. Earlier, we showed that nonhuman primates (Papio) recapitulated clinical HUS after Stx challenge and that novel therapeutic intervention rescued the animals. Here, we present detailed light and electron microscopic pathology examination of the kidneys from these Stx studies. Stx1 challenge resulted in more severe glomerular endothelial injury, whereas the glomerular injury after Stx2 also included prominent mesangiolysis and an eosinophilic inflammatory infiltration. Both toxins induced glomerular platelet-rich thrombi, interstitial hemorrhage, and tubular injury. Analysis of kidney and other organs for inflammation biomarkers showed a striking chemotactic profile, with extremely high mRNA levels for IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1α and elevated urine chemokines at 48 hours after challenge. These observations give unique insight into the pathologic consequences of each toxin in a near human setting and present potential pathways for therapeutic intervention. PMID:23402998

  18. Shiga toxin-induced complement-mediated hemolysis and release of complement-coated red blood cell-derived microvesicles in hemolytic uremic syndrome.

    Science.gov (United States)

    Arvidsson, Ida; Ståhl, Anne-Lie; Hedström, Minola Manea; Kristoffersson, Ann-Charlotte; Rylander, Christian; Westman, Julia S; Storry, Jill R; Olsson, Martin L; Karpman, Diana

    2015-03-01

    Shiga toxin (Stx)-producing Escherichia coli (STEC) cause hemolytic uremic syndrome (HUS). This study investigated whether Stx2 induces hemolysis and whether complement is involved in the hemolytic process. RBCs and/or RBC-derived microvesicles from patients with STEC-HUS (n = 25) were investigated for the presence of C3 and C9 by flow cytometry. Patients exhibited increased C3 deposition on RBCs compared with controls (p microvesicles during the acute phase, which decreased after recovery. Stx2 bound to P1 (k) and P2 (k) phenotype RBCs, expressing high levels of the P(k) Ag (globotriaosylceramide), the known Stx receptor. Stx2 induced the release of hemoglobin and lactate dehydrogenase in whole blood, indicating hemolysis. Stx2-induced hemolysis was not demonstrated in the absence of plasma and was inhibited by heat inactivation, as well as by the terminal complement pathway Ab eculizumab, the purinergic P2 receptor antagonist suramin, and EDTA. In the presence of whole blood or plasma/serum, Stx2 induced the release of RBC-derived microvesicles coated with C5b-9, a process that was inhibited by EDTA, in the absence of factor B, and by purinergic P2 receptor antagonists. Thus, complement-coated RBC-derived microvesicles are elevated in HUS patients and induced in vitro by incubation of RBCs with Stx2, which also induced hemolysis. The role of complement in Stx2-mediated hemolysis was demonstrated by its occurrence only in the presence of plasma and its abrogation by heat inactivation, EDTA, and eculizumab. Complement activation on RBCs could play a role in the hemolytic process occurring during STEC-HUS. Copyright © 2015 by The American Association of Immunologists, Inc.

  19. Fatal case of hemolytic-uremic syndrome in an adult due to a rare serogroup O91 Entero hemorrhagic Escherichia coli associated with a Clostridium difficile infection. More than meets the eye.

    Science.gov (United States)

    Guillard, Thomas; Limelette, Anne; Le Magrex-Debar, Elisabeth; Wynckel, Alain; Gouali, Malika; Mariani-Kurkdjian, Patricia; Guyot-Colosio, Charlotte; de Champs, Christophe

    2015-08-01

    Hemolytic-uremic syndrome due to enterohemorrhagic Escherichia coli, belonging to serogroup O91 has rarely been described. We report here a case of post-diarrheal HUS due to EHEC O91 in an elderly patient for whom diagnosis was delayed given a previously diagnosed C. difficile infection. This case highlights the usefulness of Shiga-toxin detection. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Síndrome Hemolítico-Urêmica Pós-parto: Relato de Caso Postpartum Hemolytic Uremic Syndrome: A Case Report

    Directory of Open Access Journals (Sweden)

    José Geraldo Lopes Ramos

    2002-09-01

    Full Text Available A síndrome hemolítico-urêmica (SHU é processo microangiopático associado a insuficiência renal, determinando alta morbidade e mortalidade. A gestação pode ser um fator precipitante, por meio de mecanismos ainda não bem estabelecidos. Entram no diagnóstico diferencial a pré-eclâmpsia, a síndrome HELLP, o fígado gorduroso agudo da gestação e a púrpura trombocitopênica trombótica. Relatamos um caso de SHU ocorrendo no pós-parto imediato em paciente com diagnóstico inicial de pré-eclâmpsia. O diagnóstico diferencial foi fundamentado na perda abrupta da função renal, acompanhada de instabilidade pressórica e sinais clínicos e laboratoriais de hemólise. São destacados os métodos diagnósticos disponíveis, manejo terapêutico e fatores prognósticos baseados em revisão de literatura.The hemolytic - uremic syndrome (HUS presents with a triad of acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia associated with high morbidity and mortality. On the differential diagnosis, other entities must be considered like preeclampsia, HELLP syndrome, acute fatty liver of pregnancy and thrombotic thrombocytopenic purpura. We report a case of HUS occurring in the immediate postpartum period in a patient initially diagnosed as having preeclampsia. The differential diagnosis was based on abrupt renal failure, blood pressure increase and clinical and laboratorial evidence of hemolysis. Attention is directed to investigation, clinical management and prognosis based on review of the literature.

  1. Maintenance of kidney function following treatment with eculizumab and discontinuation of plasma exchange after a third kidney transplant for atypical hemolytic uremic syndrome associated with a CFH mutation.

    Science.gov (United States)

    Davin, Jean-Claude; Gracchi, Valentina; Bouts, Antonia; Groothoff, Jaap; Strain, Lisa; Goodship, Tim

    2010-04-01

    Kidney transplant in patients with atypical hemolytic uremic syndrome (aHUS) is associated with a poor outcome because of recurrent disease, especially in patients known to have a factor H mutation. Long-term prophylactic plasma exchange and combined liver-kidney transplant have prevented graft loss caused by recurrence. However, the mortality associated with liver transplant is not negligible, and prophylactic plasma exchange requires permanent vascular access and regular hospitalization and exposes the patient to potential allergic reactions to plasma. Eculizumab is a high-affinity humanized monoclonal antibody that binds to C5 and thus prevents generation of C5a and the membrane attack complex. We report the case of a 17-year-old girl with aHUS associated with a mutation in the gene for complement factor H (CFH; c.3572C>T, Ser1191Leu) who was highly dependent on plasma exchange. Because of severe allergic reactions to plasma after the third renal graft, eculizumab was introduced in place of plasma exchange without problems. This and other reports suggest that the promise of complement inhibitors in the management of aHUS is going to be fulfilled.

  2. Timing and utility of ultrasound in diarrhea-associated hemolytic uremic syndrome: 7-year experience of a large tertiary care hospital.

    Science.gov (United States)

    Glatstein, Miguel; Miller, Elka; Garcia-Bournissen, Facundo; Scolnik, Dennis

    2010-05-01

    The authors reviewed the clinical, laboratory, and imaging data from cases of diarrhea-associated hemolytic uremic syndrome (HUS D+), diagnosed at our institution, from 2001 to 2008. The timing and utility of ultrasonographic features of HUS D+ were analyzed. The aim of the study was to determine factors that could aid in the early diagnosis of this disease. A total of 13 children with HUS D+ were identified out of 23 patients with HUS diagnosed during this time period. Evidence of Escherichia coli 0157:H7 was found in 9 cases (70%). Ultrasound studies were ordered in 10 patients (71%), all of which showed renal sonographic findings compatible with HUS. Ultrasound was performed at a mean of 13 days after onset of the diarrhea. Of note, 2 patients whose ultrasounds were performed at the beginning of their diarrheal illness manifested ultrasonographic features suggestive of HUS when there was only a mild increase in serum creatinine and no decrease in hemoglobin or platelets, suggesting that ultrasonography can identify renal involvement early in the course of the disease before other systemic signs appear. Early renal ultrasound may be a useful adjunct in the initial evaluation in children with bloody diarrhea. Evidence of increased renal echogenicity in a patient with bloody diarrhea could aid in early recognition of HUS when other diagnoses such as intussusceptions are being entertained, potentially allowing early intervention.

  3. Quantitative MRI shows cerebral microstructural damage in hemolytic-uremic syndrome patients with severe neurological symptoms but no changes in conventional MRI

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    Weissenborn, Karin; Worthmann, Hans; Heeren, Meike [Hannover Medical School, Clinic for Neurology, Hannover (Germany); Bueltmann, Eva; Donnerstag, Frank; Giesemann, Anja M.; Goetz, Friedrich; Lanfermann, Heinrich; Ding, Xiao-Qi [Hannover Medical School, Institute of Diagnostic and Interventional Neuroradiology, Hannover (Germany); Kielstein, Jan; Schwarz, Anke [Hannover Medical School, Clinic for Nephrology and Hypertension, Hannover (Germany)

    2013-07-15

    Severe neurological symptoms in Shiga toxin-producing Escherichia coli infection associated hemolytic-uremic syndrome (STEC-HUS) are often accompanied by none or only mild alterations of cerebral magnetic resonance imaging (MRI). This study aims to analyze if quantitative MRI is able to reveal cerebral pathological alterations invisible for conventional MRI. In nine patients with STEC-HUS associated severe neurological symptoms but inconspicuous cerebral MRI findings maps of the parameters T2 relaxation time, relative proton density (PD), apparent diffusion coefficient (ADC), and fractional anisotropy (FA) were generated. Quantitative values of these parameters were measured at the basal ganglia, thalamus, and white matter of the frontal and parietal lobe and compared to those of nine age- and sex-matched controls. Significant T2 prolongation (p < 0.01) was found in the basal ganglia of all patients compared to controls. PD and ADC were not significantly altered. A significant reduction of FA in patients was seen at caput nuclei caudati (p < 0.01). Prolonged T2 relaxation time indicates cerebral microstructural damages in these patients despite their inconspicuous MRI findings. T2 relaxometry could be used as a complementary tool for the assessment of metabolic-toxic brain syndromes. (orig.)

  4. Síndrome hemolítico-urêmica esporádica pós-parto Sporadic postpartum hemolytic uremic syndrome

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    Elza M. Moreira

    2008-08-01

    Full Text Available Anemia hemolítica microangiopática associado à trombocitopenia participa de um grupo de doenças que freqüentemente apresentam suas características clínicas muito semelhantes, sendo difícil distingui-las. A síndrome hemolítico-urêmica é dividida em duas apresentações: a forma não esporádica, que acomete comumente crianças após infecção bacteriana causando diarréia sanguinolenta, possui bom prognóstico; e a forma esporádica, que acomete adultos, sendo bem descritos casos em mulheres pósparto, é a forma sistêmica de trombocitopenia microangiopática de pior prognóstico com alta morbidade e mortalidade, cuja falência renal é o distúrbio predominante. Relatamos um caso de síndrome hemolítico-urêmica pós-parto em paciente previamente sadia, que apresentou quadro de insuficiência renal, anemia hemolítica e trombocitopenia. Instituída a terapêutica de suporte adequada e precocemente, a paciente evoluiu satisfatoriamente com normalização dos níveis pressóricos e recuperação da função renal.Microangiopathic hemolytic associated with thrombocytopenia is part of a disease group that frequently show likeness and that's why become difficult to separate them. There are two types of hemolytic uremic syndrome (HUS; the non sporadic type and the epidemic or "typical" type that is common on childreen that is associated with diarrhea and infection caused by verotoxinaproducing E. coli with a good prognostic; and the sporadic postpartum period. It is the systemic type of mocroangiophatic thrombocytopenia of poor prognostic with high morbidity and mortality which renal failure is the main disturb. We reported a case of HUS occuring in postpartum previously healthy, that showed abrupt renal failure, hemolytic anemia and thrombocytopenia. After proper therapy the patient developed a normal blood pressure and recovery renal function.

  5. Síndrome hemolítico-urêmica relacionada à infecção invasiva pelo Streptococcus pneumoniae Hemolytic-uremic syndrome complicating invasive pneumococcal disease

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    Anna Leticia de O. Cestari

    2008-03-01

    Full Text Available OBJETIVO: A doença pneumocócica é importante problema de saúde pública e raramente há associação desta infecção com a síndrome hemolítico-urêmica (SHU grave. O objetivo deste artigo é relatar o caso de um paciente com esta associação. DESCRIÇÃO DO CASO: Criança do sexo masculino, com 17 meses de idade, admitida no hospital com insuficiência respiratória aguda e necessitando de suporte ventilatório. O exame radiológico mostrava extensa opacidade homogênea em hemitórax direito. A hemocultura foi positiva para Streptococcus pneumoniae. Nos exames de admissão, notaram-se: hemoglobina de 6,5g/dL, 38.000 plaquetas/mm³, uréia de 79mg/dL e creatinina de 1,64mg/dL. No primeiro dia, apresentou oligoanúria e hipervolemia, necessitando de hemodiafiltração. Evoluiu com disfunção de múltiplos órgãos e óbito no sétimo dia. A necrópsia mostrou áreas extensas de necrose cortical e tubular renal, com depósito de fibrina nas arteríolas. COMENTÁRIOS: A SHU associada ao pneumococo apresenta morbidade e mortalidade elevadas. Em crianças com doença pneumocócica invasiva e acometimento hematológico ou renal grave, deve-se estar atento a esta rara complicação. Merecem investigação os seguintes aspectos relacionados à doença: a função da detecção precoce de antígenos T ativados no diagnóstico e terapêutica, o papel do fator H na patogênese, o método ideal de substituição renal e a definição do prognóstico em longo prazo.OBJECTIVE: Pneumococcal diseases are a major public health problem. Severe hemolytic-uremic syndrome is an uncommon complication. The aim of this study is to report a child with this complication. CASE DESCRIPTION: A male child with 17 months old was admitted to the hospital, due to acute respiratory failure, needing ventilatory support. Roentgenogram demonstrated massive condensation of right lung and Streptococcus pneumonia was isolated from blood cultures. Laboratory tests showed

  6. Antibody response to Shiga toxins in Argentinean children with enteropathic hemolytic uremic syndrome at acute and long-term follow-up periods.

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    Romina J Fernández-Brando

    Full Text Available Shiga toxin (Stx-producing Escherichia coli (STEC infection is associated with a broad spectrum of clinical manifestations that include diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS. Systemic Stx toxemia is considered to be central to the genesis of HUS. Distinct methods have been used to evaluate anti-Stx response for immunodiagnostic or epidemiological analysis of HUS cases. The development of enzyme-linked immunosorbent assay (ELISA and western blot (WB assay to detect the presence of specific antibodies to Stx has introduced important advantages for serodiagnosis of HUS. However, application of these methods for seroepidemiological studies in Argentina has been limited. The aim of this work was to develop an ELISA to detect antibodies against the B subunit of Stx2, and a WB to evaluate antibodies against both subunits of Stx2 and Stx1, in order to analyze the pertinence and effectiveness of these techniques in the Argentinean population. We studied 72 normal healthy children (NHC and 105 HUS patients of the urban pediatric population from the surrounding area of Buenos Aires city. Using the WB method we detected 67% of plasma from NHC reactive for Stx2, but only 8% for Stx1. These results are in agreement with the broad circulation of Stx2-expressing STEC in Argentina and the endemic behavior of HUS in this country. Moreover, the simultaneous evaluation by the two methods allowed us to differentiate acute HUS patients from NHC with a great specificity and accuracy, in order to confirm the HUS etiology when pathogenic bacteria were not isolated from stools.

  7. Antibody response to Shiga toxins in Argentinean children with enteropathic hemolytic uremic syndrome at acute and long-term follow-up periods.

    Science.gov (United States)

    Fernández-Brando, Romina J; Bentancor, Leticia V; Mejías, María Pilar; Ramos, María Victoria; Exeni, Andrea; Exeni, Claudia; Laso, María del Carmen; Exeni, Ramón; Isturiz, Martín A; Palermo, Marina S

    2011-04-29

    Shiga toxin (Stx)-producing Escherichia coli (STEC) infection is associated with a broad spectrum of clinical manifestations that include diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Systemic Stx toxemia is considered to be central to the genesis of HUS. Distinct methods have been used to evaluate anti-Stx response for immunodiagnostic or epidemiological analysis of HUS cases. The development of enzyme-linked immunosorbent assay (ELISA) and western blot (WB) assay to detect the presence of specific antibodies to Stx has introduced important advantages for serodiagnosis of HUS. However, application of these methods for seroepidemiological studies in Argentina has been limited. The aim of this work was to develop an ELISA to detect antibodies against the B subunit of Stx2, and a WB to evaluate antibodies against both subunits of Stx2 and Stx1, in order to analyze the pertinence and effectiveness of these techniques in the Argentinean population. We studied 72 normal healthy children (NHC) and 105 HUS patients of the urban pediatric population from the surrounding area of Buenos Aires city. Using the WB method we detected 67% of plasma from NHC reactive for Stx2, but only 8% for Stx1. These results are in agreement with the broad circulation of Stx2-expressing STEC in Argentina and the endemic behavior of HUS in this country. Moreover, the simultaneous evaluation by the two methods allowed us to differentiate acute HUS patients from NHC with a great specificity and accuracy, in order to confirm the HUS etiology when pathogenic bacteria were not isolated from stools.

  8. An outbreak of diarrhea and hemolytic uremic syndrome from Escherichia coli O157:H7 in fresh-pressed apple cider.

    Science.gov (United States)

    Besser, R E; Lett, S M; Weber, J T; Doyle, M P; Barrett, T J; Wells, J G; Griffin, P M

    1993-05-05

    Escherichia coli O157:H7 causes hemorrhagic colitis and the hemolytic uremic syndrome. In the fall of 1991, an outbreak of E coli O157:H7 infections in southeastern Massachusetts provided an opportunity to identify transmission by a seemingly unlikely vehicle. Case-control study to determine the vehicle of infection. New England cider producers were surveyed to assess production practices and determined the survival time of E coli O157:H7 organisms in apple cider. Illness was significantly associated with drinking one brand of apple cider. Thirteen (72%) of 18 patients but only 16 (33%) of 49 controls reported drinking apple cider in the week before illness began (odds ratio [OR], 8.3; 95% confidence interval [CI], 1.8 to 39.7). Among those who drank cider, 12 (92%) of 13 patients compared with two (13%) of 16 controls drank cider from cider mill A (lower 95% CI, 2.9; P cider in a manner similar to that used by other small cider producers: apples were not washed, cider was not pasteurized, and no preservatives were added. In the laboratory, E coli O157:H7 organisms survived for 20 days in unpreserved refrigerated apple cider. Addition of sodium benzoate 0.1% reduced survival to less than 7 days. Fresh-pressed, unpreserved apple cider can transmit E coli O157:H7 organisms, which cause severe infections. Risk of transmission can be reduced by washing and brushing apples before pressing, and preserving cider with sodium benzoate. Consumers can reduce their risk by only drinking cider made from apples that have been washed and brushed.

  9. Mutations of factor H impair regulation of surface-bound C3b by three mechanisms in atypical hemolytic uremic syndrome.

    Science.gov (United States)

    Lehtinen, Markus J; Rops, Angelique L; Isenman, David E; van der Vlag, Johan; Jokiranta, T Sakari

    2009-06-05

    Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy associated with mutations in complement proteins, most frequently in the main plasma alternative pathway regulator factor H (FH). The hotspot for the FH mutations is in domains 19-20 (FH19-20) that are indispensable for FH activity on C3b bound covalently to host cells. In aHUS, down-regulation of cell-bound C3b by FH is impaired, but it is not clear whether this is due to an altered FH binding to surface-bound C3b or to cell surface structures. To explore the molecular pathogenesis of aHUS we tested binding of 14 FH19-20 point mutants to C3b and its C3d fragment, mouse glomerular endothelial cells (mGEnC-1), and heparin. The cell binding correlated well, but not fully, with heparin binding and the cell binding site was overlapping but distinct from the C3b/C3d binding site that was shown to extend to domain 19. Our results show that aHUS-associated FH19-20 mutants have different combinations of three primary defects: impaired binding to C3b/C3d, impaired binding to the mGEnC-1 cells/heparin, and, as a novel observation, an enhanced mGEnC-1 cell or heparin binding. We propose a model of the molecular pathogenesis of aHUS where all three mechanisms lead eventually to impaired control of C3b on the endothelial cell surfaces. Based on the results with the aHUS patient mutants and the overlap in FH19-20 binding sites for mGEnC-1/heparin and C3b/C3d we conclude that binding of FH19-20 to C3b/C3d is essential for target discrimination by the alternative pathway.

  10. Molecular microbiological investigation of an outbreak of hemolytic-uremic syndrome caused by dry fermented sausage contaminated with Shiga-like toxin-producing Escherichia coli.

    Science.gov (United States)

    Paton, A W; Ratcliff, R M; Doyle, R M; Seymour-Murray, J; Davos, D; Lanser, J A; Paton, J C

    1996-01-01

    Shiga-like toxin-producing Escherichia coli (SLTEC) strains are a diverse group of organisms which are known to cause diarrhea and hemorrhagic colitis in humans. This can lead to potentially fatal systemic sequelae, such as hemolytic-uremic syndrome (HUS). Strains belonging to more than 100 different O:H serotypes have been associated with severe SLTEC disease in humans, of which only O157 strains (which are uncommon in Australia) have a distinguishable cultural characteristic (sorbitol negative). During an outbreak of HUS in Adelaide, South Australia, a sensitive PCR assay specific for Shiga-like toxin genes (slt) was used to test cultures of feces and suspected foods. This enabled rapid confirmation of infection and identified a locally produced dry fermented sausage (mettwurst) as the source of infection. Cultures of feces from 19 of 21 HUS patients and 7 of 8 mettwurst samples collected from their homes were PCR positive for slt-I and slt-II genes. SLTEC isolates belonging to serotype O111:H- was subsequently isolated from 16 patients and 4 mettwurst samples. Subsequent restriction fragment length polymorphism analysis of chromosomal DNA from these isolates with slt-specific probes indicated that at least three different O111:H- genotypes were associated with the outbreak. Pulsed-field gel electrophoresis of genomic DNA restricted with XbaI showed that two of these restriction fragment length polymorphism types were closely related, but the third was quite distinct. However, SLTEC strains of other serotypes, including O157:H-, were also isolated from some of the HUS patients. PMID:8784557

  11. Virulence profiling and quantification of verocytotoxin-producing Escherichia coli O145:H28 and O26:H11 isolated during an ice cream-related hemolytic uremic syndrome outbreak.

    Science.gov (United States)

    Buvens, Glenn; Possé, Björn; De Schrijver, Koen; De Zutter, Lieven; Lauwers, Sabine; Piérard, Denis

    2011-03-01

    In September-October 2007, a mixed-serotype outbreak of verocytotoxin-producing Escherichia coli (VTEC) O145:H28 and O26:H11 occurred in the province of Antwerp, Belgium. Five girls aged between 2 and 11 years developed hemolytic uremic syndrome, and seven other coexposed persons with bloody diarrhea were identified. Laboratory confirmation of O145:H28 infection was obtained for three hemolytic uremic syndrome patients, one of whom was coinfected with O26:H11. The epidemiological and laboratory investigations revealed ice cream as the most likely source of the outbreak. The ice cream was produced at a local dairy farm using pasteurized milk. VTEC of both serotypes with indistinguishable pulsed-field gel electrophoresis patterns were isolated from patients, ice cream, and environmental samples. Quantitative analysis of the ice cream indicated concentrations of 2.4 and 0.03 CFU/g for VTEC O145 and O26, respectively. Virulence typing revealed that the repertoire of virulence genes carried by the O145:H28 outbreak strain was comparable to that of O157 VTEC and more exhaustive as compared to the O26:H11 outbreak strain and nonrelated clinical strains belonging to these serotypes. Taken together, these data suggest that O145:H28 played the most important role in this outbreak.

  12. Mutations of Factor H Impair Regulation of Surface-bound C3b by Three Mechanisms in Atypical Hemolytic Uremic Syndrome*

    Science.gov (United States)

    Lehtinen, Markus J.; Rops, Angelique L.; Isenman, David E.; van der Vlag, Johan; Jokiranta, T. Sakari

    2009-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy associated with mutations in complement proteins, most frequently in the main plasma alternative pathway regulator factor H (FH). The hotspot for the FH mutations is in domains 19–20 (FH19–20) that are indispensable for FH activity on C3b bound covalently to host cells. In aHUS, down-regulation of cell-bound C3b by FH is impaired, but it is not clear whether this is due to an altered FH binding to surface-bound C3b or to cell surface structures. To explore the molecular pathogenesis of aHUS we tested binding of 14 FH19–20 point mutants to C3b and its C3d fragment, mouse glomerular endothelial cells (mGEnC-1), and heparin. The cell binding correlated well, but not fully, with heparin binding and the cell binding site was overlapping but distinct from the C3b/C3d binding site that was shown to extend to domain 19. Our results show that aHUS-associated FH19–20 mutants have different combinations of three primary defects: impaired binding to C3b/C3d, impaired binding to the mGEnC-1 cells/heparin, and, as a novel observation, an enhanced mGEnC-1 cell or heparin binding. We propose a model of the molecular pathogenesis of aHUS where all three mechanisms lead eventually to impaired control of C3b on the endothelial cell surfaces. Based on the results with the aHUS patient mutants and the overlap in FH19–20 binding sites for mGEnC-1/heparin and C3b/C3d we conclude that binding of FH19–20 to C3b/C3d is essential for target discrimination by the alternative pathway. PMID:19351878

  13. Molecular analysis of Shiga toxigenic Escherichia coli O111:H- proteins which react with sera from patients with hemolytic-uremic syndrome.

    Science.gov (United States)

    Voss, E; Paton, A W; Manning, P A; Paton, J C

    1998-04-01

    Western blot analysis was used to assess the reactivity of convalescent-phase sera from patients who were associated with an outbreak of hemolytic-uremic syndrome (HUS) caused by fermented sausage contaminated with Shiga toxin-producing Escherichia coli (STEC). The predominant STEC isolated from HUS patients belonged to serotype O111:H-, and reactivity to O111:H- whole-cell lysates, treated or untreated with proteinase K, was examined. As expected, all five serum samples demonstrated a marked anti-lipopolysaccharide response, but several protein bands were also immunoreactive, particularly one with an apparent size of 94 kDa. One convalescent-phase serum sample was subsequently used to screen an O111:H- cosmid bank and 2 of 900 cosmid clones were found to be positive, both of which contained a similar DNA insert. Western blot analysis of one of these clones identified three major immunoreactive protein bands of approximately 94, 70, and 50 kDa. An immune response to the three proteins was detectable with all five convalescent-phase serum samples but not with healthy human serum. Immunoreactive 94- and 50-kDa species were produced by a deletion derivative of the cosmid containing a 7-kb STEC DNA insert. Sequence analysis of this region indicated that it is part of the locus for enterocyte effacement, including the eaeA gene which encodes intimin. The deduced amino acid sequence of the O111:H- intimin was 88.6% identical to intimin from O157:H7 STEC, and the most divergent region was the 200 residues at the carboxyl terminus, which were only 75% identical. Such variation may be antigenically significant as serum from a HUS patient infected only with the O111:H- STEC reacted with intimin from an enteropathogenic E. coli O111 strain, as well as several other eaeA-positive STEC isolates, but not with an eaeA-positive STEC belonging to serotype O157:H-. Sera from two of the other HUS patients also failed to react with intimin from this latter strain. However, intimin

  14. Molecular Analysis of Shiga Toxigenic Escherichia coli O111:H− Proteins Which React with Sera from Patients with Hemolytic-Uremic Syndrome

    Science.gov (United States)

    Voss, Elena; Paton, Adrienne W.; Manning, Paul A.; Paton, James C.

    1998-01-01

    Western blot analysis was used to assess the reactivity of convalescent-phase sera from patients who were associated with an outbreak of hemolytic-uremic syndrome (HUS) caused by fermented sausage contaminated with Shiga toxin-producing Escherichia coli (STEC). The predominant STEC isolated from HUS patients belonged to serotype O111:H−, and reactivity to O111:H− whole-cell lysates, treated or untreated with proteinase K, was examined. As expected, all five serum samples demonstrated a marked anti-lipopolysaccharide response, but several protein bands were also immunoreactive, particularly one with an apparent size of 94 kDa. One convalescent-phase serum sample was subsequently used to screen an O111:H− cosmid bank and 2 of 900 cosmid clones were found to be positive, both of which contained a similar DNA insert. Western blot analysis of one of these clones identified three major immunoreactive protein bands of approximately 94, 70, and 50 kDa. An immune response to the three proteins was detectable with all five convalescent-phase serum samples but not with healthy human serum. Immunoreactive 94- and 50-kDa species were produced by a deletion derivative of the cosmid containing a 7-kb STEC DNA insert. Sequence analysis of this region indicated that it is part of the locus for enterocyte effacement, including the eaeA gene which encodes intimin. The deduced amino acid sequence of the O111:H− intimin was 88.6% identical to intimin from O157:H7 STEC, and the most divergent region was the 200 residues at the carboxyl terminus, which were only 75% identical. Such variation may be antigenically significant as serum from a HUS patient infected only with the O111:H− STEC reacted with intimin from an enteropathogenic E. coli O111 strain, as well as several other eaeA-positive STEC isolates, but not with an eaeA-positive STEC belonging to serotype O157:H−. Sera from two of the other HUS patients also failed to react with intimin from this latter strain. However

  15. Síndrome urémico hemolítico. Tratamiento de la glomerulopatía secundaria Hemolytic uremic syndrome. Treatment of secondary glomerulopathy

    Directory of Open Access Journals (Sweden)

    María G. Caletti

    2005-12-01

    Full Text Available La insuficiencia renal crónica es la complicación más grave del síndrome urémico hemolítico (SUH. En el año 1996 se publicó la secuencia histológica de su evolución en pacientes con períodos oligoanúricos prolongados. En los últimos años se han propuesto diferentes esquemas terapéuticos para enlentecer la evolución a la insuficiencia renal crónica terminal en distintas nefropatías, diabéticas y no diabéticas, cuya expresión puede comenzar aun en la adolescencia. En este trabajo se comenta la respuesta a dos esquemas terapéuticos de dos grupos de pacientes con SUH que presentaron proteinuria con o sin hipertensión arterial e insuficiencia renal. Se enfatiza la indicación de la dieta hiposódica y controlada en proteínas en el mismo momento del alta del paciente y la incorporación de un inhibidor de la enzima de conversión de angiotensina II, iECA, (enalapril al comienzo de la aparición de la proteinuria.Chronic renal failure (CRF is the most severe complication of hemolytic uremic syndrome (HUS. In 1996, the histological sequence of changes in patients with long lasting oligoanuric periods was clarified. In the last years different therapeutic schemes have been proposed in order to slacken the development of terminal CRF in different renal conditions secondary to diabetes and other diseases. Some of these cases can suffer the onset of renal failure at adolescence. In this review, response to two treatment schemes in different patients with HUS and proteinuria with or without hypertension or renal failure is commented. Early indication of poor sodium diet and strict control of protein intake at the very moment of hospital discharge is strongly recommended, as well as angiotensin II conversion inhibiting enzymes (iACE at the appearance of proteinuria.

  16. Severe form of hemolytic-uremic syndrome with multiple organ failure in a child: a case report [v1; ref status: indexed, http://f1000r.es/24q

    Directory of Open Access Journals (Sweden)

    Dino Mijatovic

    2014-03-01

    Full Text Available Introduction: Hemolytic-uremic syndrome (HUS is a leading cause of acute renal failure in infants and young children. It is traditionally defined as a triad of acute renal failure, hemolytic anemia and thrombocytopenia that occur within a week after prodromal hemorrhagic enterocolitis. Severe cases can also be presented by acute respiratory distress syndrome (ARDS, toxic megacolon with ileus, pancreatitis, central nervous system (CNS disorders and multiple organ failure (MOF. Case presentation: A previously healthy 4-year old Caucasian girl developed acute renal failure, thrombocytopenia and hemolytic anemia following a short episode of abdominal pain and bloody diarrhea. In the next week of, what initially appeared as typical HUS, she developed MOF, including ileus, pancreatitis, hepatitis, coma and ARDS, accompanied by hemodynamic instability and extreme leukocytosis. Nonetheless, the girl made a complete recovery after one month of the disease. She was successfully treated in the intensive care unit and significant improvement was noticed after plasmapheresis and continuous veno-venous hemodialysis. Conclusions: Early start of plasmapheresis and meticulous supportive treatment in the intensive care unit, including renal placement therapy, may be the therapy of choice in severe cases of HUS presented by MOF. Monitoring of prognostic factors is important for early performance of appropriate diagnostic and therapeutical interventions.

  17. Hemolytic Uremic Syndrome in Children

    Science.gov (United States)

    ... the presence of E. coli O157:H7 . Kidney Biopsy Biopsy is a procedure that involves taking a ... Grants & Grant History Research Resources Research at NIDDK Technology Advancement & Transfer Meetings & Events Health Information Diabetes Digestive ...

  18. [Hemolytic uremic syndrome in children

    NARCIS (Netherlands)

    Heuvelink, A.E.; Loo, D.M.W.M. te; Monnens, L.A.H.

    2001-01-01

    In Europe, haemolytic uraemic syndrome (HUS) is the most frequent cause of acute renal insufficiency during childhood. In the Netherlands about 20 children per year are seriously affected. Following a prodromal phase of mostly bloody diarrhoea, the main symptoms become evident, namely, haemolytic an

  19. 非典型溶血尿毒综合征分子遗传学研究进展%Progress on molecular genetics in atypical hemolytic uremic syndrome

    Institute of Scientific and Technical Information of China (English)

    高力敏

    2011-01-01

    非典型溶血尿毒综合征是一种罕见的有遗传倾向的疾病,易患基因主要是补体旁路途径活化的调控基因:补体因子H基因、膜辅助蛋白基因和补体因子Ⅰ基因.但其总突变率约为50%,突变类型包括错义突变、无义突变、缺失突变、插入突变和剪切位点突变.遗传方式有常染色体隐性遗传和常染色体显性遗传,显性遗传的三个突变基因均为不完全外显.%Atypical hemolytic uremic syndrome(aHUS) has recently been shown to be a rare disease of genetic predisposition, including genes of complement factor H(CFH), membrane cofactor protein(MCP, CD46)and complement factor Ⅰ(CFI), which are complement regulatory genes. Genes mutation is about 50%,involving the three genes mutation, including nonsense mutation, missen mutation, silent mutation, splice mutation and insertion mutation. Autosomal dominant inheritance and autosomal recessive inheritance have been reported, however, for autosomal dominant inheritance, the three genes mutations are incomplete penetrance.

  20. Inherited complement regulatory protein deficiency predisposes to human disease in acute injury and chronic inflammatory statesthe examples of vascular damage in atypical hemolytic uremic syndrome and debris accumulation in age-related macular degeneration.

    Science.gov (United States)

    Richards, Anna; Kavanagh, David; Atkinson, John P

    2007-01-01

    In this chapter, we examine the role of complement regulatory activity in atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD). These diseases are representative of two distinct types of complement-mediated injury, one being acute and self-limited, the other reflecting accumulation of chronic damage. Neither condition was previously thought to have a pathologic relationship to the immune system. However, alterations in complement regulatory protein genes have now been identified as major predisposing factors for the development of both diseases. In aHUS, heterozygous mutations leading to haploinsufficiency and function-altering polymorphisms in complement regulators have been identified, while in AMD, polymorphic haplotypes in complement genes are associated with development of disease. The basic premise is that a loss of function in a plasma or membrane inhibitor of the alternative complement pathway allows for excessive activation of complement on the endothelium of the kidney in aHUS and on retinal debris in AMD. These associations have much to teach us about the host's innate immune response to acute injury and to chronic debris deposition. We all experience cellular injury and, if we live long enough, will deposit debris in blood vessel walls (atherosclerosis leading to heart attacks and strokes), the brain (amyloid proteins leading to Alzheimer's disease), and retina (lipofuscin pigments leading to AMD). These are three common causes of morbidity and mortality in the developed world. The clinical, genetic, and immunopathologic understandings derived from the two examples of aHUS and AMD may illustrate what to anticipate in related conditions. They highlight how a powerful recognition and effector system, the alternative complement pathway, reacts to altered self. A response to acute injury or chronic debris accumulation must be appropriately balanced. In either case, too much activation or too little regulation promotes

  1. Hemolytic anemia

    Science.gov (United States)

    Anemia - hemolytic ... bones that helps form all blood cells. Hemolytic anemia occurs when the bone marrow isn't making ... destroyed. There are several possible causes of hemolytic anemia. Red blood cells may be destroyed due to: ...

  2. Clinical Analysis of Six Cases of Postpartum Hemolytic Uremic Syndrome%产后溶血性尿毒症综合征6例临床分析

    Institute of Scientific and Technical Information of China (English)

    许咏梅; 周信芳; 梁宝权

    2014-01-01

    Objective To investigate the clinic features of postpartum hemolytic uremic syndrome (PHUS)for early diagnosis,prompt therapy and better prognosis.Methods A retrospective study was conducted on clinical data of 6 PHUS patients with gestational age over 33 weeks in Suzhou Hospital Affiliated to Nanjing Medical University from January 2008 to December 2012.Clinical symptoms and signs,hemolytic uremic related indexes,ultrasonograph and peripheral blood smear of them were analyzed. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Suzhou Hospital Affiliated to Nanjing Medical University.Results All 6 patients had pregnancy combined with severe preeclampsia.After antispasmodic,antihypertensive treatment and promot fetal lung mature,they gave birth by cesarean section,and no neonatal death.The main symptoms were gradually oliguria and anuria without remote cause,hemolytic anemia,thrombocytopenia and sharp decline of renal function after 1-2 days of cesarean section.Through comprehensive treatment based on continuous renal replacement therapy (CRRT)and plasma exchange,the patient′s conditions were stable and improved,and all patients were discharged from hospital.After 1 year follow up ,3 cases(50.0%)were lost to follow up,1 case(16.7%) with chronic renal insufficiency.Conclusions Preeclampsia is one of the important remote causes of PHUS.It′s necessary to strengthen renal function monitoring of pregnant women with preeclampsia after childbirth,in order to make early diagnosis and give specialized treatment in time,which are significant measures to reduce maternal mortality and ensure mother′s healthy.%目的:探讨产后溶血性尿毒症综合征(PHUS)的临床特征,为该病的早期诊断、及时治疗和改善预后提供依据。方法选择2008年1月至2012年12月南京医科大学附属苏州医院收治的6例PHUS患者的病历资料为研究对象,孕龄≥33孕周。采用回顾性分析法分析其临

  3. Escherichia coli enterohemorrágica y síndrome urémico hemolítico en Argentina Enterohemorrhagic Escherichia coli and hemolytic-uremic syndrome in Argentina

    Directory of Open Access Journals (Sweden)

    Mariana A. Rivero

    2004-08-01

    Full Text Available El síndrome urémico hemolítico (SUH.es un desorden multisistémico caracterizado por presentar insuficiencia renal aguda, anemia hemolítica microangiopática y trombocitopenia. Constituye la principal causa de insuficiencia renal aguda y la segunda causa de insuficiencia renal crónica y de transplante renal en niños en la Argentina. Actualmente, nuestro país presenta el registro más alto de SUH en todo el mundo, con aproximadamente 420 casos nuevos declarados anualmente y una incidencia de 12.2/100 000 niños menores de 5 años de edad. Se reconocen múltiples agentes etiológicos, aunque se considera a la infección por Escherichia coli enterohemorrágica (EHEC como la principal etiología de SUH. La gran mayoría de brotes epidémicos y casos esporádicos en humanos se han asociado con el serotipo O157:H7, aunque otros serotipos han sido también aislados, y éstos son un subgrupo de E. coli verocitotoxigénico (VTEC..El bovino es considerado el principal reservorio de VTEC. El contagio al hombre frecuentemente se debe al consumo de alimentos cárneos y lácteos contaminados, deficientemente cocidos o sin pasteurizar, o al contacto directo con los animales o con sus heces, consumo de agua, frutas o verduras contaminadas. También puede producirse contagio mediante el contacto interhumano.The hemolytic-uremic syndrome (HUS is a multisystemic disorder that is characterized by the onset of acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. It is the most common cause of acute renal failure and the second cause of chronic renal failure and renal transplantation in children in Argentina. Our country has the highest incidence of HUS in the world, with approximately 420 new cases observed each year with an incidence of 12.2 cases per 100 000 children in the age group 0-5 years. Numerous etiologic factors have been associated with HUS but the infection with enterohemorrhagic Escherichia coli (EHEC is considered the

  4. Complement in hemolytic anemia.

    Science.gov (United States)

    Brodsky, Robert A

    2015-01-01

    Complement is increasingly being recognized as an important driver of human disease, including many hemolytic anemias. Paroxysmal nocturnal hemoglobinuria (PNH) cells are susceptible to hemolysis because of a loss of the complement regulatory proteins CD59 and CD55. Patients with atypical hemolytic uremic syndrome (aHUS) develop a thrombotic microangiopathy (TMA) that in most cases is attributable to mutations that lead to activation of the alternative pathway of complement. For optimal therapy, it is critical, but often difficult, to distinguish aHUS from other TMAs, such as thrombotic thrombocytopenic purpura; however, novel bioassays are being developed. In cold agglutinin disease (CAD), immunoglobulin M autoantibodies fix complement on the surface of red cells, resulting in extravascular hemolysis by the reticuloendothelial system. Drugs that inhibit complement activation are increasingly being used to treat these diseases. This article discusses the pathophysiology, diagnosis, and therapy for PNH, aHUS, and CAD.

  5. Hemolytic uremic syndrome recurrence after renal transplantation.

    Science.gov (United States)

    Loirat, Chantal; Fremeaux-Bacchi, Véronique

    2008-09-01

    About 60% of non-Stx-associated aHUS are due to the defect of protection of endothelial cells from complement activation, secondary to mutations in the genes of CFH, MCP, IF, BF, or C3. In addition, 10% of patients have anti-CFH antibodies. While the risk of post-transplant recurrence is less than 1% in Stx-HUS patients, it is approximately 80% in CFH or IF-mutated patients, 20% in MCP-mutated patients, and 30% in patients with no mutation. Patients with anti-CFH antibodies probably also are at risk of recurrence. While MCP-mutated patients can reasonably go to transplantation, recent reports suggest that plasmatherapy started before surgery and maintained life-long may prevent recurrence in CFH-mutated patients. Four successful liver-kidney transplantation utilizing plasmatherapy in CFH-mutated children have been reported recently. In summary, the risk of post-transplant recurrence can now be approached according to genotype. Therefore, aHUS patients should undergo complement determination, screening for anti-CFH antibodies, and genotyping before transplantation. Kidney or kidney + liver transplantation with concomitant plasmatherapy need to be evaluated by prospective trials in patients with hereditary complement abnormalities.

  6. Microangiopatias trombóticas: púrpura trombocitopênica trombótica e síndrome hemolítico-urêmica Thrombotic microangiopathies: thrombotic thrombocytopenic purpura / hemolytic uremic syndrome

    Directory of Open Access Journals (Sweden)

    Maria Goretti Polito

    2010-09-01

    complemento. Uma série de mutações e polimorfismo em genes que codificam proteínas reguladoras do complemento sozinhas ou em combinação podem levar a SHU atípica. Aproximadamente 60% dos casos de SHU atípica têm mutações do tipo "perda da função" em genes que codificam as proteínas reguladoras do complemento, as quais protegem as células hospedeiras da ativação do complemento: fator H do complemento (FHC, fator I (FIC e proteína cofator de membrana (PCM ou CD46, ou mutações do tipo "ganho da função" em genes que codificam o FHC ou C3. Além disso, aproximadamente 10% dos pacientes com SHU atípica têm deficiência na função do FHC devido a anticorpos anti-FHC. Mesmo que as MATs sejam condições altamente heterogêneas, um terço dos pacientes tem deficiência severa da ADA-MTS13. Transfusões de plaquetas são contraindicadas nesses pacientes. Infusão de plasma ou plasma exchange (PE é o único tratamento eficiente.Thrombotic microangiopathies (TMAs are pathological conditions characterized by generalized microvascular occlusion by platelet thrombi, thrombocytopenia, and microangiopathic hemolytic anemia. Two typical phenotypes of TMAs are hemolytic- uremic syndrome (HUS and thrombotic thrombocytopenic purpura (TTP. Other disorders occasionally present with similar manifestations. Depending on whether renal or brain lesions prevail, two pathologically indistinguishable but somehow clinically different disorders have been described: HUS and TTP. Injury to the endothelial cell is the central and likely inciting factor in the sequence of events leading to TMA. Loss of physiological thromboresistance, leukocyte adhesion to damaged endothelium, complement consumption, abnormal von Willebrand factor release and fragmentation, and increased vascular shear stress may then sustain and amplify the microangiopathic process. Intrinsic abnormalities of the complement system and of the von Willebrand factor pathway may account for a genetic predisposition to the

  7. Postdiarrheal Shiga Toxin-Mediated Hemolytic Uremic Syndrome Similar to Septic Shock Síndrome urémico hemolítico símil shock séptico, posterior a diarrea mediada por toxina shiga

    Directory of Open Access Journals (Sweden)

    Patricia G. Valles

    2005-10-01

    Full Text Available The inflammatory response of host endothelial cells is included in the development of vascular damage observed in enterohemorrhagic Escherichia coli (EHEC infection, resulting in hemolytic uremic syndrome (HUS. The response to a non-conventional treatment for a group of D+ HUS (diarrhea positive HUS patients, with clinical hemodynamic parameters of septic shock was evaluated in this prospective study (1999-2003. Twelve children 2.8 ± 0.6 years old, with D+ HUS produced by E. coli infection with serological evidence of Shiga toxin, presenting severe unstable hemodynamic parameters and neurological dysfunction at onset, were studied. The protocol included fresh frozen plasma infusions, methylprednisolone pulses (10mg/k/day for three consecutive days and plasma exchange for five days, starting after admission to the intensive care unit (ICU. The twelve patients with increased pediatric risk of mortality (PRISM score: 18 ± 2 after admission to intensive care unit (ICU, required dialysis for 17.4 ± 4 days, mechanical ventilator assistance for 10 ± 1 days and early inotropic drugs support for 10.5 ± 1 days. Neurological dysfunction included generalized tonic-clonic seizures lasting for 5.4 ± 1 days, n:8. Focal seizures were present in the remaining patients. Dilated cardiomyopathy was present in 6 children. Eight children suffered hemorrhagic colitis. Nine patients survived. Within one year of the injury, neurological sequelae, Glasgow outcome scale (GOS 3 and 4, were present in two patients, chronic renal failure in one patient. We suggest that early introduction of this protocol could benefit D+ HUS patients with hemodynamic instability and neurological dysfunction at onset. Further studies are likely to elucidate the mechanisms involved in this early adverse clinical presentation of D+ HUS patients.La respuesta inflamatoria de la célula endotelial se incluye en el desarrollo del daño vascular observado en la infección por Escherichia coli

  8. Immune hemolytic anemia

    Science.gov (United States)

    Anemia - immune hemolytic; Autoimmune hemolytic anemia (AIHA) ... for no reason, the condition is called idiopathic autoimmune hemolytic anemia . The antibodies may also be caused by: Complication ...

