The uremic toxin indoxyl sulfate reflects cardio-renal risk and intestinal-renal relationship

2011 ◽  
Vol 152 (43) ◽  
pp. 1724-1730 ◽  
Author(s):  
István Kiss
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Morbidity And Mortality ◽  
Renal Diseases ◽  
Uremic Toxin ◽  
Cardiovascular Risks ◽  
Endogenous Protein ◽  
Uremic Syndrome

Uremic syndrome and condition is primarily a result of kidney failure in which uremic toxins are accumulated. More and more attention is paid to possibilities for removal of uremic toxins, which not only means dialysis, but also takes into account special dietary considerations and treatments, which aim to absorb the toxins or reduce their production. These uremic toxins, which also increase the cardiovascular risks, play a major part in morbidity and mortality of patients suffering from chronic renal failure and those receiving renal replacement therapy. One of them is a member of the indol group, the indoxyl sulfate. This toxin is difficult to remove with dialysis and is an endogenous protein-bound uremic toxin. Today we know that indoxyl sulfate is a vascular-nephrotoxic agent, which is able to enhance progression of cardiovascular and renal diseases. It is of particular importance that because of its redox potency, this toxin causes oxidative stress and antioxidant effects at the same time and, on top of that, it is formed in the intestinal system. Its serum concentration depends on the nutrition and the tubular function and, therefore, it can also signal the progression of chronic renal failure independently of glomerular filtration rate. Successful removal of indoxyl sulfate reduces the morbidity and mortality and improves survival. Therefore, it could be a possible target or area to facilitate the reduction of uremia in chronic renal failure. The use of probiotics and prebiotics with oral adsorbents may prove to be a promising opportunity to reduce indoxyl sulfate accumulation. Orv. Hetil., 2011, 152, 1724–1730.

Concentrations in Serum and Urinary Excretion of Guanidine, 1-Methylguanidine, and 1,1-Dimethylguanidine in Chronic Renal Failure

1973 ◽  
Vol 19 (6) ◽  
pp. 583-585 ◽  
Author(s):  
Israel M Stein ◽  
Michael J Micklus
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Urinary Excretion ◽  
Uremic Toxins ◽  
Mean Values ◽  
Uremic Syndrome ◽  
The Mean ◽  
Uremic Patients ◽  
Urine Specimens ◽  
Serum And Urine

Abstract Guanidine (G), 1-methylguanidine (MG), and 1,1-dimethylguanidine (DMG) have long been implicated as uremic "toxins." A method has been developed for determining G, MG, and DMG in serum and urine. Specimens were chromatographed on carboxylate resin, with use of 1 molar NaOH, and quantitated colorimetrically with a modification of the Voges— Proskauer reaction. The mean values for G and MG in the serum of uremic patients were 0.3 and 0.4 mg per liter, respectively. DMG was not detected. Although the urinary excretion of MG is significantly increased in renal failure, the concentrations of G, MG, and DMG in serum are not markedly increased, and it is therefore unlikely that G, MG, or DMG contribute to the toxic manifestations of the uremic syndrome.

scholarly journals A history of uremic toxicity and of the European Uremic Toxin Work Group (EUTox)

2021 ◽  
Author(s):  
Raymond Vanholder ◽  
Angel Argiles ◽  
Joachim Jankowski ◽  
Keyword(s):  
Work Group ◽  
Target Identification ◽  
Kidney Injury ◽  
Uremic Toxins ◽  
Uremic Toxin ◽  
Post Translational Modifications ◽  
History Of ◽  
Advanced Stages ◽  
Uremic Syndrome

Abstract The uremic syndrome is a complex clinical picture developing in the advanced stages of chronic kidney disease (CKD) resulting in a myriad of complications and a high early mortality. This picture is to a significant extent defined by retention of metabolites and peptides that with a preserved kidney function are excreted or degraded by the kidneys. In as far as those solutes have a negative biological/biochemical impact, they are called uremic toxins. Here, we describe the historical evolution of the scientific knowledge about uremic toxins and the role played in this process by the European Uremic Toxin Work Group (EUTox) during the last two decades. The earliest knowledge about a uremic toxin goes back to the early 17th century when the existence of what later would appear to be urea was recognized. It cost about two further centuries to better define the role of urea and its link to kidney failure and one more century to identify the relevance of post-translational modifications caused by urea such as carbamoylation. The knowledge progressively extended, especially from 1980 on, by the identification of more and more toxins and their adverse biological/biochemical impact. Progress of knowledge was paralleled and impacted by evolution of dialysis strategies. The last two decades, when Insights grew exponentially, coincides with the foundation and activity of EUTox