  9. Types of Hemolytic Anemia

    Science.gov (United States)

    ... from the NHLBI on Twitter. Types of Hemolytic Anemia There are many types of hemolytic anemia. The ... the condition, but you develop it. Inherited Hemolytic Anemias With inherited hemolytic anemias, one or more of ...

  10. New aspects in the pathogenesis of enteropathic hemolytic uremic syndrome

    NARCIS (Netherlands)

    Karch, Helge; Friedrich, Alexander W; Gerber, Angela; Zimmerhackl, Lothar B; Schmidt, M Alexander; Bielaszewska, Martina

    2006-01-01

    Shiga toxin (Stx) subtyping suggests that the clinical outcome of infections caused by Shiga toxin-producing ESCHERICHIA COLI (STEC) depends, in large part, on the STX genotype of the infecting strain. Whereas the presence of the STX2 or STX2C genotype is associated with the ability of STEC to cause

  11. Mechanisms underlying uremic encephalopathy.

    Science.gov (United States)

    Scaini, Giselli; Ferreira, Gabriela Kozuchovski; Streck, Emilio Luiz

    2010-06-01

    In patients with renal failure, encephalopathy is a common problem that may be caused by uremia, thiamine deficiency, dialysis, transplant rejection, hypertension, fluid and electrolyte disturbances or drug toxicity. In general, encephalopathy presents with a symptom complex progressing from mild sensorial clouding to delirium and coma. This review discusses important issues regarding the mechanisms underlying the pathophysiology of uremic encephalopathy. The pathophysiology of uremic encephalopathy up to now is uncertain, but several factors have been postulated to be involved; it is a complex and probably multifactorial process. Hormonal disturbances, oxidative stress, accumulation of metabolites, imbalance in excitatory and inhibitory neurotransmitters, and disturbance of the intermediary metabolism have been identified as contributing factors. Despite continuous therapeutic progress, most neurological complications of uremia, like uremic encephalopathy, fail to fully respond to dialysis and many are elicited or aggravated by dialysis or renal transplantation. On the other hand, previous studies showed that antioxidant therapy could be used as an adjuvant therapy for the treatment of these neurological complications.

  12. Actualización en el tratamiento del síndrome urémico hemolítico endémico: Patogénesis y tratamiento de la complicación sistémica más grave de las infecciones por Escherichia coli productor de toxina Shiga Update on the treatment of endemic hemolytic uremic syndrome: Pathogenesis and treatment of the most severe systemic complication of infections by Shiga toxin-producing Escherichia coli

    Directory of Open Access Journals (Sweden)

    Romina J. Fernández-Brando

    2011-08-01

    Full Text Available La forma típica o post-diarreica del síndrome urémico hemolítico (SUH es la complicación más grave de las infecciones por cepas de Escherichia coli productoras de toxina Shiga (STEC. En la Argentina el SUH es un problema crítico de salud pública, ya que representa la principal causa de falla renal aguda en la infancia, la segunda causa de falla renal crónica, y aporta el 20% de los casos de transplante renal durante la infancia y la adolescencia. A pesar de los avances en el conocimiento de su patogénesis, el único tratamiento actual de los pacientes con SUH es de sostén, y no existen terapias específicas ni preventivas. En la presente revisión expondremos los conocimientos básicos de los mecanismos patogénicos y discutiremos los enfoques terapéuticos tradicionales e innovadores, con especial foco en la situación nacional y los aportes hechos por grupos de la Argentina.The typical form of hemolytic uremic syndrome (HUS is the major complication of Shiga toxin-producing Escherichia coli (STEC infections. HUS is a critical health problem in Argentina since it is the main cause of acute renal failure in children and the second cause of chronic renal failure, giving account for 20% of renal transplants in children and adolescents in our country. In spite of the extensive research in the field, the mainstay of treatment for patients with HUS is supportive therapy, and there are no specific therapies preventing or ameliorating the disease course. In this review, we present the current knowledge about pathogenic mechanisms and discuss traditional and innovative therapeutic approaches, with special focus in national status and contributions made by Argentinean groups.

  13. Electrocardiographic abnormalities and uremic cardiomyopathy

    NARCIS (Netherlands)

    Stewart, GA; Gansevoort, RT; Mark, PB; Rooney, E; McDonagh, TA; Dargie, HJ; Stuart, R; Rodger, C; Jardine, AG

    2005-01-01

    Background. Progressive renal disease is associated with an increased risk of cardiovascular death, specifically sudden death. We investigated the link between uremic cardiomyopathy, QT interval and dispersal, and arrhythmias (by ambulatory ECG monitoring) in patients at different stages of progress

  14. Guanidino compounds as uremic (neuro)toxins.

    Science.gov (United States)

    De Deyn, Peter Paul; Vanholder, Raymond; Eloot, Sunny; Glorieux, Griet

    2009-01-01

    Neurological and vascular impairment are important sources of morbidity in patients with renal failure. A portion of patients still suffers from uremic encephalopathy or other signs of nervous system impairment. Several reports demonstrate increased incidence of cardiac infarction and cerebrovascular accidents in chronic renal failure patients, even in those otherwise adequately dialyzed. Epileptic and cognitive symptoms are among the most typical manifestations of uremic encephalopathy. Several guanidino compounds (GCs) may play an important role in the etiology of uremic encephalopathy. Four GCs appeared to be substantially increased as well in serum, cerebrospinal fluid, and brain of uremic patients. These compounds, "uremic" GCs, are creatinine, guanidine (G), guanidinosuccinic acid (GSA), and methylguanidine. All four compounds are experimental convulsants in concentrations similar to those found in uremic brain. We described a possible mechanism for the contribution of GCs to uremic hyperexcitability, referring to the in vitro effects of uremic GCs on inhibitory and excitatory amino acid receptors. It was demonstrated that the excitatory effects of uremic GCs on the central nervous system can be explained by the activation of N-methyl-d-aspartate receptors by GSA, concomitant inhibition of gamma-aminobutyric acid type A receptors by uremic GCs, and other depolarizing effects. These effects might also indicate the putative contribution of uremic GCs to the etiology of uremic encephalopathy. In this article, we review the uremic GCs with particular attention to their neurotoxicity. We elaborate in detail on the mechanisms of action of the neurotoxic uremic GCs and summarize the kinetics of these toxins.

  15. Brain activation in uremic anorexia.

    Science.gov (United States)

    Aguilera, Abelardo; Sánchez-Tomero, José Antonio; Selgas, Rafael

    2007-01-01

    This article reviews current knowledge about mechanisms responsible for uremic events, especially those that involve the central nervous system (CNS). Anorexia is a frequent complication of the uremic syndrome that contributes to malnutrition in patients on dialysis. Uremic anorexia has been associated with many factors. Traditionally, anorexia in dialysis patients has been regarded as a sign of uremic toxicity; therefore, 2 hypotheses have been proposed: the "middle molecule" and "peak concentration" hypotheses; both of these remain unproved. Recently, our group has proposed the tryptophan-serotonin hypothesis, which is based on a disorder in the amino acid profile that may be acquired when the patient is in uremic status. It is characterized by low concentrations of large neutral and branched chain amino acids in the cerebrospinal fluid. This situation permits a high level of tryptophan transport across the blood-brain barrier and enhances the synthesis of serotonin (the final target responsible for inhibiting appetite). The role of inflammation in the genesis of anorexia-malnutrition is also emphasized. In summary, in the CNS, factors associated with uremic anorexia include high levels within the cerebrospinal fluid of proinflammatory cytokines, leptin, and free tryptophan and serotonin (hyperserotoninergic-like syndrome), along with deficiency of neural nitric oxide (nNO) and disorders in various receptors such as melanocortin receptor-4 (MC4-R). Uremic anorexia is a complex complication associated with malnutrition and high levels of morbidity and mortality. Several uremia-acquired disorders in the CNS such as high cerebrospinal fluid levels of anorexigen substances and disorders in appetite regulator receptors may explain the lack of appetite.

  16. [Uremic encephalopathy in regular dialysis treatment: uremic stroke?].

    Science.gov (United States)

    Prencipe, Michele Antonio; Del Giudice, Antonio; Di Giorgio, Giuseppe; Aucella, Filippo

    2014-01-01

    This case report a 59 years-old male in regular dialysis treatment with neurologic emergency characterized by neurologic signs as deep sopor the cause of which was uremic encephalopathy. At presentation, laboratory investigations revealed creatinine 12,75 mg/dl, BUN 174 mg/% and hyperkalemia 7,5 mq/L. The most common abnormal test results were EEG and ECG. CT brain showed no evidence of hemorrhagic areas or hematoma subdural. The patient was treated with hemodialysis and after the first hour of hemodialysis, laboratory control revealed hypokaliemia with metabolic acidosis due to arteiovenous fistula recirculation. After placement of jugular venous hemodialysis catheter and intensive treatment, the patient showed gradual improvement of uremic stroke due to arteriovenous fistula recirculation for high grade venous stenoses. Arteriovenous fistula dysfunction remains a major contributor to the morbidity and mortality of hemodialysis patients. The failure of a newly created AVF to mature and to develop stenosis in an estabilished AVF are two common clinical predicaments. The goal is to identify a dysfunctional AVF early enough to intervene in a timely manner, either to assist the maturation process or to prevent thrombosis. Most clinical features of neurologic complications in uremics are nonspecific and do not reliable, but it is important to identify specific causes such as vascular access recirculation for adequate treatment and regression of uremic stroke.

  17. Endogenous guanidino compounds as uremic neurotoxins.

    Science.gov (United States)

    De Deyn, P P; D'Hooge, R; Van Bogaert, P P; Marescau, B

    2001-02-01

    Epileptic and cognitive symptomatologies are among the most typical manifestations of uremic encephalopathy. Several guanidino compounds (GCs) may play an important role in the etiology of uremic encephalopathy. Four GCs appeared to be highly increased as well in serum, cerebrospinal fluid, and brain of uremic patients, whereas the levels of other metabolically relevant GCs were not or only moderately increased and others were even decreased. These highly increased compounds or "uremic" GCs are creatinine (CTN), guanidine (G), guanidinosuccinic acid (GSA), and methylguanidine (MG). All four compounds were shown to be experimental convulsants in brain concentrations similar to those found in uremic brain. We have described a possible mechanism for the contribution of GCs to uremic hyperexcitability, referring to the in vitro effects of uremic GCs on inhibitory and excitatory amino acid receptors. The excitatory effects of uremic GCs on the central nervous system may be explained by the activation of N-methyl-D-aspartate (NMDA) receptors by GSA, concomitant inhibition of GABA(A) receptors by uremic GCs, and other depolarizing effects. These effects might also indicate the putative contribution of uremic GCs to the etiology of uremic encephalopathy.

  18. [Autoimmune hemolytic anemia in children].

    Science.gov (United States)

    Becheur, M; Bouslama, B; Slama, H; Toumi, N E H

    2015-01-01

    Autoimmune hemolytic anemia is a rare condition in children which differs from the adult form. It is defined by immune-mediated destruction of red blood cells caused by autoantibodies. Characteristics of the autoantibodies are responsible for the various clinical entities. Classifications of autoimmune hemolytic anemia include warm autoimmune hemolytic anemia, cold autoimmune hemolytic anemia, and paroxysmal cold hemoglobinuria. For each classification, this review discusses the epidemiology, etiology, clinical presentation, laboratory evaluation, and treatment options.

  19. Autoimmune Hemolytic Anemia.

    Science.gov (United States)

    Liebman, Howard A; Weitz, Ilene C

    2017-03-01

    Autoimmune hemolytic anemia is an acquired autoimmune disorder resulting in the production of antibodies directed against red blood cell antigens causing shortened erythrocyte survival. The disorders can present as a primary disorder (idiopathic) or secondary to other autoimmune disorders, malignancies, or infections. Treatment involves immune modulation with corticosteroids and other agents.

  20. Thrombocytopenia is not mandatory to diagnose haemolytic and uremic syndrome

    Directory of Open Access Journals (Sweden)

    Sallée Marion

    2013-01-01

    Full Text Available Abstract Background Hemolytic and uremic syndrome (HUS diagnosis involves association of non immune hemolytic anemia, thrombocytopenia, and renal failure. HUS without thrombocytopenia has been observed, we call it partial HUS. Its real frequency and outcome are unknown. The aim of this study was to determine the prevalence of patients with normal platelets count in two HUS cohorts and to compare their outcome to patients with thrombocytopenia. Methods We retrospectively identified HUS diagnosis in two different cohorts. The first cohort was from a single center and consisted of all cases of HUS whatever the aetiology, the second was multicentric and consisted of atypical HUS patients. These cohorts were divided into two groups depending on the presence or absence of thrombocytopenia. Clinical and biological data were compared between thrombopenic and non thrombopenic group. Results We identified 13% (20/150 of patients with normal platelets count: 10 episodes (18% of HUS in six patients (14% in the monocentric cohort and 14 patients (13% with 17 episodes (12% in the multicentric cohort of atypical HUS. Groups differed in platelets count and LDH level. In both cohorts, renal outcome was similar to patient presenting with thrombocytopenia. Conclusion HUS with normal platelets count is not infrequent. Relative to classical clinical presentation of HUS, partial HUS has similar characteristics and identical poor renal outcome and so must be treated in the same way.

  1. Normal and pathologic concentrations of uremic toxins.

    Science.gov (United States)

    Duranton, Flore; Cohen, Gerald; De Smet, Rita; Rodriguez, Mariano; Jankowski, Joachim; Vanholder, Raymond; Argiles, Angel

    2012-07-01

    An updated review of the existing knowledge regarding uremic toxins facilitates the design of experimental studies. We performed a literature search and found 621 articles about uremic toxicity published after a 2003 review of this topic. Eighty-seven records provided serum or blood measurements of one or more solutes in patients with CKD. These records described 32 previously known uremic toxins and 56 newly reported solutes. The articles most frequently reported concentrations of β2-microglobulin, indoxyl sulfate, homocysteine, uric acid, and parathyroid hormone. We found most solutes (59%) in only one report. Compared with previous results, more recent articles reported higher uremic concentrations of many solutes, including carboxymethyllysine, cystatin C, and parathyroid hormone. However, five solutes had uremic concentrations less than 10% of the originally reported values. Furthermore, the uremic concentrations of four solutes did not exceed their respective normal concentrations, although they had been previously described as uremic retention solutes. In summary, this review extends the classification of uremic retention solutes and their normal and uremic concentrations, and it should aid the design of experiments to study the biologic effects of these solutes in CKD.

  2. Drug-induced immune hemolytic anemia

    Science.gov (United States)

    Immune hemolytic anemia secondary to drugs; Anemia - immune hemolytic - secondary to drugs ... Drugs that can cause this type of hemolytic anemia include: Cephalosporins (a class of antibiotics), most common ...

  3. Warm autoimmune hemolytic anemia.

    Science.gov (United States)

    Naik, Rakhi

    2015-06-01

    Warm autoimmune hemolytic anemia (AIHA) is defined as the destruction of circulating red blood cells (RBCs) in the setting of anti-RBC autoantibodies that optimally react at 37°C. The pathophysiology of disease involves phagocytosis of autoantibody-coated RBCs in the spleen and complement-mediated hemolysis. Thus far, treatment is aimed at decreasing autoantibody production with immunosuppression or reducing phagocytosis of affected cells in the spleen. The role of complement inhibitors in warm AIHA has not been explored. This article addresses the diagnosis, etiology, and treatment of warm AIHA and highlights the role of complement in disease pathology.

  4. Hemolytic anemia caused by chemicals and toxins

    Science.gov (United States)

    ... This list is not all-inclusive. Alternative Names Anemia - hemolytic - caused by chemicals or toxins References Michel M. Autoimmune and intravascular hemolytic anemias. In: Goldman L, Schafer ...

  5. Beta-hemolytic streptococcal bacteremia

    DEFF Research Database (Denmark)

    Nielsen, Hans Ulrik; Kolmos, Hans Jørn; Frimodt-Møller, Niels

    2002-01-01

    Bacteremia with beta-hemolytic Streptococci groups A, B, C and G has a mortality rate of approximately 20%. In this study we analyzed the association of various patient risk factors with mortality. Records from 241 patients with beta-hemolytic streptococcal bacteremia were reviewed with particular...

  6. Uremic pleuritis in chronic hemodialysis patients.

    Science.gov (United States)

    Rashid-Farokhi, Farin; Pourdowlat, Guitti; Nikoonia, Mohammad-Reza; Behzadnia, Neda; Kahkouee, Shahram; Nassiri, Amir-Ahmad; Masjedi, Mohammad-Reza

    2013-01-01

    Chronic hemodialysis (HD) patients are predisposed to several complications associated with pleural effusion. In addition, uremia can directly cause pleuritis. However, there are inadequate data about pathogenesis and natural course of uremic pleuritis. In this study, 76 chronic HD patients with pleural effusion admitted to the Respiratory Center of Masih Daneshvari Hospital, in Tehran, Iran between June 2005 and May 2011 were evaluated to figure out the etiology of their pleural disease. Among these patients, patients with uremic pleuritis were identified and studied. The rate of uremic pleuritis was 23.7%. Other frequent etiologies of pleural effusion were parapneumonic effusion (23.7%), cardiac failure (19.7%), tuberculosis (6.6%), volume overload, malignancy, and unknown. In patients with uremic pleuritis, dyspnea was the most common symptom, followed by cough, weight loss, anorexia, chest pain, and fever. Compared to patients with parapneumonic effusion, patients with uremic effusion had a significantly higher rate of dyspnea and lower rate of cough and fever. Pleural fluid analysis showed that these patients had a significantly lower pleural to serum lactic dehydrogenase ratio, total pleural leukocytes, and polymorphonuclear count compared to patients with parapneumonic effusion. Improvement was achieved in 94.1% of patients with uremic pleuritis by continuation of HD, chest tube insertion or pleural decortication; an outcome better than the previous reports. Despite the association with an exudative effusion, inflammatory pleural reactions in patients with uremic pleuritis may not be as severe as infection-induced effusions. Owing to the advancement in HD technology and other interventions, outcome of uremic pleuritis may be improved.

  7. The uremic environment and muscle dysfunction in man and rat

    DEFF Research Database (Denmark)

    Harrison, Adrian Paul; Nielsen, Arne Høj; Eidemak, I.;

    2006-01-01

    patients prior to and after a session of hemodialysis (HD) treatment, alongside in vitro measurements of muscle function in isolated rat muscles incubated in normal or uremic conditions approximating to those found in uremic rats (rat uremic: RU) or uremic humans (human uremic: HU). Results: HD......-twitch). In isolated rat muscles, a uremic environment had no significant effect on slow-twitch soleus during field stimulation, however, in fast-twitch extensor digitorum longus, a significant 23% (RU) and 22% (HU) faster rate of decline in force was measured, compared to controls (p

  8. Hemolytic disease of the newborn

    Science.gov (United States)

    ... about 120 days in the body. In this disorder, red blood cells in the blood are destroyed earlier than normal. ... Hemolytic disease of the fetus and newborn (HDFN); Erythroblastosis fetalis; ... - HDN; ABO incompatibility - HDN; Rh incompatibility - HDN

  9. Hemolytic Transfusion Reactions

    Directory of Open Access Journals (Sweden)

    Fatih Mehmet Azık

    2011-12-01

    Full Text Available The prevalence of fatal hemolytic transfusion reactions (HTRs is approximately 1:200000 per unit. Acute HTRs occur during or within 24 h after administration of a blood product. Transfusion of incompatible red blood cells (RBCs, and, more rarely, of a large volume of incompatible plasma usually are the causative agents. Delayed HTRs are caused by a secondary immune response to an antigen on the donor’s RBCs. Different mechanisms lead to intra- and extravascular hemolysis, such as complete complement activation, phagocytosis of RBCs covered with C3b by macrophages after incomplete complement activation, or destruction of RBCs covered only with IgG by direct cell to cell contact with K cells. The clinical consequences of HTRs are triggered via several pathophysiological pathways. Formation of anaphylatoxins, release of cytokines causing a systemic inflammatory response syndrome, activation of the kinin system, the intrinsic clotting cascade and fibrinolysis result in hypotension, disseminated intravascular coagulation, diffuse bleeding, and disruption of microcirculation leading to renal failure and shock. In this review, the symptoms of HTR are introduced, laboratory investigations and treatment are described, and some recommendations for prevention are given. (Journal of Current Pediatrics 2011; 9: 127-32

  10. Uremic escape of renal allograft rejection

    Energy Technology Data Exchange (ETDEWEB)

    van Schilfgaarde, R. (Rijksuniversiteit Leiden (Netherlands). Academisch Ziekenhuis); van Breda Vriesman, P.J.C. (Rijksuniversiteit Limburg Maastricht (Netherlands). Dept. of Immunopathology)

    1981-10-01

    It is demonstrated in rats that, in the presence of early postoperative severe but transient uremia, the survival of first set Brown-Norway (BN) renal allografts in Lewis (LEW) recipients is at least three times prolonged when compared to non-uremic controls. This phenomenon is called 'uremic escape of renal allograft rejection'. By means of lethal X-irradiation of donors of BN kidneys transplanted into transiently uremic and non-uremic LEW recipients, the presence of passenger lymphocyte immunocompetence is demonstrated to be obilgatory for this phenomenon to occur. As a result of mobile passenger lymphocyte immunocompetence, a graft-versus-host (GVH) reaction is elicited in the spleens of LEW recipients of BN kidneys which amplifies the host response. The splenomegaly observed in LEW recipients of BN kidneys is caused not only by this GVH reaction, which is shown to be exquisitely sensitive to even mild uremia. It is also contributed to by a proliferative response of the host against the graft (which latter response is equated with an in vivo equivalent of a unilateral mixed lymphocyte reaction (MLR)), since the reduction in spleen weights caused by abrogation of mobile passenger lymphocyte immunocompetence brought about by lethal donor X-irradiation is increased significantly by early postoperative severe but transient uremia. It is concluded that in uremic escape of renal allograft rejection both reactions are suppressed by uremia during the early post-operative period.

  11. The kidney and uremic toxin removal: glomerulus or tubule?

    NARCIS (Netherlands)

    Masereeuw, R.; Mutsaers, H.A.M.; Toyohara, T.; Abe, T.; Jhawar, S.; Sweet, D.H.; Lowenstein, J.

    2014-01-01

    Chronic kidney disease (CKD) is a condition that affects approximately 10% of the adult population in developed countries. In patients with CKD adequate renal clearance is compromised, resulting in the accumulation of a plethora of uremic solutes. These uremic retention solutes, also known as uremic

  12. The kidney and uremic toxin removal : glomerulus or tubule?

    NARCIS (Netherlands)

    Masereeuw, Roos; Mutsaers, Henricus A M; Toyohara, Takafumi; Abe, Takaaki; Jhawar, Sachin; Sweet, Douglas H; Lowenstein, Jerome

    2014-01-01

    Chronic kidney disease (CKD) is a condition that affects approximately 10% of the adult population in developed countries. In patients with CKD adequate renal clearance is compromised, resulting in the accumulation of a plethora of uremic solutes. These uremic retention solutes, also known as uremic

  13. Establishment of a uremic apolipoprotein E knockout mouse model to explore the mechanism of uremic atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To establish a uremic apoE-/-mouse model to observe serum biochemical parameters and features of aortic root atherosclerosis (AS) in the model. Methods A uremic model was induced surgically in apoE-/- mice:electrocautery of the right kidney at 8 weeks of age and nephrectomy (NX) of the left one 2 weeks later. Control mice were sham-operated. Two weeks after NX,renal functions were detected in the uremic and control mice to evaluate the efficiency of the model. After 10 weeks of NX,blood samples we...

  14. Undetectable Glycosylated Hemoglobin in Autoimmune Hemolytic Anemia

    OpenAIRE

    Mitani, Noriyuki; Taguchi, Akihiko; Sakuragi, Shizu; Matsui, Kumiko; Tanaka, Yoshinori; Matsuda, Kazuhiro; Shinohara, Kenji

    2005-01-01

    We encountered two cases of autoimmune hemolytic anemia (AIHA) with undetectable glycosylated hemoglobin (HbA1C) level at diagnosis. Hemolytic anemia improved by administration of prednisolone (PSL) and HbA1C became measurable after response.

  15. Severe autoimmune hemolytic anemia with renal neoplasm.

    Science.gov (United States)

    Rhodes, Emily C; Parikh, Sahil P; Bhattacharyya, Nishith

    2014-02-01

    Autoimmune hemolytic anemia is a type of hemolytic anemia characterized by autoantibodies directed against red blood cells shortening their survival. When autoimmune hemolytic anemia is secondary to a paraneoplastic process, severe anemia can occur leading to significant morbidity and even mortality. Here we discuss the literature and present the case of a child with autoimmune hemolytic anemia from a paraneoplastic syndrome secondary to a renal tumor.

  16. Arterial hypertension in children with hemolytic uremic syndrome after kidney transplantation.

    Science.gov (United States)

    Hoenecke, Johannes; Hartmann, Hans; Melk, Anette

    2015-08-01

    The development of arterial hypertension after KTX is a well-known complication. HUS is a systemic disease associated with arterial hypertension during long-term follow-up. Our goal was to report on the severity of arterial hypertension after KTX in patients with typical and atypical HUS. We analyzed the course of 197 patients with HUS, of which 22 (n = 10 with typical HUS; n = 12 with atypical HUS) developed ESRF and received KTX as renal replacement therapy. We analyzed data from 1766 casual BP and 85 24-h ABPM measurements. In addition, we evaluated the used antihypertensive strategy. Comparison between the two patient groups revealed that patients with atypical HUS had significantly higher casual SBP-SDS and DBP-SDS values after KTX despite similar intensity of antihypertensive treatment. These data were supported by analysis of ABPM profiles showing comparable results for the interval 1-5 yr after KTX. Patients with atypical HUS had a greater severity of arterial hypertension despite similar treatment strategies and intensity of treatment. Our observation, even though in a small cohort, supports recent genetic studies showing arterial hypertension closely associated with HUS-causing mutations in patients with atypical HUS.

  17. When You are About to Diagnose Chronic Hemolytic Uremic Syndrome, Please Think More Deep

    Directory of Open Access Journals (Sweden)

    Doaa Mohammed Youssef

    2010-01-01

    Full Text Available Antiphospholipid syndrome is one type of immunological diseases which may be primary or secondary characterized by repeated thrombosis that it may be called “sticky blood syndrome”. Although a well-known disease in gynecology, there is no sufficient data in pediatrics field; so we see that it is important to discuss this interesting case.

  18. Thymoma with Autoimmune Hemolytic Anemia

    OpenAIRE

    Kensuke Suzuki; Minehiko Inomata; Shiori Shiraishi; Ryuji Hayashi; Kazuyuki Tobe

    2014-01-01

    A 38-year-old Japanese male was referred to our hospital with abnormal chest X-ray results and severe Coombs-positive hemolytic anemia. He was diagnosed with a stage IV, WHO type A thymoma and was treated with oral prednisolone (1 mg/kg/day) and subsequent chemotherapy. After chemotherapy, the patient underwent surgical resection of the thymoma. Hemolysis rapidly disappeared and did not return after the discontinuation of oral corticosteroids. Corticosteroid therapy may be preferable to chemo...

  19. Continuous enteral feeding in uremic rats.

    Science.gov (United States)

    Maniar, S; Laouari, D; Motel, V; Kleinknecht, C

    1996-01-01

    Because of constant uremia-induced anorexia, food restriction of normal rats is generally used to study the consequences of uremia. The effects of a normal food supply in uremic rats has never been tested, since no author has succeeded in providing normal intakes. Uremic rats either fed ad lib (U rats, n = 12) or force-fed through a gastric catheter (UF rats, n = 10), and sham-operated rats (C rats, n = 10) were compared from days 7 to 21 after surgery. U rats had lower food intake (13.8 vs. 17 g/day), weight gain (5.16 vs. 6.23 g/day), length gain (4 vs. 5 mm/day), nitrogen balance (228 vs. 279 mg/day) and muscle fractional protein synthesis rate (9.5 vs. 10.6%) measured in vivo by 3H-phenylalanine injection (p feeding may provide a model for normal nutritional supply in uremia.

  20. Role of Complement in Autoimmune Hemolytic Anemia

    OpenAIRE

    Berentsen, Sigbjørn

    2015-01-01

    Summary The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorder...

  1. Pathophysiology of hemolytic transfusion reactions.

    Science.gov (United States)

    Davenport, Robertson D

    2005-07-01

    Hemolytic transfusion reactions (HTR) are systemic reactions provoked by immunologic red blood cell (RBC) incompatibility. Clinical and experimental observations of such reactions indicate that they proceed through phases of humoral immune reaction, activation of phagocytes, productions of cytokine mediators, and wide-ranging cellular responses. HTR have many features in common with the systemic inflammatory response syndrome (SIRS). Knowledge of the pathophysiologic mechanisms in HTR suggest that newer biological agents that target complement intermediates or proinflammatory cytokines may be effective agents in the treatment of severe HTRs.

  2. Autoimmune hemolytic anaemia in Hodgkin's lymphoma.

    Science.gov (United States)

    Shah, Mihir B; Nanjapp, Veena; Devaraj, H S; Sindhu, K S

    2013-07-01

    Autoimmune hemolytic anaemia is a rare presentation of Hodgkin's lymphoma though its association with Non- Hodgkin's lymphoma is well known. It is usually detected at the time of diagnosis when it accompanies Hodgkin's and rarely precedes it. It is a warm immune hemolytic anemia which is responsive to steroids and rituximab. We hereby report a case of advanced Hodgkin's disease who presented as AIHA.

  3. Renal (uremic) encephalopathy in a goat.

    Science.gov (United States)

    Radi, Z A; Thomsen, B V; Summers, B A

    2005-10-01

    Renal encephalopathy was diagnosed in a 2-year-old male boar goat with a history of chronic weight loss and ataxia. Histopathological examination of the brain revealed a striking myelin vacuolation distributed mainly in two patterns: (i) along the junction of the neocortex and corona radiata, and (ii) in the bundles of the internal capsule as it dissects through the basal nuclei. The kidneys had diffuse severe tubular and glomerular necrosis and degeneration. The neural lesions are consistent with renal (uremic) encephalopathy. To the authors' knowledge, this is the first report of renal encephalopathy in a goat.

  4. Immune-mediated hemolytic anemia.

    Science.gov (United States)

    Rosse, Wendell F; Hillmen, Peter; Schreiber, Alan D

    2004-01-01

    Hemolytic anemia due to immune function is one of the major causes of acquired hemolytic anemia. In recent years, as more is known about the immune system, these entities have become better understood and their treatment improved. In this section, we will discuss three areas in which this progress has been apparent. In Section I, Dr. Peter Hillmen outlines the recent findings in the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH), relating the biochemical defect (the lack of glycosylphosphatidylinositol [GPI]-linked proteins on the cell surface) to the clinical manifestations, particularly hemolysis (and its effects) and thrombosis. He discusses the pathogenesis of the disorder in the face of marrow dysfunction insofar as it is known. His major emphasis is on innovative therapies that are designed to decrease the effectiveness of complement activation, since the lack of cellular modulation of this system is the primary cause of the pathology of the disease. He recounts his considerable experience with a humanized monoclonal antibody against C5, which has a remarkable effect in controlling the manifestations of the disease. Other means of controlling the action of complement include replacing the missing modulatory proteins on the cell surface; these studies are not as developed as the former agent. In Section II, Dr. Alan Schreiber describes the biochemistry, genetics, and function of the Fc gamma receptors and their role in the pathobiology of autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura due to IgG antibodies. He outlines the complex varieties of these molecules, showing how they vary in genetic origin and in function. These variations can be related to three-dimensional topography, which is known in some detail. Liganding IgG results in the transduction of a signal through the tyrosine-based activation motif and Syk signaling. The role of these receptors in the pathogenesis of hematological diseases due to IgG antibodies is

  5. Role of Complement in Autoimmune Hemolytic Anemia.

    Science.gov (United States)

    Berentsen, Sigbjørn

    2015-09-01

    The classification of autoimmune hemolytic anemias and the complement system are reviewed. In autoimmune hemolytic anemia of the warm antibody type, complement-mediated cell lysis is clinically relevant in a proportion of the patients but is hardly essential for hemolysis in most patients. Cold antibody-mediated autoimmune hemolytic anemias (primary cold agglutinin disease, secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria) are entirely complement-mediated disorders. In cold agglutinin disease, efficient therapies have been developed in order to target the pathogenic B-cell clone, but complement modulation remains promising in some clinical situations. No established therapy exists for secondary cold agglutinin syndrome and paroxysmal cold hemoglobinuria, and the possibility of therapeutic complement inhibition is interesting. Currently, complement modulation is not clinically documented in any autoimmune hemolytic anemia. The most relevant candidate drugs and possible target levels of action are discussed.

  6. Thrombosis in the uremic milieu--emerging role of "thrombolome".

    Science.gov (United States)

    Shashar, Moshe; Francis, Jean; Chitalia, Vipul

    2015-01-01

    Chronic kidney disease (CKD) is characterized by retention of a number of toxins, which unleash cellular damage. CKD environment with these toxins and a host of metabolic abnormalities (collectively termed as uremic milieu) is highly thrombogenic. CKD represents a strong and independent risk factor for both spontaneous venous and arterial (postvascular injury) thrombosis. Emerging evidence points to a previously unrecognized role of some of the prothrombotic uremic toxins. Here, we provide an overview of thrombosis in CKD and an update on indolic uremic toxins, which robustly increase tissue factor, a potent procoagulant, in several vascular cell types enhancing thrombosis. This panel of uremic toxins, which we term "thrombolome" (thrombosis and metabolome), represents a novel risk factor for thrombosis and can be further explored as biomarker for postvascular interventional thrombosis in patients with CKD.

  7. Maximal conservative therapy of calcific uremic ateriolopathy.

    Science.gov (United States)

    Van Noten, Charlotte; Janssen van Doorn, Karin; Vermander, Evert; Vlayen, Sonja; Verpooten, Gert A; Couttenye, Marie-Madeleine

    2012-07-01

    We present the case of a 61-year- old female patient in long-term hemodialysis who developed calcific uremic arteriolopathy (CUA) upon administration of the oral calcimimetic agent cinacalcet for treatment of secondary hyperparathyroidism. In May 2009, the baseline serum values were parathormone (PTH) 310 pg/ml, calcium 9.1 mg/dl and phosphorous 6.9 mg/dl. Necrotic wounds in the suprapubic fat tissue were successfully treated first, by correcting the calcium phosphorous product; second, through treatment with sodium thiosulfate and third, through intensive wound care with hyperbaric oxygen therapy and vacuum-assisted closure therapy, with no need for parathyroidectomy. Multiple factors have been described to play a role in the development of CUA. Based on the findings of this case, the treatment of CUA should be aimed at correcting different causes simultaneously.

  8. Hemolytic and Hemoxidative Activities in Mycoplasma penetrans

    OpenAIRE

    Kannan, T. R.; Joel B Baseman

    2000-01-01

    Mycoplasma penetrans is a newly isolated Mollicute from the urine of patients infected with human immunodeficiency virus that demonstrates the capacity to adhere to and invade human cells. A previous report, based on assays with mouse red blood cells (RBCs), indicated that M. penetrans lacked hemolytic activity. In our studies, we incubated different isolates of M. penetrans with various RBC species and observed hemolytic zones surrounding individual mycoplasma colonies. All M. penetrans stra...

  9. Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia

    OpenAIRE

    Barcellini, W.; Fattizzo, B.

    2015-01-01

    Several hemolytic markers are available to guide the differential diagnosis and to monitor treatment of hemolytic conditions. They include increased reticulocytes, an indicator of marrow compensatory response, elevated lactate dehydrogenase, a marker of intravascular hemolysis, reduced haptoglobin, and unconjugated hyperbilirubinemia. The direct antiglobulin test is the cornerstone of autoimmune forms, and blood smear examination is fundamental in the diagnosis of congenital membrane defects ...

  10. Effect of calcium phosphate crystals induced by uremic serum on calcification of human aortic smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    刘曜蓉

    2013-01-01

    Objective To investigate the impact of calcium phosphate crystals induced by uremic serum on calcification of human aortic smooth muscle cells (HASMCs) .Methods Uremic serum was incubated at 37℃for 3days.Calcium phosphate crystals and uremic supernatant were isolated from uremic serum by ultracentrifugation.

  11. Uremic parkinsonism with atypical phenotypes and radiologic features.

    Science.gov (United States)

    Yoon, Jee-Eun; Kim, Ji Sun; Park, Jeong-Ho; Lee, Kyung-Bok; Roh, Hakjae; Park, Sung Tae; Cho, Jin Whan; Ahn, Moo-young

    2016-04-01

    Uremic encephalopathy with bilateral basal ganglia lesions has been reported as an acute neurometabolic disease which shows reversible clinical course and brain imaging features. The exact nature and pathophysiology have not been well established. We encountered two patients who showed a relapsing and aggravating course and an atypical phenotype including parkinsonism with paroxysmal dystonic head tremor and acute onset monoparesis of the lower extremity. They also showed unusual radiological findings which revealed combined lesions in the basal ganglia and cortex, persistent hemorrhagic transformation, and focal ischemic lesion in the internal capsule. Herein, we present the unusual phenomenology with atypical radiologic findings and suggest the possible multifactorial pathogenesis of uremic encephalopathy.

  12. Acupuncture Treatment for 34 Cases of Uremic Cutaneous Pruritus

    Institute of Scientific and Technical Information of China (English)

    高红梅; 张万祥; 王莹

    2002-01-01

    @@ Chronic renal insufficiency is the result of renal injuries and progressive deterioration caused by various reasons. At the late stage, i.e. the period of uremia, it may be complicated with abnormalities of various systems. Along with the development and popularization of hemodialysis, the survival time of uremic patients can be prolonged, but uremic pruritus affects greatly the quality of life of the patients. For this purpose, we have treated 68 cases of the patients with acupuncture and western medicine respectively, and made clinical observations on the therapeutic results. A report follows.

  13. Hematological outcome in neonatal alloimmune hemolytic disease

    NARCIS (Netherlands)

    Rath, Mirjam Eva Aafke

    2013-01-01

    This thesis focuses on several aspects related to the hematological outcome of infants with hemolytic disease of the fetus and newborn (HDFN) due to red blood cell alloimmunization, including pathogenesis and management of the disease. The presence of leukocytopenie and thrombocytopenia support the

  14. [Biermer's disease and autoimmune hemolytic anemia].

    Science.gov (United States)

    Nafil, Hatim; Tazi, Illias; Mahmal, Lahoucine

    2012-01-01

    Biermer's disease is an autoimmune atrophic gastritis of the fundus predominantly responsible for a malabsorption of vitamin B12. Despite its association with several autoimmune disorders, few observations have reported an association with autoimmune hemolytic anemia (AIHA). We report a case of Biermer's disease associated with AIHA in a patient of 66 years old.

  15. AUTOIMMUNE HEMOLYTIC ANAEMIA IN CHILDHOOD: CASE REPORT

    Directory of Open Access Journals (Sweden)

    Preeti

    2015-06-01

    Full Text Available The hemolytic anemia brought about by autoimmune antibodies against red cells resulting in shortening of red cell survival. And excessive erythropoiesis as a compensatory response of the marrow is autoimmune hemolytic anemia. There are two types due to wa rm antibodies and cold antibodies. Warm antibodies mediated anemia has hemolysis in spleen mediated by IgG antibody. Macrophage Fc receptor can detect IgG coated red cells in absence of C 3b. It acts in the range of 37 - 42deg c. (1 Cold antibody mediated anemia is mediated by IgM antibody, they bind avidly at 4 deg c. carry hemolysis at low temp. Liver is the major site of hemolysis. Autoimmune hemolytic anemia presents as sudden onset of pallor, jaundice, dark coloured urine, and he pato splenomegaly. In 5 cases cold antibodies were positive, 3 cases warm were positive too. 4 of the 5 cases were females and steroids were effective in management of cold auto immune hemolytic anemia.

  16. Autoimmune hemolytic anemia secondary to chicken pox

    Directory of Open Access Journals (Sweden)

    Abraham M Ittyachen

    2013-01-01

    Full Text Available Autoimmune hemolytic anemia (AIHA is a rare complication of chicken pox. It is described mainly in children. Even in children it is a rare complication and the long-term prognosis remains to be elucidated. Herein we report an adult, a 23-year-old male who developed AIHA secondary to chicken pox.

  17. Hematological outcome in neonatal alloimmune hemolytic disease

    NARCIS (Netherlands)

    Rath, Mirjam Eva Aafke

    2013-01-01

    This thesis focuses on several aspects related to the hematological outcome of infants with hemolytic disease of the fetus and newborn (HDFN) due to red blood cell alloimmunization, including pathogenesis and management of the disease. The presence of leukocytopenie and thrombocytopenia support the

  18. Successful Colectomy for Hemorrhagic Colitis with Hemolytic Uremic Syndrome and Acute Encephalopathy due to Escherichia coli O157 Infection

    OpenAIRE

    Tetsuro Tominaga; Masahiro Oikawa; Hiroaki Takeshita; Masaki Kunizaki; Kazuo Tou; Takafumi Abo; Shigekazu Hidaka; Atsushi Nanashima; Terumitsu Sawai; Takeshi Nagayasu

    2014-01-01

    An 81-year-old man was admitted to a primary care hospital due to bloody diarrhea. The findings of abdominal computed tomography indicated ischemic colitis, so conservative therapy was started. On the 4th hospital day, the patient was transferred to our hospital because of renal dysfunction. Physical examination showed clouding of consciousness and abdominal distention. Abdominal computed tomography revealed massive ascites and thickening of the whole colonic wall. With a diagnosis of acute a...

  19. A waterborne outbreak of Escherichia coli O157:H7 infections and hemolytic uremic syndrome: implications for rural water systems.

    Science.gov (United States)

    Olsen, Sonja J; Miller, Gayle; Breuer, Thomas; Kennedy, Malinda; Higgins, Charles; Walford, Jim; McKee, Gary; Fox, Kim; Bibb, William; Mead, Paul

    2002-04-01

    In the summer of 1998, a large outbreak of Escherichia coli O157:H7 infections occurred in Alpine, Wyoming. We identified 157 ill persons; stool from 71 (45%) yielded E. coli O157:H7. In two cohort studies, illness was significantly associated with drinking municipal water (town residents: adjusted odds ratio=10.1, 95% confidence intervals [CI]=1.8-56.4; visitors attending family reunion: relative risk=9.0, 95% CI=1.3-63.3). The unchlorinated water supply had microbiologic evidence of fecal organisms and the potential for chronic contamination with surface water. Among persons exposed to water, the attack rate was significantly lower in town residents than in visitors (23% vs. 50%, p<0.01) and decreased with increasing age. The lower attack rate among exposed residents, especially adults, is consistent with the acquisition of partial immunity following long-term exposure. Serologic data, although limited, may support this finding. Contamination of small, unprotected water systems may be an increasing public health risk.

  20. An audit analysis of a guideline for the investigation and initial therapy of diarrhea negative (atypical) hemolytic uremic syndrome.

    NARCIS (Netherlands)

    Johnson, S.; Stojanovic, J.; Ariceta, G.; Bitzan, M.; Besbas, N.; Frieling, M.; Karpman, D.; Landau, D.; Langman, C.; Licht, C.; Pecoraro, C.; Riedl, M.; Siomou, E.; Kar, N.C. van de; Walle, J.V.; Loirat, C.; Taylor, C.M.

    2014-01-01

    BACKGROUND: In 2009, the European Paediatric Study Group for Haemolytic Uraemic Syndrome (HUS) published a clinical practice guideline for the investigation and initial therapy of diarrhea-negative HUS (now more widely referred to as atypical HUS, aHUS). The therapeutic component of the guideline (c

  1. Putative uremic encephalopathy in horses: five cases (1978-1998).

    Science.gov (United States)

    Frye, M A; Johnson, J S; Traub-Dargatz, J L; Savage, C J; Fettman, M J; Gould, D H

    2001-02-15

    To determine historical, physical examination, clinicopathologic, and postmortem findings in horses with putative uremic encephalopathy. Design-Retrospective study. Animals-5 horses with renal failure and neurologic disease not attributable to abnormalities in any other organ system. Medical records from 1978 to 1998 were examined for horses with renal disease and neurologic signs not attributable to primary neurologic, hepatic, or other diseases. Signalment, history, physical examination findings, clinicopathologic data, renal ultrasonographic findings, and postmortem data were reviewed. Of 332 horses with renal disease, 5 met selection criteria. Historical findings, physical examination findings, clinicopathologic data, ultrasonographic data, and postmortem findings were consistent with chronic renal failure. Swollen astrocytes were detected in all 4 horses examined at necropsy. A single criterion was not determined to be pathognomonic for uremic encephalopathy in horses. Uremic encephalopathy should be considered as a differential diagnosis in horses with evidence of chronic renal failure and encephalopathic neurologic sign not attributable to other causes. Astrocyte swelling, which was common to all 4 horses examined at necropsy, may serve as a microscopic indicator of uremic encephalopathy in horses.

  2. Therapeutic complement inhibition in complement-mediated hemolytic anemias: Past, present and future.

    Science.gov (United States)

    Risitano, Antonio M; Marotta, Serena

    2016-06-01

    The introduction in the clinic of anti-complement agents represented a major achievement which gave to physicians a novel etiologic treatment for different human diseases. Indeed, the first anti-complement agent eculizumab has changed the treatment paradigm of paroxysmal nocturnal hemoglobinuria (PNH), dramatically impacting its severe clinical course. In addition, eculizumab is the first agent approved for atypical Hemolytic Uremic Syndrome (aHUS), a life-threatening inherited thrombotic microangiopathy. Nevertheless, such remarkable milestone in medicine has brought to the fore additional challenges for the scientific community. Indeed, the list of complement-mediated anemias is not limited to PNH and aHUS, and other human diseases can be considered for anti-complement treatment. They include other thrombotic microangiopathies, as well as some antibody-mediated hemolytic anemias. Furthermore, more than ten years of experience with eculizumab led to a better understanding of the individual steps of the complement cascade involved in the pathophysiology of different human diseases. Based on this, new unmet clinical needs are emerging; a number of different strategies are currently under development to improve current anti-complement treatment, trying to address these specific clinical needs. They include: (i) alternative anti-C5 agents, which may improve the heaviness of eculizumab treatment; (ii) broad-spectrum anti-C3 agents, which may improve the efficacy of anti-C5 treatment by intercepting the complement cascade upstream (i.e., preventing C3-mediated extravascular hemolysis in PNH); (iii) targeted inhibitors of selective complement activating pathways, which may prevent early pathogenic events of specific human diseases (e.g., anti-classical pathway for antibody-mediated anemias, or anti-alternative pathway for PNH and aHUS). Here we briefly summarize the status of art of current and future complement inhibition for different complement-mediated anemias

  3. Uremic Encephalopathy: MR Imaging Findings and Clinical Correlation.

    Science.gov (United States)

    Kim, D M; Lee, I H; Song, C J

    2016-09-01

    Uremic encephalopathy is a metabolic disorder in patients with renal failure. The purpose of this study was to describe the MR imaging findings of uremic encephalopathy. This study retrospectively reviewed MR imaging findings in 10 patients with clinically proved uremic encephalopathy between May 2005 and December 2014. Parameters evaluated were lesion location and appearance; MR signal intensity of the lesions on T1WI, T2WI, and T2 fluid-attenuated inversion recovery images; the presence or absence of restricted diffusion on diffusion-weighted images and apparent diffusion coefficient maps; and the reversibility of documented signal-intensity abnormalities on follow-up MR imaging. MR imaging abnormalities accompanying marked elevation of serum creatinine (range, 4.3-11.7 mg/dL) were evident in the 10 patients. Nine patients had a history of chronic renal failure with expansile bilateral basal ganglia lesions, and 1 patient with acute renal failure had reversible largely cortical lesions. Two of 6 patients with available arterial blood gas results had metabolic acidosis. All basal ganglia lesions showed expansile high signal intensity (lentiform fork sign) on T2WI. Varied levels of restricted diffusion and a range of signal intensities on DWI were evident and were not correlated with serum Cr levels. All cortical lesions demonstrated high signal intensity on T2WI. Four patients with follow-up MR imaging after hemodialysis showed complete resolution of all lesions. The lentiform fork sign is reliable in the early diagnosis of uremic encephalopathy, regardless of the presence of metabolic acidosis. Cytotoxic edema and/or vasogenic edema on DWI/ADC maps may be associated with uremic encephalopathy. © 2016 by American Journal of Neuroradiology.

  4. Canine autoimmune hemolytic anemia: management challenges

    Directory of Open Access Journals (Sweden)

    Swann JW

    2016-07-01

    Full Text Available James W Swann,1 Barbara J Skelly2 1Queen Mother Hospital for Animals, The Royal Veterinary College, Hatfield, Hertfordshire, 2Department of Veterinary Medicine, University of Cambridge, Cambridge, UK Abstract: Immune-mediated hemolytic anemia is one of the most common manifestations of canine immune-mediated disease, yet treatment regimens remain nonstandardized and, in some cases, controversial. The main reason for this, as for most diseases in veterinary medicine, is the lack of large-scale placebo-controlled trials so that the efficacy of one treatment over another can be established. Most of the evidence used for treatment comes from retrospective studies and from personal preference and experience, and because of this, treatment regimens tend to vary among institutions and individual clinicians. Management of immune-mediated hemolytic anemia includes immunosuppression, thromboprophylaxis, and supportive care measures to help prevent and treat concurrent conditions. Keywords: IMHA, canine immune-mediated disease, management regimens

  5. The Clinical Pictures of Autoimmune Hemolytic Anemia

    OpenAIRE

    Packman, Charles H.

    2015-01-01

    Summary Autoimmune hemolytic anemia is characterized by shortened red blood cell survival and a positive Coombs test. The responsible autoantibodies may be either warm reactive or cold reactive. The rate of hemolysis and the severity of the anemia may vary from mild to severe and life-threatening. Diagnosis is made in the laboratory by the findings of anemia, reticulocytosis, a positive Coombs test, and specific serologic tests. The prognosis is generally good but renal failure and death some...

  6. Post-Babesiosis Warm Autoimmune Hemolytic Anemia.

    Science.gov (United States)

    Woolley, Ann E; Montgomery, Mary W; Savage, William J; Achebe, Maureen O; Dunford, Kathleen; Villeda, Sarah; Maguire, James H; Marty, Francisco M

    2017-03-09

    Background Babesiosis, a tickborne zoonotic disease caused by intraerythrocytic protozoa of the genus babesia, is characterized by nonimmune hemolytic anemia that resolves with antimicrobial treatment and clearance of parasitemia. The development of warm-antibody autoimmune hemolytic anemia (also known as warm autoimmune hemolytic anemia [WAHA]) in patients with babesiosis has not previously been well described. Methods After the observation of sporadic cases of WAHA that occurred after treatment of patients for babesiosis, we conducted a retrospective cohort study of all the patients with babesiosis who were cared for at our center from January 2009 through June 2016. Data on covariates of interest were extracted from the medical records, including any hematologic complications that occurred within 3 months after the diagnosis and treatment of babesiosis. Results A total of 86 patients received a diagnosis of babesiosis during the 7.5-year study period; 18 of these patients were asplenic. WAHA developed in 6 patients 2 to 4 weeks after the diagnosis of babesiosis, by which time all the patients had had clinical and laboratory responses to antimicrobial treatment of babesiosis, including clearance of Babesia microti parasitemia. All 6 patients were asplenic (Pbabesiosis WAHA in patients who did not have a history of autoimmunity; asplenic patients appeared to be particularly at risk.

  7. HEMOLYTIC ANEMIA IMUNNE-MEDIATED IN DOGS

    Directory of Open Access Journals (Sweden)

    R. C. Castilho

    2016-11-01

    Full Text Available Due to the reduction in the number of red blood cells, caused by the immune system, the immune-mediated hemolytic anemia (IMHA is the most common disease among the hemolytic anemias and occurs more frequently in dogs (Nelson & Couto, 2010, wherein the most affected breeds are Cocker Spaniel, Poodle, Doberman and Collie (ETTINGER; FELDMAN 2004; THRALL et al 2007.. There is no pathognomonic sign for the diagnosis of the immune-mediated hemolytic anemia; however, laboratory findings show regenerative anemia, spherocytosis, positive results in Coombs' test and rarely, monocytes with hemosiderin or erythrocytes phagocytosis, but even with these findings, the primary and secondary IMHA can not be differentiate from each other. Differentiation can only be achieved when there is a deep investigation into the cause of the anemia. The IMHA therapeutics starts with the support treatment and follows with an immunosuppressive therapy. In relation to IMHA Mortality rates, the numbers range from 25% to 50% (Thrall, 2007, or above 70% (CARR; Panciera; Kidd, 2002.

  8. Investigations on the adsorbents for uremic middle molecular toxins (II)

    Institute of Scientific and Technical Information of China (English)

    WANG; Hong

    2001-01-01

    [1]Yu, Z. Y., Blood Purification, 2nd ed., Beijing: Modern Publishing House, 1994, 273.[2]Babb, A., Popovich, R., Christopher, T. et al., The genesis of the square meter-hour hypothesis, Trans. Am. Soc. Artif. Intern. Organs., 1971, 17: 81.[3]Babb, A., Farrell-ell, R., Uvelli, D. et al., Hemodialyzer evaluation by examination of solute molecular spectra, Trans. Am.Soc. Artif. Intern. Organs., 1972, 18: 98.[4]Babb, A., Strand, H., Uvelli, D. et al., Quantitative description of dialysis treatment: A dialysis index, Kidney Int., 1975, 5:23.[5]Scribner, G. E., The search for the uremic toxin(s), Kidney Int., 1975, 7: 270-274.[6]Giovanetti, S., Barsotti G., Uremic intoxication, Nephron., 1975, 14: 123.[7]Zimmerman, L., Jornvall, H., Bergstrom, J. et al., Characterization of middle molecule compounds, Int. J. Attif. Organs (Suppl.), 1980, 4: 33.[8]Yuan, Z., Zhang, J., Zhao, F. Z. et al., Isolation and preliminary characterization of properties of middle molecules from sera of uremic patients, Chemical Journal of Chinese Universities (in Chinese), 1989, 10:401.[9]Yuan, Z., He, B. L., The proposal and advances of middle molecule hypothesis, Ion Exchange and Adsorption (in Chinese),1997, 13(1): 98.[10]Chu, J. G., Yuan, Z., Teng, X. L. et al., Separation and analysis of middle molecular substances from both of uremic and normal sera, Science in China, Series B (in Chinese), 2000, 30(3): 250.[11]Ftlrst, P., Bergstrom, J., Gordon, A. et al., Separation of peptides of “middle molecular” weight from biological fluids of patients with uremia, Kidney Int., 1975, 7: 272.[12]Zimmerman, L., Baldesten, A., Bergstrom, J. et al., Isotachophoretic separation of middle molecule peptides in uremic body fluids, Clin. Nephrol., 1980, 13: 183.[13]Mabuchi, H., Nakahashi, H., Medium-sized peptides in the blood of patients with uremia, Nephrol., 1983, 33: 232.[14]Mabuchi, H., Nakahashi, H., Profiling of urinary medium sized peptides in

  9. Initiation and Regulation of Complement during Hemolytic Transfusion Reactions

    Directory of Open Access Journals (Sweden)

    Sean R. Stowell

    2012-01-01

    Full Text Available Hemolytic transfusion reactions represent one of the most common causes of transfusion-related mortality. Although many factors influence hemolytic transfusion reactions, complement activation represents one of the most common features associated with fatality. In this paper we will focus on the role of complement in initiating and regulating hemolytic transfusion reactions and will discuss potential strategies aimed at mitigating or favorably modulating complement during incompatible red blood cell transfusions.

  10. Chorea due to basal ganglia involvement in a uremic diabetic patient

    Directory of Open Access Journals (Sweden)

    Faik Ilik

    2014-04-01

    Full Text Available Syndromes associated with acute bilateral lesions of the basal ganglia in diabetic uremic patients are uncommon. Uremic encephalopathy is typical of patients showing cortical involvement, with symptoms including confusion, seizures, tremors, or myoclonus. Whenever basal ganglia are anatomically involved, movement disorders arise, including chorea. In this article we present a case with basal ganglia involvement in a uremic diabetic patient causes chorea because of rare presentation. [Cukurova Med J 2014; 39(2.000: 353-356

  11. Uremic Encephalopathy with Atypical Magnetic Resonance Features on Diffusion-Weighted Images

    OpenAIRE

    Kang, Eugene; Jeon, Se Jeong; Choi, See-Sung

    2012-01-01

    Uremic encephalopathy is a well-known disease with typical MR findings including bilateral vasogenic or cytotoxic edema at the cerebral cortex or basal ganglia. Involvement of the basal ganglia has been very rarely reported, typically occurring in uremic-diabetic patients. We recently treated a patient who had non-diabetic uremic encephalopathy with an atypical lesion distribution involving the supratentorial white matter, without cortical or basal ganglia involvement. To the best of our know...

  12. Synergistic hemolytic reactions between staphylococci and Micrococcus lylae.

    Science.gov (United States)

    Lämmler, C; Brückler, J

    1989-06-01

    The primary culture of a clinical specimen obtained from a dog with an acute squamous eczema revealed three different bacterial species which demonstrated synergistic hemolytic activities on sheep blood agar plates. The three cultures were identified as beta-hemolytic Staphylococcus intermedius, as a coagulase-negative staphylococcal species, producing a delta-like hemolysin and as non-hemolytic Micrococcus lylae. The coagulase-negative staphylococcal species as well as M. lylae produced synergistically with beta-hemolytic S. intermedius zones of complete hemolysis. The occurrence of three different synergistically active bacterial species from one clinical specimen might be of clinical significance.

  13. [Pharmacokinetics of defibrotide in uremic patients undergoing hemodialysis].

    Science.gov (United States)

    Rossi, R; Farma, A; Maggi, G C; Marelli, A

    1991-12-01

    Defibrotide pharmacokinetics were studied in 6 voluntary healthy subjects and in 10 uremic patients undergoing dialysis during which (instead of heparin) defibrotide was administered to prevent fibrino-formation in the circuit. Blood concentrations of the drug were assessed (expressed with reference to the residual glycidic deoxyribose) during a standard dialysis using defibrotide, 3.5, 15, 30, 45, 60 and 90 minutes after the defibrotide bolus (200 mg) had been injected into the arterial channel. The half-lives of the alpha and beta plasmatic phases were found to be equal at 3.79 and 41.4 min in dialysed subjects and at 1.13 and 16.54 in healthy volunteers. These results indicate that in uremic patients undergoing dialysis at intervals using defibrotide, a longer time is required to eliminate the drug from the circulation. This variation does not however appear to be significant in terms of the therapeutic use of the drug during dialysis.

  14. Uremic encephalopathy and other brain disorders associated with renal failure.

    Science.gov (United States)

    Seifter, Julian Lawrence; Samuels, Martin A

    2011-04-01

    Kidney failure is one of the leading causes of disability and death and one of the most disabling features of kidney failure and dialysis is encephalopathy. This is probably caused by the accumulation of uremic toxins. Other important causes are related to the underlying disorders that cause kidney failure, particularly hypertension. The clinical manifestations of uremic encephalopathy include mild confusional states to deep coma, often with associated movement disorders, such as asterixis. Most nephrologists consider cognitive impairment to be a major indication for the initiation of renal replacement therapy with dialysis with or without subsequent transplantation. Sleep disorders, including Ekbom's syndrome (restless legs syndrome) are also common in patients with kidney failure. Renal replacement therapies are also associated with particular neurologic complications including acute dialysis encephalopathy and chronic dialysis encephalopathy, formerly known as dialysis dementia. The treatments and prevention of each are discussed. © Thieme Medical Publishers.

  15. Uremic encephalopathy with atypical magnetic resonance features on diffusion-weighted images.

    Science.gov (United States)

    Kang, Eugene; Jeon, Se Jeong; Choi, See-Sung

    2012-01-01

    Uremic encephalopathy is a well-known disease with typical MR findings including bilateral vasogenic or cytotoxic edema at the cerebral cortex or basal ganglia. Involvement of the basal ganglia has been very rarely reported, typically occurring in uremic-diabetic patients. We recently treated a patient who had non-diabetic uremic encephalopathy with an atypical lesion distribution involving the supratentorial white matter, without cortical or basal ganglia involvement. To the best of our knowledge, this is only the second reported case of non-diabetic uremic encephalopathy with atypical MR findings.

  16. Uremic Encephalopathy with Atypical Magnetic Resonance Features on Diffusion-Weighted Images

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Eu Gene; Jeon, Se Jeong; Choi, See Sung [Dept. of Radiology, Wonkwang University School of Medicine and Hospital, Iksan (Korea, Republic of)

    2012-11-15

    Uremic encephalopathy is a well-known disease with typical MR findings including bilateral vasogenic or cytotoxic edema at the cerebral cortex or basal ganglia. Involvement of the basal ganglia has been very rarely reported, typically occurring in uremic-diabetic patients. We recently treated a patient who had non-diabetic uremic encephalopathy with an atypical lesion distribution involving the supratentorial white matter, without cortical or basal ganglia involvement. To the best of our knowledge, this is only the second reported case of non-diabetic uremic encephalopathy with atypical MR findings.

  17. Binding Affinity and Capacity for the Uremic Toxin Indoxyl Sulfate

    Directory of Open Access Journals (Sweden)

    Eric Devine

    2014-01-01

    Full Text Available Protein binding prevents uremic toxins from removal by conventional extracorporeal therapies leading to accumulation in maintenance dialysis patients. Weakening of the protein binding may enhance the dialytic elimination of these toxins. In ultrafiltration and equilibrium dialysis experiments, different measures to modify the plasma binding affinity and capacity were tested: (i, increasing the sodium chloride (NaCl concentration to achieve a higher ionic strength; (ii, increasing the temperature; and (iii, dilution. The effects on the dissociation constant KD and the protein bound fraction of the prototypical uremic toxin indoxyl sulfate (IS in plasma of healthy and uremic individuals were studied. Binding of IS corresponded to one site binding in normal plasma. KD increased linearly with the NaCl concentration between 0.15 (KD = 13.2 ± 3.7 µM and 0.75 M (KD = 56.2 ± 2.0 µM. Plasma dilution further reduced the protein bound toxin fraction by lowering the protein binding capacity of the plasma. Higher temperatures also decreased the protein bound fraction of IS in human plasma. Increasing the NaCl concentration was effective to weaken the binding of IS also in uremic plasma: the protein bound fraction decreased from 89% ± 3% to 81% ± 3% at 0.15 and 0.75 M NaCl, respectively. Dilution and increasing the ionic strength and temperature enhance the free fraction of IS allowing better removal of the substance during dialysis. Applied during clinical dialysis, this may have beneficial effects on the long-term outcome of maintenance dialysis patients.

  18. Reversible MRI changes in a patient with uremic encephalopathy.

    Science.gov (United States)

    Schmidt, M; Sitter, T; Lederer, S R; Held, E; Schiffl, H

    2001-01-01

    A 19-year-old patient on chronic ambulatory peritoneal dialysis experienced severe neurologic disturbances caused by uremia. Increased signal intensity was seen bilaterally in the cortical and subcortical areas of the occipital and parietal lobe on cranial magnetic resonance imaging (MRI). Insufficient peritoneal dialysis efficacy was documented and the patient was switched from peritoneal to hemodialysis. Cranial MRI indicated a marked regression of the lesions to nearly normal, confirming the diagnosis of uremic encephalopathy.

  19. Increased parathyroid expression of klotho in uremic rats

    DEFF Research Database (Denmark)

    Hofman-Bang, J.; Martuseviciene, G.; Santini, M.A.

    2010-01-01

    /6 nephrectomy rat model of secondary hyperparathyroidism. Parathyroid klotho gene expression and protein were significantly increased in severely uremic hyperphosphatemic rats, but not affected by moderate uremia and normal serum phosphorus. Calcitriol suppressed klotho gene and protein expression in severe...... secondary hyperparathyroidism, despite a further increase in plasma phosphate. Both FGFR1 IIIC and Na+/K+-ATPase gene expression were significantly elevated in severe secondary hyperparathyroidism. Parathyroid gland klotho expression and the plasma calcium ion concentration were inversely correlated. Thus...

  20. Gases as uremic toxins: is there something in the air?

    Science.gov (United States)

    Jankowski, Joachim; Westhof, Timm; Vaziri, Nosratola D; Ingrosso, Diego; Perna, Alessandra F

    2014-03-01

    The field of uremic toxicity comprises the study of a large number of different substances, classified in relation to various characteristics, for example, protein-binding, dimensions, and so forth. The endogenous compounds of a gaseous nature have received much attention lately from the scientific community because of their increasingly recognized importance in health and disease. Among these substances, some are uremic toxins per se, others are related to uremic toxins, or can become toxic under some circumstances. We divided them into two broad categories: organic and inorganic compounds. Among the organic compounds are phenols, indols, 2-methoxyresorcinol, p-hydroxy hippuric acid and phenyl acetic acid, trimethylamine, and dimethylamine; among the inorganic solutes are ammonia, nitric oxide, carbon monoxide, and hydrogen sulfide. In this article, these substances are described in relation to the elements that they affect or by which they are affected in uremia, which are the blood, breath, stools, and the gastrointestinal tract. In addition, the effect of the dialysis procedure on exhaled gases are described.

  1. Perceptions of and preferences for sweet taste in uremic children.

    Science.gov (United States)

    Bellisle, F; Dartois, A M; Kleinknecht, C; Broyer, M

    1990-07-01

    Uremic children have low energy intakes, with little appetite for sweet foods. Likewise, sucrose-rich diets are poorly accepted by uremic rats, which suggests that uremia causes a relative aversion for sucrose. Hemodialyzed children (no. = 39, mean age = 160 mo) and healthy controls (no. = 25, mean age = 122 mo) were compared for perception of sweet taste intensity in two familiar foods (soft white cheese and apple sauce) and for preference for sweetness. The food stimuli were prepared in five sucrose concentrations: 1%, 5%, 10%, 15%, and 20% for cheese; 10%, 20%, 30%, 40%, and 60% for apple sauce. Children were presented with pairs of stimuli of adjacent concentrations and asked, in a forced choice, to identify the sweeter stimulus and to express their preferences. The hemodialyzed children made more mistakes (19%) than the controls (5%) when asked to rank sweetness in the soft cheese (i.e., with low concentrations). Both groups made an equal number of mistakes when asked to rank sweetness in the apple sauce. Preferences for sweetness were markedly different. In cheese, the highest sucrose concentration was preferred by 21.9% of the hemodialyzed children vs 41% of the controls. The lowest sucrose concentration was selected by 15.6% of the hemodialyzed children vs 4.6% of the controls. Similar preference trends were observed for apple sauce. We conclude that abnormally low preferences for sweet foods can contribute to insufficient caloric intake in uremic children.

  2. Lipoprotein(a) accelerates atherosclerosis in uremic mice

    DEFF Research Database (Denmark)

    Pedersen, Tanja X; McCormick, Sally P; Tsimikas, Sotirios

    2010-01-01

    lipoprotein-associated OxPL. Thus, Lp(a) may be particularly atherogenic in a uremic setting. We therefore investigated whether transgenic (Tg) expression of human Lp(a) increases atherosclerosis in uremic mice. Moderate uremia was induced by 5/6 nephrectomy (NX) in Tg mice with expression of human apo(a) (n...... = 19), human apoB-100 (n = 20), or human apo(a) + human apoB [Lp(a)] (n = 15), and in wild-type (WT) controls (n = 21). The uremic mice received a high-fat diet, and aortic atherosclerosis was examined 35 weeks later. LDL-cholesterol was increased in apoB-Tg and Lp(a)-Tg mice, but it was normal in apo...... with both apo(a) and Lp(a). In conclusion, expression of apo(a) or Lp(a) increased uremia-induced atherosclerosis. Binding of OxPL on apo(a) and Lp(a) may contribute to the atherogenicity of Lp(a) in uremia....

  3. Calcific Uremic Arteriolopathy: Pathophysiology, Reactive Oxygen Species and Therapeutic Approaches

    Directory of Open Access Journals (Sweden)

    Kurt M. Sowers

    2010-01-01

    Full Text Available Calcific uremic arteriolopathy (CUA/calciphylaxis is an important cause of morbidity and mortality in patients with chronic kidney disease requiring renal replacement. Once thought to be rare, it is being increasingly recognized and reported on a global scale. The uremic milieu predisposes to multiple metabolic toxicities including increased levels of reactive oxygen species and inflammation. Increased oxidative stress and inflammation promote this arteriolopathy by adversely affecting endothelial function resulting in a prothrombotic milieu and significant remodeling effects on vascular smooth muscle cells. These arteriolar pathological effects include intimal hyperplasia, inflammation, endovascular fibrosis and vascular smooth muscle cell apoptosis and differentiation into bone forming osteoblast-like cells resulting in medial calcification. Systemic factors promoting this vascular condition include elevated calcium, parathyroid hormone and hyperphosphatemia with consequent increases in the calcium × phosphate product. The uremic milieu contributes to a marked increased in upstream reactive oxygen species—oxidative stress and subsequent downstream increased inflammation, in part, via activation of the nuclear transcription factor NFκB and associated downstream cytokine pathways. Consitutive anti-calcification proteins such as Fetuin-A and matrix GLA proteins and their signaling pathways may be decreased, which further contributes to medial vascular calcification. The resulting clinical entity is painful, debilitating and contributes to the excess morbidity and mortality associated with chronic kidney disease and end stage renal disease. These same histopathologic conditions also occur in patients without uremia and therefore, the term calcific obliterative arteriolopathy could be utilized in these conditions.

  4. Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia

    Directory of Open Access Journals (Sweden)

    W. Barcellini

    2015-01-01

    Full Text Available Several hemolytic markers are available to guide the differential diagnosis and to monitor treatment of hemolytic conditions. They include increased reticulocytes, an indicator of marrow compensatory response, elevated lactate dehydrogenase, a marker of intravascular hemolysis, reduced haptoglobin, and unconjugated hyperbilirubinemia. The direct antiglobulin test is the cornerstone of autoimmune forms, and blood smear examination is fundamental in the diagnosis of congenital membrane defects and thrombotic microangiopathies. Marked increase of lactate dehydrogenase and hemosiderinuria are typical of intravascular hemolysis, as observed in paroxysmal nocturnal hemoglobinuria, and hyperferritinemia is associated with chronic hemolysis. Prosthetic valve replacement and stenting are also associated with intravascular and chronic hemolysis. Compensatory reticulocytosis may be inadequate/absent in case of marrow involvement, iron/vitamin deficiency, infections, or autoimmune reaction against bone marrow-precursors. Reticulocytopenia occurs in 20–40% of autoimmune hemolytic anemia cases and is a poor prognostic factor. Increased reticulocytes, lactate dehydrogenase, and bilirubin, as well as reduced haptoglobin, are observed in conditions other than hemolysis that may confound the clinical picture. Hemoglobin defines the clinical severity of hemolysis, and thrombocytopenia suggests a possible thrombotic microangiopathy or Evans’ syndrome. A comprehensive clinical and laboratory evaluation is advisable for a correct diagnostic and therapeutic workup of the different hemolytic conditions.

  5. Clinical Applications of Hemolytic Markers in the Differential Diagnosis and Management of Hemolytic Anemia.

    Science.gov (United States)

    Barcellini, W; Fattizzo, B

    2015-01-01

    Several hemolytic markers are available to guide the differential diagnosis and to monitor treatment of hemolytic conditions. They include increased reticulocytes, an indicator of marrow compensatory response, elevated lactate dehydrogenase, a marker of intravascular hemolysis, reduced haptoglobin, and unconjugated hyperbilirubinemia. The direct antiglobulin test is the cornerstone of autoimmune forms, and blood smear examination is fundamental in the diagnosis of congenital membrane defects and thrombotic microangiopathies. Marked increase of lactate dehydrogenase and hemosiderinuria are typical of intravascular hemolysis, as observed in paroxysmal nocturnal hemoglobinuria, and hyperferritinemia is associated with chronic hemolysis. Prosthetic valve replacement and stenting are also associated with intravascular and chronic hemolysis. Compensatory reticulocytosis may be inadequate/absent in case of marrow involvement, iron/vitamin deficiency, infections, or autoimmune reaction against bone marrow-precursors. Reticulocytopenia occurs in 20-40% of autoimmune hemolytic anemia cases and is a poor prognostic factor. Increased reticulocytes, lactate dehydrogenase, and bilirubin, as well as reduced haptoglobin, are observed in conditions other than hemolysis that may confound the clinical picture. Hemoglobin defines the clinical severity of hemolysis, and thrombocytopenia suggests a possible thrombotic microangiopathy or Evans' syndrome. A comprehensive clinical and laboratory evaluation is advisable for a correct diagnostic and therapeutic workup of the different hemolytic conditions.

  6. SEVERE IMMUNE HEMOLYTIC ANEMIA AFTER LIVER TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    A. I. Sushkov

    2013-01-01

    Full Text Available Clinical case of successful treatment of severe immune hemolytic anemia after liver transplantation is represen- ted in this article. The cause of complication was so-called passenger lymphocyte syndrome (a type of graft- versus-host disease. Two plasmapheresis sessions and Ig (0.5 g/kg in combination with increased maintenance immunosuppression with a short course of oral methylprednisolone in a total dose of 150 mg during 12 days were effective. The patient was discharged from hospital 34 days after transplantation in a satisfactory condition with a stable hemoglobin level. 

  7. Diagnosis and classification of autoimmune hemolytic anemia.

    Science.gov (United States)

    Bass, Garrett F; Tuscano, Emily T; Tuscano, Joseph M

    2014-01-01

    Uncompensated autoantibody-mediated red blood cell (RBC) consumption is the hallmark of autoimmune hemolytic anemia (AIHA). Classification of AIHA is pathophysiologically based and divides AIHA into warm, mixed or cold-reactive subtypes. This thermal-based classification is based on the optimal autoantibody-RBC reactivity temperatures. AIHA is further subcategorized into idiopathic and secondary with the later being associated with a number of underlying infectious, neoplastic and autoimmune disorders. In most cases AIHA is confirmed by a positive direct antiglobulin test (DAT). The standard therapeutic approaches to treatment of AIHA include corticosteroids, splenectomy, immunosuppressive agents and monoclonal antibodies.

  8. [Autoimmune hemolytic anemia: diagnosis and management].

    Science.gov (United States)

    Philippe, Pierre

    2007-12-01

    Autoimmune hemolytic anemia (AIHA) is diagnosed in the presence of anemia, usually macrocytic and of variable intensity, reticulocytosis, and a positive direct and/or indirect antiglobulin test, after ruling out other types of hemolytic anemia. A positive direct antiglobulin test alone is not sufficient to diagnose AIHA and may be positive in many patients without anemia or negative in some patients with AIHA. AIHA may be classified into two major categories according to the optimal temperature of antibody activity: warm-reacting autoantibodies (usually IgG) optimal around 37 degrees C and cold-reacting autoantibodies, optimal at 4 degrees C (usually IgM). This classification guides the selection of tests and treatment. AIHA is widely reported to be associated with a variety of other diseases, although these associations are often fortuitous. A minimal set of useful investigations is appropriate since AIHA may be secondary to viral infections, lymphoid malignancies, or autoimmune disorders such as lupus. Transfusion should remain rare in AHAI, but close contact with the transfusion service is necessary if it is to succeed. As for many autoimmune and/or systemic diseases, numerous types of treatment have been proposed but have not been validated in controlled multicenter studies. These are necessary to improve the management of these rare disorders.

  9. Immunotherapy Treatments of Warm Autoimmune Hemolytic Anemia

    Directory of Open Access Journals (Sweden)

    Bainan Liu

    2013-01-01

    Full Text Available Warm autoimmune hemolytic anemia (WAIHA is one of four clinical types of autoimmune hemolytic anemia (AIHA, with the characteristics of autoantibodies maximally active at body temperature. It produces a variable anemia—sometimes mild and sometimes severe. With respect to the absence or presence of an underlying condition, WAIHA is either idiopathic (primary or secondary, which determines the treatment strategies in practice. Conventional treatments include immune suppression with corticosteroids and, in some cases, splenectomy. In recent years, the number of clinical studies with monoclonal antibodies and immunosuppressants in the treatment of WAIHA increased as the knowledge of autoimmunity mechanisms extended. This thread of developing new tools of treating WAIHA is well exemplified with the success in using anti-CD20 monoclonal antibody, Rituximab. Following this success, other treatment methods based on the immune mechanisms of WAIHA have emerged. We reviewed these newly developed immunotherapy treatments here in order to provide the clinicians with more options in selecting the best therapy for patients with WAIHA, hoping to stimulate researchers to find more novel immunotherapy strategies.

  10. Autoimmune hemolytic anemia: transfusion challenges and solutions

    Directory of Open Access Journals (Sweden)

    Barros MM

    2017-03-01

    Full Text Available Melca M O Barros, Dante M Langhi Jr, José O Bordin Department of Clinical and Experimental Oncology, Universidade Federal de São Paulo, São Paulo, Brazil Abstract: Autoimmune hemolytic anemia (AIHA is defined as the increased destruction of red blood cells (RBCs in the presence of anti-RBC autoantibodies and/or complement. Classification of AIHA is based on the optimal auto-RBC antibody reactivity temperatures and includes warm, cold-reactive, mixed AIHA, and drug-induced AIHA subtypes. AIHA is a rare disease, and recommendations for transfusion are based mainly on results from retrospective data and relatively small cohort studies, including heterogeneous patient samples or single case reports. In this article, we will review the challenges and solutions to safely transfuse AIHA patients. We will reflect on the indication for transfusion in AIHA and the difficulty in the accomplishment of immunohematological procedures for the selection of the safest and most compatible RBC units. Keywords: hemolytic anemia, RBC autoantibodies, autoimmunity, hemolysis, direct ­antiglobulin test

  11. Comparison of uremic pruritus between patients undergoing hemodialysis and peritoneal dialysis

    Directory of Open Access Journals (Sweden)

    Ji-Won Min

    2016-06-01

    Conclusion: Our data demonstrate the difference in prevalence, intensity, and risk factors of uremic pruritus between HD and PD patients. These findings suggest that careful consideration for uremic pruritus might be needed in end-stage renal disease patients according to the dialysis modality.

  12. Calcium Phosphate Crystals from Uremic Serum Promote Osteogenic Differentiation in Human Aortic Smooth Muscle Cells.

    Science.gov (United States)

    Liu, Yaorong; Zhang, Lin; Ni, Zhaohui; Qian, Jiaqi; Fang, Wei

    2016-11-01

    Recent study demonstrated that calcium phosphate (CaP) crystals isolated from high phosphate medium were a key contributor to arterial calcification. The present study further investigated the effects of CaP crystals induced by uremic serum on calcification of human aortic smooth muscle cells. This may provide a new insight for the development of uremic cardiovascular calcification. We tested the effects of uremic serum or normal serum on cell calcification. Calcification was visualized by staining and calcium deposition quantified. Expression of various bone-calcifying genes was detected by real-time PCR, and protein levels were quantified by western blotting or enzyme-linked immunosorbent assays. Pyrophosphate was used to investigate the effects of CaP crystals' inhibition. Finally, CaP crystals were separated from uremic serum to determine its specific pro-calcification effects. Uremic serum incubation resulted in progressively increased calcification staining and increased calcium deposition in HASMCs after 4, 8 and 12 days (P vs 0 day crystals with pyrophosphate incubation prevented calcium deposition and bone-calcifying gene over-expression increased by uremic serum. CaP crystals, rather than the rest of uremic serum, were responsible for these effects. Uremic serum accelerates arterial calcification by mediating osteogenic differentiation. This effect might be mainly attributed to the CaP crystal content.

  13. A zebrafish model for uremic toxicity: role of the complement pathway.

    Science.gov (United States)

    Berman, Nathaniel; Lectura, Melisa; Thurman, Joshua M; Reinecke, James; Raff, Amanda C; Melamed, Michal L; Quan, Zhe; Evans, Todd; Meyer, Timothy W; Hostetter, Thomas H

    2013-01-01

    Many organic solutes accumulate in end-stage renal disease (ESRD) and some are poorly removed with urea-based prescriptions for hemodialysis. However, their toxicities have been difficult to assess. We have employed an animal model, the zebrafish embryo, to test the toxicity of uremic serum compared to control. Serum was obtained from stable ESRD patients predialysis or from normal subjects. Zebrafish embryos 24 h postfertilization were exposed to experimental media at a water:human serum ratio of 3:1. Those exposed to serum from uremic subjects had significantly reduced survival at 8 h (19 ± 18 vs. 94 ± 6%, p 50 kDa, respectively). Heating serum abrogated its toxicity. EDTA, a potent inhibitor of complement by virtue of calcium chelation, reduced the toxicity of uremic serum compared to untreated uremic serum (96 ± 5 vs. 28 ± 20% survival, p < 0.016, chelated vs. nonchelated serum, respectively). Anti-factor B, a specific inhibitor of the alternative complement pathway, reduced the toxicity of uremic serum, compared to untreated uremic serum (98 ± 6 vs. 3 ± 9% survival, p < 0.016, anti-factor B treated vs. nontreated, respectively). Uremic serum is thus more toxic to zebrafish embryos than normal serum. Furthermore, this toxicity is associated with a fraction of large size, is inactivated by heat, and is reduced by both specific and nonspecific inhibitors of complement activation. Together these data lend support to the hypothesis that at least some uremic toxicities may be mediated by complement.

  14. Uremic Toxins Enhance Statin-Induced Cytotoxicity in Differentiated Human Rhabdomyosarcoma Cells

    Directory of Open Access Journals (Sweden)

    Hitoshi Uchiyama

    2014-09-01

    Full Text Available The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF. Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins—hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate—on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated. In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated. However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated. These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins.

  15. Nonextracorporeal Methods for Decreasing Uremic Solute Concentration : A Future Way To Go?

    NARCIS (Netherlands)

    Meijers, Bjorn; Glorieux, Griet; Poesen, Ruben; Bakker, Stephan J. L.

    2014-01-01

    The uremic milieu is consequential to a disrupted balance between availability of retention solutes and the excretory capacity of the kidneys. Although metabolism is the prime contributor to the internal milieu, a significant fraction of uremic retention solute originates from other sources. The mai

  16. Value of carotid intimal–medial thickness as independent predictor of endothelial dysfunction in uremic patients

    Directory of Open Access Journals (Sweden)

    Hosni A. Younis

    2011-06-01

    Conclusion: (1 The study confirmed that carotid IMT and brachial artery FMD can be used in interventional studies in which cardiovascular risk is modified and increased in the uremic patients. (2 There was negative correlation between brachial FMD and C-IMT in the uremic patients.

  17. Cardiac effect of vitamin D receptor modulators in uremic rats.

    Science.gov (United States)

    Mizobuchi, Masahide; Ogata, Hiroaki; Yamazaki-Nakazawa, Ai; Hosaka, Nozomu; Kondo, Fumiko; Koiwa, Fumihiko; Kinugasa, Eriko; Shibata, Takanori

    2016-10-01

    Vitamin D receptor (VDR) modulators (VDRMs) are commonly used to control secondary hyperparathyroidism (SHPT) associated with chronic kidney disease, and are associated with beneficial outcomes in cardiovascular disease. In this study, we compared the cardiac effect of VS-105, a novel VDRM, with that of paricalcitol in 5/6 nephrectomized uremic rats. Male Sprague-Dawley rats were 5/6 nephrectomized, fed a standard diet for 4 weeks to establish uremia, and then treated (intraperitoneally, 3 times/week) with vehicle (propylene glycol), paricalcitol (0.025 and 0.15μg/kg), or VS-105 (0.05 and 0.3μg/kg) for 4 weeks. In uremic rats, neither VDRM (low and high doses) altered serum creatinine and phosphorus levels. Serum calcium was significantly higher with high dose paricalcitol compared to sham rats. PTH levels were significantly decreased with low dose paricalcitol and VS-105, and were further reduced in the high dose groups. Interestingly, serum FGF23 was significantly higher with high dose paricalcitol compared to sham rats, whereas VS-105 had no significant effect on FGF23 levels. Left ventricle (LV) weight and LV mass index determined by echocardiography were significantly suppressed in both high dose VDRM groups. This suppression was more evident with VS-105. Western blotting showed significant decreases in a fibrosis marker TGF-β1 in both high dose VDRM groups (vs. vehicle) and Masson trichrome staining showed significant decreases in cardiac fibrosis in these groups. These results suggest that VS-105 is less hypercalcemic than paricalcitol and has favorable effects on SHPT and cardiac parameters that are similar to those of paricalcitol in uremic rats. The cardioprotective effect is a noteworthy characteristic of VS-105.

  18. Acid-Base Balance in Uremic Rats with Vascular Calcification

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    Alan Peralta-Ramírez

    2014-07-01

    Full Text Available Background/Aims: Vascular calcification (VC, a major complication in humans and animals with chronic kidney disease (CKD, is influenced by changes in acid-base balance. The purpose of this study was to describe the acid-base balance in uremic rats with VC and to correlate the parameters that define acid-base equilibrium with VC. Methods: Twenty-two rats with CKD induced by 5/6 nephrectomy (5/6 Nx and 10 nonuremic control rats were studied. Results: The 5/6 Nx rats showed extensive VC as evidenced by a high aortic calcium (9.2 ± 1.7 mg/g of tissue and phosphorus (20.6 ± 4.9 mg/g of tissue content. Uremic rats had an increased pH level (7.57 ± 0.03 as a consequence of both respiratory (PaCO2 = 28.4 ± 2.1 mm Hg and, to a lesser degree, metabolic (base excess = 4.1 ± 1 mmol/l derangements. A high positive correlation between both anion gap (AG and strong ion difference (SID with aortic calcium (AG: r = 0.604, p = 0.02; SID: r = 0.647, p = 0.01 and with aortic phosphorus (AG: r = 0.684, p = 0.007; SID: r = 0.785, p = 0.01 was detected. Conclusions: In an experimental model of uremic rats, VC showed high positive correlation with AG and SID.

  19. Nicorandil-Induced Hyperkalemia in a Uremic Patient

    Directory of Open Access Journals (Sweden)

    Hung-Hao Lee

    2012-01-01

    Full Text Available Nicorandil is an antianginal agent with nitrate-like and ATP-sensitive potassium channel activator properties. After activation of potassium channels, potassium ions are expelled out of the cells, which lead to membrane hyperpolarization, closure of voltage-gated calcium channels, and finally vasodilation. We present a uremic case suffering from repeated junctional bradycardia, especially before hemodialysis. After detailed evaluation, nicorandil was suspected to be the cause of hyperkalemia which induced bradycardia. This case reminds us that physicians should be aware of this potential complication in patients receiving ATP-sensitive potassium channel activator.

  20. [Severe hemolytic jaundice and Wilson's disease].

    Science.gov (United States)

    Storck, D; Bareiss, P; Jesel, B; Warter, J

    1976-12-01

    The onset of spontaneous hemolytic jaundice in a young subject should lead to the search for Wilson's disease when clinical examination reveals cirrhosis. This hemolysis may evolve in the form of severe jaundice to a stage where the cirrhosis remains usually latent or well tolerated. The intervention of a toxic, allergic of infective factor liable to produce a hepatic lesion which frees a dose of copper sufficient to trigger off hemolysis, is discussed. The mechanism of the latter, that of the coagulation disorders observed, liver cell failure and widespread intravascular coagulation, are analysed in this paper and compared with data in the literature. The dramatic character of the case indicates that it is necessary to treat as a routine with penicillamine all homozygous forms of Wilson's disease.

  1. Iron deficiency and hemolytic anemia reversed by ventricular septal myectomy

    Science.gov (United States)

    Costa, Steven M.; Cable, Christian

    2015-01-01

    Hemolytic anemia has been reported to occur in the setting of aortic stenosis and prosthetic heart valves, but much more rarely in association with obstructive hypertrophic cardiomyopathy (HC). Of the few descriptions of hemolytic anemia secondary to HC, all but one case involved bacterial endocarditis contributing to left ventricular outflow tract obstruction. We present the case of a 67-year-old man with recurrent hemolytic anemia and HC, without infective endocarditis. Attempts at iron repletion and augmentation of beta-blocker therapy proved his anemia to be refractory to medical management. Ventricular septal myectomy led to the resolution of hemolysis, anemia, and its coexisting symptoms. PMID:26424952

  2. FGF23 fails to inhibit uremic parathyroid glands.

    Science.gov (United States)

    Canalejo, Rocío; Canalejo, Antonio; Martinez-Moreno, Julio Manuel; Rodriguez-Ortiz, M Encarnacion; Estepa, Jose C; Mendoza, Francisco Javier; Munoz-Castaneda, Juan Rafael; Shalhoub, Victoria; Almaden, Yolanda; Rodriguez, Mariano

    2010-07-01

    Fibroblast growth factor 23 (FGF23) modulates mineral metabolism by promoting phosphaturia and decreasing the production of 1,25-dihydroxyvitamin D(3). FGF23 decreases parathyroid hormone (PTH) mRNA and secretion, but despite a marked elevation in FGF23 in uremia, PTH production increases. Here, we investigated the effect of FGF23 on parathyroid function in normal and uremic hyperplastic parathyroid glands in rats. In normal parathyroid glands, FGF23 decreased PTH production, increased expression of both the parathyroid calcium-sensing receptor and the vitamin D receptor, and reduced cell proliferation. Furthermore, FGF23 induced phosphorylation of extracellular signal-regulated kinase 1/2, which mediates the action of FGF23. In contrast, in hyperplastic parathyroid glands, FGF23 did not reduce PTH production, did not affect expression of the calcium-sensing receptor or vitamin D receptor, and did not affect cell proliferation. In addition, FGF23 failed to activate the extracellular signal-regulated kinase 1/2-mitogen-activated protein kinase pathway in hyperplastic parathyroid glands. We observed very low expression of the FGF23 receptor 1 and the co-receptor Klotho in uremic hyperplastic parathyroid glands, which may explain the lack of response to FGF23 in this tissue. In conclusion, in hyperparathyroidism secondary to renal failure, the parathyroid cells resist the inhibitory effects of FGF23, perhaps as a result of the low expression of FGF23 receptor 1 and Klotho in this condition.

  3. Uremic pruritus in hemodialysis patients: treatment with desloratidine versus gabapentin

    Directory of Open Access Journals (Sweden)

    Diego Marquez

    2012-06-01

    Full Text Available INTRODUCTION: Uremic pruritus is common among dialysis patients. Effective treatments are not readily available. Early evidence with antihistamines and gabapentin indicate variable effects. OBJECTIVE: To compare the efficacy and side effects of gabapentin and desloratadine in patients with dialysis pruritus. METHODS: Prospective, open-label, cross-over clinical trial in 22 patients on chronic hemodialysis with sustained pruritus over a period of at least 60 days. After a one-week run-in period, we assigned patients to three weeks of either gabapentin 300 mg thrice weekly or desloratadine 5 mg thrice weekly. After a one-week washout period, each patient crossed-over to the alternate regimen for three more weeks. The primary endpoint of the study was the change in the visual analogue pruritus score (VAS. RESULTS: Nineteen subjects completed the two treatment blocks and were available for analysis. VAS scores decreased with both treatments (5.95 to 4.6 with gabapentin, p = 0.07; 5.89 to 3.4 with desloratadine, p = 0.004, but only desloratadine reached statistical significance. There were no differences when comparing the final pruritus score with gabapentin and desloratadine (4.6 versus 3.4, p = 0.16 Excessive sedation was common with gabapentin. Desloratadine was well tolerated. CONCLUSION: Desloratadine provides significant relief of uremic pruritus compared with no therapy. gabapentin has marginal efficacy. Desloratadine is better tolerated than gabapentin.

  4. Indolic Uremic Solutes Enhance Procoagulant Activity of Red Blood Cells through Phosphatidylserine Exposure and Microparticle Release

    Directory of Open Access Journals (Sweden)

    Chunyan Gao

    2015-10-01

    Full Text Available Increased accumulation of indolic uremic solutes in the blood of uremic patients contributes to the risk of thrombotic events. Red blood cells (RBCs, the most abundant blood cells in circulation, may be a privileged target of these solutes. However, the effect of uremic solutes indoxyl sulfate (IS and indole-3-acetic acid (IAA on procoagulant activity (PCA of erythrocyte is unclear. Here, RBCs from healthy adults were treated with IS and IAA (mean and maximal concentrations reported in uremic patients. Phosphatidylserine (PS exposure of RBCs and their microparticles (MPs release were labeled with Alexa Fluor 488-lactadherin and detected by flow cytometer. Cytosolic Ca2+ ([Ca2+] with Fluo 3/AM was analyzed by flow cytometer. PCA was assessed by clotting time and purified coagulation complex assays. We found that PS exposure, MPs generation, and consequent PCA of RBCs at mean concentrations of IS and IAA enhanced and peaked in maximal uremic concentrations. Moreover, 128 nM lactadherin, a PS inhibitor, inhibited over 90% PCA of RBCs and RMPs. Eryptosis or damage, by indolic uremic solutes was due to, at least partially, the increase of cytosolic [Ca2+]. Our results suggest that RBC eryptosis in uremic solutes IS and IAA plays an important role in thrombus formation through releasing RMPs and exposing PS. Lactadherin acts as an efficient anticoagulant in this process.

  5. Uremic Solutes in Chronic Kidney Disease and Their Role in Progression

    Science.gov (United States)

    van den Brand, Jan A. J. G.; Mutsaers, Henricus A. M.; van Zuilen, Arjan D.; Blankestijn, Peter J.; van den Broek, Petra H.; Russel, Frans G. M.; Masereeuw, Rosalinde; Wetzels, Jack F. M.

    2016-01-01

    Background To date, over 150 possible uremic solutes have been listed, but their role in the progression of CKD is largely unknown. Here, the association between a selected panel of uremic solutes and progression in CKD patients was investigated. Methods Patients from the MASTERPLAN study, a randomized controlled trial in CKD patients with a creatinine clearance between 20 and 70 ml/min per 1.73m2, were selected based on their rate of eGFR decline during the first five years of follow-up. They were categorized as rapid (decline >5 ml/min per year) or slow progressors. Concentrations of eleven uremic solutes were obtained at baseline and after one year of follow-up. Logistic regression was used to compare the odds for rapid to slow progression by uremic solute concentrations at baseline. Variability in uremic solute levels was assessed using scatter plots, and limits of variability were calculated. Results In total, 40 rapidly and 40 slowly progressing patients were included. Uremic solutes were elevated in all patients compared to reference values for healthy persons. The serum levels of uremic solutes were not associated with rapid progression. Moreover, we observed substantial variability in solute levels over time. Conclusions Elevated concentrations of uremic solutes measured in this study did not explain differences in rate of eGFR decline in CKD patients, possibly due to lack of power as a result of the small sample size, substantial between patient variability, and variability in solute concentrations over time. The etiology of intra-individual variation in uremic solute levels remains to be elucidated. PMID:28033375

  6. Candida species exhibit differential in vitro hemolytic activities

    OpenAIRE

    Luo, Gang; Lakshman P Samaranayake; Yau, Joyce Y. Y.

    2001-01-01

    A total of 80 Candida isolates representing 14 species were examined for their respective responses to an in vitro hemolytic test. A modification of a previously described plate assay system where the yeasts are incubated on glucose (3%)-enriched sheep blood agar in a carbon dioxide (5%)-rich environment for 48 h was used to evaluate the hemolytic activity. A group of eight Candida species which included Candida albicans (15 isolates), C. dubliniensis (2), C. kefyr (2), C. krusei (4), C. zeyl...

  7. Immune Hemolytic Anemia in a Patient with Tuberculous Lymphadenitis

    OpenAIRE

    Manjunath Nandennavar; Sanju Cyriac; Krishnakumar,; T G Sagar

    2011-01-01

    Anemia in tuberculosis is usually anemia of chronic disease. Severe hemolytic anemia is exceedingly rare in tuberculosis patients. We report a patient diagnosed with tubercular lymphadenitis complicated by Coomb′s positive hemolytic anemia. Patient responded well to antituberculous treatment. Hematological parameters improved after initiation of antituberculosis treatment. To the best of our knowledge, this is the first case from India of an adult patient with tuberculous lymphadenitis presen...

  8. AUTOIMMUNE HEMOLYTIC ANEMIA IN A PATIENT WITH ENDOBRONCHIAL TUBERCULOSIS

    OpenAIRE

    Sangeeth Kumar; Prabhudas; Vivekananda M.; Bheemaraya; Chaitra

    2013-01-01

    ABSTRACT - A 23 year old male presented with severe autoimmune hemolytic anemia in association with constitutional symptoms suggest ive of TB with calcified lesion on X ray chest. A diagnosis of endobronchial TB was c onfirmed with bronchoscopy and sputum for Ziehl Neelsen stain was positive and the patient responded to antituberculosis treatment. There are few case reports of auto immune hemolytic anemia with endobronchial TB.

  9. Two cases of autoimmune hemolytic anemia secondary to brucellosis: a review of hemolytic disorders in patients with brucellosis.

    Science.gov (United States)

    Eskazan, Ahmet Emre; Dal, Mehmet Sinan; Kaya, Safak; Dal, Tuba; Ayyildiz, Orhan; Soysal, Teoman

    2014-01-01

    Brucellosis is a worldwide zoonotic disease associated with hemolytic complications, including thrombotic microangiopathy (TMA) and hemolytic anemia. Autoimmune hemolytic anemia (AIHA) is a rare clinical presentation of this disease. In this report, we describe the cases of two patients with brucellosis who presented with Coombs-positive AIHA. We also include a review of the literature on the hemolytic complications of brucellosis. Both patients were successfully treated with a combination of doxycycline and rifampicin in addition to steroids. In the medical literature, there are several cases of TMA associated with brucellosis, although only a few cases of Coombs test-positive AIHA have been reported. Antibiotic therapy is the mainstay of treatment, and the selection of antibiotics and duration of treatment do not differ between brucellosis patients with and without hemolysis. Although rare, the potential for brucellosis should always be kept in mind in patients who present with hemolysis, especially those living in areas where brucellosis is endemic.

  10. Neonatal hemolytic anemia due to pyknocytosis.

    Science.gov (United States)

    Vos, Michel J; Martens, Daniëlle; van de Leur, Sjef J; van Wijk, Richard

    2014-12-01

    A newborn boy was referred to our hospital because of hemolytic anemia and severe hyperbilirubinemia. Extensive investigations aimed at determining the cause of hemolysis was initiated at the time of admission and 3 months after blood transfusion. Notably, no intrinsic erythrocyte abnormalities could be detected. The only possible cause explaining the progressive anemia and unconjugated hyperbilirubinemia was the finding of pyknocytes, severely distorted erythrocytes, on the blood film at hospital admission. We propose a role for an increased free fraction of plasma unconjugated bilirubin in the formation of pyknocytes through bilirubin membrane toxicity with subsequent anemia and progressive hyperbilirubinemia. Pyknocytosis is a transitory erythrocyte-related condition which can result in severe anemia and hyperbilirubinemia. Recognition of pyknocytes by microscopic analysis of a blood film is essential for a correct diagnosis. Treatment consists of correction of the anemia by top-up blood transfusion and light therapy to prevent toxic bilirubin buildup. High levels of free unconjugated bilirubin could be the underlying cause for the formation of pyknocytes.

  11. Elderly female with Autoimmune hemolytic anemia

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    Anupam Dey

    2015-01-01

    Full Text Available Autoimmune hemolytic anemia (AIHA is a rare disease with an estimated prevalence of around 17/100,000. It is often difficult to diagnose and treat AIHA, especially in elderly. A 60-year-old female was admitted with the complaints of low grade fever, on-off for 6 months, progressive fatigue and dyspnea on exertion. She was transfused with three units of blood within these 6 months. Examination revealed pallor, edema, hemic murmur, and palpable liver. Hb was 2.9 gm%, T Bil 5.2 mg/dl, ESR 160 mm, and reticulocyte count 44.05%. Direct Coombs test was positive, anti-nuclear antibody (ANA and Anti ds DNA were positive. A diagnosis of systemic lupus erythematosus (SLE with AIHA was considered and patient was transfused with two units of packed red cells and put on steroid (prednisolone at 1 mg/kg body weight daily. After 3 weeks, her Hb had increased to 10.4 gm% with gross clinical improvement.

  12. Isolation and purification of uremic middle molecules by multi-step liquid chromatography

    Institute of Scientific and Technical Information of China (English)

    储结根; 何炳林; 刘晓航; 袁直

    2002-01-01

    Isolation and comparison of uremic sera and urine and normal sera and urine were performed by gel permeation chromatography, anion exchange chromatography and re-versed-phase high performance liquid chromatography. Two uremic middle molecular fractions (A and B) were obtained from uremic sera and urine and normal urine by gel permeation chromatography, but not from normal sera. The anion exchange chromatographic results of fraction A from different origins demonstrate that subfraction A-3 could be excreted in urine by healthy subject, but accumulated in uremic serum for renal failure of patient with uremia. After desalinization subfraction A-3 was analyzed by MALDI-TOF-MS. The results show that subfraction A-3 consists of six compounds with molecular weight 839, 873, 1007.94, 1106, 1680 and 2015 respectively. Finally, by reversed-phase high performance liquid chromatography, subfraction A-3 was further resolved into six independent fractions. Thus, the isolation and purification of six middle molecular c

  13. Middle-Molecule Uremic Toxins and Outcomes in Chronic Kidney Disease.

    Science.gov (United States)

    Massy, Ziad A; Liabeuf, Sophie

    2017-01-01

    In patients with chronic kidney disease (CKD), uremic toxins constitute a specific nontraditional risk factor. Research in this field started in the early 1990s, and a growing body of preclinical and epidemiological evidence suggests that elevated levels of uremic toxins are associated with poor outcomes in a CKD setting. The present review focuses on a specific class of uremic toxins (the "middle molecules"), which includes well-known candidates like beta-2 microglobulin and fibroblast growth factor 23. Here, we summarize the epidemiological evidence linking the middle-molecule uremic toxin (and especially the larger ones) with hard clinical end points. Our findings highlight the urgent need for clinical trials of interventions designed to decrease levels of these middle molecules in CKD patients. © 2017 S. Karger AG, Basel.

  14. VDR activation and uremic cardiopathy: myths and paradoxes

    Directory of Open Access Journals (Sweden)

    Diego Brancaccio

    2015-04-01

    Full Text Available The role of vitamin D receptor (VDR activators for the control of secondary hyperparathyroidism has been clarified during the last few decades; however, their possible activity in conditioning cardiovascular comorbidity and mortality has become of interest more recently. On the basis of experimental studies showing that VDR activating therapy is associated with a reduction of cardiac hypertrophy, the PRIMO Study (an international randomized controlled trial [RCT] was carried out a few years ago, but the results were disappointing, as the group of uremic patients on dialysis treated for 48 weeks with paricalcitol showed no differences in comparison with controls in terms of regression of heart hypertrophy. The aim of this editorial is to analyze the possible reasons for such results, and to help understand the actual role of VDR activators in dialysis patients in controlling cardiovascular morbidity and mortality.

  15. Parathyroid hormone dependent T cell proliferation in uremic rats

    DEFF Research Database (Denmark)

    Lewin, E; Ladefoged, Jens; Brandi, L

    1993-01-01

    Chronic renal failure (CRF) is combined with an impairment of the immune system. The T cell may be a target for the action of parathyroid hormone (PTH). Rats with CRF have high blood levels of PTH. Therefore, the present investigation examined some aspects of the T cell function in both normal...... and CRF rats before and after parathyroidectomy and after an isogenic kidney transplantation. The T cell proliferative response to phytohemagglutinin (PHA) stimulation was significantly higher in peripheral blood mononuclear cell (PBMC) cultures obtained from CRF rats than from normal rats. After...... parathyroidectomy the T cells of normal as well as of uremic rats could still be significantly stimulated by PHA, but now no significant difference was seen. When CRF was reversed after an isogenic kidney transplantation and PTH reversed to levels in the normal range, the T cell proliferative response to PHA...

  16. The Uremic Toxin Acrolein Promotes Suicidal Erythrocyte Death

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    Mohamed Siyabeldin E. Ahmed

    2013-05-01

    Full Text Available Background: Anemia is a major complication of end stage renal disease. The anemia is mainly the result of impaired formation of erythrocytes due to lack of erythropoietin and iron deficiency. Compelling evidence, however, points to the contribution of accelerated erythrocyte death, which decreases the life span of circulating erythrocytes. Erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and by cell membrane scrambling with phosphatidylserine-exposure at the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i. Erythrocytes could be sensitized to cytosolic Ca2+ by ceramide. In end stage renal disease, eryptosis may possibly be stimulated by uremic toxins. The present study explored, whether the uremic toxin acrolein could trigger eryptosis. Methods: Cell volume was estimated from forward scatter, phosphatidylserine-exposure from annexin-V-binding, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and ceramide from fluorescent antibodies. Results: A 48 h exposure to acrolein (30 - 50 µM did not significantly modify [Ca2+]i but significantly decreased forward scatter and increased annexin-V-binding. Acrolein further triggered slight, but significant hemolysis and increased ceramide formation in erythrocytes. Acrolein (50 µM induced annexin-V-binding was significantly blunted in the nominal absence of extracellular Ca2+. Acrolein augmented the annexin-V-binding following treatment with Ca2+ ionophore ionomycin (1 µM. Conclusion: Acrolein stimulates suicidal erythrocyte death or eryptosis, an effect at least in part due to stimulation of ceramide formation with subsequent sensitisation of the erythrocytes to cytosolic Ca2+.

  17. Bilateral basal ganglia and unilateral cortical involvement in a diabetic uremic patient.

    Science.gov (United States)

    Yoon, Chang Hyo; Seok, Jung Im; Lee, Dong Kuck; An, Gee Sung

    2009-06-01

    We report a 57-year-old woman with uremic encephalopathy who presented with dysarthria, dysphagia, hypophonia, and drowsiness. The patient's radiologic findings were rather unusual in that magnetic resonance imaging (MRI) showed abnormal findings involving the basal ganglia bilaterally and frontal cortex unilaterally. After intensified hemodialysis, her symptoms and follow-up brain MRI showed marked improvement. We postulated that the underlying mechanism of uremic encephalopathy based on diffusion-weighted imaging and apparent diffusion coefficient maps.

  18. A study of median nerve entrapment neuropathy at wrist in uremic patients

    OpenAIRE

    2015-01-01

    Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy seen in uremic patients. The study was undertaken to estimate the frequency of CTS in uremic patients and to identify the most sensitive electrodiagnostic test. Study was conducted on 80 subjects of age 30–60 years. End-stage kidney disease patients were recruited for the clinical evaluation, motor nerve conduction studies (NCS), sensory NCS, F wave study and median-versus-ulnar comparison studies (palm-to-wrist mixed compa...

  19. Effect of Two Different Iron Supplementation on the Quality of Life of Uremic Hemodialysis Patients

    Institute of Scientific and Technical Information of China (English)

    刘雪梅; 刘子栋; 朱忠华; 邓安国

    2004-01-01

    UREMIC RENAL FAILURE is a common chronicdisease. Hemodialysis therapy has increased thelifespan of uremic patients significantly. Patientquality of life (QL), however, is also an importantindicator of the effectiveness of the medical carethat patients receive and therapies that prolonglifespan may actually compromise quality of life.1In recent years, intravenous iron has been studiedas an adjunctive therapy for anemia in hemodialysispatients. Based on protocols published previously,we selected hemodialysis ...

  20. Sodium potassium adenosine triphosphatase (Na/K-ATPase) as a therapeutic target for uremic cardiomyopathy.

    Science.gov (United States)

    Wang, Xiaoliang; Liu, Jiang; Drummond, Christopher A; Shapiro, Joseph I

    2017-05-01

    Clinically, patients with significant reductions in renal function present with cardiovascular dysfunction typically termed, uremic cardiomyopathy. It is a progressive series of cardiac pathophysiological changes, including left ventricular diastolic dysfunction and hypertrophy (LVH) which sometimes progress to left ventricular dilation (LVD) and systolic dysfunction in the setting of chronic kidney disease (CKD). Uremic cardiomyopathy is almost ubiquitous in patients afflicted with end stage renal disease (ESRD). Areas covered: This article reviews recent epidemiology, pathophysiology of uremic cardiomyopathy and provide a board overview of Na/K-ATPase research with detailed discussion on the mechanisms of Na/K-ATPase/Src/ROS amplification loop. We also present clinical and preclinical evidences as well as molecular mechanism of this amplification loop in the development of uremic cardiomyopathy. A potential therapeutic peptide that targets on this loop is discussed. Expert opinion: Current clinical treatment for uremic cardiomyopathy remains disappointing. Targeting the ROS amplification loop mediated by the Na/K-ATPase signaling function may provide a novel therapeutic target for uremic cardiomyopathy and related diseases. Additional studies of Na/K-ATPase and other strategies that regulate this loop will lead to new therapeutics.

  1. Autoimmune hemolytic anemia: From lab to bedside

    Directory of Open Access Journals (Sweden)

    R K Chaudhary

    2014-01-01

    Full Text Available Autoimmune hemolytic anemia (AIHA is not an uncommon clinical disorder and requires advanced, efficient immunohematological and transfusion support. Many AIHA patients have underlying disorder and therefore, it is incumbent upon the clinician to investigate these patients in detail, as the underlying condition can be of a serious nature such as lymphoproliferative disorder or connective tissue disorder. Despite advances in transfusion medicine, simple immunohematological test such as direct antiglobulin test (DAT still remains the diagnostic hallmark of AIHA. The sensitive gel technology has enabled the immunohematologist not only to diagnose serologically such patients, but also to characterize red cell bound autoantibodies with regard to their class, subclass and titer in a rapid and simplified way. Detailed characterization of autoantibodies is important, as there is a relationship between in vivo hemolysis and strength of DAT; red cell bound multiple immunoglobulins, immunoglobulin G subclass and titer. Transfusing AIHA patient is a challenge to the immunohematologist as it is encountered with difficulties in ABO grouping and cross matching requiring specialized serological tests such as alloadsorption or autoadsorption. At times, it may be almost impossible to find a fully matched unit to transfuse these patients. However, transfusion should not be withheld in a critically ill patient even in the absence of compatible blood. The "best match" or "least incompatible units" can be transfused to such patients under close supervision without any serious side-effects. All blood banks should have the facilities to perform the necessary investigations required to issue "best match" packed red blood cells in AIHA. Specialized techniques such as elution and adsorption, which at times are helpful in enhancing blood safety in AIHA should be established in all transfusion services.

  2. Cefotetan-induced hemolytic anemia after perioperative prophylaxis.

    Science.gov (United States)

    Martin, Monte E; Laber, Damian A

    2006-03-01

    Cephalosporin-induced hemolytic anemia is an acquired form of hemolytic anemia caused by interaction of drug with the immune system. Drug adsorption, drug-dependent antibody, and autoimmune induction are the three mechanisms of hemolysis. Cefotetan-induced hemolytic anemia (CIHA) has been described to occur through all three mechanisms. We report four cases of CIHA that occurred after appropriate perioperative use of cefotetan. All of our patients developed an acute and severe hemolytic episode that caused significant symptoms and led to hospitalization within 1-2 weeks after exposure to cefotetan. The hemolytic process was self-limited, and all our patients responded to supportive measures and blood transfusion. This report adds to our knowledge of CIHA, a rare complication of cefotetan use. Our cases suggest that cefotetan-induced acute severe hemolysis is caused by membrane modification (nonimmunologic protein adsorption) in addition to immune complex formation. Prompt diagnosis and aggressive supportive measures are essential in minimizing morbidity and mortality from hemolysis. Physicians should warn their patients about this complication. Given that hemolysis occurs when the subject is no longer under direct clinical supervision, patient awareness on how to recognize signs and symptoms of hemolysis is paramount to reducing the likelihood of this potentially lethal side effect. Finally, physicians might consider restricting cefotetan use.

  3. Hemolytic Anemia after Aortic Valve Replacement: a Case Report

    Directory of Open Access Journals (Sweden)

    Feridoun Sabzi

    2015-10-01

    Full Text Available Hemolytic anemia is exceedingly rare and an underestimated complication after aortic valve replacement (AVR.The mechanism responsible for hemolysis most commonly involves a regurgitated flow or jet that related to paravalvar leak or turbulence of subvalvar stenosis. It appears to be independent of its severity as assessed by echocardiography. We present a case of a 24-year-old man with a history of AVR in 10 year ago that developed severe hemolytic anemia due to a mild subvalvar stenosis caused by pannus formation and mild hypertrophic septum. After exclusion of other causes of hemolytic anemia and the lack of clinical and laboratory improvement, the patient underwent redo valve surgery with pannus and subvalvar hypertrophic septum resection. Anemia and heart failure symptoms gradually resolved after surgery

  4. Autoimmune hemolytic anemia in patients with β-thalassemia major.

    Science.gov (United States)

    Xu, Lu-Hong; Fang, Jian-Pei; Weng, Wen-Jun; Huang, Ke; Zhang, Ya-Ting

    2012-04-01

    Hemolysis is a common feature in patients with β-thalassemia major. As a result, autoimmune hemolytic anemia complicating β-thalassemia is easily overlooked. Here, the authors described the clinical features and management of 7 patients with β-thalassemia major and autoimmune hemolytic anemia. These patients had fever, cough, and tea-colored urine on admission. The laboratory investigations showed a significant drop in hemoglobin and increased serum bilirubin. Coombs' tests revealed that anti-immunoglobulin G (IgG) and anti-C3 was positive in 7 and 5 cases, respectively, whereas anti-Rh E alloantibody was positive in 3 cases. All the patients received corticosteroids treatments and blood transfusions. Patients with anti-Rh E alloantibodies also received immunoglobulin treatments. Six of the patients responded well to the management, but 1 patient developed recurrent autoimmune hemolytic anemia that required cyclosporin A treatment. All the patients remained well by following up for more than 6 months.

  5. Group A β-hemolytic streptococcal pharyngotonsillitis outbreak

    Science.gov (United States)

    Culqui, Dante R; Manzanares-Laya, Sandra; Van Der Sluis, Sarah Lafuente; Fanlo, Albert Anton; Comas, Rosa Bartolomé; Rossi, Marcello; Caylá, Joán A

    2014-01-01

    The aim was to describe an outbreak of group A β-hemolytic streptococcal pharyngotonsillitis in health care professionals. This is a cross-sectional descriptive study of 17 clients who dined at the same table in a restaurant in Barcelona in July 2012. The frequency, timing and severity of symptoms were analyzed, as were demographic variables and others concerning the food ingested. The attack rate was 58.8%. Six of the 10 clients were positive for group A β-hemolytic streptococcal. Six of the 13 individuals who handled the food involved in the dinner had symptoms. No association was identified with the food consumed. There is epidemiological evidence of foodborne group A β-hemolytic streptococcal transmission, but respiratory transmission could not be ruled out. PMID:24897054

  6. Comparative study of hemolytic activity of Bordetella species

    Directory of Open Access Journals (Sweden)

    C N Khobragade

    2009-11-01

    Full Text Available Background and objectives: Bordetella species colonize the respiratory tract of mammals and thereby cause the whooping cough. Most of the species produce adenylate cyclase - a toxin ( hemolysin responsible for increasing intracellular cyclic AMP (cAMP levels in mammalian neutrophils and macrophages and as a consequence their phagocytic function get impaired . This study was carried out to isolate species of Bordetella and to study the hemolytic activity of each species on RBCs of sheep, human and poultry at varied culture conditions by altering the temperature, pH and cell age."nMaterials and Methods: Three pathogenic Bordetella species were isolated from fifty suspected whooping cough patients on Bordet-Gengou agar and identified by their biochemical profiles. The hemolytic activity of B. pertussis, B. parapertussis and B. bronchiseptica was investigated in terms of cell bound and cell free hemolysin on human, poultry and sheep RBCs at variable pH, temperature and cell age in Stainer Scholt broth. The hemolysin activity was also determined qualitatively on blood agar containing different blood samples."nResults: All the species revealed optimum hemolytic activity in pH range 7.5-8.0 (in slight alkaline condition, temperature 37°C and cell age up to 20-24 hrs. The cell bound hemolytic activity was found to be maximum than cell free activity and varied with blood samples of different species. B. pertussis showed maximum hemolytic activity on human red blood cells followed by poultry and sheep RBCs. B. parapertussis and B. bronchiseptica showed maximum hemolytic activity on sheep and poultry RBCs respectively."nConclusion: The findings of our study revealed that different determinants are involved in host interactions and virulence of Bordetella species.

  7. [Hemolytic anemia in adults: Main causes and diagnostic procedure].

    Science.gov (United States)

    Loustau, Valentine; Guillaud, Constance; Garcon, Loïc; Godeau, Bertrand; Michel, Marc

    2011-05-01

    Hemolytic anemia (HA) is not an exceptional situation in adults. While establishing the hemolytic mechanism of an anemia is usually rather easy, finding the etiology may be quite difficult as both some hereditary (corpuscular) and acquired causes of HA may occur during adulthood. The diagnosis of HA therefore requires a multiple step procedure taking into account both patient's and family history, a careful analysis of the blood smear and a direct antiglobulin test. Based on these first data, the diagnosis procedure may then require more specific tests whose indications are discussed in this review.

  8. Adult patent ductus arteriosus complicated by endocarditis and hemolytic anemia.

    Science.gov (United States)

    Sabzi, Feridoun; Faraji, Reza

    2015-01-01

    An adult with a large patent ductus arteriosus may present with fatigue, dyspnea or palpitations or in rare presentation with endocarditis. The case illustrated unique role of vegetation of endocarditis in hemolytic anemia in adult with patent ductus arteriosus (PDA). Despite treatment of endocarditis with complete course of appropriate antibiotic therapy and normality of C- reactive protein, erythrocyte sedimentation rate and leukocytosis and wellness of general condition, transthoracic echocardiography revealed large vegetation in PDA lumen, surgical closure of PDA completely relieved hemolysis, and fragmented red cell disappeared from peripheral blood smear. The 3-month follow-up revealed complete occlusion of PDA and abolishment of hemolytic anemia confirmed by clinical and laboratory examination.

  9. Giant cell hepatitis and autoimmune hemolytic anemia after chickenpox.

    Science.gov (United States)

    Baran, Maşallah; Özgenç, Funda; Berk, Ömer; Gökçe, Demir; Kavakli, Kaan; Yilmaz, Funda; Şen, Sait; Yağci, Raşit Vural

    2010-12-01

    Autoimmune hemolytic anemia with giant cell hepatitis is a distinct entity in children. It is usually fatal with progressive liver disease. Immunosuppressive treatment with conventional drugs offers some response; however, it is usually only temporary. Alternative therapeutic options with monoclonals have been reported with promising remission of the disease. We report a case with autoimmune hemolytic anemia+giant cell hepatitis after varicella infection. She was resistant to standard immunosuppressive combinations, and rescue therapy with rituximab was used. Remission was not achieved with the drug and the child died with septic complication.

  10. Detection of alpha- and beta-hemolytic-like activity from Campylobacter jejuni.

    OpenAIRE

    Misawa, N; Hirayama, K.; Itoh, K.; Takahashi, E.

    1995-01-01

    Alpha-hemolytic-like activity from Campylobacter jejuni was clearly apparent when the medium pH ranged from 6.0 to 6.5, but the hemolytic zones disappeared when the pH of the medium increased. Beta-hemolytic-like activity just beneath the bacterial growth appeared after prolonged incubation. The hemolytic activity was not influenced by the species of blood.

  11. A Case of Autoimmune Hemolytic Anemia Associated with an Ovarian Teratoma

    OpenAIRE

    Kim, Ickkeun; Lee, Jue Yong; Kwon, Jung Hye; Jung, Joo Young; Song, Hun Ho; Park, Young lee; Ro, Eusun; Choi, Kyung Chan

    2006-01-01

    Autoimmune hemolytic anemia associated with an ovarian teratoma is a very rare disease. However, treating teratoma is the only method to cure the hemolytic anemia, so it is necessary to include ovarian teratoma in the differential diagnosis of autoimmune hemolytic anemia. We report herein on a case of a young adult patient who had severe autoimmune hemolytic anemia that was induced by an ovarian teratoma. A 25-yr-old woman complained of general weakness and dizziness for 1 week. The hemoglobi...

  12. Correction of hyperphosphatemia suppresses cardiac remodeling in uremic rats.

    Science.gov (United States)

    Yamazaki-Nakazawa, Ai; Mizobuchi, Masahide; Ogata, Hiroaki; Kumata, Chiaki; Kondo, Fumiko; Ono, Naoko; Koiwa, Fumihiko; Uda, Susumu; Kinugasa, Eriko; Akizawa, Tadao

    2014-02-01

    Hyperphosphatemia is associated with cardiovascular disease in patients with chronic kidney disease. To examine the effects of correction of hyperphosphatemia, we investigated the association between phosphate metabolism and cardiac remodeling in uremic rats. Four groups were studied for 8 weeks: (1) control (sham), (2) 5/6 nephrectomized (Nx) rats fed a normal phosphate regular diet (Nx + NP), (3) Nx rats fed a high phosphate (1.2 %) diet (Nx + HP), and (4) Nx rats fed a high phosphate diet containing 2 % lanthanum carbonate (Nx + HP + La). The relationship between phosphate metabolism and cardiac remodeling was analyzed. Nx + HP rats showed a significant increase in serum phosphate and PTH compared with Nx + NP rats, while Nx + HP + La rats showed slight decreases in these levels. Both Nx + HP and Nx + HP + La rats showed a significant increase in fibroblast growth factor-23 (FGF23) compared with Nx + NP rats. Urinary phosphate excretion showed a similar trend to that of FGF23. Nx + HP rats showed a significant increase in LV weight and matrix deposition compared with Nx + NP rats, and this increase was also significantly suppressed in Nx + HP + La rats. Serum phosphate levels and PTH were significantly correlated with LV weight and matrix deposition, but FGF23 levels did not show the correlation. FGF23 had a high correlation with urinary phosphate excretion. These results suggest that correction of hyperphosphatemia by lanthanum carbonate could suppress cardiac remodeling independently of changes in FGF23.

  13. Microbiota and prebiotics modulation of uremic toxin generation.

    Science.gov (United States)

    Koppe, Laetitia; Fouque, Denis

    2017-06-01

    Recent data have shown that the host-intestinal microbiota interaction is intrinsically linked with overall health. Chronic kidney disease (CKD) could influence intestinal microbiota and gut dysbiosis is also considered as a cause of progression of kidney disease. An increasing body of evidence indicates that dysbiosis is a key contributor of uremic retention solutes (URS) accumulating in patients with CKD. The discovery of the kidney-gut axis has created new therapeutic opportunities for nutritional intervention in order to prevent adverse outcomes. One of these strategies is prebiotics, which refers to nondigestible food ingredients or substances that beneficial affect growth and/or activity of limited health-promoting bacteria in the gastrointestinal tract. The influence of prebiotics on the production and concentration of URS have been investigated in various animal and human CKD studies. However, to date, there is still paucity of high-quality intervention trials. Randomized controlled trials and adequately powered intervention studies are needed before recommending prebiotics in clinical practice. This review will outline the interconnection between CKD progression, dysbiosis and URS production and will discuss mechanisms of action and efficacy of prebiotics as a new CKD management tool, with a particular emphasis on URS generation.

  14. Adsorption capacity of poly(ether imide) microparticles to uremic toxins.

    Science.gov (United States)

    Tetali, Sarada D; Jankowski, Vera; Luetzow, Karola; Kratz, Karl; Lendlein, Andreas; Jankowski, Joachim

    2016-01-01

    Uremia is a phenomenon caused by retention of uremic toxins in the plasma due to functional impairment of kidneys in the elimination of urinary waste products. Uremia is presently treated by dialysis techniques like hemofiltration, dialysis or hemodiafiltration. However, these techniques in use are more favorable towards removing hydrophilic than hydrophobic uremic toxins. Hydrophobic uremic toxins, such as hydroxy hipuric acid (OH-HPA), phenylacetic acid (PAA), indoxyl sulfate (IDS) and p-cresylsulfate (pCRS), contribute substantially to the progression of chronic kidney disease (CKD) and cardiovascular disease. Therefore, objective of the present study is to test adsorption capacity of highly porous microparticles prepared from poly(ether imide) (PEI) as an alternative technique for the removal of uremic toxins. Two types of nanoporous, spherically shaped microparticles were prepared from PEI by a spraying/coagulation process.PEI particles were packed into a preparative HPLC column to which a mixture of the four types of uremic toxins was injected and eluted with ethanol. Eluted toxins were quantified by analytical HPLC. PEI particles were able to adsorb all four toxins, with the highest affinity for PAA and pCR. IDS and OH-HPA showed a partially non-reversible binding. In summary, PEI particles are interesting candidates to be explored for future application in CKD.

  15. Incidence of congenital hemolytic anemias in young cholelithiasis patients

    Science.gov (United States)

    Ezer, Ali; Torer, Nurkan; Nursal, Tarik Zafer; Kizilkilic, Ebru; Caliskan, Kenan; Colakoglu, Tamer; Moray, Gokhan

    2010-01-01

    AIM: To clarify the incidence of congenital hemolytic anemias (CHA) in young cholelithiasis patients and to determine a possible screening test based on the results. METHODS: Young cholelithiasis patients (cholelithiasis patients (age under 35) with 2-5 gallstones, the clinician/surgeon should pay attention to MCV and Hb levels as indicative of CHA. PMID:21086564

  16. Evaluation of Neonatal Hemolytic Jaundice: Clinical and Laboratory Parameters

    Directory of Open Access Journals (Sweden)

    Anet Papazovska Cherepnalkovski

    2015-12-01

    CONCLUSIONS: The laboratory profile in ABO/Rh isoimmunisation cases depicts hemolytic mechanism of jaundice. These cases carry a significant risk for early and severe hyperbilirubinemia and are eligible for neurodevelopmental follow-up. Hematological parameters and blood grouping are simple diagnostic methods that assist the etiological diagnosis of neonatal hyperbilirubinemia.

  17. Impairment of bone health in pediatric patients with hemolytic anemia.

    Directory of Open Access Journals (Sweden)

    Michael M Schündeln

    Full Text Available INTRODUCTION: Sickle cell anemia and thalassemia result in impaired bone health in both adults and youths. Children with other types of chronic hemolytic anemia may also display impaired bone health. STUDY DESIGN: To assess bone health in pediatric patients with chronic hemolytic anemia, a cross-sectional study was conducted involving 45 patients with different forms of hemolytic anemia (i.e., 17 homozygous sickle cell disease and 14 hereditary spherocytosis patients. Biochemical, radiographic and anamnestic parameters of bone health were assessed. RESULTS: Vitamin D deficiency with 25 OH-vitamin D serum levels below 20 ng/ml was a common finding (80.5% in this cohort. Bone pain was present in 31% of patients. Analysis of RANKL, osteoprotegerin (OPG and osteocalcin levels indicated an alteration in bone modeling with significantly elevated RANKL/OPG ratios (control: 0.08+0.07; patients: 0.26+0.2, P = 0.0007. Osteocalcin levels were found to be lower in patients compared with healthy controls (68.5+39.0 ng/ml vs. 118.0+36.6 ng/ml, P = 0.0001. Multiple stepwise regression analysis revealed a significant (P<0.025 influence of LDH (partial r2 = 0.29, diagnosis of hemolytic anemia (partial r2 = 0.05 and age (partial r2 = 0.03 on osteocalcin levels. Patients with homozygous sickle cell anemia were more frequently and more severely affected by impaired bone health than patients with hereditary spherocytosis. CONCLUSION: Bone health is impaired in pediatric patients with hemolytic anemia. In addition to endocrine alterations, an imbalance in the RANKL/OPG system and low levels of osteocalcin may contribute to this impairment.

  18. Red blood cell vesiculation in hereditary hemolytic anemia

    Science.gov (United States)

    Alaarg, Amr; Schiffelers, Raymond M.; van Solinge, Wouter W.; van Wijk, Richard

    2013-01-01

    Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterized by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely assessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary hemolytic anemias. PMID

  19. Red blood cell vesiculation in hereditary hemolytic anemia

    Directory of Open Access Journals (Sweden)

    Amr eAlaarg

    2013-12-01

    Full Text Available Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterised by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely asessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary

  20. Red blood cell vesiculation in hereditary hemolytic anemia.

    Science.gov (United States)

    Alaarg, Amr; Schiffelers, Raymond M; van Solinge, Wouter W; van Wijk, Richard

    2013-12-13

    Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterized by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely assessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary hemolytic anemias.

  1. In vitro assessment of recombinant, mutant immunoglobulin G anti-D devoid of hemolytic activity for treatment of ongoing hemolytic disease of the fetus and newborn

    DEFF Research Database (Denmark)

    Nielsen, Leif K; Green, Trine H; Sandlie, Inger

    2008-01-01

    A specific treatment for ongoing hemolytic disease of the fetus and newborn (HDFN) due to anti-D would be very attractive. One approach could be administration to the mother of nonhemolytic anti-D, which by crossing the placenta can block the binding of hemolytic maternal anti-D.......A specific treatment for ongoing hemolytic disease of the fetus and newborn (HDFN) due to anti-D would be very attractive. One approach could be administration to the mother of nonhemolytic anti-D, which by crossing the placenta can block the binding of hemolytic maternal anti-D....

  2. Chronic kidney disease and fibrosis: the role of uremic retention solutes

    Directory of Open Access Journals (Sweden)

    Henricus A.M. Mutsaers

    2015-08-01

    Full Text Available Chronic kidney disease (CKD is a major global health concern, and the uremic state is highly associated with fibrogenesis in several organs and tissues. Fibrosis is characterized by excessive production and deposition of extracellular matrix proteins with a detrimental impact on organ function. Another key feature of CKD is the retention and subsequent accumulation of solutes that are normally cleared by the healthy kidney. Several of these uremic retention solutes, including indoxyl sulfate and p-cresyl sulfate, have been suggested to be CKD-specific triggers for the development and perpetuation of fibrosis. The purpose of this brief review is to gather and discuss the current body of evidence linking uremic retention solutes to the fibrotic response during CKD, with a special emphasis on the pathophysiological mechanisms in the kidney.

  3. Scanning Electron Microscopic Observation on Morphologic Characteristics of Sperms in Uremic Patients

    Institute of Scientific and Technical Information of China (English)

    Long-gen XU; Shi-fang SHI; Hai-zhen ZHONG; Xiao-feng HUANG; Xiao-ping QI; Qi-zhe SONG; Xin-hong WANG; Li YAN; Zong-fu SHAO

    2004-01-01

    Objective To observe the morphologic characteristics of spermatozoon ultramicro scopic structure in uremic subjects Method Semen sample from 10 patients with uremia and 5 healthy men were observed under light microscope and scanning electronic microscope.Results Abnormalities were found in sperms of uremic patients either in the sperm head (acrosome, acrosomic deficit, nuclear abnormality, pointed head, headless and double head of spermatozoon), neck (rupture, separation and enlargement), or tail (mitochondrial swelling, mitochondrial deficit, tailless, double tail, short tail and curled tail); whereas none of the above-mentioned abnormalities was observed in healthy men.Conclusion Sperms of uremic patients had many morphologic and structural abnor malities in the head, neck and tail.

  4. The plasma leptin concentration is closely associated with the body fat mass in nondiabetic uremic patients

    DEFF Research Database (Denmark)

    Clausen, P; Nielsen, P K; Olgaard, K

    1999-01-01

    Plasma leptin is associated with the body mass index and, more precisely, with the body fat mass. Plasma leptin has been found to be elevated in uremic patients. This study aimed at investigating the plasma leptin concentration and associations between plasma leptin, body fat mass, and glomerular...... filtration rate in nondiabetic predialysis uremic patients and in nondiabetic patients on chronic hemodialysis. Plasma leptin, body fat mass, and creatinine clearance were measured in 22 predialysis uremic patients, 18 hemodialysis patients, and 24 healthy control subjects. The logarithmically transformed...... plasma leptin concentration was closely associated with the body fat mass in all groups (r = 0.93, r = 0.83, and r = 0.72, respectively; p

  5. Ulcerative Uremic Stomatitis - Review of the Literature and A Rare Case Report

    Directory of Open Access Journals (Sweden)

    Shantala Arunkumar

    2015-01-01

    Full Text Available Uremic Stomatitis (US represents a comparatively uncommon intraoral complication seen, mostly, in cases of end-stage renal disease or undiagnosed or untreated chronic renal failure. Its frequency has diminished due to the advent of renal dialysis. Clinically uremic stomatitis is characterized by the presence of painful plaques and crusts that are usually distributed on the buccal and labial mucosa, dorsal or ventral surface of the tongue, gingiva, and floor of the mouth. Ultimate treatment consists of improvement of blood urea concentration and underlying renal failure is supported by enhancement of oral hygiene with antiseptic mouthwashes and antimicrobial/antifungal agents, if necessary. Here we report a rare case of ulcerative type of uremic stomatitis occurring in a patient of chronic renal failure due to sudden relapse of uremia and reviewed the possible pathophysiology of oral symptoms of chronic renal failure.

  6. Vitamin E protection of obesity-enhanced vascular calcification in uremic rats.

    Science.gov (United States)

    Peralta-Ramírez, A; Montes de Oca, A; Raya, A I; Pineda, C; López, I; Guerrero, F; Diez, E; Muñoz-Castañeda, J R; Martinez, J; Almaden, Y; Rodríguez, M; Aguilera-Tejero, E

    2014-02-15

    This study aimed to determine the extent of extraskeletal calcification in uremic Zucker rats, by comparing obese and lean phenotypes, and to evaluate the influence of vitamin E (VitE) on the development of calcifications in both uremic rats and human vascular smooth muscle cells (HVSMCs) cultured in vitro. Zucker rats of lean and obese phenotypes with normal renal function [control (C); C-lean and C-obese groups] and with uremia [5/6 nephrectomy (Nx); Nx-lean and Nx-obese groups] and uremic rats treated with VitE (Nx-lean + VitE and Nx-obese + VitE groups) were studied. Uremic groups were subjected to Nx, fed a 0.9% phosphorus diet, and treated with calcitriol (80 ng/kg ip). The aortic calcium concentration was significantly higher (P Nx-obese rats (10.0 ± 2.1 mg/g tissue) than in Nx-lean rats (3.6 ± 1.3 mg/g tissue). A decrease in plasma glutathione peroxidase activity was observed in Nx-obese rats compared with Nx-lean rats (217.2 ± 18.2 vs. 382.3 ± 15.5 nmol·min(-1)·ml(-1), P Nx-lean, Nx-obese, Nx-lean + VitE, and Nx-obese + VitE rats were also evidenced in other soft tissues. In HVSMCs incubated with high phosphate, VitE also prevented oxidative stress and reduced calcium content, bone alkaline phosphatase, and gene expression of core-binding factor-α1. In conclusion, uremic obese rats develop more severe calcifications than uremic lean rats and VitE reduces oxidative stress and vascular calcifications in both rats and cultures of HVSMCs.

  7. A Waterborne Outbreak of Escherichia coli O157:H7 Infections and Hemolytic Uremic Syndrome: Implications for Rural Water Systems1

    Science.gov (United States)

    Miller, Gayle; Breuer, Thomas; Kennedy, Malinda; Higgins, Charles; Walford, Jim; McKee, Gary; Fox, Kim; Bibb, William; Mead, Paul

    2002-01-01

    In the summer of 1998, a large outbreak of Escherichia coli O157:H7 infections occurred in Alpine, Wyoming. We identified 157 ill persons; stool from 71 (45%) yielded E. coli O157:H7. In two cohort studies, illness was significantly associated with drinking municipal water (town residents: adjusted odds ratio=10.1, 95% confidence intervals [CI]=1.8-56.4; visitors attending family reunion: relative risk=9.0, 95% CI=1.3-63.3). The unchlorinated water supply had microbiologic evidence of fecal organisms and the potential for chronic contamination with surface water. Among persons exposed to water, the attack rate was significantly lower in town residents than in visitors (23% vs. 50%, p<0.01) and decreased with increasing age. The lower attack rate among exposed residents, especially adults, is consistent with the acquisition of partial immunity following long-term exposure. Serologic data, although limited, may support this finding. Contamination of small, unprotected water systems may be an increasing public health risk. PMID:11971769

  8. A Web Server and Mobile App for Computing Hemolytic Potency of Peptides

    Science.gov (United States)

    Chaudhary, Kumardeep; Kumar, Ritesh; Singh, Sandeep; Tuknait, Abhishek; Gautam, Ankur; Mathur, Deepika; Anand, Priya; Varshney, Grish C.; Raghava, Gajendra P. S.

    2016-03-01

    Numerous therapeutic peptides do not enter the clinical trials just because of their high hemolytic activity. Recently, we developed a database, Hemolytik, for maintaining experimentally validated hemolytic and non-hemolytic peptides. The present study describes a web server and mobile app developed for predicting, and screening of peptides having hemolytic potency. Firstly, we generated a dataset HemoPI-1 that contains 552 hemolytic peptides extracted from Hemolytik database and 552 random non-hemolytic peptides (from Swiss-Prot). The sequence analysis of these peptides revealed that certain residues (e.g., L, K, F, W) and motifs (e.g., “FKK”, “LKL”, “KKLL”, “KWK”, “VLK”, “CYCR”, “CRR”, “RFC”, “RRR”, “LKKL”) are more abundant in hemolytic peptides. Therefore, we developed models for discriminating hemolytic and non-hemolytic peptides using various machine learning techniques and achieved more than 95% accuracy. We also developed models for discriminating peptides having high and low hemolytic potential on different datasets called HemoPI-2 and HemoPI-3. In order to serve the scientific community, we developed a web server, mobile app and JAVA-based standalone software (http://crdd.osdd.net/raghava/hemopi/).

  9. Primary Biliary Cirrhosis and Hemolytic Anemia Confusing Serum Bilirubin Levels

    Directory of Open Access Journals (Sweden)

    M Brackstone

    2000-01-01

    Full Text Available Hemolysis is observed in more than 50% of patients with cirrhosis. However, there has been little documention of the association of primary biliary cirrhosis with autoimmune hemolytic anemia. Two cases, found within a single practice, of primary biliary cirrhosis coexisting with autoimmune hemolysis and a third case coexisting with hereditary spherocytosis are presented. Anemia in such patients is commonly attributed to chronic disease, and hyperbilirubinemia is attributed to primary biliary cirrhosis. These patients were considered for liver transplantation until the diagnosis of a comorbid hemolytic process was established. This association may be more prevalent than previously recognized. A diagnosis of comorbid hemolysis must always be considered in context with anemia and serum bilirubin levels that rise out of proportion to the severity of the primary biliary cirrhosis.

  10. Hemolytic anemia and metabolic acidosis: think about glutathione synthetase deficiency.

    Science.gov (United States)

    Ben Ameur, Salma; Aloulou, Hajer; Nasrallah, Fehmi; Kamoun, Thouraya; Kaabachi, Naziha; Hachicha, Mongia

    2015-02-01

    Glutathione synthetase deficiency (GSSD) is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with hemolytic anemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low glutathione synthetase activity in erythrocytes or cultured skin fibroblasts. The prognosis seems to depend on early diagnosis and treatment. We report a 4 months old Tunisian male infant who presented with severe metabolic acidosis with high anion gap and hemolytic anemia. High level of 5-oxoproline was detected in her urine and diagnosis of GSSD was made. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. He died of severe metabolic acidosis and sepsis at the age of 15 months.

  11. Evaluation of anticonvulsant, antimicrobial and hemolytic activity of Aitchisonia rosea

    Directory of Open Access Journals (Sweden)

    Shahid Rasool

    2015-12-01

    Full Text Available The purpose of this study was to evaluate the anticonvulsant, antimicrobial and hemolytic effect of Aitchisonia rosea. The anticonvulsant effect was studied at doses 400 and 800 mg/kg against pentylenetetrazole, strychnine and picrotoxin-induced seizures in albino mice. The antimicrobial assay was conducted by disc diffusion method and minimum inhibitory concentration. Hemolytic effect was analyzed by reported method. Phenolic compounds present in the n-butanol fraction of the plant were estimated by HPLC. The plant showed maximum response against drug-induced convulsions and provided protection to animals at both doses. It also showed maximum zone of inhibition and highly significant MIC against all bacterial and fungal strains. The plant protected the RBCs from hemolysis. The highest amount of phenolics found was caffeic acid (7.5 ± 0.04.

  12. Case reports: delayed hemolytic transfusion reaction in sickle cell disease.

    Science.gov (United States)

    Syed, S K; Sears, D A; Werch, J B; Udden, M M; Milam, J D

    1996-10-01

    This article reports the details of delayed hemolytic transfusion reactions in four patients with sickle cell disease. These cases demonstrate the characteristics of the reactions, the significant risks involved, and the principles useful in diagnosis and treatment. Patients with sickle cell disease are at particular risk for delayed hemolytic transfusion reactions because they may be transfused at intervals over many years; they frequently form alloantibodies because of antigenic differences from the donor population; and they may receive emergency care in different hospitals where transfusion records are not available. In addition, exchange transfusions, which are often used for patients with sickle cell disease and which were given in three of these cases, raise the risks through increased exposure to foreign erythrocyte antigens and through an increased volume of erythrocytes susceptible to hemolysis. It was concluded that the hazards of these transfusion reactions justify preventive measures, such as extended erythrocyte phenotyping of patients with sickle cell disease and extended phenotypic matching of transfused cells.

  13. Pure red cell aplasia following autoimmune hemolytic anemia: An enigma

    Directory of Open Access Journals (Sweden)

    M Saha

    2013-01-01

    Full Text Available A 26-year-old previously healthy female presented with a 6-month history of anemia. The laboratory findings revealed hemolytic anemia and direct antiglobulin test was positive. With a diagnosis of autoimmune hemolytic anemia (AIHA, prednisolone was started but was ineffective after 1 month of therapy. A bone marrow trephine biopsy revealed pure red cell aplasia (PRCA showing severe erythroid hypoplasia. The case was considered PRCA following AIHA. This combination without clear underlying disease is rare. Human parvovirus B19 infection was not detected in the marrow aspirate during reticulocytopenia. The patient received azathioprine, and PRCA improved but significant hemolysis was once again documented with a high reticulocyte count. The short time interval between AIHA and PRCA phase suggested an increased possibility of the evolution of a single disease.

  14. Pure red cell aplasia following autoimmune hemolytic anemia: an enigma.

    Science.gov (United States)

    Saha, M; Ray, S; Kundu, S; Chakrabarti, P

    2013-01-01

    A 26-year-old previously healthy female presented with a 6-month history of anemia. The laboratory findings revealed hemolytic anemia and direct antiglobulin test was positive. With a diagnosis of autoimmune hemolytic anemia (AIHA), prednisolone was started but was ineffective after 1 month of therapy. A bone marrow trephine biopsy revealed pure red cell aplasia (PRCA) showing severe erythroid hypoplasia. The case was considered PRCA following AIHA. This combination without clear underlying disease is rare. Human parvovirus B19 infection was not detected in the marrow aspirate during reticulocytopenia. The patient received azathioprine, and PRCA improved but significant hemolysis was once again documented with a high reticulocyte count. The short time interval between AIHA and PRCA phase suggested an increased possibility of the evolution of a single disease.

  15. Autoimmune Hemolytic Anemia and Red Blood Cell Autoantibodies.

    Science.gov (United States)

    Quist, Erin; Koepsell, Scott

    2015-11-01

    Autoimmune hemolytic anemia is a rare disorder caused by autoreactive red blood cell (RBC) antibodies that destroy RBCs. Although autoimmune hemolytic anemia is rare, RBC autoantibodies are encountered frequently and can complicate transfusion workups, impede RBC alloantibody identification, delay distribution of compatible units, have variable clinical significance that ranges from benign to life-threatening, and may signal an underlying disease or disorder. In this review, we discuss the common presenting features of RBC autoantibodies, laboratory findings, ancillary studies that help the pathologist investigate the clinical significance of autoantibodies, and how to provide appropriate patient care and consultation for clinical colleagues. Pathologists must be mindful of, and knowledgeable about, this entity because it not only allows for direct clinical management but also can afford an opportunity to preemptively treat an otherwise silent malignancy or disorder.

  16. Renal cell carcinoma presenting as hemolytic anemia in pregnancy.

    Science.gov (United States)

    Monga, M; Benson, G S; Parisi, V M

    1995-03-01

    A patient presented at 29 weeks' gestation with severe hemolytic anemia. She was subsequently diagnosed as having renal cell carcinoma and had a radical nephrectomy at 31 weeks' gestation, which demonstrated stage I disease. This was followed by a normal vaginal delivery of a healthy infant at term and complete resolution of her anemia. This unusual presentation of renal cell carcinoma in pregnancy is discussed.

  17. Evaluation of Neonatal Hemolytic Jaundice: Clinical and Laboratory Parameters

    OpenAIRE

    Anet Papazovska Cherepnalkovski; Vjekoslav Krzelj; Beti Zafirovska-Ivanovska; Todor Gruev; Josko Markic; Natasa Aluloska; Nikolina Zdraveska; Katica Piperkovska

    2015-01-01

    BACKGROUND: Neonatal jaundice that occurs in ABO or Rhesus issoimunisation has been recognized as one of the major risk factors for development of severe hyperbilirubinemia and bilirubin neurotoxicity. AIM: Aim of our study was to investigate clinical and laboratory parameters associated with hemolytic jaundice due to Rh and ABO incompatibility and compare results with the group of unspecific jaundice. MATERIAL AND METHODS: One hundred sixty seven (167) neonatal hyperbilirubinemia cas...

  18. Autoimmune Hemolytic Anemia and Hodgkin's Disease: An Unusual Pediatric Association

    OpenAIRE

    Maria Miguel Gomes; Tereza Oliva; Armando Pinto

    2016-01-01

    Autoimmune hemolytic anemia (AIHA) is a recognized complication of lymphoproliferative disorders. AIHA associated with Hodgkin’s disease (HD) is uncommon especially in the pediatric population. The diagnosis of AIHA is usually associated with HD at the time of initial presentation or during the course of disease, but it could precede it by years to months. In adults the association of AIHA and HD is more frequent in advanced stages and in the nodular sclerosis and mixed cellularity type HD. W...

  19. Apicoaortic conduit for severe hemolytic anemia after aortic valve replacement.

    Science.gov (United States)

    Hatori, Kyohei; Ohki, Satoshi; Obayashi, Tamiyuki; Koyano, Tetsuya; Yasuhara, Kiyomitsu; Hirai, Hanako

    2015-06-01

    We describe the case of an 82-year-old woman who had undergone aortic mechanical valve replacement for aortic stenosis with a small annulus, and coronary artery bypass grafting. Four years after the operation, she began to experience hemolysis. Prosthetic valve obstruction was observed but there was no paravalvular leakage or aortic regurgitation through the mechanical valve. We elected to perform apicoaortic bypass in this patient with severe hemolytic anemia secondary to a mechanical valve malfunction.

  20. Inflammatory Cytokines as Uremic Toxins: “Ni Son Todos Los Que Estan, Ni Estan Todos Los Que Son”

    Science.gov (United States)

    Castillo-Rodríguez, Esmeralda; Pizarro-Sánchez, Soledad; Sanz, Ana B.; Ramos, Adrian M.; Sanchez-Niño, Maria Dolores; Martin-Cleary, Catalina; Fernandez-Fernandez, Beatriz; Ortiz, Alberto

    2017-01-01

    Chronic kidney disease is among the fastest growing causes of death worldwide. An increased risk of all-cause and cardiovascular death is thought to depend on the accumulation of uremic toxins when glomerular filtration rate falls. In addition, the circulating levels of several markers of inflammation predict mortality in patients with chronic kidney disease. Indeed, a number of cytokines are listed in databases of uremic toxins and uremic retention solutes. They include inflammatory cytokines (IL-1β, IL-18, IL-6, TNFα), chemokines (IL-8), and adipokines (adiponectin, leptin and resistin), as well as anti-inflammatory cytokines (IL-10). We now critically review the cytokines that may be considered uremic toxins. We discuss the rationale to consider them uremic toxins (mechanisms underlying the increased serum levels and evidence supporting their contribution to CKD manifestations), identify gaps in knowledge, discuss potential therapeutic implications to be tested in clinical trials in order to make this knowledge useful for the practicing physician, and identify additional cytokines, cytokine receptors and chemokines that may fulfill the criteria to be considered uremic toxins, such as sIL-6R, sTNFR1, sTNFR2, IL-2, CXCL12, CX3CL1 and others. In addition, we suggest that IL-10, leptin, adiponectin and resistin should not be considered uremic toxins toxins based on insufficient or contradictory evidence of an association with adverse outcomes in humans or preclinical data not consistent with a causal association. PMID:28333114

  1. Inflammatory Cytokines as Uremic Toxins: "Ni Son Todos Los Que Estan, Ni Estan Todos Los Que Son".

    Science.gov (United States)

    Castillo-Rodríguez, Esmeralda; Pizarro-Sánchez, Soledad; Sanz, Ana B; Ramos, Adrian M; Sanchez-Niño, Maria Dolores; Martin-Cleary, Catalina; Fernandez-Fernandez, Beatriz; Ortiz, Alberto

    2017-03-23

    Chronic kidney disease is among the fastest growing causes of death worldwide. An increased risk of all-cause and cardiovascular death is thought to depend on the accumulation of uremic toxins when glomerular filtration rate falls. In addition, the circulating levels of several markers of inflammation predict mortality in patients with chronic kidney disease. Indeed, a number of cytokines are listed in databases of uremic toxins and uremic retention solutes. They include inflammatory cytokines (IL-1β, IL-18, IL-6, TNFα), chemokines (IL-8), and adipokines (adiponectin, leptin and resistin), as well as anti-inflammatory cytokines (IL-10). We now critically review the cytokines that may be considered uremic toxins. We discuss the rationale to consider them uremic toxins (mechanisms underlying the increased serum levels and evidence supporting their contribution to CKD manifestations), identify gaps in knowledge, discuss potential therapeutic implications to be tested in clinical trials in order to make this knowledge useful for the practicing physician, and identify additional cytokines, cytokine receptors and chemokines that may fulfill the criteria to be considered uremic toxins, such as sIL-6R, sTNFR1, sTNFR2, IL-2, CXCL12, CX3CL1 and others. In addition, we suggest that IL-10, leptin, adiponectin and resistin should not be considered uremic toxins toxins based on insufficient or contradictory evidence of an association with adverse outcomes in humans or preclinical data not consistent with a causal association.

  2. Serratamolide is a hemolytic factor produced by Serratia marcescens.

    Directory of Open Access Journals (Sweden)

    Robert M Q Shanks

    Full Text Available Serratia marcescens is a common contaminant of contact lens cases and lenses. Hemolytic factors of S. marcescens contribute to the virulence of this opportunistic bacterial pathogen. We took advantage of an observed hyper-hemolytic phenotype of crp mutants to investigate mechanisms of hemolysis. A genetic screen revealed that swrW is necessary for the hyper-hemolysis phenotype of crp mutants. The swrW gene is required for biosynthesis of the biosurfactant serratamolide, previously shown to be a broad-spectrum antibiotic and to contribute to swarming motility. Multicopy expression of swrW or mutation of the hexS transcription factor gene, a known inhibitor of swrW expression, led to an increase in hemolysis. Surfactant zones and expression from an swrW-transcriptional reporter were elevated in a crp mutant compared to the wild type. Purified serratamolide was hemolytic to sheep and murine red blood cells and cytotoxic to human airway and corneal limbal epithelial cells in vitro. The swrW gene was found in the majority of contact lens isolates tested. Genetic and biochemical analysis implicate the biosurfactant serratamolide as a hemolysin. This novel hemolysin may contribute to irritation and infections associated with contact lens use.

  3. The reliability and representativity of non-dynamic bone histomorphometry in uremic osteodystrophy

    DEFF Research Database (Denmark)

    Heaf, J G; Pødenphant, J; Gammelgaard, Bente

    1993-01-01

    In order to evaluate the reliability and representativity of iliac crest bone biopsy in uremic osteodystrophy, non-dynamic bone histomorphometry was performed post-mortem on the right and left iliac crests and the 3rd lumbar vertebra in 20 patients with chronic uremia. High (> 0.8) right-left cor...

  4. Isolation and purification of uremic middle molecules by multi-step liquid chromatography

    Institute of Scientific and Technical Information of China (English)

    储结根; 刘晓航; 袁直; 何炳林

    2002-01-01

    Isolation and comparison of uremic sera and urine and normal sera and urine were performed by gel permeation chromatography, anion exchange chromatography and reversed-phase high performance liquid chromatography. Two uremic middle molecular fractions (A and B) were obtained from uremic sera and urine and normal urine by gel permeation chromatography, but not from normal sera. The anion exchange chromatographic results of fraction A from different origins demonstrate that subfraction A-3 could be excreted in urine by healthy subject, but accumulated in uremic serum for renal failure of patient with uremia. After desalinization subfraction A-3 was analyzed by MALDI-TOF-MS. The results show that subfraction A-3 consists of six compounds with molecular weight 839, 873, 1007.94, 1106, 1680 and 2015 respectively. Finally, by reversed-phase high performance liquid chromatography, subfraction A-3 was further resolved into six independent fractions. Thus, the isolation and purification of six middle molecular compounds in subfraction A-3 came true by our method.

  5. STUDY OF UREMIC TOXIN FLUXES ACROSS NANOFABRICATED HEMODIALYSIS MEMBRANES USING IRREVERSIBLE THERMODYNAMICS

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    Assem Hedayat

    2013-03-01

    Conclusions: Nanofabricated hemodialysis membranes with a reduced thickness and an applied electric potential can enhance the effective diffusivity and electro-migration flux of the respective uremic toxins by 3 orders of magnitude as compared to those passing through the high flux hemodialyzer.

  6. Cardiac and Renal Effects of Atrasentan in Combination with Enalapril and Paricalcitol in Uremic Rats

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    Cynthia Ritter

    2014-09-01

    Full Text Available Background/Aims: The search for new therapies providing cardiorenal protection in chronic kidney disease (CKD has led to treatments that combine conventional renin-angiotensin-aldosterone-system inhibitors with other drugs that exhibit potential in disease management. Methods: In rats made uremic by renal ablation, we examined the effects of addition of the endothelin-A receptor antagonist atrasentan to a previously examined combination of enalapril (angiotensin converting enzyme inhibitor and paricalcitol (vitamin D receptor activator on cardiac and renal parameters. The effects of the individual and combined drugs were examined after a 3-month treatment. Results: A decrease in systolic blood pressure, serum creatinine and proteinuria, and improvement of renal histology in uremic rats were attributed to enalapril and/or paricalcitol treatment; atrasentan alone had no effect. In heart tissue, individual treatment with the drugs blunted the increase in cardiomyocyte size, and combined treatment additively decreased cardiomyocyte size to normal levels. Perivascular fibrosis was blunted in uremic control rats with atrasentan or enalapril treatment. Conclusions: We found distinct cardiac and renal effects of atrasentan. Combination treatment with atrasentan, enalapril and paricalcitol provided positive effects on cardiac remodeling in uremic rats, whereas combination treatment did not offer further protective effects on blood pressure, proteinuria or renal histology.

  7. Skin Autofluorescence Is Associated with Endothelial Dysfunction in Uremic Subjects on Hemodialysis.

    Directory of Open Access Journals (Sweden)

    Chun-Cheng Wang

    Full Text Available Elevated levels of advanced glycation end products (AGEs within tissues may contribute to endothelial dysfunction, an early indicator of atherosclerosis. We aimed to investigate whether levels of skin AGEs could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis.One hundred and nineteen uremic patients on hemodialysis and 57 control subjects with moderate-to-high cardiovascular risk factors and without chronic kidney disease (CKD were enrolled. We used ultrasound to measure flow-mediated vasodilation (FMD. An AGE reader measured skin autoflurorescence (AF. We then compared differences in FMD and skin AF values between the two groups. The uremic subjects had significantly higher levels of skin AF (3.47±0.76 AU vs. 2.21±0.45 arbitrary units; P<0.01 and significantly lower levels of FMD (4.79%±1.88% vs. 7.19%±2.17%; P<0.01 than the non-CKD subjects. After adjusting for all potential covariates, we found that skin AF level independently predicted FMD in both the hemodialysis and the non-CKD groups. In the hemodialysis group, skin AF ≥ 3.05 arbitrary units predicted abnormal FMD at a sensitivity of 87.9% and a specificity of 78.6% (P<0.01.Skin AF could be a useful marker to predict endothelial dysfunction in uremic subjects on hemodialysis.

  8. Separation of uremic toxins from urine with resorcinarene-based ion chromatography columns.

    Science.gov (United States)

    Panahi, Tayyebeh; Weaver, Douglas J; Lamb, John D; Harrison, Roger G

    2015-01-01

    People with chronic kidney disease suffer from uremic toxins which accumulate in their bodies. Detection and quantification of uremic toxins help diagnose kidney problems and start patient care. The aim of this research was to seek a new method to assist this diagnosis by trace level detection and separation of guanidine containing uremic toxins in water and urine. To detect and quantify the uremic toxins, new stationary phases for ion chromatography (IC) columns based on glutamic acid functionalized resorcinarenes bound to divinylbenzene macroporous resin were prepared. The new column packing material afforded separation of the five compounds: guanidinoacetic acid, guanidine, methylguanidine, creatinine, and guanidinobenzoic acid in 30min. Peak resolutions ranged from 7.6 to 1.3. Gradient elutions at ambient temperature with methanesulfonic acid (MSA) solution as eluent resulted in detection levels in water from 10 to 47ppb and in synthetic urine from 28 to 180ppb. Limits of quantification for the analytes using pulsed amperometric detection were 30-160ppb in water and 93-590ppb in urine. Trace levels of creatinine (1ppm) were detected in the urine of a healthy individual using the columns.

  9. Cerebro-renal interactions: impact of uremic toxins on cognitive function.

    Science.gov (United States)

    Watanabe, Kimio; Watanabe, Tsuyoshi; Nakayama, Masaaki

    2014-09-01

    Cognitive impairment (CI) associated with chronic kidney disease (CKD) has received attention as an important problem in recent years. Causes of CI with CKD are multifactorial, and include cerebrovascular disease, renal anemia, secondary hyperparathyroidism, dialysis disequilibrium, and uremic toxins (UTs). Among these causes, little is known about the role of UTs. We therefore selected 21 uremic compounds, and summarized reports of cerebro-renal interactions associated with UTs. Among the compounds, uric acid, indoxyl sulfate, p-cresyl sulfate, interleukin 1-β, interleukin 6, TNF-α, and PTH were most likely to affect the cerebro-renal interaction dysfunction; however, sufficient data have not been obtained for other UTs. Notably, most of the data were not obtained under uremic conditions; therefore, the impact and mechanism of each UT on cognition and central nervous system in uremic state remains unknown. At present, impacts and mechanisms of UT effects on cognition are poorly understood. Clarifying the mechanisms and establishing novel therapeutic strategies for cerebro-renal interaction dysfunction is expected to be subject of future research.

  10. Cerebral oxidative stress induces spatial working memory dysfunction in uremic mice: neuroprotective effect of tempol.

    Science.gov (United States)

    Fujisaki, Kiichiro; Tsuruya, Kazuhiko; Yamato, Mayumi; Toyonaga, Jiro; Noguchi, Hideko; Nakano, Toshiaki; Taniguchi, Masatomo; Tokumoto, Masanori; Hirakata, Hideki; Kitazono, Takanari

    2014-03-01

    Chronic kidney disease (CKD) is frequently associated with uremic encephalopathy and cognitive impairment. Recent studies have demonstrated that cerebral oxidative stress contributes to cognitive dysfunction. Although oxidative stress has been reported to increase in the uremic rat brain, the relationship between increased oxidative stress and cognitive impairment in uremia is unclear. In the present study, the effects of tempol (TMP), an antioxidant drug, were investigated in uremic mice. CKD was induced in male C57BL/6 mice (n = 8) by left nephrectomy and 2/3 electrocoagulation of the right renal cortex. Working memory performance was tested by the radial arm water maze test. We have prepared two protocols ('time course study' and 'treatment study'). First, we examined the working memory test and histological examination of mouse brains after 4 and 8 weeks. Next, we investigated the effect of TMP (3 mM) against uremia-induced neurodegeneration and oxidative stress in the mouse brain. Eight weeks after CKD induction, vehicle-treated mice made significantly more errors than sham-operated control mice, while TMP improved working memory performance in CKD mice. CKD was associated with accumulation of 8-hydroxy-2'-deoxyguanosine in the hippocampal neuronal cells, but not in TMP-treated CKD mice. Increased numbers of pyknotic neuronal cells were observed in the hippocampus of CKD mice at 8 weeks, but pyknotic neuronal cell numbers were decreased under the influence of TMP in uremic mice. The present study provided evidence that uremia is associated with spatial working memory dysfunction in mice and that treatment with TMP protects against cerebral oxidative stress and improves cognitive dysfunction in uremic mice, suggesting their potential usefulness for the treatment of cognitive dysfunction in uremia.

  11. Uremic anorexia: a consequence of persistently high brain serotonin levels? The tryptophan/serotonin disorder hypothesis.

    Science.gov (United States)

    Aguilera, A; Selgas, R; Codoceo, R; Bajo, A

    2000-01-01

    Anorexia is a frequent part of uremic syndrome, contributing to malnutrition in dialysis patients. Many factors have been suggested as responsible for uremic anorexia. In this paper we formulate a new hypothesis to explain the appetite disorders in dialysis patients: "the tryptophan/serotonin disorder hypothesis." We review current knowledge of normal hunger-satiety cycle control and the disorders described in uremic patients. There are four phases in food intake regulation: (1) the gastric phase, during which food induces satiety through gastric distention and satiety peptide release; (2) the post absorptive phase, during which circulating compounds, including glucose and amino acids, cause satiety by hepatic receptors via the vagus nerve; (3) the hepatic phase, during which adenosine triphosphate (ATP) concentration is the main stimulus inducing hunger or satiety, with cytokines inhibiting ATP production; and (4) the central phase, during which appetite is regulated through peripheral (circulating plasma substances and neurotransmitters) and brain stimuli. Brain serotonin is the final target for peripheral mechanisms controlling appetite. High brain serotonin levels and a lower serotonin/dopamine ratio cause anorexia. Plasma and brain amino acid concentrations are recognized factors involved in neurotransmitter synthesis and appetite control. Tryptophan is the substrate of serotonin synthesis. High plasma levels of anorectics such as tryptophan (plasma and brain), cholecystokinin, tumor necrosis factor alpha, interleukin-1, and leptin, and deficiencies of nitric oxide and neuropeptide Y have been described in uremia; all increase intracerebral serotonin. We suggest that brain serotonin hyperproduction due to a uremic-dependent excess of tryptophan may be the final common pathway involved in the genesis of uremic anorexia. Various methods of ameliorating anorexia by decreasing the central effects of serotonin are proposed.

  12. Speckle tracking echocardiography detects uremic cardiomyopathy early and predicts cardiovascular mortality in ESRD.

    Science.gov (United States)

    Kramann, Rafael; Erpenbeck, Johanna; Schneider, Rebekka K; Röhl, Anna B; Hein, Marc; Brandenburg, Vincent M; van Diepen, Merel; Dekker, Friedo; Marx, Nicolaus; Floege, Jürgen; Becker, Michael; Schlieper, Georg

    2014-10-01

    Cardiovascular mortality is high in ESRD, partly driven by sudden cardiac death and recurrent heart failure due to uremic cardiomyopathy. We investigated whether speckle-tracking echocardiography is superior to routine echocardiography in early detection of uremic cardiomyopathy in animal models and whether it predicts cardiovascular mortality in patients undergoing dialysis. Using speckle-tracking echocardiography in two rat models of uremic cardiomyopathy soon (4-6 weeks) after induction of kidney disease, we observed that global radial and circumferential strain parameters decreased significantly in both models compared with controls, whereas standard echocardiographic readouts, including fractional shortening and cardiac output, remained unchanged. Furthermore, strain parameters showed better correlations with histologic hallmarks of uremic cardiomyopathy. We then assessed echocardiographic and clinical characteristics in 171 dialysis patients. During the 2.5-year follow-up period, ejection fraction and various strain parameters were significant risk factors for cardiovascular mortality (primary end point) in a multivariate Cox model (ejection fraction hazard ratio [HR], 0.97 [95% confidence interval (95% CI), 0.95 to 0.99; P=0.012]; peak global longitudinal strain HR, 1.17 [95% CI, 1.07 to 1.28; P<0.001]; peak systolic and late diastolic longitudinal strain rates HRs, 4.7 [95% CI, 1.23 to 17.64; P=0.023] and 0.25 [95% CI, 0.08 to 0.79; P=0.02], respectively). Multivariate Cox regression analysis revealed circumferential early diastolic strain rate, among others, as an independent risk factor for all-cause mortality (secondary end point; HR, 0.43; 95% CI, 0.25 to 0.74; P=0.002). Together, these data support speckle tracking as a postprocessing echocardiographic technique to detect uremic cardiomyopathy and predict cardiovascular mortality in ESRD.

  13. Serological profile and hemolytic disease in term neonates with ABO incompatibility

    OpenAIRE

    Desiana Dharmayani; Djajadiman Gatot; Rinawati Rohsiswatmo; Bambang Tridjaja

    2009-01-01

    Background Hemolytic disease of the newborn (HDN) due to ABO blood type incompatibility is one of the most common cause of neonatal hyperbilirubunemia that potentially leads to bilirubin encephalopathy. Data on ABO-hemolytic disease of the newborn (ABO-HDN), especially regarding umbilical cord blood serological profile, are limited. Objective To identify the serological profile and hemolytic disease in term neonates with ABO incompatibility. Methods This was a cross-secti...

  14. The role of rituximab in adults with warm antibody autoimmune hemolytic anemia.

    Science.gov (United States)

    Dierickx, Daan; Kentos, Alain; Delannoy, André

    2015-05-21

    Warm antibody hemolytic anemia is the most common form of autoimmune hemolytic anemia. When therapy is needed, corticosteroids remain the cornerstone of initial treatment but are able to cure only a minority of patients (hemolytic anemia in adults, although no prospective study convincingly supports this attitude. A recent randomized study strongly suggests that in first-line treatment, rituximab combined with steroids is superior to monotherapy with steroids. If this finding is confirmed, rituximab will emerge as a major component of the management of warm antibody hemolytic anemia not only after relapse but as soon as treatment is needed.

  15. Efficacy of epigallocatechin-3-gallate and Amla (Emblica officinalis) extract for the treatment of diabetic-uremic patients.

    Science.gov (United States)

    Chen, Tung-Sheng; Liou, Show-Yih; Wu, Hsi-Chin; Tsai, Fuu-Jen; Tsai, Chang-Hai; Huang, Chih-Yang; Chang, Yen-Lin

    2011-01-01

    Uremic patients with diabetes suffer from high levels of oxidative stress due to regular hemodialysis therapy (neutrophil activation induced by hemo-incompatibility between the hemodialyser and blood) and complications associated with diabetes. Several plasma biomarkers were screened in 13 uremic diabetic patients after receiving the mixture of (-)-epigallocatechin gallate (EGCG), a major component of green tea extract, and Amla extract (AE), from Emblica officinalis, the Indian gooseberry, for 3 months. We found that oral administration of a 1:1 mixture of EGCG and AE for 3 months significantly improved antioxidant defense as well as diabetic and atherogenic indices in uremic patients with diabetes. Furthermore, no significant changes in hepatic function, renal function, or inflammatory responses were observed. These results suggest that a 1:1 combination of EGCG and AE is a safe and effective treatment for uremic patients with diabetes.

  16. Involvement of organic anion transporters in the efflux of uremic toxins across the blood-brain barrier.

    Science.gov (United States)

    Deguchi, Tsuneo; Isozaki, Kouya; Yousuke, Kouno; Terasaki, Tetsuya; Otagiri, Masaki

    2006-02-01

    Renal failure causes multiple physiological changes involving CNS dysfunction. In cases of uremia, there is close correlation between plasma levels of uremic toxins [e.g. 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), hippurate (HA) and indoleacetate (IA)] and the degree of uremic encephalopathy, suggesting that uremic toxins are involved in uremic encephalopathy. In order to evaluate the relevance of uremic toxins to CNS dysfunction, we investigated directional transport of uremic toxins across the blood-brain barrier (BBB) using in vivo integration plot analysis and the brain efflux index method. We observed saturable efflux transport of [(3)H]CMPF, [(14)C]HA and [(3)H]IA, which was inhibited by probenecid. For all uremic toxins evaluated, apparent efflux clearance across the BBB was greater than apparent influx clearance, suggesting that these toxins are predominantly transported from the brain to blood across the BBB. Saturable efflux transport of [(3)H]CMPF, [(14)C]HA and [(3)H]IA was completely inhibited by benzylpenicillin, which is a substrate of rat organic anion transporter 3 (rOat3). Taurocholate and digoxin, which are common substrates of rat organic anion transporting polypeptide (rOatp), partially inhibited the efflux of [(3)H]CMPF. Transport experiments using a Xenopus laevis oocyte expression system revealed that CMPF, HA and IA are substrates of rOat3, and that CMPF (but not HA or IA) is a substrate of rOap2. These results suggest that rOat3 mediates brain-to-blood transport of uremic toxins, and that rOatp2 is involved in efflux of CMPF. Thus, conditions typical of uremia can cause inhibition of brain-to-blood transport involving rOat3 and/or rOatp2, leading to accumulation of endogenous metabolites and drugs in the brain.

  17. Exploring binding characteristics and the related competition of different protein-bound uremic toxins.

    Science.gov (United States)

    Deltombe, Olivier; de Loor, Henriette; Glorieux, Griet; Dhondt, Annemieke; Van Biesen, Wim; Meijers, Björn; Eloot, Sunny

    2017-08-01

    Little is known about potential differences in binding characteristics of protein-bound uremic toxins (PBUTs) in patients with chronic kidney disease (CKD) versus healthy controls. The question arises whether eventual differences are attributed to (i) the elevated levels of competing uremic toxins, and/or (ii) post-translational modifications of albumin. We evaluated the binding characteristics of hippuric acid (HA), indole-3-acetic acid (IAA), indoxyl sulfate (IS), and p-cresylsulfate (pCS) by deriving a binding curve in three distinct conditions: (i) serum from healthy controls (healthy serum), (ii) blank serum from hemodialysis patients (blank HD serum; i.e. cleared from uremic toxins), and (iii) non-treated serum from HD patients (HD serum). Additionally, the mutual binding competition of these uremic toxins was studied in blank HD in pairs. In both experiments, equilibrium dialysis (37 °C, 5 h) was used to separate the free and bound fractions of each PBUT. Free and total PBUT concentrations were quantified by an ultra-high performance liquid chromatography method with tandem mass spectrometer detection and the percentage protein binding (%PB) of each PBUT was calculated. For all four compounds, the binding capacity of healthy serum was higher than blank HD serum, which was comparable to non-treated HD serum, except for HA. The competition experiments revealed that at high uremic concentrations, mutual competition was observed for the strongly bound PBUTs IS and pCS. The %PB of the weakly bound HA and IAA was lower (trend) only for the addition to blank HD serum containing the strongly bound IS or pCS. There is an intrinsic impact on protein binding in uremia, revealing a lower binding capacity, as compared to healthy controls. Competitive binding is only relevant for the strongly bound PBUTs at high uremic concentrations. In addition, at least part of the effect on binding capacity can be attributed to post-translational modifications of albumin. Copyright

  18. Fatal hemolytic anemia associated with metformin: A case report

    Directory of Open Access Journals (Sweden)

    Packer Clifford D

    2008-09-01

    Full Text Available Abstract Introduction Metformin is a widely prescribed biguanide antidiabetic drug that has been implicated as a cause of hemolytic anemia in three previous case reports. We report a case of rapidly fatal hemolysis that was temporally associated with the initiation of metformin treatment for diabetes. Clinicians need to be aware of this rare but potentially serious side effect of metformin. Case presentation A 56-year-old Caucasian man with type 2 diabetes mellitus was started on metformin to improve glycemic control. Shortly afterwards, he developed progressive fatigue, exertional dyspnea, cranberry-colored urine and jaundice. Laboratory studies showed severe hemolysis, with a drop in hemoglobin from 14.7 to 6.6 g/dl over 4 days, markedly elevated lactate dehydrogenase, bilirubin and reticulocyte counts, and a low haptoglobin level. A peripheral blood smear showed no schistocytes, and a direct Coombs test was positive for anti-IgG and negative for anti-C3. Despite corticosteroid treatment and transfusion of packed red blood cells, the patient developed increasing dyspnea, hypotension, further decline in hemoglobin to 3.3 g/dl, and fatal cardiorespiratory arrest 12 hours after admission. Conclusion The serologic findings in this case suggest an autoimmune hemolytic anemia, caused either by a drug-induced autoantibody or a warm autoantibody. Based on the temporal association with metformin and the lack of other clear precipitating causes, we propose that metformin-induced hemolysis with a drug-induced autoantibody is a strong possibility. This mechanism differs from a previously described case with a possible antibody to the erythrocyte-drug complex. It has been shown, however, that hemolysis may occur via multiple mechanisms from the same drug. Clinicians should consider the possibility of metformin-associated immune hemolytic anemia in patients with otherwise unexplained hemolysis.

  19. Autoimmune Hemolytic Anemia as a Complication of Nivolumab Therapy.

    Science.gov (United States)

    Palla, Amruth R; Kennedy, Devin; Mosharraf, Hossain; Doll, Donald

    2016-01-01

    Recently, immunotherapeutic drugs, including PD-1 inhibitors (nivolumab, pembrolizumab), PD-L1 inhibitors (atezolizumab, avelumab), and CTLA4 inhibitors (ipiliumumab), have emerged as important additions to the armamentarium against certain malignancies and have been incorporated into therapeutic protocols for first-, second-, or third-line agents for these metastatic cancers. Immune checkpoint inhibitor nivolumab is currently FDA approved for the treatment of patients with metastatic malignant melanoma [Redman et al.: BMC Med 2016;14: 20], metastatic non-small cell lung cancer [Guibert and Mazières: Expert Opin Biol Ther 2015;15: 1789-1797], metastatic renal cell cancer [Farolfi et al.: Expert Opin Drug Metab Toxicol 2016;12: 1089-1096], and relapsed or refractory classic Hodgkin's lymphoma [Villasboas and Ansell: Expert Rev Anticancer Ther 2016;16: 5-12]. Given the current and increasing indications for these drugs, it is essential for all physicians to become well versed with their common adverse effects and to be observant for other less documented clinical conditions that could be unmasked with the use of such medications. A definite association between autoimmune hemolytic anemia and the immune checkpoint inhibitor nivolumab has not been clearly documented, although a few cases have been reported recently [Kong et al.: Melanoma Res 2016;26: 202-204; Schwab et al.: Case Rep Oncol 2016;9: 373-378; Tardy et al.: Hematol Oncol 2016, DOI: 10.1002/hon.2338]. We report a case of fatal autoimmune hemolytic anemia refractory to steroids in a patient treated with nivolumab for metastatic lung cancer, and reflect on the other reported cases of autoimmune hemolytic anemia after the use of nivolumab.

  20. Etiopathogenesis of hemolytic reactions in total artificial heart recipients.

    Science.gov (United States)

    Vasků, J; Urbánek, P

    1997-12-01

    Hemolysis in total artificial heart (TAH) recipients was analyzed. From a total of 66 long-term experiments lasting from 30-314 days performed in the Brno Research Center, in 53 animals, the total red blood cell (RBC) count, hematocrit, total hemoglobin, and free plasma hemoglobin were investigated. We could essentially divide the whole group of calves in 2 subgroups. The first subgroup was calves with hemolytic reactions, and the second subgroup was calves without any hemolytic reaction at all. In the first subgroup, hemolysis occurred in 47% of the overall number of animals during extracorporeal circulation (ECC), in 15% during ECC and later periodically during the experiment, in 8% during ECC and then continuously during the experiment, and finally in 10% not during ECC but repeatedly during the experiment. In 20% of the animals from the overall number, hemolysis did not occur at all (second subgroup). These results testify to the great individual differences within 1 breed (Bohemian with a substantial component of Holstein). These differences are further modified by exogenous and endogenous factors. First, the inborn resistance of the RBC membrane and also thrombi formation and the mineralization of the driving diaphragm are very important. The extreme situation of decreased RBC membrane resistance was proved using a calf from another breed, the slow growing Scottish Highland breed, which did not survive 22 days of pumping due to intractable lethal hemolysis. These factors are also indicated by the hemolytic action of some drugs (e.g., Dopegyt) used during the experiment for another reason. Also important are the mechanical forces of pumping, surface moieties of the biomaterial, mineralization of the driving diaphragms, thrombi formation, infection, etc. Essentially, the hemolytic reaction in the TAH recipient has a multifactorial character. Hemolysis is undoubtedly an important factor, which can have a profound impact on the length of survival. The

  1. Primary biliary cholangitis associated with warm autoimmune hemolytic anemia.

    Science.gov (United States)

    Gonzalez-Moreno, Emmanuel I; Martinez-Cabriales, Sylvia A; Cruz-Moreno, Miguel A; Borjas-Almaguer, Omar D; Cortez-Hernandez, Carlos A; Bosques-Padilla, Francisco J; Garza, Aldo A; Gonzalez-Gonzalez, Jose A; Garcia-Compean, Diego; Ocampo-Candiani, Jorge; Maldonado-Garza, Hector J

    2016-02-01

    There are many autoimmune diseases associated with primary biliary cholangitis (PBC), known as primary biliary cirrhosis; however, the association between PBC and warm autoimmune hemolytic anemia (wAIHA) has rarely been reported. It is documented that hemolysis is present in over 50% of the patients with chronic liver disease, regardless of the etiologies. Due to the clear and frequent relationship between PBC and many autoimmune diseases, it is reasonable to suppose that wAIHA may be another autoimmune disorder seen in association with PBC. Here we reported a 53-year-old female patient diagnosed with wAIHA associated with PBC.

  2. Hydropic degeneration of the anterior pituitary gland (adenohypophysis) in uremic rats.

    Science.gov (United States)

    Levine, Seymour; Saltzman, Arthur

    2004-03-01

    We observed hydropic degeneration of the anterior pituitary in rats made uremic by nephrotoxic chemicals, especially when the uremic rats were given a pure carbohydrate diet beforehand. The hydropic degeneration caused loss of nuclear and cytoplasmic content of many or most anterior pituitary cells. It was readily visible in paraffin sections by light microscopy. It was exaggerated when water was injected after the nephrotoxin and it was greatly reduced if saline was injected after the nephrotoxin. Low serum sodium levels in affected rats and the response to saline injection suggested that the mechanism for development of hydropic degeneration of the anterior pituitary gland involved hyponatremia. Depletion of total body sodium probably accounts for the enhancement of hydropic degeneration by the pure carbohydrate diet. Morphologic lesions of the anterior pituitary related to hyponatremia and uremia have not been described previously.

  3. Trimethoprim-induced immune hemolytic anemia in a pediatric oncology patient presenting as an acute hemolytic transfusion reaction.

    Science.gov (United States)

    Gupta, Sweta; Piefer, Cindy L; Fueger, Judy T; Johnson, Susan T; Punzalan, Rowena C

    2010-12-01

    A 10-year-old male with acute leukemia presented with post-chemotherapy anemia. During red cell transfusion, he developed hemoglobinuria. Transfusion reaction workup was negative. Drug-induced immune hemolytic anemia was suspected because of positive direct antiglobulin test, negative eluate, and microspherocytes on smear pre- and post-transfusion. Drug studies using the indirect antiglobulin test were strongly positive with trimethoprim and trimethoprim-sulfamethoxazole but negative with sulfamethoxazole. The patient recovered after discontinuing the drug, with no recurrence in 2 years. Other causes of anemia should be considered in patients with worse-than-expected anemia after chemotherapy. Furthermore, hemolysis during transfusion is not always a transfusion reaction.

  4. Cobalt-doped nanohydroxyapatite: synthesis, characterization, antimicrobial and hemolytic studies

    Energy Technology Data Exchange (ETDEWEB)

    Tank, Kashmira P., E-mail: kashmira_physics@yahoo.co.in [Saurashtra University, Crystal Growth Laboratory, Physics Department (India); Chudasama, Kiran S.; Thaker, Vrinda S. [Saurashtra University, Bioscience Department (India); Joshi, Mihir J., E-mail: mshilp24@rediffmail.com [Saurashtra University, Crystal Growth Laboratory, Physics Department (India)

    2013-05-15

    Hydroxyapatite (Ca{sub 10}(PO{sub 4}){sub 6}(OH){sub 2}; HAP) is a major mineral component of the calcified tissues, and it has various applications in medicine and dentistry. In the present investigation, cobalt-doped hydroxyapatite (Co-HAP) nanoparticles were synthesized by surfactant-mediated approach and characterized by different techniques. The EDAX was carried out to estimate the amount of doping in Co-HAP. The transmission electron microscopy result suggested the transformation of morphology from needle shaped to spherical type on increasing the doping concentration. The powder XRD study indicated the formation of a new phase of brushite for higher concentration of cobalt. The average particle size and strain were calculated using Williamson-Hall analysis. The average particle size was found to be 30-60 nm. The FTIR study confirmed the presence of various functional groups in the samples. The antimicrobial activity was evaluated against four organisms Pseudomonas aeruginosa and Shigella flexneri as Gram negative as well as Micrococcus luteus and Staphylococcus aureus as Gram positive. The hemolytic test result suggested that all samples were non-hemolytic. The photoluminescence study was carried out to identify its possible applicability as a fluorescent probe.

  5. Listeria monocytogenes and hemolytic Listeria innocua in poultry.

    Science.gov (United States)

    Milillo, S R; Stout, J C; Hanning, I B; Clement, A; Fortes, E D; den Bakker, H C; Wiedmann, M; Ricke, S C

    2012-09-01

    Listeria monocytogenes is a ubiquitous, saprophytic, Gram-positive bacterium and occasional food-borne pathogen, often associated with ready-to-eat meat products. Because of the increased consumer interest in organic, all natural, and free range poultry products, it is important to understand L. monocytogenes in the context of such systems. Pasture-reared poultry were surveyed over the course of two 8-wk rearing periods. Cecal, soil, and grass samples were collected for Listeria isolation and characterization. Seven of 399 cecal samples (or 1.75%) were Listeria-positive. All positive cecal samples were obtained from broilers sampled at 2 wk of age. Grass and soil samples were collected from the pasture both before and after introduction of the poultry. Environmental samples collected after introduction of poultry were significantly more likely to contain Listeria (P Listeria, sigB allelic typing, and hlyA PCR tests found that both L. monocytogenes and L. innocua, including hemolytic L. innocua, were recovered from the cecal and environmental (grass/soil) samples. The sigB allelic typing also revealed that (1) positive samples could be composed of 2 or more allelic types; (2) allelic types found in cecal samples could also be found in the environment; and (3) allelic types could persist through the 2 rearing periods. Our data indicate that both pasture-reared poultry and their environment can be contaminated with L. monocytogenes and hemolytic L. innocua.

  6. Anti-Kpa-induced severe delayed hemolytic transfusion reaction.

    Science.gov (United States)

    Koshy, R; Patel, B; Harrison, J S

    2009-01-01

    Kpa is a low-frequency antigen occurring in less than 2 percent of the Caucasian population. Mild to moderate delayed hemolytic transfusion reactions (DHTR) and hemolytic disease of the fetus and newborn attributable to anti-Kpa have been reported. Severe overt DHTR has not been reported with anti-Kpa. A case of a severe DHTR attributed to anti-Kpa after multiple RBC transfusions is being reported. A 52-year-old Caucasian woman received multiple units of RBCs for a lower gastrointestinal bleed. She was referred to our institution for hepatic and renal failure, which was supported by laboratory findings of peak LDH, bilirubin, BUN, and creatinine elevations. Hemoglobin had dropped on Day 10 after transfusion. The DAT and antibody screen (ABS) were negative. Initial workup and subsequent ABS were negative. Anti-Kpa was identified when an additional RBC panel was tested. One of the RBC units transfused was incompatible by antihuman globulin (AHG) crossmatch with the patient's plasma and typed positive for Kpa. DHTR was confirmed after extensive workup. The patient responded to supportive therapy and experienced an uneventful recovery. DHTR may not be considered when DAT and ABS are negative. However, correlation of recent transfusion with signs and symptoms should alert the clinician to entertain and investigate a DHTR that should include the AHG crossmatch of all implicated RBC units. The severity of the reaction also raises concerns as to when and what antigen specificity should be considered for inclusion in the antibody screening cells.

  7. Autoimmune Hemolytic Anemia in Children: Mayo Clinic Experience.

    Science.gov (United States)

    Sankaran, Janani; Rodriguez, Vilmarie; Jacob, Eapen K; Kreuter, Justin D; Go, Ronald S

    2016-04-01

    We studied 35 pediatric patients with autoimmune hemolytic anemia seen at Mayo Clinic from 1994 to 2014. The median age was 10.0 years and 65.7% were males. Most had warm antibodies (80.0%) and some secondary to viral (14.3%) or autoimmune disorders (31.4%). Seven (20.0%) patients presented with Evans syndrome, 3 of whom also had common variable immunodeficiency. The median hemoglobin at diagnosis was 6.1 g/dL and 62.8% patients required red cell transfusions. The severity of anemia was worse among children below 10 years (median 5.5 vs. 7.0 g/dL, P=0.01). Steroid was the initial treatment for 88.5% patients, with overall response rate of 82.7% (68.5% complete, 14.2% partial) and median response duration of 10.7 months (range, 0.2 to 129.7+ mo). After median follow-up of 26.6 months, 8 (22.8%) patients relapsed. Salvage treatments included splenectomy, intravenous immunoglobulin, rituximab, and mycophenolate mofetil. Infectious complications occurred in 9 (25.7%) patients and 1 patient died of cytomegalovirus infection. Four patients had cold agglutinin disease and 3 (75.0%) responded to steroids. Autoimmune hemolytic anemia is a rare disorder in pediatric population and most respond well to steroids regardless of the type of antibody. Infectious complications are common and screening for immunodeficiency is recommended among those with Evans syndrome.

  8. Current approaches for the treatment of autoimmune hemolytic anemia.

    Science.gov (United States)

    Jaime-Pérez, José Carlos; Rodríguez-Martínez, Marisol; Gómez-de-León, Andrés; Tarín-Arzaga, Luz; Gómez-Almaguer, David

    2013-10-01

    Autoimmune hemolytic anemia (AIHA) is an infrequent group of diseases defined by autoantibody mediated red blood cell destruction. Correct diagnosis and classification of this condition are essential to provide appropriate treatment. AIHA is divided into warm and cold types according to the characteristics of the autoantibody involved and by the presence of an underlying or associated disorder into primary and secondary AIHA. Due to its low frequency, treatment for AIHA is largely based on small prospective trials, case series, and empirical observations. This review describes in detail the different treatment approaches for autoimmune hemolytic anemia. Warm antibody type AIHA should be treated with steroids, to which most patients respond, although relapse can occur and maintenance doses are frequently required. Splenectomy is an effective second line treatment and can provide long-term remission without medication. Rituximab is a useful alternative for steroid refractory patients, those requiring high maintenance doses and unfavorable candidates for surgery. Promising therapeutic modifications with this monoclonal antibody are emerging including drug combinations, lower doses, and long-term use. Primary cold agglutinin disease has been recognized as having a lymphoproliferative monoclonal origin. It is unresponsive to both steroids and splenectomy. Rituximab is currently the best therapeutic alternative for this condition, and several treatment regimens are available with variable responses.

  9. Cerebellar Lesions of Uremic Encephalopathy on MRI in Hemodialyzed Diabetic Patient: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kil, Min Chul; Lee, Seung Young; Cha, Sang Hoon; Cho, Bum Sang; Kang, Min Ho [Dept. of Radiology, Chungbuk National Universty Hospital, Cheongju (Korea, Republic of)

    2012-01-15

    Uremic encephalopathy (UE) is a well-known complication of uremia, but its pathophysiology remains unknown. It is widely reported that in UE, the bilateral basal ganglia (BG) shows hyperintensities on T2/fluid attenuated inversion recovery magnetic resonance imaging (MRI), but cerebellar lesions are extremely rare, with to the best of our knowledge, only one case reported to date. We describe the findings from computed tomography and MRI for typical BG and cerebellar vermis lesions.

  10. Response of the growth plate of uremic rats to human growth hormone and corticosteroids

    Directory of Open Access Journals (Sweden)

    A.P.F. Barbosa

    2007-08-01

    Full Text Available Children with chronic renal failure in general present growth retardation that is aggravated by corticosteroids. We describe here the effects of methylprednisolone (MP and recombinant human growth hormone (rhGH on the growth plate (GP of uremic rats. Uremia was induced by subtotal nephrectomy in 30-day-old rats, followed by 20 IU kg-1 day-1 rhGH (N = 7 or 3 mg kg-1 day-1 MP (N = 7 or 20 IU kg-1 day-1 rhGH + 3 mg kg-1 day-1 MP (N = 7 treatment for 10 days. Control rats with intact renal function were sham-operated and treated with 3 mg kg-1 day-1 MP (N = 7 or vehicle (N = 7. Uremic rats (N = 7 were used as untreated control animals. Structural alterations in the GP and the expression of anti-proliferating cell nuclear antigen (PCNA and anti-insulin-like growth factor I (IGF-I by epiphyseal chondrocytes were evaluated. Uremic MP rats displayed a reduction in the proliferative zone height (59.08 ± 4.54 vs 68.07 ± 7.5 µm, P < 0.05 and modifications in the microarchitecture of the GP. MP and uremia had an additive inhibitory effect on the proliferative activity of GP chondrocytes, lowering the expression of PCNA (19.48 ± 11.13 vs 68.64 ± 7.9% in control, P < 0.0005 and IGF-I (58.53 ± 0.96 vs 84.78 ± 2.93% in control, P < 0.0001, that was counteracted by rhGH. These findings suggest that in uremic rats rhGH therapy improves longitudinal growth by increasing IGF-I synthesis in the GP and by stimulating chondrocyte proliferation.

  11. High dose intravenous iron, mineral homeostasis and intact FGF23 in normal and uremic rats

    DEFF Research Database (Denmark)

    Gravesen, Eva; Hofman-Bang, Jacob; Mace, Maria L.

    2013-01-01

    High iron load might have a number of toxic effects in the organism. Recently intravenous (iv) iron has been proposed to induce elevation of fibroblast growth factor 23 (FGF23), hypophosphatemia and osteomalacia in iron deficient subjects. High levels of FGF23 are associated with increased......, iron isomaltoside 1000 (IIM) and ferric carboxymaltose (FCM), on plasma levels of FGF23 and phosphate was examined in normal and uremic iron repleted rats....

  12. [Severe autoimmune hemolytic anemia after ABO match living donor liver transplantation].

    Science.gov (United States)

    Kohata, Katsura; Fujiwarw, Tohru; Yamamoto, Joji; Yamada, Minami; Ishizawa, Kenichi; Satoh, Kazushige; Sekiguchi, Satoshi; Kameoka, Junichi; Satomi, Susumu; Harigae, Hideo

    2010-01-01

    A case of severe autoimmune hemolytic anemia after ABO matched living donor liver transplantation. We present here a case of severe autoimmune hemolytic anemia after ABO matched living donor liver transplantation. The patient is 56 y.o male. He received living donor liver transplantation from his ABO matched son in May 2007. In July, he was suffered from a progressive anemia, and diagnosed as autoimmune hemolytic anemia by the laboratory examinations. Intensive treatment including predonisolone, azathiopurine, rituximab, plasma exchange, was given, however, the disease was resistant to the treatment. By the administration of cyclophosphamide combined with rituximab, remission was finally achieved. To date, immune mediated hemolytic anemia after ABO matched living donor liver transplantation has not been reported, although several cases of ABO mismatched living donor liver transplantation have been reported. His severe but transient clinical course of anemia suggests that the transient emergence of donor lymphocytes may be responsible for onset of hemolytic anemia.

  13. Concurrent reactive arthritis, Graves' disease, and warm autoimmune hemolytic anemia: a case report.

    Science.gov (United States)

    Chiang, Elizabeth; Packer, Clifford D

    2009-08-13

    Warm antibody autoimmune hemolytic anemia is due to the presence of warm agglutinins that react with protein antigens on the surface of red blood cells causing premature destruction of circulating red blood cells. We report the first case of concurrent reactive arthritis, Graves' disease, and autoimmune hemolytic anemia. A 40-year-old man with reactive arthritis, Graves' disease, type 2 diabetes mellitus, mitral valve prolapse, and Gilbert's disease presented with a one month history of jaundice, fatigue, and black stools. After diagnosis of warm autoimmune hemolytic anemia, the patient was started on prednisone 1 mg/kg with rapid improvement in his anemia and jaundice. Our subject's mother and possibly his maternal grandmother also had autoimmune hemolytic anemia, which raises the possibility of hereditary autoimmune hemolytic anemia, a rarely reported condition.

  14. The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin.

    Science.gov (United States)

    Perna, Alessandra F; Zacchia, Miriam; Trepiccione, Francesco; Ingrosso, Diego

    2017-01-10

    Lanthionine is a nonproteinogenic amino acid, composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage. It is biosynthesized from the condensation of two cysteine molecules, while the related compound homolanthionine is formed from the condensation of two homocysteine molecules. The reactions can be carried out by either cystathionine-β-synthase (CBS) or cystathionine-γ-lyase (CSE) independently, in the alternate reactions of the transsulfuration pathway devoted to hydrogen sulfide biosynthesis. Low plasma total hydrogen sulfide levels, probably due to reduced CSE expression, are present in uremia, while homolanthionine and lanthionine accumulate in blood, the latter several fold. Uremic patients display a derangement of sulfur amino acid metabolism with a high prevalence of hyperhomocysteinemia. Uremia is associated with a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity, due to the accumulation of retention products. Lanthionine inhibits hydrogen sulfide production in hepatoma cells, possibly through CBS inhibition, thus providing some basis for the biochemical mechanism, which may significantly contribute to alterations of metabolism sulfur compounds in these subjects (e.g., high homocysteine and low hydrogen sulfide). We therefore suggest that lanthionine is a novel uremic toxin.

  15. The Sulfur Metabolite Lanthionine: Evidence for a Role as a Novel Uremic Toxin

    Directory of Open Access Journals (Sweden)

    Alessandra F. Perna

    2017-01-01

    Full Text Available Lanthionine is a nonproteinogenic amino acid, composed of two alanine residues that are crosslinked on their β-carbon atoms by a thioether linkage. It is biosynthesized from the condensation of two cysteine molecules, while the related compound homolanthionine is formed from the condensation of two homocysteine molecules. The reactions can be carried out by either cystathionine-β-synthase (CBS or cystathionine-γ-lyase (CSE independently, in the alternate reactions of the transsulfuration pathway devoted to hydrogen sulfide biosynthesis. Low plasma total hydrogen sulfide levels, probably due to reduced CSE expression, are present in uremia, while homolanthionine and lanthionine accumulate in blood, the latter several fold. Uremic patients display a derangement of sulfur amino acid metabolism with a high prevalence of hyperhomocysteinemia. Uremia is associated with a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity, due to the accumulation of retention products. Lanthionine inhibits hydrogen sulfide production in hepatoma cells, possibly through CBS inhibition, thus providing some basis for the biochemical mechanism, which may significantly contribute to alterations of metabolism sulfur compounds in these subjects (e.g., high homocysteine and low hydrogen sulfide. We therefore suggest that lanthionine is a novel uremic toxin.

  16. Uremic myopathy: Is oxidative stress implicated in muscle dysfunction in uremia?

    Directory of Open Access Journals (Sweden)

    Antonia eKaltsatou

    2015-03-01

    Full Text Available Renal failure is accompanied by progressive muscle weakness and premature fatigue, in part linked to hypokinesis and in part to uremic toxicity. These changes are associated with various detrimental biochemical and morphological alterations. All of these pathological parameters are collectively termed ureamic myopathy. Various interventions while helpful can’t fully remedy the pathological phenotype. Complex mechanisms that stimulate muscle dysfunction in uremia have been proposed, and oxidative stress could be implicated. Skeletal muscles continuously produce reactive oxygen species (ROS and reactive nitrogen species (RNS at rest and more so during contraction. The aim of this mini review is to provide an update on recent advances in our understanding of how ROS and RNS generation might contribute to muscle dysfunction in uremia. Thus a systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. While few studies met our criteria their findings are discussed making reference to other available literature data. Oxidative stress can direct muscle cells into a catabolic state and chronic exposure to it leads to wasting. Moreover, redox disturbances can significantly affect force production per se. We conclude that oxidative stress can be in part responsible for some aspects of uremic myopathy. Further research is needed to discern clear mechanisms and to help efforts to counteract muscle weakness and exercise intolerance in uremic patients.

  17. Effect of AST-120 on Endothelial Dysfunction in Adenine-Induced Uremic Rats

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    Yuko Inami

    2014-01-01

    Full Text Available Aim. Chronic kidney disease (CKD represents endothelial dysfunction. Monocyte adhesion is recognized as the initial step of arteriosclerosis. Indoxyl sulfate (IS is considered to be a risk factor for arteriosclerosis in CKD. Oral adsorbent AST-120 retards deterioration of renal function, reducing accumulation of IS. In the present study, we determined the monocyte adhesion in the adenine-induced uremic rats in vivo and effects of AST-120 on the adhesion molecules. Methods. Twenty-four rats were divided into control, control+AST-120, adenine, and adenine+AST-120 groups. The number of monocytes adherent to the endothelium of thoracic aorta by imaging the entire endothelial surface and the mRNA expressions of adhesion and atherosclerosis-related molecules were examined on day 49. The mRNA expressions of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells were also examined. Results. Adenine increased the number of adherent monocytes, and AST-120 suppressed the increase. The monocyte adhesion was related to serum creatinine and IS in sera. Overexpression of VCAM-1 and TGF-β1 mRNA in the arterial walls was observed in uremic rats. IS induced increase of the ICAM-1 and VCAM-1 mRNA expressions in vitro. Conclusion. It appears that uremic condition introduces the monocyte adhesion to arterial wall and AST-120 might inhibit increasing of the monocyte adherence with CKD progression.

  18. Protein-bound uremic toxins stimulate crosstalk between leukocytes and vessel wall.

    Science.gov (United States)

    Pletinck, Anneleen; Glorieux, Griet; Schepers, Eva; Cohen, Gerald; Gondouin, Bertrand; Van Landschoot, Maria; Eloot, Sunny; Rops, Angelique; Van de Voorde, Johan; De Vriese, An; van der Vlag, Johan; Brunet, Philippe; Van Biesen, Wim; Vanholder, Raymond

    2013-12-01

    Leukocyte activation and endothelial damage both contribute to cardiovascular disease, a major cause of morbidity and mortality in CKD. Experimental in vitro data link several protein-bound uremic retention solutes to the modulation of inflammatory stimuli, including endothelium and leukocyte responses and cardiovascular damage, corroborating observational in vivo data. However, the impact of these uremic toxins on the crosstalk between endothelium and leukocytes has not been assessed. This study evaluated the effects of acute and continuous exposure to uremic levels of indoxylsulfate (IS), p-cresylsulfate (pCS), and p-cresylglucuronide (pCG) on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using intravital microscopy. Superfusion with IS induced strong leukocyte adhesion, enhanced extravasation, and interrupted blood flow, whereas pCS caused a rapid increase in leukocyte rolling. Superfusion with pCS and pCG combined caused impaired blood flow and vascular leakage but did not further enhance leukocyte rolling over pCS alone. Intravenous infusion with IS confirmed the superfusion results and caused shedding of heparan sulfate, pointing to disruption of the glycocalyx as the mechanism likely mediating IS-induced flow stagnation. These results provide the first clear in vivo evidence that IS, pCS, and pCG exert proinflammatory effects that contribute to vascular damage by stimulating crosstalk between leukocytes and vessels.

  19. Effect of skin care with an emollient containing a high water content on mild uremic pruritus.

    Science.gov (United States)

    Okada, Kazuyoshi; Matsumoto, Koichi

    2004-10-01

    Skin care is very important for preventing uremic pruritus. However, mild uremic pruritus has usually been treated with antihistamine and urea-containing ointments. We therefore examined the effects of an aqueous gel with higher water content. Twenty hemodialysis patients with mild pruritus who were not being treated with any emollient were divided into two groups of 10 each. Patients in one group were treated with an aqueous gel containing 80% water. This emollient was applied twice daily for 2 weeks. No emollient was applied for the next 2 weeks. The other group of patients were not treated with any emollient for the 4 weeks. Visual analog scale scores for itching in the experimental group at week 2 were significantly decreased compared with that at week 0 (3.5 +/- 0.3 vs 0.6 +/- 0.2, P emollient was stopped. There were no significant changes in the control group during the study. It is concluded that the aqueous gel with high water content reduced itching and improved xerosis in patients with mild uremic pruritus. It is reasonable that skin care with an emollient containing a high water content is first started for hemodialysis patients with xerosis, even if they do not feel itching.

  20. Uremic Toxins and Lipases in Haemodialysis: A Process of Repeated Metabolic Starvation

    Directory of Open Access Journals (Sweden)

    Bernd Stegmayr

    2014-04-01

    Full Text Available Severe kidney disease results in retention of uremic toxins that inhibit key enzymes for lipid breakdown such as lipoprotein lipase (LPL and hepatic lipase (HL. For patients in haemodialysis (HD and peritoneal dialysis (PD the LPL activity is only about half of that of age and gender matched controls. Angiopoietin, like protein 3 and 4, accumulate in the uremic patients. These factors, therefore, can be considered as uremic toxins. In animal experiments it has been shown that these factors inhibit the LPL activity. To avoid clotting of the dialysis circuit during HD, anticoagulation such as heparin or low molecular weight heparin are added to the patient. Such administration will cause a prompt release of the LPL and HL from its binding sites at the endothelial surface. The liver rapidly degrades the release plasma compound of LPL and HL. This results in a lack of enzyme to degrade triglycerides during the later part of the HD and for another 3–4 h. PD patients have a similar baseline level of lipases but are not exposed to the negative effect of anticoagulation.

  1. Molecular mechanisms for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.

    Science.gov (United States)

    Watanabe, Hiroshi

    2013-01-01

    Chronic kidney disease (CKD), marked by a progressive loss in renal function, is a leading cause of hemodialysis initiation and cardiovascular disease (CVD). There are currently 13.3 million patients with CKD and 300 thousand patients are currently undergoing hemodialysis in Japan. Therefore, preventing the initiation of dialysis and reducing the risk of cardiovascular death are high-priority issues from the viewpoint of public health and economic implications. Understanding the molecular mechanism responsible for the progression of CKD and cardiovascular damage regarding crosstalk between the kidney and cardiovascular system is an important issue in controlling the pathogenesis of CKD-CVD. However, the mechanisms involved in CKD-CVD are not well understood. This hinders the development of new treatment strategies. We have been investigating the role of protein bound uremic toxins, that are difficult to remove by hemodialysis, on the onset and progression of CKD and CVD. The relationship between their redox properties and the pathogenesis of CKD-CVD was examined. In this review, we focus on two sulfate conjugated uremic toxins, namely, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), and summarize recent studies that provide new insights on the molecular mechanisms responsible for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.

  2. Positive predictive value of diagnosis coding for hemolytic anemias in the Danish National Patient Register

    Science.gov (United States)

    Hansen, Dennis Lund; Overgaard, Ulrik Malthe; Pedersen, Lars; Frederiksen, Henrik

    2016-01-01

    Purpose The nationwide public health registers in Denmark provide a unique opportunity for evaluation of disease-associated morbidity if the positive predictive values (PPVs) of the primary diagnosis are known. The aim of this study was to evaluate the predictive values of hemolytic anemias registered in the Danish National Patient Register. Patients and methods All patients with a first-ever diagnosis of hemolytic anemia from either specialist outpatient clinic contact or inpatient admission at Odense University Hospital from January 1994 through December 2011 were considered for inclusion. Patients with mechanical reason for hemolysis such as an artificial heart valve, and patients with vitamin-B12 or folic acid deficiency were excluded. Results We identified 412 eligible patients: 249 with a congenital hemolytic anemia diagnosis and 163 with acquired hemolytic anemia diagnosis. In all, hemolysis was confirmed in 359 patients, yielding an overall PPV of 87.1% (95% confidence interval [CI]: 83.5%–90.2%). A diagnosis could be established in 392 patients of whom 355 patients had a hemolytic diagnosis. Diagnosis was confirmed in 197 of the 249 patients with congenital hemolytic anemia, yielding a PPV of 79.1% (95% CI: 73.5%–84.0%). Diagnosis of acquired hemolytic anemia could be confirmed in 136 of the 163 patients, resulting in a PPV of 83.4% (95% CI: 76.8%–88.8%). For hemoglobinopathy PPV was 84.1% (95% CI: 77.4%–89.4%), for hereditary spherocytosis PPV was 80.6% (95% CI: 69.5%–88.9%), and for autoimmune hemolytic anemia PPV was 78.4% (95% CI: 70.4%–85.0%). Conclusion The PPV of hemolytic anemias was moderately high. The PPVs were comparable in the three main categories of overall hemolysis, and congenital and acquired hemolytic anemia. PMID:27445504

  3. Protein-Bound Uremic Toxins from Gut Microbiota and Inflammatory Markers in Chronic Kidney Disease.

    Science.gov (United States)

    Borges, Natália A; Barros, Amanda F; Nakao, Lia S; Dolenga, Carla J; Fouque, Denis; Mafra, Denise

    2016-11-01

    Protein-bound uremic toxins from gut microbiota tend to accumulate in chronic kidney disease (CKD) patients and are poorly removed by current dialysis techniques. These toxins induce inflammation and are associated with cardiovascular disease (CVD). The aim of this study was to report the relationship between uremic toxins and inflammatory and cardiovascular markers in CKD patients. This was a cross sectional study. Twenty-one nondialysis patients were included (43% men, 63.0 ± 7.8 years, glomerular filtration rate: 34.4 ± 12.5 mL/min) as well as 29 hemodialysis (HD) patients [58% men, 52.7 ± 10.3 years, time on dialysis 54 (31-94.5 months)]. Total levels of uremic toxins (IS, p-CS, and IAA) were assessed by high-performance liquid chromatography with fluorescence detection. C-reactive protein, Interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and calprotectin plasma levels were determined by immunometric assays. HD patients presented higher inflammatory markers and uremic toxins levels than nondialysis patients. IL-6 levels were positively correlated with IS (r = 0.49; P = .03), p-CS (r = 0.35; P = .04) and IAA (r = 0.36; P = .03). A positive correlation was also observed between MCP-1 levels with IS (r = 0.72; P = .001), p-CS (r = 0.48; P = .001) and IAA (r = 0.75; P = .0001). Linear regression showed that IS was an independent predictor for IL-6 and MCP-1 levels after adjustment. Plasma uremic toxins were associated with higher IL-6 and MCP-1 levels in CKD patients, potentially playing a role in the development of CVD. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  4. Does the adequacy parameter Kt/V(urea reflect uremic toxin concentrations in hemodialysis patients?

    Directory of Open Access Journals (Sweden)

    Sunny Eloot

    Full Text Available Hemodialysis aims at removing uremic toxins thus decreasing their concentrations. The present study investigated whether Kt/V(urea, used as marker of dialysis adequacy, is correlated with these concentrations. Predialysis blood samples were taken before a midweek session in 71 chronic HD patients. Samples were analyzed by colorimetry, HPLC, or ELISA for a broad range of uremic solutes. Solute concentrations were divided into four groups according to quartiles of Kt/V(urea, and also of different other parameters with potential impact, such as age, body weight (BW, Protein equivalent of Nitrogen Appearance (PNA, Residual Renal Function (RRF, and dialysis vintage. Dichotomic concentration comparisons were performed for gender and Diabetes Mellitus (DM. Analysis of Variance in quartiles of Kt/V(urea did not show significant differences for any of the solute concentrations. For PNA, however, concentrations showed significant differences for urea (P<0.001, uric acid (UA, p-cresylsulfate (PCS, and free PCS (all P<0.01, and for creatinine (Crea and hippuric acid (HA (both P<0.05. For RRF, concentrations varied for β₂-microglobulin (P<0.001, HA, free HA, free indoxyl sulfate, and free indole acetic acid (all P<0.01, and for p-cresylglucuronide (PCG, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF, free PCS, and free PCG (all P<0.05. Gender and body weight only showed differences for Crea and UA, while age, vintage, and diabetes mellitus only showed differences for one solute concentration (UA, UA, and free PCS, respectively. Multifactor analyses indicated a predominant association of concentration with protein intake and residual renal function. In conclusion, predialysis concentrations of uremic toxins seem to be dependent on protein equivalent of nitrogen appearance and residual renal function, and not on dialysis adequacy as assessed by Kt/V(urea. Efforts to control intestinal load of uremic toxin precursors by dietary or other

  5. Cryptococcal meningitis in patients with autoimmune hemolytic anemia.

    Science.gov (United States)

    Yang, YaLi; Sang, Junjun; Pan, Weihua; Du, Lin; Liao, Wanqing; Chen, Jianghan; Zhu, Yuanjie

    2014-08-01

    To summarize the epidemiology, clinical features, treatment, and outcome of cryptococcal meningitis (CM) in autoimmune hemolytic anemia (AIHA) patients and to provide a reference for the prevention and control of AIHA complicated with CM, we evaluated five cases of CM in patients with AIHA treated in our hospital from 2003 to 2013 and eight related foreign cases. All of the clinical isolates were Cryptococcus neoformans var. grubii and grouped into the VNI genotype and serotype A. The clinical features exhibit significant features. Headache, nausea, and fever are common symptoms of AIHA complicated with CM. The early clinical manifestations lack specificity, which may lead to delayed diagnosis and treatment. Long-term use of prednisone (≥15 mg day(-1)), poor control of anemia, and splenectomy are risk factors for AIHA complicated with cryptococcal infection. The combination of intravenous amphotericin B and oral 5-fluorocytosine remains the preferred treatment for AIHA complicated with CM.

  6. Efficacy and safety of splenectomy in adult autoimmune hemolytic anemia

    Science.gov (United States)

    Giudice, Valentina; Rosamilio, Rosa; Ferrara, Idalucia; Seneca, Elisa; Serio, Bianca

    2016-01-01

    Abstract Autoimmune hemolytic anemia (AIHA) is a rare hematologic disease, primarily affecting adults or children with immunodeficiency disease. First-line therapy consists of long course of steroids administration, with an early complete response rate (CRr) of 75-80%, but up to 20-30% of patients requires a second-line therapy. Rituximab is the first choice in refractory old AIHA patients, because of its safety and efficacy (early CRr at 80-90% and at 68% at 2-3 years). For this reason, splenectomy is even less chosen as second-line therapy in elderly, even though laparoscopic technique decreased complication and mortality rates. However, splenectomy can be still considered a good therapeutic option with a CRr of 81% at 35.6 months in patients older than 60 year-old, when rituximab administration cannot be performed. PMID:28352823

  7. Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia.

    Science.gov (United States)

    Berentsen, Sigbjørn; Tjønnfjord, Geir E

    2012-05-01

    Exact diagnosis of the subtype has essential therapeutic consequences in autoimmune hemolytic anemia. Cold-antibody types include primary chronic cold agglutinin disease (CAD) and rare cases of cold agglutinin syndrome (CAS) secondary to cancer or acute infection. Primary CAD is a clonal lymphoproliferative disorder. Not all patients require pharmacological therapy, but treatment seems indicated more often than previously thought. Corticosteroids should not be used to treat primary CAD. Half of the patients respond to rituximab monotherapy; median response duration is 11 months. The most efficient treatment to date is fludarabine and rituximab in combination, resulting in responses in 75%, complete responses in 20% and median response duration of more than 66 months. Toxicity may be a concern, and an individualized approach is discussed. Erythrocyte transfusions can be given provided specific precautions are undertaken. No evidence-based therapy exists in secondary CAS, but optimal treatment of the underlying disorder is essential when feasible.

  8. Hemolytic disease of the newborn due to isoimmunization with anti-E antibodies: a case report.

    Science.gov (United States)

    Sarici, S Umit; Alpay, Faruk; Yeşilkaya, Ediz; Ozcan, Okan; Gökçay, Erdal

    2002-01-01

    Minor blood group hemolytic disease is extremely rare, since the overall potency of minor blood groups in inducing antibodies is significantly lower when compared with that of Rh (D) antigen. We hereby report a very rare case of severe neonatal anti-E hemolytic disease due to E minor blood group incompatibility. A term newborn born to a 27-year-old, gravida 3, para 3 mother was referred due to a high and increasing serum bilirubin level despite phototherapy on the 4th day of life. On admission physical examination was normal except for the jaundice, and results of the laboratory investigation demonstrated a moderate-to-severe anemia (hemoglobin 7.8 g/dl) and a severe hemolytic hyperbilirubinemia (serum total and indirect bilirubin levels 36 mg/ dl and 32.8 mg/dl, respectively; reticulocyte count 15%; and a positive direct antiglobulin test). As there was no apparent cause of the hemolytic disease such as Rh or ABO incompatibilities, further investigation (a positive indirect antiglobulin test and a positive irregular anti-E antibody in both the patient and mother, and minor blood group antigen profiles in family members compatible with E minor blood group isoimmunization) revealed the presence of anti-E hemolytic disease due to E minor blood group incompatibility. Two exchange transfusions with a 12-hour-interval were performed with minor blood group compatible fresh whole blood, and the patient was discharged in a healthy condition on the 10th postnatal day. If the most common causes of severe neonatal hemolytic disease such as Rh and ABO incompatibilities cannot be demonstrated in a newborn with significant hemolytic hyperbilirubinemia, anti-E hemolytic disease should strongly be considered in differential diagnosis. It should be kept in mind that a very severe from of minor group antibody hemolytic disease characterized by anemia and severe hyperbilirubinemia many exchange transfusions may be encountered during the course of the disease.

  9. Complex regional pain syndrome 1 – the Swiss cohort study

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    Perez Roberto SGM

    2008-06-01

    Full Text Available Abstract Background Little is known about the course of Complex Regional Pain Syndrome 1 and potential factors influencing the course of this disorder over time. The goal of this study is a to set up a database with patients suffering from suspected CRPS 1 in an initial stadium, b to perform investigations on epidemiology, diagnosis, prognosis, and socioeconomics within the database and c to develop a prognostic risk assessment tool for patients with CRPS 1 taking into account symptomatology and specific therapies. Methods/design Prospective cohort study. Patients suffering from a painful swelling of the hand or foot which appeared within 8 weeks after a trauma or a surgery and which cannot be explained by conditions that would otherwise account for the degree of pain and dysfunction will be included. In accordance with the recommendations of International Classification of Functioning, Disability and Health (ICF model, standardised and validated questionnaires will be used. Patients will be monitored over a period of 2 years at 6 scheduled visits (0 and 6 weeks, 3, 6, 12, and 24 months. Each visit involves a physical examination, registration of therapeutic interventions, and completion of the various study questionnaires. Outcomes involve changes in health status, quality of life and costs/utility. Discussion This paper describes the rationale and design of patients with CRPS 1. Ideally, potential risk factors may be identified at an early stage in order to initiate an early and adequate treatment in patients with increased risk for delayed recovery. Trial registration Not applicable

  10. Positive predictive value of diagnosis coding for hemolytic anemias in the Danish National Patient Register

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    Hansen DL

    2016-06-01

    Full Text Available Dennis Lund Hansen,1 Ulrik Malthe Overgaard,2 Lars Pedersen,3 Henrik Frederiksen1,3 1Department of Haematology, Odense University Hospital, Odense, 2Department of Haematology, Herlev Hospital, Herlev, 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Purpose: The nationwide public health registers in Denmark provide a unique opportunity for evaluation of disease-associated morbidity if the positive predictive values (PPVs of the primary diagnosis are known. The aim of this study was to evaluate the predictive values of hemolytic anemias registered in the Danish National Patient Register. Patients and methods: All patients with a first-ever diagnosis of hemolytic anemia from either specialist outpatient clinic contact or inpatient admission at Odense University Hospital from January 1994 through December 2011 were considered for inclusion. Patients with mechanical reason for hemolysis such as an artificial heart valve, and patients with vitamin-B12 or folic acid deficiency were excluded. Results: We identified 412 eligible patients: 249 with a congenital hemolytic anemia diagnosis and 163 with acquired hemolytic anemia diagnosis. In all, hemolysis was confirmed in 359 patients, yielding an overall PPV of 87.1% (95% confidence interval [CI]: 83.5%–90.2%. A diagnosis could be established in 392 patients of whom 355 patients had a hemolytic diagnosis. Diagnosis was confirmed in 197 of the 249 patients with congenital hemolytic anemia, yielding a PPV of 79.1% (95% CI: 73.5%–84.0%. Diagnosis of acquired hemolytic anemia could be confirmed in 136 of the 163 patients, resulting in a PPV of 83.4% (95% CI: 76.8%–88.8%. For hemoglobinopathy PPV was 84.1% (95% CI: 77.4%–89.4%, for hereditary spherocytosis PPV was 80.6% (95% CI: 69.5%–88.9%, and for autoimmune hemolytic anemia PPV was 78.4% (95% CI: 70.4%–85.0%. Conclusion: The PPV of hemolytic anemias was moderately high. The PPVs were comparable in the three main

  11. Hemolytic anemia as first presentation of Wilson's disease with uncommon ATP7B mutation.

    Science.gov (United States)

    Ye, Xing-Nong; Mao, Li-Ping; Lou, Yin-Jun; Tong, Hong-Yan

    2015-01-01

    Wilson's disease (WD) is a rare inherited disorder of copper metabolism and the main manifestations are liver and brain disorders. Hemolytic anemia is an unusual complication of WD. We describe a 15-year-old girl who developed hemolytic anemia as the first manifestation of Wilson's disease. An Arg952Lys mutation was found in exon 12 of the ATP7B gene, which is uncommon among Chinese Han individuals. From this case and reviews, we can achieve a better understanding of WD. Besides, we may conclude that the probable diagnosis of WD should be considered in young patients with unexplained hemolytic anemia, especially in patients with hepatic and/or neurologic disorder.

  12. [A case of steroid resistant autoimmune hemolytic anemia in ulcerative colitis].

    Science.gov (United States)

    Choi, Hyun Jong; Hong, Su Jin; Kim, Young Jee; Ko, Bong Min; Lee, Moon Sung; Shim, Chan Sup; Kim, Hyun Jung; Hong, Dae Sik

    2008-02-01

    Autoimmunity is thought to play a central role in the pathogenesis of inflammatory bowel disease and associated extraintestinal manifestations. Autoimmune hemolytic anemia associated with ulcerative colitis is a rare occurrence. No more than 50 cases have been described in the international literatures, and only 2 cases reported in Korea. A 29-year-old woman who was diagnosed as ulcerative colitis two years ago was complicated with autoimmune hemolytic anemia, and did not respond to steroid therapy. Ultimately, total colectomy and splenectomy were carried out for the treatment of ulcerative colitis and hemolytic anemia. After the operation, anemia was resolved. We present the case with a review of literature.

  13. Do all hemolytic anemias that occur after mitral valve repair require surgical treatment?

    Science.gov (United States)

    Gungunes, Askin; Akpinar, Ibrahim; Dogan, Mehmet; Baser, Kazim; Yildirim, Ismail Safa; Haznedaroglu, Ibrahim C

    2010-12-01

    We report on a 29-year-old woman with severe hemolytic anemia following mitral valve annuloplasty. Although hemolysis due to mechanical prosthetic mitral valve is well recognized, hemolytic anemia associated with mitral valve repair is an uncommon condition. Reoperation may be considered if the patient has serious and persistent anemia. Although valve replacement is suggested to be a unique intervention, it may not be the solution every time because of mechanical effects. Various mechanisms of hemolysis related to mitral valve repair were suggested, but sufficient and precise data is not available. In this case, we tried to emphasize whether all hemolytic anemias that occur after mitral valve repair require surgical treatment.

  14. Hemolytic activity of venom from crown-of-thorns starfish Acanthaster planci spines

    OpenAIRE

    Lee, Chi-Chiu; Tsai, Wann-Sheng; Hsieh, Hernyi Justin; Hwang, Deng-Fwu

    2013-01-01

    Background The crown-of-thorns starfish Acanthaster planci is a venomous species from Taiwan whose venom provokes strong hemolytic activity. To understand the hemolytic properties of A. planci venom, samples were collected from A. planci spines in the Penghu Islands, dialyzed with distilled water, and lyophilized into A. planci spine venom (ASV) powder. Results Both crude venom and ASV cause 50% hemolysis at a concentration of 20 μg/mL. The highest hemolytic activity of ASV was measured at pH...

  15. Emodin via colonic irrigation modulates gut microbiota and reduces uremic toxins in rats with chronic kidney disease.

    Science.gov (United States)

    Zeng, Yu-Qun; Dai, Zhenhua; Lu, Fuhua; Lu, Zhaoyu; Liu, Xusheng; Chen, Cha; Qu, Pinghua; Li, Dingcheng; Hua, Zhengshuang; Qu, Yanni; Zou, Chuan

    2016-04-05

    Gut microbiota plays a dual role in chronic kidney disease (CKD) and is closely linked to production of uremic toxins. Strategies of reducing uremic toxins by targeting gut microbiota are emerging. It is known that Chinese medicine rhubarb enema can reduce uremic toxins and improve renal function. However, it remains unknown which ingredient or mechanism mediates its effect. Here we utilized a rat CKD model of 5/6 nephrectomy to evaluate the effect of emodin, a main ingredient of rhubarb, on gut microbiota and uremic toxins in CKD. Emodin was administered via colonic irrigation at 5ml (1mg/day) for four weeks. We found that emodin via colonic irrigation (ECI) altered levels of two important uremic toxins, urea and indoxyl sulfate (IS), and changed gut microbiota in rats with CKD. ECI remarkably reduced urea and IS and improved renal function. Pyrosequencing and Real-Time qPCR analyses revealed that ECI resumed the microbial balance from an abnormal status in CKD. We also demonstrated that ten genera were positively correlated with Urea while four genera exhibited the negative correlation. Moreover, three genera were positively correlated with IS. Therefore, emodin altered the gut microbiota structure. It reduced the number of harmful bacteria, such as Clostridium spp. that is positively correlated with both urea and IS, but augmented the number of beneficial bacteria, including Lactobacillus spp. that is negatively correlated with urea. Thus, changes in gut microbiota induced by emodin via colonic irrigation are closely associated with reduction in uremic toxins and mitigation of renal injury.

  16. Origins of the E. coli Strain Causing an Outbreak of Hemolytic–Uremic Syndrome in Germany

    Science.gov (United States)

    Rasko, David A.; Webster, Dale R.; Sahl, Jason W.; Bashir, Ali; Boisen, Nadia; Scheutz, Flemming; Paxinos, Ellen E.; Sebra, Robert; Chin, Chen-Shan; Iliopoulos, Dimitris; Klammer, Aaron; Peluso, Paul; Lee, Lawrence; Kislyuk, Andrey O.; Bullard, James; Kasarskis, Andrew; Wang, Susanna; Eid, John; Rank, David; Redman, Julia C.; Steyert, Susan R.; Frimodt-Møller, Jakob; Struve, Carsten; Petersen, Andreas M.; Krogfelt, Karen A.; Nataro, James P.; Schadt, Eric E.; Waldor, Matthew K.

    2011-01-01

    BACKGROUND A large outbreak of diarrhea and the hemolytic–uremic syndrome caused by an unusual serotype of Shiga-toxin–producing Escherichia coli (O104:H4) began in Germany in May 2011. As of July 22, a large number of cases of diarrhea caused by Shiga-toxin–producing E. coli have been reported — 3167 without the hemolytic–uremic syndrome (16 deaths) and 908 with the hemolytic–uremic syndrome (34 deaths) — indicating that this strain is notably more virulent than most of the Shiga-toxin–producing E. coli strains. Preliminary genetic characterization of the outbreak strain suggested that, unlike most of these strains, it should be classified within the enteroaggregative pathotype of E. coli. METHODS We used third-generation, single-molecule, real-time DNA sequencing to determine the complete genome sequence of the German outbreak strain, as well as the genome sequences of seven diarrhea-associated enteroaggregative E. coli serotype O104:H4 strains from Africa and four enteroaggregative E. coli reference strains belonging to other serotypes. Genomewide comparisons were performed with the use of these enteroaggregative E. coli genomes, as well as those of 40 previously sequenced E. coli isolates. RESULTS The enteroaggregative E. coli O104:H4 strains are closely related and form a distinct clade among E. coli and enteroaggregative E. coli strains. However, the genome of the German outbreak strain can be distinguished from those of other O104:H4 strains because it contains a prophage encoding Shiga toxin 2 and a distinct set of additional virulence and antibiotic-resistance factors. CONCLUSIONS Our findings suggest that horizontal genetic exchange allowed for the emergence of the highly virulent Shiga-toxin–producing enteroaggregative E. coli O104:H4 strain that caused the German outbreak. More broadly, these findings highlight the way in which the plasticity of bacterial genomes facilitates the emergence of new pathogens. PMID:21793740

  17. Effects of DPP-4 inhibitors on the heart in a rat model of uremic cardiomyopathy.

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    Lyubov Chaykovska

    Full Text Available BACKGROUND: Uremic cardiomyopathy contributes substantially to mortality in chronic kidney disease (CKD patients. Glucagon-like peptide-1 (GLP-1 may improve cardiac function, but is mainly degraded by dipeptidyl peptidase-4 (DPP-4. METHODOLOGY/PRINCIPAL FINDINGS: In a rat model of chronic renal failure, 5/6-nephrectomized [5/6N] rats were treated orally with DPP-4 inhibitors (linagliptin, sitagliptin, alogliptin or placebo once daily for 4 days from 8 weeks after surgery, to identify the most appropriate treatment for cardiac dysfunction associated with CKD. Linagliptin showed no significant change in blood level AUC(0-∞ in 5/6N rats, but sitagliptin and alogliptin had significantly higher AUC(0-∞ values; 41% and 28% (p = 0.0001 and p = 0.0324, respectively. No correlation of markers of renal tubular and glomerular function with AUC was observed for linagliptin, which required no dose adjustment in uremic rats. Linagliptin 7 µmol/kg caused a 2-fold increase in GLP-1 (AUC 201.0 ng/l*h in 5/6N rats compared with sham-treated rats (AUC 108.6 ng/l*h (p = 0.01. The mRNA levels of heart tissue fibrosis markers were all significantly increased in 5/6N vs control rats and reduced/normalized by linagliptin. CONCLUSIONS/SIGNIFICANCE: DPP-4 inhibition increases plasma GLP-1 levels, particularly in uremia, and reduces expression of cardiac mRNA levels of matrix proteins and B-type natriuretic peptides (BNP. Linagliptin may offer a unique approach for treating uremic cardiomyopathy in CKD patients, with no need for dose-adjustment.

  18. Parathyroid hormone levels in pubertal uremic adolescents treated with growth hormone.

    Science.gov (United States)

    Picca, Stefano; Cappa, Marco; Martinez, Chiara; Moges, Seyoum Ido; Osborn, John; Perfumo, Francesco; Ardissino, Gianluigi; Bonaudo, Roberto; Montini, Giovanni; Rizzoni, Gianfranco

    2004-01-01

    We have previously described severe hyperparathyroidism during the pubertal growth spurt in three uremic adolescents treated with recombinant human growth hormone (rhGH). Here we investigate the possible role of puberty in the genesis of hyperparathyroidism during rhGH treatment of a large cohort of patients. Data from 67 uremic patients treated with rhGH from five Italian pediatric nephrology centers were retrospectively recorded every 3 months starting 1 year before rhGH administration. The mean (+/-SD) rhGH treatment observation period was 19.9+/-5.9 months. The mean age at the start of rhGH treatment was 8.3+/-3.6 years. Of the 67 patients, 15 reached pubertal stage 2 during the 1st year of rhGH treatment and 12 of these 15 progressed to pubertal stage 3. The relative increase in parathyroid hormone (PTH) levels after rhGH initiation was greater in pubertal [1.95, 95% confidence interval (CI) 1.43-2.66] than in prepubertal patients (1.19, 95% CI 1.01-1.40). Increases in PTH levels were significantly different between the two groups (Delta=1.64, 95% CI 1.16-3.19, P=0.007). Multiple regression analysis showed an inverse correlation between PTH and calcium levels and a positive correlation between PTH and pubertal stage 3. There was no correlation with phosphate levels and calcitriol dosage. In conclusion, these results suggest that in uremic adolescents treated with rhGH puberty may influence PTH levels.

  19. Positive predictive value of diagnosis coding for hemolytic anemias in the Danish National Patient Register

    DEFF Research Database (Denmark)

    Hansen, Dennis Lund; Overgaard, Ulrik Malthe; Pedersen, Lars

    2016-01-01

    PURPOSE: The nationwide public health registers in Denmark provide a unique opportunity for evaluation of disease-associated morbidity if the positive predictive values (PPVs) of the primary diagnosis are known. The aim of this study was to evaluate the predictive values of hemolytic anemias...... registered in the Danish National Patient Register. PATIENTS AND METHODS: All patients with a first-ever diagnosis of hemolytic anemia from either specialist outpatient clinic contact or inpatient admission at Odense University Hospital from January 1994 through December 2011 were considered for inclusion....... Patients with mechanical reason for hemolysis such as an artificial heart valve, and patients with vitamin-B12 or folic acid deficiency were excluded. RESULTS: We identified 412 eligible patients: 249 with a congenital hemolytic anemia diagnosis and 163 with acquired hemolytic anemia diagnosis. In all...

  20. The first report of cabergoline-induced immune hemolytic anemia in an adolescent with prolactinoma.

    Science.gov (United States)

    Gürbüz, Fatih; Yağcı-Küpeli, Begül; Kör, Yılmaz; Yüksel, Bilgin; Zorludemir, Suzan; Gürbüz, Berrak Bilginer; Küpeli, Serhan

    2014-01-01

    Prolactinomas are common pituitary tumors that can cause gonadal dysfunction and infertility related to hyperprolactinemia. Dopamine agonists are the first-line treatment in these patients. Cabergoline leads to significant reduction in serum prolactin levels and tumor size in patients with prolactinoma. Dopamine agonists have been associated with adverse effects such as nausea, vomiting and psychosis. We report here a case with cabergoline-induced immune hemolytic anemia. The patient had cabergoline treatment history for prolactinoma and presented with weakness, fatigue, nausea, and paleness. Laboratory findings revealed severe anemia-related immune hemolysis. There were no causes identified to explain hemolytic anemia except cabergoline. Therefore, cabergoline therapy was stopped and subsequently hemolytic anemia resolved and did not occur again. This is the first reported pediatric case with prolactinoma and cabergoline-induced hemolytic anemia. Clinicians should be watchful for this rare side effect induced by cabergoline.

  1. A case of delayed hemolytic transfusion reaction in sickle cell disease patient

    Science.gov (United States)

    Dogra, Ashu; Sidhu, Meena

    2016-01-01

    Sickle cell disease (SCD) is autosomal recessive, genetically transmitted hemoglobinopathy responsible for considerable morbidity and mortality. It is prevalent in many parts of India including Central India, where the prevalence in different communities has ranged from 9.4% to 22%. Perioperative management may include transfusion of red blood cells. Hemolytic transfusion reactions can occur, and these can be either acute or delayed. We present a case of delayed hemolytic transfusion reaction in a patient with SCD. PMID:27605854

  2. Effect of Intrauterine Transfusion on Neonatal Outcomes in Rh Hemolytic Disease

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    Handan Akkuş

    2010-05-01

    Full Text Available Introduction: The aim of this study was to evaluate the neonates with Rh hemolytic disease according to the severity of hemolytic disease (slight, moderate and severe and the presence of intrauterine transfusion (IUT for necessity of postnatal exchange transfusion or phototherapy application and severity of neonatal anemia. Materials and Method: The neonates admitted to Neonatal Intensive Care Unit with Rhesus hemolytic disease between January 2000 and November 2008 were included in this retrospective study. Cord blood hemoglobine and bilirubin levels, reticulocyte count, maximum bilirubin level, number of intrauterine transfusion, duration of phototherapy, requirement of postnatal exchange transfusion or redblood cell transfusions were all recorded. Results: A total of 44 neonates were included in the study. The mean gestational age and birth weight of infants were 37.6±0.3 week and 3031±53 g, respectively. Slight, moderate and severe hemolytic disease was determined in 13 (29.5%, 13 (29.5% and 18 (41% of infants, respectively. IUT was performed in 12 infants (27% and 9 of them (75% had severe hemolytic disease and this ratio was significantly higher compared with the infants without IUT. Similarly, requirement of postnatal exchange transfusion was also higher in infants who had IUT compared with the infants who did not have IUT. No significant difference was determined between infants with and without IUT in terms of duration of phototherapy, maximum bilirubin levels and transfusion requirement.Conclusion: The incidence of severe hemolytic disease and postnatal exchange requirement were significantly higher in infants with IUT compared with the infants without IUT. Therefore, it is concluded that if Rhesus hemolytic disease is severe in utero, it may present as severe hemolytic disease in the postnatal period. (Journal of Current Pediatrics 2010; 8: 1-6

  3. Hemolytic Anemia as a Presenting Feature of Wilson’s Disease: A Case Report

    OpenAIRE

    Sharma, Sunita; Toppo, Anupa; B Rath; Harbhajanka, Aparna; P Lalita Jyotsna

    2010-01-01

    Wilson’s disease is a rare inherited disorder of copper metabolism causing severe damage to vital organs. Liver and brain disorders are the main manifestations. Severe hemolytic anemia is an unusual complication of Wilson’s disease. We present a case who developed spherocytic acute hemolytic anemia (Coomb’s negative) as the initial manifestation of Wilson’s disease. On examination Kayser- Fleischer ring was found. Laboratory data supported a diagnosis of Wilson’s disease.

  4. Comparative characterization of the leukocidic and hemolytic activity of Moraxella bovis.

    Science.gov (United States)

    Hoien-Dalen, P S; Rosenbusch, R F; Roth, J A

    1990-02-01

    The cytotoxic effect of Moraxella bovis 118F on bovine neutrophils was evaluated and characterized by use of a 51Cr release assay. Neutrophils harvested from healthy adult cattle were labeled with 51Cr. The leukocidic activity produced by M bovis 118F, a hemolytic strain of M bovis, was heat-labile. A live culture of strain 118F, at a ratio of 100 bacteria/neutrophil, released 97.7% of the 51Cr from labeled neutrophils. Neither a heat-killed preparation of M bovis 118F nor a live or heat-killed preparation of M bovis IBH63 (a nonhemolytic and nonpathogenic strain) induced significant (P greater than 0.05) release of 51Cr. Moraxella bovis 118F broth culture filtrates prepared for evaluation of leukocidic activity also were evaluated for hemolytic activity. These 2 toxic activities had several characteristics in common. Both were filterable, heat-labile, produced by a hemolytic strain, and were released during early logarithmic phase growth from broth cultures. Leukocidic and hemolytic activities were protected from degradation by phenylmethyl sulfonyl fluoride, a serine protease inhibitor. Leukocidic and hemolytic activities were dependent on calcium ions. Filtrate resulted in 54.1% 51Cr release from labeled neutrophils and contained 646.7 hemolytic U/ml, respectively, when saline (0.85% NaCl) + 10 mM CaCl2 solution was used as diluent. Neither saline solution nor saline + 10 mM MgCl2 solution supported leukocidic or hemolytic activity. Serum, obtained from several calves 10 to 38 days after M bovis inoculation, substantially neutralized leukocidic and hemolytic activities, compared with paired preinoculation serum samples.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Hemolytic Activity and Siderophore Production in Different Aeromonas Species Isolated from Fish

    OpenAIRE

    Santos, Jesús A.; González, César J.; Otero, Andrés; García-López, María-Luisa

    1999-01-01

    The hemolytic activity and siderophore production of several strains of motile aeromonads were determined. The hemolytic activity of Aeromonas caviae and Aeromonas eucrenophila was enhanced after trypsinization of the samples. The enhancement of hemolysis was observed in strains that carried an aerolysin-like gene, detected by a PCR procedure. Siderophore production was demonstrated in all but one strain of Aeromonas jandaei. No apparent relationship was observed between the presence of plasm...

  6. Hemolytic anemia following mitral valve repair: A case presentation and literature review

    OpenAIRE

    AbouRjaili, Georges; Torbey, Estelle; Alsaghir, Taher; Olkovski, Yefim; Costantino, Thomas

    2012-01-01

    Hemolytic anemia is a known complication after valve replacement, but the incidence of hemolysis following valve repair is unknown. A case involving mitral annuloplasty complicated by hemolytic anemia, which resolved after replacement of the valve, is presented. Only 70 cases of hemolysis after mitral valve repair have been reported in the literature. In nearly all of these cases, replacement or rerepair of the valve was the definitive treatment for hemolysis.

  7. Tubercular lymphadenitis and abdominal tuberculosis with autoimmune hemolytic anemia and severe intravascular hemolysis

    Directory of Open Access Journals (Sweden)

    Ashutosh M Somalwar

    2013-01-01

    Full Text Available Tuberculosis, a common disease in the developing world and a resurging problem in the developed world, is associated with numerous hematological manifestations. The most common manifestation is normochromic normocytic anemia of chronic disease. Hemolytic anemia is rare, and there are only a few previously reported cases. We report a case of autoimmune hemolytic anemia with severe intravascular hemolysis in a case of abdominal tuberculosis. To our knowledge, this is one of the few cases reported in the literature.

  8. Concurrent reactive arthritis, Graves’ disease, and warm autoimmune hemolytic anemia: a case report

    OpenAIRE

    Chiang, Elizabeth; Packer, Clifford D

    2009-01-01

    Warm antibody autoimmune hemolytic anemia is due to the presence of warm agglutinins that react with protein antigens on the surface of red blood cells causing premature destruction of circulating red blood cells. We report the first case of concurrent reactive arthritis, Graves’ disease, and autoimmune hemolytic anemia. A 40-year-old man with reactive arthritis, Graves’ disease, type 2 diabetes mellitus, mitral valve prolapse, and Gilbert’s disease presented with a one month history of jaund...

  9. Effects of co-existing microalgae and grazers on the production of hemolytic toxins in Karenia mikimotoi

    Institute of Scientific and Technical Information of China (English)

    YANG Weidong; ZHANG Naisheng; CUI Weimin; XU Yanyan; LI Hongye; LIU Jiesheng

    2011-01-01

    Karenia mikimotoi (Miyake & Kominami ex Oda) Hansen & Moestrup is associated with harmful algal blooms in temperate and subtropical zones of the world.The hemolytic substances produced by K.mikimotoi are thought to cause mortality in fishes and invertebrates.We evaluated the composition of the hemolytic toxin produced by K.mikimotoi cultured in the laboratory using thin-layer chromatography.In addition,we evaluated the effect of co-occuring algae (Prorocentrum donghaiense and Alexandrium tamarense) and the cladoceran grazer Moina mongolica on hemolytic toxin production in K.mikimotoi.The hemolytic toxins from K.mikimotoi were a mixture of 2 liposaccharides and I lipid.Waterbome clues from P.donghaiense and A.tamarense inhibited the growth of K.mikimotoi but increased the production of hemolytic toxins.Conversely,K.mikimotoi strongly inhibited the growth of caged P.donghaiense and A.tamarense.In addition,the ingestion of K.mikimotoi by M.mongolica induced the production of hemolytic toxins in K.mikimotoi.Taken together,our results suggest that the presence of other microalgae and grazers may be as important as environmental factors for controlling the production of hemolytic substances.K.mikimotoi secreted allelochemicals other than unstable fatty acids with hemolytic activity.The production of hemolytic toxins in dinoflagellates was not only dependent on resource availability,but also on the risk of predation.Hemolytic toxins likely play an important role as chemical deterrents secreted by K.mikimotoi.

  10. Effect of α-lipoic Acid on Hemolytic Activity of Iranian Vipera Lebetina Venom

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    Amoozgari, Z. (MSc

    2015-05-01

    Full Text Available Background and Objective: Snake venom is a complex of several toxic elements and enzymes. It has the agents with the ability to destroy cellular and subcellular membrane and to bring about hemolysis of red blood cells (RBC. Two types of direct and indirect hemolytic activity are known in snake venom in that phospholipase A2 is responsible for the indirect lysis. The aim of this study was to investigate the effect of α-lipoic acid on hemolytic activity of Iranian Vipera Lebetina venom. Material and Methods: Protein concentration of the crude venom of Vipera Lebetina was determined using bovine serum albumin as a standard. Direct hemolytic activity of venom was determined by using the Human RBC and Indirect hemolytic activity was assayed on RBC in the presence of egg yolk. Then, α-lipoic acid with different concentrations in 100 mM Tris-HCL buffer was applied and its effect on hemolysis of RBC was studied. Results: direct hemolytic activity on RBC was not observed while its indirect activity was detected to be increased proportional to different concentration of α-lipoic acid. The range of indirect hemolysis was increased up to 60% by 60µm α-lipoic acid. Conclusion: Not only has α-lipoic acid no inhibitory effects on the hemolytic activity of Iranian Vipera Lebetina venom but also has the positive effects on it.

  11. Intravenous Immunoglobulin G Treatment in ABO Hemolytic Disease of the Newborn, is it Myth or Real?

    Science.gov (United States)

    Beken, Serdar; Hirfanoglu, Ibrahim; Turkyilmaz, Canan; Altuntas, Nilgun; Unal, Sezin; Turan, Ozden; Onal, Esra; Ergenekon, Ebru; Koc, Esin; Atalay, Yildiz

    2014-03-01

    Intravenous Immunoglobulin G (IVIG) therapy has been used as a component of the treatment of hemolytic disease of the newborn. There is still no consensus on its use in ABO hemolytic disease of the newborn routinely. The aim of this study is to determine whether administration of IVIG to newborns with ABO incompatibility is necessary. One hundred and seventeen patients with ABO hemolytic disease and positive Coombs test were enrolled into the study. The subjects were healthy except jaundice. Infants were divided into two groups: Group I (n = 71) received one dose of IVIG (1 g/kg) and LED phototherapy whereas Group II (n = 46) received only LED phototherapy. One patient received erythrocyte transfusion in Group I, no exchange transfusion was performed in both groups. Mean duration of phototherapy was 3.1 ± 1.3 days in Group I and 2.27 ± 0.7 days in Group II (p ABO hemolytic disease. Meticulus follow-up of infants with ABO hemolytic disease and LED phototherapy decreases morbidity. IVIG failed to show preventing hemolysis in ABO hemolytic disease.

  12. Cholesterol-dependent hemolytic activity of Passiflora quadrangularis leaves

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    L.N. Yuldasheva

    2005-07-01

    Full Text Available Plants used in traditional medicine are rich sources of hemolysins and cytolysins, which are potential bactericidal and anticancer drugs. The present study demonstrates for the first time the presence of a hemolysin in the leaves of Passiflora quadrangularis L. This hemolysin is heat stable, resistant to trypsin treatment, has the capacity to froth, and acts very rapidly. The hemolysin activity is dose-dependent, with a slope greater than 1 in a double-logarithmic plot. Polyethylene glycols of high molecular weight were able to reduce the rate of hemolysis, while liposomes containing cholesterol completely inhibited it. In contrast, liposomes containing phosphatidylcholine were ineffective. The Passiflora hemolysin markedly increased the conductance of planar lipid bilayers containing cholesterol but was ineffective in cholesterol-free bilayers. Successive extraction of the crude hemolysin with n-hexane, chloroform, ethyl acetate, and n-butanol resulted in a 10-fold purification, with the hemolytic activity being recovered in the n-butanol fraction. The data suggest that membrane cholesterol is the primary target for this hemolysin and that several hemolysin molecules form a large transmembrane water pore. The properties of the Passiflora hemolysin, such as its frothing ability, positive color reaction with vanillin, selective extraction with n-butanol, HPLC profile, cholesterol-dependent membrane susceptibility, formation of a stable complex with cholesterol, and rapid erythrocyte lysis kinetics indicate that it is probably a saponin.

  13. [Detection and analysis of ABO Hemolytic disease in newborn].

    Science.gov (United States)

    Lin, Zhao-Xia; Dong, Qing-Song

    2014-10-01

    This study was purposed to investigate the incidence and the model of ABO hemolytic disease in newborn (ABO-HDN) and the results of the three hemolysis test, so as to provide the evidences for clinical diagnosis and therapy. A total of 227 cases of maternal-fetal ABO incompatibility from January 2013 to October 2013 in the First Affiliated Hospital of Xiamen University were enrolled in the study. The ABO blood group of newborn and mother was detemined and three hemolysis tests (direct antiglobulin test, free antibody test, RBC antibody release test) were performed. The results indicated that in 227 cases of ABO incompatible pregnancies,186 cases were ABO-HDN (81.94%). There was no significant difference in the incidence between O-A and O-B incompatible pregnancies (P > 0.05). The positive ratio of direct antiglobulin test, free antibody test and RBC antibody release test were 59.14% (110/186), 84.78% (156/186) and 94.62% (176/186) respectively. It is concluded that the incidence of ABO-HDN is high. The main models of ABO-HDN were O-A and O-B. There was no significant difference in the incidence between O-A and O-B incompatible pregnancies. Three hemolysis tests are high sensitivity and are helpful in early diagnosis and early treatment of HDN.

  14. Neonatal Sulfhemoglobinemia and Hemolytic Anemia Associated With Intestinal Morganella morganii.

    Science.gov (United States)

    Murphy, Kiera; Ryan, Clodagh; Dempsey, Eugene M; O'Toole, Paul W; Ross, R Paul; Stanton, Catherine; Ryan, C Anthony

    2015-12-01

    Sulfhemoglobinemia is a rare disorder characterized by the presence of sulfhemoglobin in the blood. It is typically drug-induced and may cause hypoxia, end-organ damage, and death through oxygen deprivation. We present here a case of non-drug-induced sulfhemoglobinemia in a 7-day-old preterm infant complicated by hemolytic anemia. Microbiota compositional analysis of fecal samples to investigate the origin of hydrogen sulphide revealed the presence of Morganella morganii at a relative abundance of 38% of the total fecal microbiota at the time of diagnosis. M morganii was not detected in the fecal samples of 40 age-matched control preterm infants. M morganii is an opportunistic pathogen that can cause serious infection, particularly in immunocompromised hosts such as neonates. Strains of M morganii are capable of producing hydrogen sulphide, and virulence factors include the production of a diffusible α-hemolysin. The infant in this case survived intact through empirical oral and intravenous antibiotic therapy, probiotic administration, and red blood cell transfusions. This coincided with a reduction in the relative abundance of M morganii to 3%. Neonatologists should have a high index of suspicion for intestinal pathogens in cases of non-drug-induced sulfhemoglobinemia and consider empirical treatment of the intestinal microbiota in this potentially lethal condition. Copyright © 2015 by the American Academy of Pediatrics.

  15. Alloimmunization in autoimmune hemolytic anemia patient: The differential adsorption approach

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    Ravi C Dara

    2017-01-01

    Full Text Available Patients of β-thalassemia major are dependent on regular blood transfusions for their entire lifetime. Development of antibodies against red blood cell (RBC antigen which may be alloantibody or autoantibody, several times as a result of frequent red cell component transfusions, further complicates the subsequent transfusion therapy. Among the autoantibodies, warm-reactive autoantibodies are commoner and interfere in the pretransfusion testing. These RBC autoantibodies present in patient's serum potentially react with all the cells of antibody identification panel giving “pan-reactive” picture and making alloantibody identification complex. In this report, we present our approach in a thalassemia patient who presented with warm-type autoimmune hemolytic anemia, low hemoglobin of 5.8 g/dl, and three significant alloantibodies (anti-D, anti-S, and anti-Jk b which were masked by pan-reactive warm autoantibody(s. Differential adsorption was used to unmask underlying alloantibodies. We suggest that differential adsorption procedure is an effective and efficient method for autoantibody adsorption, detection, and identification of masked alloantibody(s, especially in patients with low hemoglobin and history of recent blood transfusion.

  16. Alloimmunization in autoimmune hemolytic anemia patient: The differential adsorption approach

    Science.gov (United States)

    Dara, Ravi C.; Tiwari, Aseem Kumar; Arora, Dinesh; Mitra, Subhasis; Acharya, Devi Prasad; Aggarwal, Geet; Sharma, Jyoti

    2017-01-01

    Patients of β-thalassemia major are dependent on regular blood transfusions for their entire lifetime. Development of antibodies against red blood cell (RBC) antigen which may be alloantibody or autoantibody, several times as a result of frequent red cell component transfusions, further complicates the subsequent transfusion therapy. Among the autoantibodies, warm-reactive autoantibodies are commoner and interfere in the pretransfusion testing. These RBC autoantibodies present in patient's serum potentially react with all the cells of antibody identification panel giving “pan-reactive” picture and making alloantibody identification complex. In this report, we present our approach in a thalassemia patient who presented with warm-type autoimmune hemolytic anemia, low hemoglobin of 5.8 g/dl, and three significant alloantibodies (anti-D, anti-S, and anti-Jkb) which were masked by pan-reactive warm autoantibody(s). Differential adsorption was used to unmask underlying alloantibodies. We suggest that differential adsorption procedure is an effective and efficient method for autoantibody adsorption, detection, and identification of masked alloantibody(s), especially in patients with low hemoglobin and history of recent blood transfusion. PMID:28316442

  17. Liraglutide Reduces Both Atherosclerosis and Kidney Inflammation in Moderately Uremic LDLr-/- Mice

    DEFF Research Database (Denmark)

    Bisgaard, Line S; Bosteen, Markus H; Fink, Lisbeth N

    2016-01-01

    Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis and atherosc......Chronic kidney disease (CKD) leads to uremia. CKD is characterized by a gradual increase in kidney fibrosis and loss of kidney function, which is associated with a progressive increase in risk of atherosclerosis and cardiovascular death. To prevent progression of both kidney fibrosis...... and atherosclerosis in uremic settings, insight into new treatment options with effects on both parameters is warranted. The GLP-1 analogue liraglutide improves glucose homeostasis, and is approved for treatment of type 2 diabetes. Animal studies suggest that GLP-1 also dampens inflammation and atherosclerosis. Our...... aim was to examine effects of liraglutide on kidney fibrosis and atherosclerosis in a mouse model of moderate uremia (5/6 nephrectomy (NX)). Uremic (n = 29) and sham-operated (n = 14) atherosclerosis-prone low density lipoprotein receptor knockout mice were treated with liraglutide (1000 μg/kg, s...

  18. Supplementation of Emblica officinalis (Amla) extract reduces oxidative stress in uremic patients.

    Science.gov (United States)

    Chen, Tung-Sheng; Liou, Show-Yih; Chang, Yen-Lin

    2009-01-01

    Emblica Officinalis (also known as Amla or Indian Gooseberry), a natural, traditional and functional food in Asia, has physiological benefits such as hepato-, cyto- and radio- protection, as well as hypolipidemic effects. In addition, Amla often functions as a potent antioxidant due to the high level of ascorbic acid (ranging from 1,100 to 1,700 mg/100 g of fruit) in its fruit. The aim of this study was to determine whether supplementation with Amla extract could reduce oxidative stress in patients with uremia. The findings show that supplementation with Amla extract for 4 months reduced the plasma oxidative marker, 8-iso-prostaglandin, (M0 vs. M4 = 1415 +/- 1234 pg/ml vs. 750 +/- 496 pg/ml, p Amla for 4 months. Our data suggest that Amla supplementation may increase plasma antioxidant power and decrease oxidative stress in uremic patients. However, Amla extract did not influence hepatic or renal function, or diabetic and atherogenic indices in uremic patients.

  19. Randomized, Double-blind Study with Glycerol and Paraffin in Uremic Xerosis

    Science.gov (United States)

    Balaskas, Elias; Szepietowski, Jacek C.; Bessis, Didier; Ioannides, Dimitrios; Ponticelli, Claudio; Ghienne, Corinne; Taberly, Alain

    2011-01-01

    Summary Background and objectives Uremic xerosis is a bothersome condition that is poorly responsive to moisturizing and emollient therapy. Design, setting, participants, & measurements A randomized, double-blind, intraindividual (left versus right comparison), multicentric clinical study was performed on 100 patients with moderate to severe uremic xerosis for 7 days, during which the patients applied twice daily an emulsion combining glycerol and paraffin (test product) on one allocated lower leg, and the emulsion alone (comparator) on the other lower leg. This was followed by an open-labeled use of the test product on all of the xerotic areas for 49 days. The main efficacy parameter was treatment response on each lower leg, as defined by a reduction from baseline of at least two grades in a five-point clinical score on day 7. Results Among the 99 patients analyzed, the test product was highly effective with a treatment response in 72 patients (73%), whereas 44 patients (44%) responded to the comparator (P emollient therapy is used. PMID:21258039

  20. Association of high-sensitive C-reactive protein and dialysis adequacy with uremic pruritus.

    Science.gov (United States)

    Malekmakan, Leila; Malekmakan, Alireza; Sayadi, Mehrab; Pakfetrat, Maryam; Sepaskhah, Mozhdeh; Roozbeh, Jamshid

    2015-09-01

    Uremic pruritus is a difficult symptom in chronic hemodialysis (HD) patients, and its patho-physiological mechanism remains unknown. To determine the relationship between pruritus and C-reactive protein as well as dialysis adequacy among the HD patients, we studied 241 chronic HD patients in Shiraz dialysis centers, Iran. The patients were selected by convenient sampling and the data were collected using a checklist, interview and lab tests. The mean age of our patients was 53.9 ± 16.3 years and 128 (53.1%) of them were male. There were 97 (40.2%) patients who complained of pruritus. A significant association was found between high-sensitive C-reactive protein and pruritus (P = 0.004). Also, a significant positive relationship was observed between pruritus and dialysis adequacy (P dialysis adequacy and pruritus. A better understanding of the factors implicated in the cause of uremic pruritus is essential in the development of more-effective treatments and improved quality of life in HD patients.

  1. A study of median nerve entrapment neuropathy at wrist in uremic patients.

    Science.gov (United States)

    Shende, V S; Sharma, R D; Pawar, S M; Waghmare, S N

    2015-01-01

    Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy seen in uremic patients. The study was undertaken to estimate the frequency of CTS in uremic patients and to identify the most sensitive electrodiagnostic test. Study was conducted on 80 subjects of age 30-60 years. End-stage kidney disease patients were recruited for the clinical evaluation, motor nerve conduction studies (NCS), sensory NCS, F wave study and median-versus-ulnar comparison studies (palm-to-wrist mixed comparison study, digit 4 sensory latencies study and lumbrical-interossei comparison study). Among three different diagnostic modalities, frequency of CTS was found to be 17.5% with clinical evaluation, 15% with routine NCS studies and 25% with median-versus-ulnar comparison studies. Among the median-versus-ulnar comparison studies, lumbrical-interossei comparison study was found to be most sensitive (90%). The comparative tests for CTS are more sensitive compared to routine NCS and clinical examination. Among the comparative tests, lumbrical-interossei comparison study is the most sensitive. Early diagnosis of CTS may help patients of uremia to seek proper treatment at an appropriate time.

  2. Evidence that histidine is an essential amino acid in normal and chronically uremic man.

    Science.gov (United States)

    Kopple, J D; Swendseid, M E

    1975-05-01

    The requirement for dietary histidine was investigated in four normal and three chronically uremic men. Subjects lived in a metabolic unit where they were fed three isonitrogenous diets in the following order: a 40-g protein diet (28 plus or minus SD 8 days), a semi-synthetic amino acid diet deficient in histidine (35 plus or minus 2 days), and an amino acid diet which contained histidine (31 plus or minus 5 days). With ingestion of the histidine-deficient diet, nitrogen balance gradually became negative, and serum albumin decreased in six subjects. Plasma histidine fell by 82 plus or minus 6 per cent; muscle histidine decreased by 62 plus or minus 19 per cent; the hematocrit fell by 25 plus or minus 9 per cent; and serum iron rose. Subjects felt unwell, and in five cases a skin lesion consisting of fine scales, dry skin, and mild erythema developed. After administration of the histidine-repletion diet, nitrogen balance became positive in six subjects; serum albumin increased in five cases; plasma and muscle histidine rose; serum iron fell abruptly; a reticulocytosis ensued; and the hematocrit rose. The clinical symptoms and skin lesions disappeared. These observations indicate that histidine is an essential amino acid in normal and chronically uremic man. The absence of dietary histidine is associated with failure of normal erythropoiesis.

  3. Environmental NO2 and CO Exposure: Ignored Factors Associated with Uremic Pruritus in Patients Undergoing Hemodialysis

    Science.gov (United States)

    Huang, Wen-Hung; Lin, Jui-Hsiang; Weng, Cheng-Hao; Hsu, Ching-Wei; Yen, Tzung-Hai

    2016-08-01

    Uremic pruritus (UP), also known as chronic kidney disease–associated pruritus, is a common and disabling symptom in patients undergoing maintenance hemodialysis (MHD). The pathogenesis of UP is multifactorial and poorly understood. Outdoor air pollution has well-known effects on the health of patients with allergic diseases through an inflammatory process. Air pollution–induced inflammation could occur in the skin and aggravate skin symptoms such as pruritus or impair epidermal barrier function. To assess the role of air pollutants, and other clinical variables on uremic pruritus (UP) in HD patients, we recruited 866 patients on maintenance HD. We analyzed the following variables for association with UP: average previous 12-month and 24-month background concentrations for nitrogen dioxide (NO2) and carbon monoxide (CO), and suspended particulate matter of serum ferritin levels, low-density lipoprotein levels, and environmental NO2/CO levels were positively associated with UP, and serum albumin levels were negatively associated with UP. This cross-sectional study showed that air pollutants such as NO2 and CO might be associated with UP in patients with MHD.

  4. Modified Lipids and Lipoproteins in Chronic Kidney Disease: A New Class of Uremic Toxins

    Directory of Open Access Journals (Sweden)

    Nans Florens

    2016-12-01

    Full Text Available Chronic kidney disease (CKD is associated with an enhanced oxidative stress and deep modifications in lipid and lipoprotein metabolism. First, many oxidized lipids accumulate in CKD and were shown to exert toxic effects on cells and tissues. These lipids are known to interfere with many cell functions and to be pro-apoptotic and pro-inflammatory, especially in the cardiovascular system. Some, like F2-isoprostanes, are directly correlated with CKD progression. Their accumulation, added to their noxious effects, rendered their nomination as uremic toxins credible. Similarly, lipoproteins are deeply altered by CKD modifications, either in their metabolism or composition. These impairments lead to impaired effects of HDL on their normal effectors and may strongly participate in accelerated atherosclerosis and failure of statins in end-stage renal disease patients. This review describes the impact of oxidized lipids and other modifications in the natural history of CKD and its complications. Moreover, this review focuses on the modifications of lipoproteins and their impact on the emergence of cardiovascular diseases in CKD as well as the appropriateness of considering them as actual mediators of uremic toxicity.

  5. Evaluating Hyponatremia in Non-Diabetic Uremic Patients on Peritoneal Dialysis.

    Science.gov (United States)

    Yan, Ming-Tso; Cheng, Chih-Jen; Wang, Hsiu-Yuan; Yang, Chwei-Shiun; Peng, Sheng-Jeng; Lin, Shih-Hua

    2016-01-01

    ♦ An approach to hyponatremia in uremic patients on peritoneal dialysis (PD) necessitates the assessment of intracellular fluid volume (ICV) and extracellular volume (ECV). The aim of the study was to evaluate the association of plasma sodium (Na(+)) concentration and body fluid composition and identify the causes of hyponatremia in non-diabetic PD patients. ♦ Sixty non-diabetic uremic patients on PD were enrolled. Baseline body fluid composition, biochemistry, hand-grip test, peritoneal membrane characteristics, dialysis adequacy, Na(+) and water balance, and residual renal function (RRF) were measured. These parameters were reevaluated for those who developed hyponatremia, defined as serum Na(+) concentration 7 mmol/L, during monthly visits for 1 year. Body fluid composition was determined by multi-frequency bioelectrical impedance (BIA). ♦ There was no significant correlation between serum Na(+) concentrations and any other parameters except a negative correction with overnight ultrafiltration (UF) amount (p = 0.02). The ICV/ECV ratio was positively correlated with serum albumin (p permeability (n = 2) or a normal to increased ICV/ECV ratio associated with high water intake (n = 3). ♦ Besides BW change and ultrafiltration rate, the assessment of ICV/ECV ratio is valuable in identifying the etiologies of hyponatremia in PD and provides a guide for optimal therapy. Copyright © 2016 International Society for Peritoneal Dialysis.

  6. Divergent behavior of hydrogen sulfide pools and of the sulfur metabolite lanthionine, a novel uremic toxin, in dialysis patients.

    Science.gov (United States)

    Perna, Alessandra F; Di Nunzio, Annarita; Amoresano, Angela; Pane, Francesca; Fontanarosa, Carolina; Pucci, Piero; Vigorito, Carmela; Cirillo, Giovanni; Zacchia, Miriam; Trepiccione, Francesco; Ingrosso, Diego

    2016-07-01

    Dialysis patients display a high cardiovascular mortality, the causes of which are still not completely explained, but are related to uremic toxicity. Among uremic toxins, homocysteine and cysteine are both substrates of cystathionine β-synthase and cystathionine γ-lyase in hydrogen sulfide biosynthesis, leading to the formation of two sulfur metabolites, lanthionine and homolanthionine, considered stable indirect biomarkers of its production. Hydrogen sulfide is involved in the modulation of multiple pathophysiological responses. In uremia, we have demonstrated low plasma total hydrogen sulfide levels, due to reduced cystathionine γ-lyase expression. Plasma hydrogen sulfide levels were measured in hemodialysis patients and healthy controls with three different techniques in comparison, allowing to discern the different pools of this gas. The protein-bound (the one thought to be the most active) and acid-labile forms are significantly decreased, while homolanthionine, but especially lanthionine, accumulate in the blood of uremic patients. The hemodialysis regimen plays a role in determining sulfur compounds levels, and lanthionine is partially removed by a single dialysis session. Lanthionine inhibits hydrogen sulfide production in cell cultures under conditions comparable to in vivo ones. We therefore propose that lanthionine is a novel uremic toxin. The possible role of high lanthionine as a contributor to the genesis of hyperhomocysteinemia in uremia is discussed.

  7. Impact of Indoxyl Sulfate, a Uremic Toxin, on Non-Culprit Coronary Plaque Composition Assessed on Integrated Backscatter Intravascular Ultrasound.

    Science.gov (United States)

    Yamazaki, Hiromu; Yamaguchi, Koji; Soeki, Takeshi; Wakatsuki, Tetsuzo; Niki, Toshiyuki; Taketani, Yoshio; Kitaoka, Atsunori; Kusunose, Kenya; Ise, Takayuki; Tobiume, Takeshi; Yagi, Shusuke; Iwase, Takashi; Yamada, Hirotsugu; Sata, Masataka

    2015-01-01

    Uremic toxin has emerged as an important determinant of cardiovascular risk. The aim of this study was to examine the relationship between serum uremic toxin and coronary plaque composition on integrated backscatter intravascular ultrasound (IB-IVUS). IB-IVUS was performed in 47 patients with planned treatment for angina pectoris. Non-culprit intermediate plaque analyzed in this study had to be >5 mm apart from the intervention site. 3-D IB-IVUS analysis was performed to determine percent lipid volume (LV) and fibrous volume (FV). We also measured serum uremic toxins (indoxyl sulfate [IS], asymmetric dimethylarginine [ADMA], and p-cresol [PC]). Glomerular filtration rate correlated with IS (r=-0.329, P=0.04), but did not correlate with ADMA or PC. Percent LV correlated with IS (r=0.365, P=0.02), but did not correlate with ADMA or PC. Percent FV also correlated with IS (r=-0.356, P=0.03), but did not correlate with ADMA or PC. On multivariate regression, only IS was associated with percent LV (r=0.359, P=0.04) and percent FV (r=-0.305, P=0.04) independently of potentially confounding coronary risk factors. Among the uremic toxins, serum IS might be a novel useful biomarker to detect and monitor lipid-rich coronary plaque on IB imaging.

  8. A comparison of oral and dental manifestations in diabetic and non-diabetic uremic patients receiving hemodialysis

    Directory of Open Access Journals (Sweden)

    Preethi Murali

    2012-01-01

    Full Text Available Background: The purpose of the study was to evaluate the oral and dental findings of uremic patients receiving hemodialysis and to compare the Results between diabetic and non-diabetic groups. Materials and Methods: A total of 100 patients undergoing hemodialysis were classified into diabetic and non-diabetic groups and examined for uremic oral manifestations, dental caries (DMFT, and periodontal status (CPITN. Mann-Whitney test of significance has been applied for analyzing DMFT score and chi-square test is used for analyzing CPITN score. Results: Of the study group, 46% were diabetic and only 11% of them did not have any oral manifestation. Oral manifestations observed were xerostomia and uremic odor, which contributed to 47 (23% and 37 (17%, respectively. Hyperpigmentation was present in 26 (12%, macroglossia in 23 (11%, and uremic tongue coating in 24 (11%. Mucosal petechiae were seen in 17 patients contributing to 8% of total patients. Eleven patients had tongue pallor (5%, 9 patients had glossitis with depapillation (4%, and 7 patients had dysgeusia (3%. Angular cheilitis and gingival swelling were seen in 5 patients (2%. Conclusion: The oral and dental manifestations were higher in prevalence in the study group. However, there was no significant difference between the two groups.

  9. Effect of treatment with human apolipoprotein A-I on atherosclerosis in uremic apolipoprotein-E deficient mice

    DEFF Research Database (Denmark)

    Pedersen, Tanja Xenia; Bro, Susanne; Andersen, Mikkel H

    2009-01-01

    OBJECTIVE: Uremia markedly increases the risk of atherosclerosis. Thus, effective anti-atherogenic treatments are needed for uremic patients. This study examined effects of non-lipidated recombinant human apoA-I (h-apoA-I) and a recombinant trimeric apoA-I molecule (TripA-I) on lipid metabolism a...

  10. Epidemiological usefulness of changes in hemolytic activity of Vibrio cholerae biotype El Tor during the seventh pandemic.

    OpenAIRE

    Barrett, T J; Blake, P A

    1981-01-01

    Hemolytic Vibrio cholerae biotype El Tor strains were isolated in the United States in 1973 and 1978 after they had supposedly disappeared worldwide during the 1960s and 1970s. We decided to examine the change in prevalence of hemolytic El Tor strains since the beginning of the seventh pandemic and evaluate the usefulness of hemolytic activity as an epidemiological marker. A total of 48 isolates of V. cholerae biotype El Tor isolated in the Eastern Hemisphere between 1960 and 1979, along with...

  11. Glucose intolerance in uremic patients: the relative contributions of impaired beta-cell function and insulin resistance.

    Science.gov (United States)

    Alvestrand, A; Mujagic, M; Wajngot, A; Efendic, S

    1989-04-01

    Glucose tolerance and tissue sensitivity to insulin were examined in 19 renal failure patients on chronic regular hemodialysis (group U) and in 6 matched control subjects with normal renal function (group A). Based on glucose tolerance as assessed by an oral glucose tolerance test (OGTT), glucose tolerance was normal in 5 (group U:N), borderline in 5 (group U:BL) and decreased in 9 uremic subjects (group U:D). Compared with group A the uremics demonstrated significantly (p less than 0.01) impaired insulin sensitivity as assessed by a continuous mixed infusion of somatostatin, insulin and glucose (SIGIT). In addition 19 non-diabetic subjects with normal fasting blood glucose and normal renal function, matching the uremic patients with respect to glucose tolerance as assessed by OGTT, were studied (group B). In group B impairments in both insulin secretion and insulin sensitivity tended to be more pronounced in subjects with decreased OGTT as compared with those with borderline OGTT. In contrast, insulin resistance was present to a similar degree in uremic subjects of group U:N, U:BL and U:D. During SIGIT endogenous insulin, glucagon and growth hormone (GH) were suppressed in both uremic and control subjects. This implies that insulin resistance in uremia is most likely not due to hyperglucagonemia or abnormal GH metabolism. During OGTT subjects of group U:N had significantly higher insulin response than subjects of group U:BL (p less than 0.02) and group U:D (p less than 0.01). Insulinogenic index was significantly higher in group U:N than in group U:BL (p less than 0.02) and group U:D (p = 0.01) and was higher in group U:BL than in group U:D (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Recurrent Isolated Neonatal Hemolytic Anemia: Think About Glutathione Synthetase Deficiency.

    Science.gov (United States)

    Signolet, Isabelle; Chenouard, Rachel; Oca, Florine; Barth, Magalie; Reynier, Pascal; Denis, Marie-Christine; Simard, Gilles

    2016-09-01

    Hemolytic anemia (HA) of the newborn should be considered in cases of rapidly developing, severe, or persistent hyperbilirubinemia. Several causes of corpuscular hemolysis have been described, among which red blood cell enzyme defects are of particular concern. We report a rare case of red blood cell enzyme defect in a male infant, who presented during his first months of life with recurrent and isolated neonatal hemolysis. All main causes were ruled out. At 6.5 months of age, the patient presented with gastroenteritis requiring hospitalization; fortuitously, urine organic acid chromatography revealed a large peak of 5-oxoproline. Before the association between HA and 5-oxoprolinuria was noted, glutathione synthetase deficiency was suspected and confirmed by a low glutathione synthetase concentration and a collapse of glutathione synthetase activity in erythrocytes. Moreover, molecular diagnosis revealed 2 mutations in the glutathione synthetase gene: a previously reported missense mutation (c.[656A>G]; p.[Asp219Gly]) and a mutation not yet described in the binding site of the enzyme (c.[902T>C]; p.[Leu301Pro]). However, 15 days later, a control sample revealed no signs of 5-oxoprolinuria and the clinical history discovered administration of acetaminophen in the 48 hours before hospitalization. Thus, in this patient, acetaminophen exposure allowed the diagnosis of a mild form of glutathione synthetase deficiency, characterized by isolated HA. Early diagnosis is important because treatment with bicarbonate, vitamins C and E, and elimination of trigger factors are recommended to improve long-term outcomes. Glutathione synthetase deficiency should be screened for in cases of unexplained newborn HA. Copyright © 2016 by the American Academy of Pediatrics.

  13. Expansion of CD8+ cells in autoimmune hemolytic anemia.

    Science.gov (United States)

    Smirnova, S Ju; Sidorova, Ju V; Tsvetaeva, N V; Nikulina, O F; Biderman, B V; Nikulina, E E; Kulikov, S M; Sudarikov, A B

    2016-01-01

    Autoimmune hemolytic anemia (AIHA) is a rare blood disease associated with the production of auto-antibodies and autoimmune hemolysis. A critical role of B-cells in the development of AIHA has been demonstrated before. Here, we present the analysis of the clonal T-cell populations in patients with AIHA. Thirty-three patients with AIHA were included in this study. Thirteen patients with other anemias, 14 patients with other autoimmune conditions (SLE - 6, RA - 8) and 20 healthy donors were included in the study as a control group. The clonality of T-cell was evaluated by the assessment of the T-cell receptor gamma and beta chain gene rearrangements (TCRG and TCRB). The incidence of T-cell monoclonality detected in patients with AIHA was significantly higher compared to the control group. The persistence of T-cell clones did not correlate with the level of hemoglobin and other signs of remission or relapse and did not disappear after the therapy and clinical improvement (observation period was between 1 and 10 years). There was no correlation between the T-cell clonality and the gender, age, splenectomy, duration or severity of the disease. Fractionation of T-lymphocytes (CD4+, CD8+, CD4+25+) revealed that the monoclonal T-cells belonged to the CD8+ sub-population. We assume that besides a possible causative role of the T-cell clones in AIHA to autoimmune process, these clones do not directly participate in the development and maintenance of hemolysis. Most of the AIHA patients (48.5%) demonstrated a T-cell monoclonality, which requires monitoring and should be distinguished from T-cell tumors.

  14. The Lbw2 locus promotes autoimmune hemolytic anemia.

    Science.gov (United States)

    Scatizzi, John C; Haraldsson, Maria K; Pollard, K Michael; Theofilopoulos, Argyrios N; Kono, Dwight H

    2012-04-01

    The lupus-prone New Zealand Black (NZB) strain uniquely develops a genetically imposed severe spontaneous autoimmune hemolytic anemia (AIHA) that is very similar to the corresponding human disease. Previous studies have mapped anti-erythrocyte Ab (AEA)-promoting NZB loci to several chromosomal locations, including chromosome 4; however, none of these have been analyzed with interval congenics. In this study, we used NZB.NZW-Lbw2 congenic (designated Lbw2 congenic) mice containing an introgressed fragment of New Zealand White (NZW) on chromosome 4 encompassing Lbw2, a locus previously linked to survival, glomerulonephritis, and splenomegaly, to investigate its role in AIHA. Lbw2 congenic mice exhibited marked reductions in AEAs and splenomegaly but not in anti-nuclear Abs. Furthermore, Lbw2 congenics had greater numbers of marginal zone B cells and reduced expansion of peritoneal cells, particularly the B-1a cell subset at early ages, but no reduction in B cell response to LPS. Analysis of a panel of subinterval congenic mice showed that the full effect of Lbw2 on AEA production was dependent on three subloci, with splenomegaly mapping to two of the subloci and expansions of peritoneal cell populations, including B-1a cells to one. These results directly demonstrated the presence of AEA-specific promoting genes on NZB chromosome 4, documented a marked influence of background genes on autoimmune phenotypes related to Lbw2, and further refined the locations of the underlying genetic variants. Delineation of the Lbw2 genes should yield new insights into both the pathogenesis of AIHA and the nature of epistatic interactions of lupus-modifying genetic variants.

  15. Mecanismos básicos da encefalopatia urêmica Mechanisms underlying uremic encephalopathy

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    Giselli Scaini

    2010-06-01

    Full Text Available Em pacientes com insuficiência renal, a encefalopatia é um problema comum que pode ser provocado pela uremia, deficiência de tiamina, diálise, rejeição de transplante, hipertensão, desequilíbrios hidroeletrolíticos e toxicidades medicamentosas. Em geral a encefalopatia se apresenta como um complexo de sintomas que progride de uma leve obnubilação sensitiva até delírio e coma. Esta revisão discute questões importantes com relação aos mecanismos de base da fisiopatologia da encefalopatia urêmica. A fisiopatologia da encefalopatia urêmica é até hoje incerta, mas postula-se o envolvimento de diversos fatores; trata-se de um processo complexo e provavelmente multifatorial. Distúrbios hormonais, estresse oxidativo, acúmulo de metabólitos, desequilíbrio entre os neurotransmissores excitatórios e inibitórios, e distúrbio do metabolismo intermediário foram identificados como fatores contribuintes. A despeito do progresso continuado na terapêutica, a maior parte das complicações neurológicas da uremia, como a encefalopatia urêmica, não respondem plenamente à diálise e muitas delas são desencadeadas ou agravadas pela diálise ou transplante renal. Por outro lado, estudos prévios demonstraram que a terapia antioxidante pode ser utilizada como terapia coadjuvante para o tratamento destas complicações neurológicas.In patients with renal failure, encephalopathy is a common problem that may be caused by uremia, thiamine deficiency, dialysis, transplant rejection, hypertension, fluid and electrolyte disturbances or drug toxicity. In general, encephalopathy presents with a symptom complex progressing from mild sensorial clouding to delirium and coma. This review discusses important issues regarding the mechanisms underlying the pathophysiology of uremic encephalopathy. The pathophysiology of uremic encephalopathy up to now is uncertain, but several factors have been postulated to be involved; it is a complex and probably

  16. Insufficiency of the Kanagawa hemolytic test for detecting pathogenic Vibrio parahaemolyticus in Shanghai, China.

    Science.gov (United States)

    Hongping, Wang; Jilun, Zhang; Ting, Jiang; Yixi, Bao; Xiaoming, Zhou

    2011-01-01

    We evaluated the Kanagawa hemolytic test and tdh gene test for accuracy in identifying pathogenic Vibrio parahaemolyticus isolates in Shanghai. One hundred and seventy-two V. parahaemolyticus isolates were collected from diarrhea patients, freshly harvested sea fish, or fresh water samples. Statistical data for the Kanagawa hemolytic test and tdh gene test were compared. There were 83.51% isolates (81/97) from patients and 22.22% isolates (10/45) from sea-fish positive for the tdh gene. However, none of 30 isolates from fresh water samples were tdh-positive. Positive Kanagawa hemolytic tests were obtained in 88.66%, 46.67%, and 76.67% of isolates, which were from patients, sea fish, and fresh water samples, respectively. Positive rates of the Kanagawa hemolytic tests and the tdh gene tests were significantly different in isolates from those 3 sources (P tdh gene test showed higher specificity than the Kanagawa hemolytic test on identifying pathogenic V. parahaemolyticus isolates in Shanghai, China.

  17. Hemolytic toxin from the soft coral Sarcophyton trocheliophorum: isolation and physiological characterization

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    S Karthikayalu

    2010-01-01

    Full Text Available The unifying characteristic of cnidarians is the production of protein and polypeptide toxins. The present study describes the identification of a hemolytic toxin from the soft coral Sarcophyton trocheliophorum. The crude extract was highly cytotoxic (EC50 = 50 ng/mL against human erythrocytes. It was also tested for hemolytic activity by the blood agar plate method, resulting in a hemolytic halo of 12 mm with 50 µg of protein. The stability of the venom under different physiological conditions was analyzed. The venom hemolytic activity was augmented by alkaline and neutral pH whereas it was reduced in acidic pH. The activity was stable up to 60º C. The hemolytic activity was completely abolished by the addition of serum and reduced significantly during frequent freezing-thawing cycles. Toxin purification was performed by ammonium sulfate precipitation and subsequently desalted by dialysis against 10 mM sodium phosphate buffer (pH 7.2, followed by anion exchange chromatography on DEAE cellulose column and gel filtration chromatography using Sephadex G-50 matrix. The purified active fractions possessed a prominent protein of approximately 45 kDa, as revealed by SDS-PAGE.

  18. A case of autoimmune hemolytic anemia associated with an ovarian teratoma.

    Science.gov (United States)

    Kim, Ickkeun; Lee, Jue Yong; Kwon, Jung Hye; Jung, Joo Young; Song, Hun Ho; Park, Young Iee; Ro, Eusun; Choi, Kyung Chan

    2006-04-01

    Autoimmune hemolytic anemia associated with an ovarian teratoma is a very rare disease. However, treating teratoma is the only method to cure the hemolytic anemia, so it is necessary to include ovarian teratoma in the differential diagnosis of autoimmune hemolytic anemia. We report herein on a case of a young adult patient who had severe autoimmune hemolytic anemia that was induced by an ovarian teratoma. A 25-yr-old woman complained of general weakness and dizziness for 1 week. The hemoglobin level was 4.2 g/dL, and the direct and indirect antiglobulin tests were all positive. The abdominal computed tomography scan revealed a huge left ovarian mass, and this indicated a teratoma. She was refractory to corticosteroid therapy; however, after surgical resection of the ovarian mass, the hemoglobin level and the reticulocyte count were gradually normalized. The mass was well encapsulated and contained hair and teeth. She was diagnosed as having autoimmune hemolytic anemia associated with an ovarian teratoma. To the best of our knowledge, this is the first such a case to be reported in Korea.

  19. Dexmedetomidine controls twitch-convulsive syndrome in the course of uremic encephalopathy.

    Science.gov (United States)

    Nomoto, Koichi; Scurlock, Corey; Bronster, David

    2011-12-01

    An 85 year old man with a history of chronic renal insufficiency was admitted to the cardiothoracic intensive care unit after aortic valve replacement. His postoperative course was marked by acute oliguric renal failure for high blood urea nitrogen (BUN) and acute hyperactive delirium. At this time he also developed tremors with muscle twitching; he received no other form of sedatives. A neurology consult made the diagnosis of twitch-convulsive syndrome associated with uremic encephalopathy. While the patient was receiving the dexmedetomidine infusion, the signs of the twitch-convulsive syndrome, particularly the twitching and tremors, disappeared. Within 30 minutes of the end of the dexmedetomidine infusion, symptoms of the twitch-convulsive syndrome returned, manifesting as acute tremulousness. After several dialysis treatments, his BUN decreased and the dexmedetomidine was weaned, without return of the symptoms of twitch-convulsive syndrome. Published by Elsevier Inc.

  20. Reversible posterior leukoencephalopathy syndrome in a patient with severe uremic encephalopathy.

    Science.gov (United States)

    Tatsumoto, N; Fujisaki, K; Nagae, H; Ono-Fujisaki, A; Kura-Nakamura, N; Taniguchi, M; Masutani, K; Tsuruya, K; Iida, M

    2010-08-01

    A 59-year-old male presented at our hospital with disturbance of consciousness. He had severe neurological disturbances associated with uremia caused by severe renal insufficiency. Cranial computed tomography (CT) was normal on admission. FLAIR-weighted MRI showed increased signal intensities bilaterally in the cortical and subcortical areas of the occipital lobe. Repeated hemodialysis resulted in improvement of the clinical symptoms and blood chemistry, and normalization of the MRI findings. Although the patient was discharged without neurological deficit, he had to be maintained on regular intermittent hemodialysis due to persistent renal failure. These reversible neuroradiological abnormalities may have been caused by reversible brain edema, but other pathoetiological factors should be also considered, such as abnormalities of cerebral metabolism and effects of uremic toxins.

  1. Genomic Damage in Endstage Renal Disease—Contribution of Uremic Toxins

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    Helga Stopper

    2010-10-01

    Full Text Available Patients with end-stage renal disease (ESRD, whether on conservative, peritoneal or hemodialysis therapy, have elevated genomic damage in peripheral blood lymphocytes and an increased cancer incidence, especially of the kidney. The damage is possibly due to accumulation of uremic toxins like advanced glycation endproducts or homocysteine. However, other endogenous substances with genotoxic properties, which are increased in ESRD, could be involved, such as the blood pressure regulating hormones angiotensin II and aldosterone or the inflammatory cytokine TNF-a. This review provides an overview of genomic damage observed in ESRD patients, focuses on possible underlying causes and shows modulations of the damage by modern dialysis strategies and vitamin supplementation.

  2. Novel hemagglutinating, hemolytic and cytotoxic activities of the intermediate subunit of Entamoeba histolytica lectin

    Science.gov (United States)

    Kato, Kentaro; Yahata, Kazuhide; Gopal Dhoubhadel, Bhim; Fujii, Yoshito; Tachibana, Hiroshi

    2015-01-01

    Galactose and N-acetyl-D-galactosamine (Gal/GalNAc) inhibitable lectin of Entamoeba histolytica, a common protozoan parasite, has roles in pathogenicity and induction of protective immunity in mouse models of amoebiasis. The lectin consists of heavy (Hgl), light (Lgl), and intermediate (Igl) subunits. Hgl has lectin activity and Lgl does not, but little is known about the activity of Igl. In this study, we assessed various regions of Igl for hemagglutinating activity using recombinant proteins expressed in Escherichia coli. We identified a weak hemagglutinating activity of the protein. Furthermore, we found novel hemolytic and cytotoxic activities of the lectin, which resided in the carboxy-terminal region of the protein. Antibodies against Igl inhibited the hemolytic activity of Entamoeba histolytica trophozoites. This is the first report showing hemagglutinating, hemolytic and cytotoxic activities of an amoebic molecule, Igl. PMID:26354528

  3. Attenuation of uremia by orally feeding alpha-lipoic acid on acetaminophen induced uremic rats.

    Science.gov (United States)

    Pradhan, Shrabani; Mandal, Shreya; Roy, Suchismita; Mandal, Arpita; Das, Koushik; Nandi, Dilip K

    2013-04-01

    Uremia means excess nitrogenous waste products in the blood & their toxic effects. An acute acetaminophen (paracetamol, N-acetyl p-aminophenol; APAP) overdose may result into potentially fatal hepatic and renal necrosis in humans and experimental animals. The aims of this present study were to investigate the protective effect of alpha-lipoic acid (ALA) on oxidative stress & uremia on male albino rats induced by acetaminophen. The study was performed by 24 albino male Wister strain rats which were randomly divided into four groups: Group I, control - receives normal food and water, Groups II, III & IV receive acetaminophen interperitoneally at the dose of 500 mg/kg/day for 10 days, from 11th day Groups III & IV were treated with ALA at the dose of 5 mg & 10 mg/100 g/day for 15 days, respectively. After 25 days of treatment, it was observed that there was a significant increase in plasma urea, creatinine, sodium and malondialdehyde (MDA) levels (p < 0.05) but a significant decrease in super oxide dismutase (SOD) & catalase activity & potassium level in uremic group is compared with control group & there was a significant increase in SOD & catalase (p < 0.05) & a significant decrease in serum urea, creatinine & Na and MDA (p < 0.05) in Group III & Group IV is compared with Group II & significant changes were observed in high ALA dose group. In conclusion it was observed that the ALA has nephroprotective activities by biochemical observations against acetaminophen induced uremic rats.

  4. Assessment of the characteristics and quality of life of patients with uremic peripheral neuropathy
.

    Science.gov (United States)

    Yu, Xiu-Zhi; Lu, Shi; Gou, Wei; Wang, Wei; Zou, Shui-Hong; Han, Yin-Xia; Wang, Wei-Wei; Zhang, Jin-Yuan

    2017-03-01

    This study seeks to examine the characteristics and health-related quality of life (HRQL) of patients with uremic peripheral neuropathy. Uremic patients undergoing maintenance hemodialysis (MHD) at our hospital were enrolled in this study. Data collection began in January 2011 and ended in June 2011. The patients were divided into two groups, the lesion group (110 cases) and the non-lesion group (168 cases), based on the presence or absence of peripheral neuropathy. To examine continuous changes in signs and symptoms in the lesion group, electromyography (EMG) was performed to measure sensory nerve conduction velocity (SCV), motor nerve conduction velocity (MCV), and distal latency (DL). Furthermore, HRQL was analyzed using the generic Short Form-36 (SF-36) questionnaire. Numbness and a burning sensation in the distal limbs were observed in the lesion group; in particular, these phenomena occurred in the upper limbs and the lower limbs in 3.6% (4/110) and 48.2% (53/110) of patients, respectively. With respect to motor symptoms, upper and lower limb weakness was observed in 1.8% (2/110) and 11.8% (13/110) of patients, respectively. Changes in physical signs were mainly evidenced by tendon reflexes, for example, areflexia, or tendon reflex loss was detected in the upper extremities, the knee tendon, and the Achilles tendon in 9.09% (10/110), 55.45% (61/110), and 35.5% (39/110) of patients, respectively. Relative to the non-lesion group, the lesion group had significantly slower average SCV and MCV as well as a longer average DL (p life.
.

  5. Effect of 16% Carbamide Peroxide Bleaching Gel on Enamel and Dentin Surface Micromorphology and Roughness of Uremic Patients: An Atomic Force Microscopic Study

    OpenAIRE

    2010-01-01

    Objectives: To investigate the effect of 16% carbamide peroxide bleaching gel on surface micromorphology and roughness of enamel and root dentin of uremic patients receiving hemodialysis using atomic force microscopy (AFM). Methods: A total of 20 sound molars were collected from healthy individuals (n=10) and uremic patients (n=10). The roots were separated from their crowns at the cemento-enamel junction. Dental slabs (3 mm x 2 mm x 2 mm) were obtained from the buccal surface for enamel slab...

  6. Comparison of Hemagglutination and Hemolytic Activity of Various Bacterial Clinical Isolates Against Different Human Blood Groups

    Science.gov (United States)

    HRV, Rajkumar; Devaki, Ramakrishna

    2016-01-01

    Among the various pathogenic determinants shown by microorganisms hemagglutination and hemolysin production assume greater significance in terms of laboratory identification. This study evaluated the hemagglutination and hemolytic activity of various bacterial isolates against different blood groups. One hundred and fifty bacterial strains, isolated from clinical specimens like urine, pus, blood, and other body fluids were tested for their hemagglutinating and hemolytic activity against human A, B, AB, and O group red blood cells. Among the 150 isolates 81 were Escherichia coli, 18 were Klebsiella pneumoniae, 19 were Pseudomonas aeruginosa, 10 were Pseudomonas spp, six were Proteus mirabilis, and the rest 16 were Staphylococcus aureus. Nearly 85% of the isolates agglutinated A group cells followed by B and AB group (59.3% and 60.6% respectively). Least number of isolates agglutinated O group cells (38.0%). When the hemolytic activity was tested, out of these 150 isolates 79 (52.6%) hemolyzed A group cells, 61 (40.6%) hemolyzed AB group cells, 46 (30.6%) hemolyzed B group cells, and 57 (38.6%) isolates hemolyzed O group cells. Forty-six percent of the isolates exhibited both hemagglutinating and hemolytic property against A group cells, followed by B and AB group cells (28.6% and 21.3% respectively). Least number of isolates i.e., 32 (21.3%) showed both the properties against O group cells. The isolates showed wide variation in their hemagglutination and hemolytic properties against different combinations of human blood group cells. The study highlights the importance of selection of the type of cells especially when human RBCs are used for studying the hemagglutination and hemolytic activity of bacterial isolates because these two properties are considered as characteristic of pathogenic strains. PMID:27014523

  7. Autoimmune hemolytic anemia in a patient with Malaria

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    Rajesh Sonani

    2013-01-01

    Full Text Available Autoimmune Hemolytic Anemia (AIHA, a very infrequent condition which represents a group of disorders in which presence of autoantibodies directed against self-antigens leads to shortened red cell survival. Till date, a very few cases of AIHA in Malaria patients are reported worldwide but still AIHA should be considered a relatively rare cause of anemia in malaria. A 20 year male presented with intermittent fever since seven days and yellowish discoloration of urine and sclera since 5 days. He was transfused three units of blood at a private clinic before one month. On examination, pallor, icterus and spelnomegaly were present. Hemoglobin (Hb was 3.2 gm% and peripheral smear revealed ring forms of both Plasmodium vivax and Plasmodium falciparum. Serum LDH and Serum billirubin (Indirect and Direct were high. This patient′s blood group was B +ve with positive autocontrol. Indirect Antiglobulin Test (IAT, antibody screening and antibody identification were pan-positive with reaction strength of +4 against each cell. Direct Antiglobulin Test was +4 positive anti IgG and negative with anti C3. He was treated with Artesunate and methylprednisone. Least incompatible, saline washed O Neg and B neg red cells were transfused on the 2 nd day of starting treatment. Hb was raised to 6.1 gm% on 4 th day. Patient was discharged on 9th day with Hb 7.0 gm% with oral tapering dose of steroids. In the above case, patient was suffering from high grade malarial parasitemia with co-existing autoimmune RBC destruction by IgG auto-antibodies which led to sudden drop in Hb and rise in serum LDH and indirect billirubin. Least incompatible packed red cells along with antimalarials and steroids led to clinical improvement. So far, one case report each from India, Korea, Canada and Germany and one case series report of three cases from India have been reported. Under-reporting or rarity of this phenomenon may be accountable for this.

  8. Isolation and in vitro partial characterization of hemolytic proteins from the nematocyst venom of the jellyfish Stomolophus meleagris.

    Science.gov (United States)

    Li, Rongfeng; Yu, Huahua; Xing, Ronge; Liu, Song; Qing, Yukun; Li, Kecheng; Li, Bing; Meng, Xiangtao; Cui, Jinhui; Li, Pengcheng

    2013-09-01

    Jellyfish venom contains various toxins and can cause itching, edema, muscle aches, shortness of breath, blood pressure depression, shock or even death after being stung. Hemolytic protein is one of the most hazardous components in the venom. The present study investigated the hemolytic activity of the nematocyst venom from jellyfish Stomolophus meleagris. Anion exchange chromatography, DEAE Sepharose Fast Flow, and gel filtration chromatography, Superdex200 had been employed to isolate hemolytic proteins from the nematocyst venom of jellyfish S. meleagris. Hemolysis of chicken red blood cells was used to quantify hemolytic potency of crude nematocyst venom and chromatography fractions during the purification process. Native-PAGE profile displayed one protein band in the purified hemolytic protein (SmTX); however, two protein bands with apparent molecular weights of ≈ 45 kDa and 52 kDa were observed in the reducing SDS-PAGE analysis. Approximately 70 μg/mL of SmTX caused 50% hemolysis (HU50) of the erythrocyte suspension. The hemolytic activity of SmTX was shown to be temperature and pH dependent, with the optimum temperature and pH being 37°C and pH 5.0. The present study is the first report of isolation and partial characterization of hemolytic proteins from the nematocyst venom of the jellyfish S. meleagris. The mechanism of the hemolytic activity of SmTX is not clear and deserves further investigation.

  9. Leukemoid reaction, a rare manifestation of autoimmune hemolytic anemia in a case of small duct primary sclerosing cholangitis.

    Science.gov (United States)

    Salagre, Kaustubh D; Sahay, Ravindra Nath; Patil, Anuja; Pati, Anuja; Joshi, Amita; Shukla, Akash

    2013-10-01

    A 48 year old lady presented with jaundice and exertional breathlesness. Her laboratory reports showed anaemia, reticulocytosis, leucocytosis, elevated Lactate Dehydrogenase (LDH), alkaline phosphatase levels, hyperbillirubinemia and positive direct Coomb's test. After ruling out all the other causes of autoimmunity and hemolytic anemia, she was diagnosed as leukemoid reaction due to autoimmune hemolytic anemia with primary sclerosing cholangitis. Patient showed immediate improvement after corticosteroids.

  10. Roles of organic anion/cation transporters at the blood-brain and blood-cerebrospinal fluid barriers involving uremic toxins.

    Science.gov (United States)

    Hosoya, Ken-ichi; Tachikawa, Masanori

    2011-08-01

    The blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) play key roles in the influx and efflux transport of endogenous substrates in the brain and cerebrospinal fluid. The organic anion transporter (OAT) 3 and organic cation transporter (OCT) 3, which belong to the solute carrier (SLC) 22A family, are expressed at the BBB and BCSFB, and regulate the excretion of endogenous and exogenous organic anions and cations. Our recent research provides novel molecular and functional evidence that indoxyl sulfate, an anionic uremic toxin, undergoes efflux transport at the BBB via OAT3 and creatinine, a uremic guanidino compound, undergoes efflux transport at the BCSFB via OCT3. Renal impairment is associated with the accumulation of uremic toxins in blood and uremic encephalopathy. It is conceivable that uremic encephalopathy is related to inhibition or dysfunction of efflux transport systems for uremic toxins in the brain. Here, we review the function of OAT3 and OCT3 at the BBB and BCSFB in the context of their roles in the progression of renal failure.

  11. Hemolytic and urease activities in vibrios isolated from fresh and frozen oysters

    Directory of Open Access Journals (Sweden)

    Renata Albuquerque Costa

    2013-01-01

    Full Text Available INTRODUCTION: The present study aimed to survey the Vibrio microbiota of oysters (Crassostrea rhizophorae obtained from restaurants in Fortaleza, State of Ceará, Brazil, and to identify virulence factors. METHODS: The isolated vibrios were submitted to biochemical identification and were tested for hemolytic and urease activities. RESULTS: The isolated strains belonged to 13 species, with predominance of Vibrio mimicus. Of the strain isolates only from fresh samples, 20.5% and 2.8% showed hemolytic and urease activities, respectively. CONCLUSIONS: The findings support the little-publicized claim that Vibrio species other than V. parahaemolyticus and V. vulnificus can represent a health risk to public health.

  12. Hemolytic and urease activities in vibrios isolated from fresh and frozen oysters.

    Science.gov (United States)

    Costa, Renata Albuquerque; Araújo, Rayza Lima; Vieira, Regine Helena Silva dos Fernandes

    2013-01-01

    The present study aimed to survey the Vibrio microbiota of oysters (Crassostrea rhizophorae) obtained from restaurants in Fortaleza, State of Ceará, Brazil, and to identify virulence factors. The isolated vibrios were submitted to biochemical identification and were tested for hemolytic and urease activities. The isolated strains belonged to 13 species, with predominance of Vibrio mimicus. Of the strain isolates only from fresh samples, 20.5% and 2.8% showed hemolytic and urease activities, respectively. The findings support the little-publicized claim that Vibrio species other than V. parahaemolyticus and V. vulnificus can represent a health risk to public health.

  13. Uncommon neurological manifestations of hemolytic anemia: A report of two cases

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    Ramu Chitela

    2008-01-01

    Full Text Available Neurological complications of hemolytic anemias are rather uncommon. We are reporting two cases of hemolytic anemia presenting as chorea and recurrent ischemic stroke. The first one is a case of chorea in a patient with sickle cell trait. Reviewing the literature we could find only one case report of chorea in sickle cell disease disease. The second is a case of recurrent ischemic stroke in hereditary spherocytosis. We could trace two reports on a Medline search, though their association was less certain.

  14. Bacillus cereus bacteremia and hemolytic anemia in a patient with hemoglobin SC disease.

    Science.gov (United States)

    Rodgers, G M; Barrera, E; Martin, R R

    1980-08-01

    A patient with hemoglobin SC disease and cholelithiasis was found to have Bacillus cereus bacteremia. Hemolytic anemia developed, for which common causes of hemolysis were excluded, suggesting a relationship with the bacteremia. Following in vitro incubation, type O erythrocytes were hemolyzed by the culture, but not by a bacteria-free filtrate. This case confirms the association between sickle cell disorders and cholelithiasis with B cereus infections. In addition, it provides evidence for in vivo hemolysis with B cereus bacteremia, an organism not previously associated with hemolytic anemia.

  15. Hemolytic Disease of the Newborn Due to Anti-c Isoimmunization: A Case Report.

    Science.gov (United States)

    Sheeladevi, C S; Suchitha, S; Manjunath, G V; Murthy, Srinivas

    2013-09-01

    The Rhesus (Rh) blood group is one of the most complex blood groups known in humans. It has remained of primary importance in obstetrics, being the main cause of hemolytic disease of the newborn (HDN). Anti-D causes the most severe form of HDN. Other Rh allo antibodies that are capable of causing severe HDN include anti-c, which clinically is the most important Rh antigen after the D antigen. We report a case of hemolytic disease of the newborn due to Rh anti-c in an infant of an Rh positive mother.

  16. Hemolytic Disease of the Newborn Due to Anti-c Isoimmunization: A Case Report

    OpenAIRE

    2012-01-01

    The Rhesus (Rh) blood group is one of the most complex blood groups known in humans. It has remained of primary importance in obstetrics, being the main cause of hemolytic disease of the newborn (HDN). Anti-D causes the most severe form of HDN. Other Rh allo antibodies that are capable of causing severe HDN include anti-c, which clinically is the most important Rh antigen after the D antigen. We report a case of hemolytic disease of the newborn due to Rh anti-c in an infant of an Rh positive ...

  17. Case of cytomegalovirus-associated direct anti-globulin test-negative autoimmune hemolytic anemia.

    Science.gov (United States)

    Kaneko, Saeko; Sato, Masanori; Sasaki, Goro; Eguchi, Hiroyuki; Oishi, Tsutomu; Kamesaki, Toyomi; Kawaguchi, Hiroyuki

    2013-12-01

    A 1-year-old boy developed autoimmune hemolytic anemia after a negative direct anti-globulin test. The concentration of erythrocyte membrane-associated immunoglobulin G, determined using an immunoradiometric assay, correlated with disease activity. He was positive for cytomegalovirus (CMV) both serologically and by quantitative real-time polymerase chain reaction, indicating that his autoimmune hemolytic anemia was directly caused by CMV infection. Since anti-CMV immunoglobulin G was not absorbed by the patient's erythrocytes, cross-reaction between erythrocyte antigens and CMV was not likely a causative factor for hemolysis.

  18. Alpha-Methyldopa-Induced Autoimmune Hemolytic Anemia in the Third Trimester of Pregnancy

    Directory of Open Access Journals (Sweden)

    Charalampos Grigoriadis

    2013-01-01

    Full Text Available Alpha-methyldopa has been demonstrated to be safe for use during pregnancy and is now used to treat gestational hypertension. In pregnancy, alpha-methyldopa-induced autoimmune hemolytic anemia does not have typical features and the severity of symptoms ranges from mild fatigue to dyspnea, respiratory failure, and death if left untreated. A case of alpha-methyldopa-induced autoimmune hemolytic anemia in a 36-year-old gravida 2, para 1 woman at 37+6 weeks of gestation is reported herein along with the differential diagnostic procedure and the potential risks to the mother and the fetus.

  19. Primary Sjögren syndrome presenting with hemolytic anemia and pure red cell aplasia following delivery due to Coombs-negative autoimmune hemolytic anemia and hemophagocytosis.

    Science.gov (United States)

    Komaru, Yohei; Higuchi, Takakazu; Koyamada, Ryosuke; Haji, Youichiro; Okada, Masato; Kamesaki, Toyomi; Okada, Sadamu

    2013-01-01

    A 36-year-old woman presented with hemolytic anemia without a reticulocyte response 38 days after delivery. A marked reduction in erythroid cells and an increase in macrophages with active hemophagocytosis were noted in the bone marrow. While conventional Coombs' tests were negative, the level of red blood cell (RBC)-bound immunoglobulin G (IgG) was increased. The patient was diagnosed with primary Sjögren syndrome (pSS) based on her symptoms, positive anti-SS-A antibodies, Coombs-negative autoimmune hemolytic anemia and pure red cell aplasia associated with RBC-bound IgG and hemophagocytosis. The unique presentation was considered to be a consequence of immunological derangement associated with pSS, pregnancy and delivery.

  20. Cell-associated hemolytic activity in environmental strains of Plesiomonas shigelloides expressing cell-free, iron-influenced extracellular hemolysin.

    Science.gov (United States)

    González-Rodríguez, Nieves; Santos, Jesús A; Otero, Andrés; García-López, María-Luisa

    2007-04-01

    Hemolysis is a means of providing pathogenic bacteria with heme iron in vivo. In a previous work, iron-influenced hemolytic activity against sheep erythrocytes was detected in cell-free supernatants, but not in the cell fraction of two environmental Plesiomonas shigelloides strains incubated without shaking. Both strains have the hugA gene, which encodes an outer membrane receptor required for heme iron utilization. The present study was undertaken to investigate the expression of a second hemolytic activity detected during aerated incubation in normal and iron-depleted tryptone soya broth (id-TSB). An agar overlay procedure and doubling dilution titrations were employed to detect the hemolytic activity against several erythrocyte species. The kinetics of growth and hemolytic activity were assayed at 35 degrees C in aerated normal and id-TSB and salmon extract. Overlaid colonies showed a cell-associated beta-hemolytic activity within 4 h. For aerated cell-free supernatants, titers above 16 were not attained until 30 to 48 h of incubation; the best activity was noted with dog and mouse erythrocytes. After 24 h of aerated incubation, sonicated cells yielded high hemolytic activity against dog erythrocytes without activity in supernatants, but after 48 h, only 28 to 30% of the total activity remained cell associated. The hemolytic factor was released in broths during the death phase. Hemolytic activity was not detected in fish extract. This and other studies suggest that P. shigelloides may produce at least two hemolytic factors, their expression and detection being influenced by environmental growth conditions and testing procedures. The overlay assay appears to be the best routine method for detecting hemolytic activity in P. shigelloides.

  1. Reduced immunostaining for the extracellular Ca{sup 2+} - sensing receptor in primary and uremic secondary hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Kifor, O.; Moore, F.D. Jr.; Wang, P. [Brigham and Women`s Hospital, Boston, MA (United States)] [and others

    1996-04-01

    Most parathyroid adenomas and some pathological parathyroid glands from patients with primary parathyroid hyperplasia or severe uremic secondary/tertiary hyperparathyroidism show an elevated set-point. In the present study, we investigated whether expression of the Ca{sup 2+}{sub o}-sensing receptor protein recently cloned from bovine parathyroid, a key component in Ca{sup 2+}{sub o}-regulated PTH release, is altered in primary and uremic hyperparathyroidism. Using immunohistochemistry with specific antireceptor antibodies, we compared immunoreactivity of the receptor protein in 14 adenomas, biopsies of 24 normal glands from this same group of patients, and 8 hyperplastic parathyroid glands from 2 individuals with uremic hyparathyroidism. The results show a substantial reduction in the intensity of immunostaining for the receptor protein that averaged nearly 60% for both adenomas and hyperplastic glands, as quantitated by image analysis. There was considerable variation in staining intensity among different pathological parathyroid glands, even in those from the same patient with secondary hyperparathyroidism. In addition, both adenomas and hyperplastic glands had, in some cases, isolated chief cells and groups of cells, sometimes around the periphery of an abnormal gland, with receptor staining equivalent to that of normal parathyroid cells, whereas the bulk of the cells in the same gland showed a marked decrease in staining. Thus, there is a variable, but substantial, reduction in the immunoreactivity of the Ca{sup 2+}{sub o}-sensing receptor protein in both parathyroid adenomas and uremic hyperparathyroidism, as assessed by immunohistochemistry, that probably results from reduced expression of the receptor protein and may contribute to the increase in the set-point often observed in these patients. 49 refs., 8 figs., 1 tab.

  2. Sleep Disorders, Restless Legs Syndrome, and Uremic Pruritus: Diagnosis and Treatment of Common Symptoms in Dialysis Patients

    Science.gov (United States)

    Scherer, Jennifer S.; Combs, Sara A.; Brennan, Frank

    2017-01-01

    Maintenance dialysis patients experience a high burden of physical and emotional symptoms that directly affect their quality of life and health care utilization. In this review, we specifically highlight common troublesome symptoms affecting dialysis patients: insomnia, restless legs syndrome, and uremic pruritus. Epidemiology, pathophysiology, and evidence-based current treatment are reviewed with the goal of providing a guide for diagnosis and treatment. Finally, we identify multiple additional areas of further study needed to improve symptom management in dialysis patients. PMID:27693261

  3. cblE-Type Homocystinuria Presenting with Features of Haemolytic-Uremic Syndrome in the Newborn Period

    OpenAIRE

    Palanca, Daniel; Garcia-Cazorla, Angels; Ortiz, Jessica; Jou, Cristina; Cusí, Victoria; Suñol, Mariona; Toll, Teresa; Perez, Belén; Ormazabal, Aida; Fowler, Brian; Artuch, Rafael

    2012-01-01

    This study describes a cblE type of homocystinuria associated with haemolytic-uremic syndrome (HUS) features. We report on a male infant aged 43 days presenting with failure to thrive, hypotonia, pancytopaenia, HUS symptoms (microangiopathic haemolytic anaemia and thrombocytopaenia with signs of renal involvement) and fatal evolution. An underlying cobalamin disorder was diagnosed after a bone marrow examination revealed megaloblastic changes associated with hyperhomocysteinaemia. An urinary ...

  4. Hemolytic anemia following high dose intravenous immunoglobulin in patients with chronic neurological disorders

    DEFF Research Database (Denmark)

    Markvardsen, L H; Christiansen, Ingelise; Harbo, T

    2014-01-01

    High dose intravenous immunoglobulin (IVIG) is an established treatment for various neuromuscular disorders. Recently, cases of hemolytic anemia following IVIG have been observed. The objective of this study was to determine the extent of anemia and hemolysis after IVIG and its relationship...

  5. Comparison of hemolytic activity of the intermediate subunit of Entamoeba histolytica and Entamoeba dispar lectins

    Science.gov (United States)

    Makiuchi, Takashi; Cheng, Xunjia; Tachibana, Hiroshi

    2017-01-01

    Galactose and N-acetyl-D-galactosamine-inhibitable lectin of Entamoeba histolytica has roles in pathogenicity and induction of protective immunity in rodent models of amoebiasis. Recently, the intermediate subunit of the lectin, Igl1, of E. histolytica has been shown to have hemolytic activity. However, the corresponding lectin is also expressed in a non-virulent species, Entamoeba dispar, and another subunit, Igl2, is expressed in the protozoa. Therefore, in this study, we compared the activities of Igl1 and Igl2 subunits from E. histolytica and E. dispar using various regions of recombinant Igl proteins expressed in Escherichia coli. The recombinant E. dispar Igl proteins had comparable hemolytic activities with those of E. histolytica Igl proteins. Furthermore, Igl1 gene-silenced E. histolytica trophozoites showed less hemolytic activity compared with vector-transfected trophozoites, indicating that the expression level of Igl1 protein influences the activity. These results suggest that the lower hemolytic activity in E. dispar compared with E. histolytica reflects the lower expression level of Igl1 in the E. dispar parasite. PMID:28750000

  6. Biochemical characterization, antimicrobial and hemolytic studies on skin mucus of fresh water spiny eel Mastacembelus armatus

    Institute of Scientific and Technical Information of China (English)

    Venkatachalam Uthayakumar; Venkatachalam Ramasubramanian; Dhanabalan Senthilkumar; Ramasamy Harikrishnan

    2012-01-01

    Objective: To characterize the biochemical, antimicrobial and hemolytic activities of Mastacembalus armatus skin mucus. Methods: Antimicrobial and antifungal activities of mucus extractions against human and fish pathogens were tested along with ampicillin as control. Hemolytic activity of the extraction was evaluated against sheep and cow blood cells. Amino acid and fatty acid profiles were analyzed by HPLC and gas chromatography in the mucus of fish. SDS-PAGE analysis of mucus and muscle tissue was done. Oneway-ANOVA was performed against all extraction and pathogens, amino acids and fatty acids. Result: All the mucus extracts exhibited higher inhibitory activity than antibiotic ampicillin against bacterial and fungal pathogens. The hemolytic activity was increased with higher mucus concentrations in both sheep and cow blood cells. The protein content soluble and insoluble fractions of mucus were 63.22 μg/g and 55.79μg/g, respectively. Out of 17 amino acids leucine was higher (8.54 mole %) in soluble gel, and glutamic acid was higher (6.92 mole %) in the insoluble gel, Histidine was very low (i.e. 0.20 mole%) both in soluble and (0.30 mole %) insoluble gel. In SDS-PAGE analysis, 6 bands of mucus and 9 bands of muscle were observed. Conclusions: The soluble and insoluble proteins are responsible for antimicrobial and hemolytic activity, these results indicate that mucus gel was prospective applications in fish and human therapeutics.

  7. Acute Cholestatic Hepatitis A Virus Infection Presenting with Hemolytic Anemia and Renal Failure: A Case Report

    Science.gov (United States)

    Rochling, Fedja

    2013-01-01

    Hepatitis A virus is the most common acute viral hepatitis worldwide with approximately 1.5 million cases annually. Hepatitis A virus infection in general is self-limited. In rare cases, hepatitis A virus infection may cause renal failure, hemolytic anemia, and/or cholestasis. We report the first case of acute cholestatic hepatitis A virus infection complicated by hemolytic anemia, and renal failure in one patient. A 42-year-old Caucasian male presented with cholestasis, hemolytic anemia and renal failure after consuming street tacos in Central and South America while on a business trip. His protracted course required corticosteroid therapy, multiple sessions of plasma exchange, and numerous units of packed red blood cells. This case demonstrates the importance of vaccination in high-risk adults. A prompt diagnosis of acute hepatitis A virus infection is essential, as uncommon presentations may delay diagnosis leading to permanent morbidity and potentially death in fulminant cases. We also demonstrate the efficacy of treatment of cholestatic hepatitis A virus infection, hemolytic anemia, and renal failure with corticosteroids and plasma exchange. PMID:25431704

  8. Acute Cholestatic Hepatitis A Virus Infection Presenting with Hemolytic Anemia and Renal Failure: A Case Report

    Directory of Open Access Journals (Sweden)

    Robert T. Lapp

    2013-01-01

    Full Text Available Hepatitis A virus is the most common acute viral hepatitis worldwide with approximately 1.5 million cases annually. Hepatitis A virus infection in general is self-limited. In rare cases, hepatitis A virus infection may cause renal failure, hemolytic anemia, and/or cholestasis. We report the first case of acute cholestatic hepatitis A virus infection complicated by hemolytic anemia, and renal failure in one patient. A 42-year-old Caucasian male presented with cholestasis, hemolytic anemia and renal failure after consuming street tacos in Central and South America while on a business trip. His protracted course required corticosteroid therapy, multiple sessions of plasma exchange, and numerous units of packed red blood cells. This case demonstrates the importance of vaccination in high-risk adults. A prompt diagnosis of acute hepatitis A virus infection is essential, as uncommon presentations may delay diagnosis leading to permanent morbidity and potentially death in fulminant cases. We also demonstrate the efficacy of treatment of cholestatic hepatitis A virus infection, hemolytic anemia, and renal failure with corticosteroids and plasma exchange.

  9. Immune-mediated hemolytic anemia associated with trimethoprim-sulphamethoxazole administration in a horse.

    OpenAIRE

    Thomas, H L; Livesey, M A

    1998-01-01

    A 10-year-old, thoroughbred gelding was administered sulphonamide drugs during surgical treatment of guttural pouch mycosis. The horse became anemic and a diagnosis of immune-mediated hemolytic anemia was made after other causes of anemia had been ruled out. The anemia resolved after the drugs were withdrawn.

  10. 78 FR 79469 - Strategies To Address Hemolytic Complications of Immune Globulin Infusions; Public Workshop

    Science.gov (United States)

    2013-12-30

    ... HUMAN SERVICES Food and Drug Administration Strategies To Address Hemolytic Complications of Immune... workshop. The Food and Drug Administration (FDA) is announcing a public workshop entitled ``Strategies to... identify and discuss potential risk mitigation strategies for Immune Globulin (Ig)-associated hemolysis...

  11. Autoimmune hemolytic anemia, as part of Evans' syndrome, caused by cold reactive IgG autoantibodies

    NARCIS (Netherlands)

    Jaarsma, AS; Muis, N; DeGraaf, SSN

    1996-01-01

    We describe a boy with Evans' syndrome, consisting of immune thrombocytopenic purpura at age 2 and autoimmune hemolytic anemia (AIHA) at age 4. AIHA was caused by cold Ige autoantibodies. This is unusual because AIHA is generally associated with either warm IgG antibodies or cold IgM antibodies. Tre

  12. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary hypertension associated with hemolytic anemia

    Directory of Open Access Journals (Sweden)

    Sarfraz Saleemi

    2014-01-01

    Because of a unique pathophysiology, pulmonary hypertension associated with hemolytic disorders was moved from WHO group I to group V PH diseases. Treatment strategies are also unique and include blood transfusion, iron chelation, hydroxyurea, and oxygen therapy. The role of PH-specific agents has not been established.

  13. Sigma E regulators control hemolytic activity and virulence in a shrimp pathogenic Vibrio harveyi.

    Directory of Open Access Journals (Sweden)

    Pimonsri Rattanama

    Full Text Available Members of the genus Vibrio are important marine and aquaculture pathogens. Hemolytic activity has been identified as a virulence factor in many pathogenic vibrios including V. cholerae, V. parahaemolyticus, V. alginolyticus, V. harveyi and V. vulnificus. We have used transposon mutagenesis to identify genes involved in the hemolytic activity of shrimp-pathogenic V. harveyi strain PSU3316. Out of 1,764 mutants screened, five mutants showed reduced hemolytic activity on sheep blood agar and exhibited virulence attenuation in shrimp (Litopenaeus vannamei. Mutants were identified by comparing transposon junction sequences to a draft of assembly of the PSU3316 genome. Surprisingly none of the disrupted open reading frames or gene neighborhoods contained genes annotated as hemolysins. The gene encoding RseB, a negative regulator of the sigma factor (σ(E, was interrupted in 2 out of 5 transposon mutants, in addition, the transcription factor CytR, a threonine synthetase, and an efflux-associated cytoplasmic protein were also identified. Knockout mutations introduced into the rpoE operon at the rseB gene exhibited low hemolytic activity in sheep blood agar, and were 3-to 7-fold attenuated for colonization in shrimp. Comparison of whole cell extracted proteins in the rseB mutant (PSU4030 to the wild-type by 2-D gel electrophoresis revealed 6 differentially expressed proteins, including two down-regulated porins (OmpC-like and OmpN and an upregulated protease (DegQ which have been associated with σ(E in other organisms. Our study is the first report linking hemolytic activity to the σ(E regulators in pathogenic Vibrio species and suggests expression of this virulence-linked phenotype is governed by multiple regulatory pathways within the V. harveyi.

  14. Uremic encephalopathy with isolated brainstem involvement revealed by magnetic resonance image: a case report.

    Science.gov (United States)

    Jia, Li-Jing; Qu, Zhen-Zhen; Zhang, Xue-Qian; Tian, Yu-Juan; Wang, Ying

    2017-08-08

    Uremic Encephalopathy (UE) is a neurological complication associated with acute or chronic renal failure. Imaging findings of UE may present involvement of the basal ganglia, cortical or subcortical regions, and white matter. We report a rare case of UE caused by neurogenic bladder with isolated brainstem involvement revealed by magnetic resonance imaging (MRI). Immediate therapy resulted in full recovery of neurological signs and changes on MRI. A 14-year-old Han Chinese woman with a history of chronic renal failure caused by neurogenic bladder. On admission, she was unconscious and her pupils presented different sizes, while her vital signs were normal. MRI showed high signal in the dorsal pontine base and in the mid brain on fluid-attenuated inversion-recovery (FLAIR) imaging and on T2-weighted imaging while the signal was normal on diffusion-weighted images (DWI). Blood analysis revealed renal failure and acidosis. After urinary retention treatment and acidosis correction, the patient soon recovered. Follow-up MRI 2 months after the discharge revealed complete resolution of UE in the brainstem. We reported a rare case of a patient with UE that had unusual imaging manifestations for whom timely diagnosis and treatment assured recovery.

  15. Improvement of autonomic neuropathy after mecobalamin treatment in uremic patients on hemodialysis.

    Science.gov (United States)

    Taniguchi, H; Ejiri, K; Baba, S

    1987-01-01

    The effect of mecobalamin on autonomic neuropathy was evaluated in 20 hemodialyzed uremic patients; their mean age was 53 years and the duration of hemodialysis was 6.5 years; 14 were women. The cardiac beat-to-beat variation (BBV) was used as the measure of autonomic neuropathy. Twelve patients with normal BBV test results were either given 1,500 micrograms of mecobalamin daily for three months (six patients) or were untreated (six patients). The BBV test results did not change significantly over the three months in either the treated or untreated group, nor were there any significant between-group differences. Eight patients with abnormal results on the BBV test were given 1,500 micrograms of mecobalamin daily for six months. The mean BBV values increased significantly from 3.3 beats/min before treatment to 5.8 beats/min at six months (P less than 0.005); five of these patients (including three of the four patients with diabetes) showed normal BBV values by three months. It is concluded that mecobalamin can be used in the treatment of autonomic and peripheral neuropathy in both diabetic and nondiabetic patients with chronic renal failure.

  16. Leptin as an uremic toxin: Deleterious role of leptin in chronic kidney disease.

    Science.gov (United States)

    Alix, Pascaline M; Guebre-Egziabher, Fitsum; Soulage, Christophe O

    2014-10-01

    White adipose tissue secretes a large variety of compounds named adipokines amongst which, leptin exhibits pleiotropic metabolic actions. Leptin is an anorexigenic hormone, secreted in proportion of fat mass, with additional effects on the regulation of inflammation, cardiovascular system, immunity, hematopoiesis and bone metabolism. Chronic kidney disease (CKD) is characterized by an increase of plasma leptin concentration that may be explained by a lack of renal clearance. Hyperleptinemia plays a key role in the pathogenesis of complications associated with CKD such as cachexia, protein energy wasting, chronic inflammation, insulin resistance, cardiovascular damages and bone complications. Leptin is also involved in the progression of renal disease through its pro-fibrotic and pro-hypertensive actions. Most of the adverse effects of leptin have been documented both experimentally and clinically. Leptin may therefore be considered as an uremic toxin in CKD. The aim of this review is to summarize the pathophysiological and clinical role of leptin in in vitro studies, experimental models, as well as in patients suffering from CKD.

  17. Involvement of Endoplasmic Reticulum Stress in Uremic Cardiomyopathy: Protective Effects of Tauroursodeoxycholic Acid

    Directory of Open Access Journals (Sweden)

    Wei Ding

    2016-01-01

    Full Text Available Background/Aims: Uremic cardiomyopathy (UCM is a complication in chronic kidney disease. We investigated if endoplasmic reticulum stress (ERS is involved in UCM, and determined the efficacy of tauroursodeoxycholic acid (TUDCA in UCM prevention. Methods: Mice were divided randomly into three groups: sham (saline, i.p, 5/6 nephrectomized (Nx (saline, i.p and Nx+TUDCA (250 mg/kg/day, i.p.. Renal function was assessed by measuring serum creatinine, blood urea nitrogen and by periodic acid-Schiff reagent staining. Histologic examination of cardiac fibrosis and apoptosis was determined by Masson's trichrome and TUNEL assay. Cardiac function was evaluated by echocardiography. Fibrotic factors (transforming growth factor-β, fibronectin, collagen I/IV were evaluated by real-time PCR. ERS-related proteins were measured by western blotting. Results: Impaired renal function and cardiac dysfunction were shown in 5/6 nephrectomy mice but were improved significantly by TUDCA. 5/6 nephrectomy mice exhibited marked cardiomyocyte apoptosis, cardiac fibrosis and elevated pro-fibrotic factors. ERS markers (GRP78, GRP94, P-PERK, P-eIF2a and ERS-induced apoptosis pathways (activation of CHOP and caspase-12 were increased significantly in 5/6 nephrectomy mice, and TUDCA treatment blunted these changes. Conclusions: ERS has a key role in UCM, and the cardioprotective role of TUDCA is related to inhibition of ERS-induced apoptosis by inhibition of CHOP and caspase-12 pathways.

  18. Uremic retention solute indoxyl sulfate level is associated with prolonged QTc interval in early CKD patients.

    Science.gov (United States)

    Tang, Wei-Hua; Wang, Chao-Ping; Chung, Fu-Mei; Huang, Lynn L H; Yu, Teng-Hung; Hung, Wei-Chin; Lu, Li-Fen; Chen, Po-Yuan; Luo, Ching-Hsing; Lee, Kun-Tai; Lee, Yau-Jiunn; Lai, Wen-Ter

    2015-01-01

    Total mortality and sudden cardiac death is highly prevalent in patients with chronic kidney disease (CKD). In CKD patients, the protein-bound uremic retention solute indoxyl sulfate (IS) is independently associated with cardiovascular disease. However, the underlying mechanisms of this association have yet to be elucidated. The relationship between IS and cardiac electrocardiographic parameters was investigated in a prospective observational study among early CKD patients. IS arrhythmogenic effect was evaluated by in vitro cardiomyocyte electrophysiological study and mathematical computer simulation. In a cohort of 100 early CKD patients, patients with corrected QT (QTc) prolongation had higher IS levels. Furthermore, serum IS level was independently associated with prolonged QTc interval. In vitro, the delay rectifier potassium current (IK) was found to be significantly decreased after the treatment of IS in a dose-dependent manner. The modulation of IS to the IK was through the regulation of the major potassium ion channel protein Kv 2.1 phosphorylation. In a computer simulation, the decrease of IK by IS could prolong the action potential duration (APD) and induce early afterdepolarization, which is known to be a trigger mechanism of lethal ventricular arrhythmias. In conclusion, serum IS level is independently associated with the prolonged QTc interval in early CKD patients. IS down-regulated IK channel protein phosphorylation and the IK current activity that in turn increased the cardiomyocyte APD and QTc interval in vitro and in the computer ORd model. These findings suggest that IS may play a role in the development of arrhythmogenesis in CKD patients.

  19. Predictive features of chronic kidney disease in atypical haemolytic uremic syndrome

    Science.gov (United States)

    Jamme, Matthieu; Raimbourg, Quentin; Chauveau, Dominique; Seguin, Amélie; Presne, Claire; Perez, Pierre; Gobert, Pierre; Wynckel, Alain; Provôt, François; Delmas, Yahsou; Mousson, Christiane; Servais, Aude; Vrigneaud, Laurence; Veyradier, Agnès

    2017-01-01

    Chronic kidney disease (CKD) is a frequent and serious complication of atypical haemolytic uremic syndrome (aHUS). We aimed to develop a simple accurate model to predict the risk of renal dysfunction in aHUS based on clinical and biological features available at hospital admission. Renal function at 1-year follow-up, based on an estimated glomerular filtration rate < 60mL/min/1.73m2 as assessed by the Modification of Diet in Renal Disease equation, was used as an indicator of significant CKD. Prospectively collected data from a cohort of 156 aHUS patients who did not receive eculizumab were used to identify predictors of CKD. Covariates associated with renal impairment were identified by multivariate analysis. The model performance was assessed and a scoring system for clinical practice was constructed from the regression coefficient. Multivariate analyses identified three predictors of CKD: a high serum creatinine level, a high mean arterial pressure and a mildly decreased platelet count. The prognostic model had a good discriminative ability (area under the curve = .84). The scoring system ranged from 0 to 5, with corresponding risks of CKD ranging from 18% to 100%. This model accurately predicts development of 1-year CKD in patients with aHUS using clinical and biological features available on admission. After further validation, this model may assist in clinical decision making. PMID:28542627

  20. Recombinant human erythropoietin (rHuEPO): more than just the correction of uremic anemia.

    Science.gov (United States)

    Buemi, Michele; Aloisi, Carmela; Cavallaro, Emanuela; Corica, Francesco; Floccari, Fulvio; Grasso, Giovanni; Lasco, Antonino; Pettinato, Giuseppina; Ruello, Antonella; Sturiale, Alessio; Frisina, Nicola

    2002-01-01

    Hematopoiesis is controlled by numerous interdependent humoral and endocrine factors. Erythropoietin (EPO), a hydrophobic sialoglycoproteic hormone, plays a crucial role in the regulation of hematopoiesis, and induces proliferation, maturation and differentiation of the erythroid cell line precursors. Thanks to recombinant DNA techniques, different recombinant hormones can now be produced at low cost and in large amounts. This has led to greater understanding of the pathophysiological factors regulating hematopoiesis. This in turn, hasprompted the search for new therapeutic approaches. EPO might also be used to treat patients with different types of anemia: uremics, newborns, patients with anemia from cancer or myeloproliferative disease, thalassemia, bone marrow transplants, chronic infectious diseases. Besides erythroid cells, EPO affects other blood cell lines, such as myeloid cells, lymphocytes and megakaryocytes. It can also enhance polymorphonuclear cell phagocytosis and reduce macrophage activation, thus modulating the inflammatory process. Hematopoietic and endothelial cells probably have the same origin, and the discovery of eyrthropoietin receptors also on mesangial, myocardial and smooth muscle cells has prompted research into the non-erythropoietic function of the hormone. EPO has an important, direct, hemodynamic and vasoactive effect, which does not depend only on an increase in hematocrit and viscosity. Moreover, EPO and its receptors have been found in the brain, suggesting a role in preventing neuronal death. Finally, the recently discovered interaction between EPO and vascular endothelial growth factor (VEGF), and the ability of EPO to stimulate endothelial cell mitosis and motility may be of importance in neovascularization and wound healing.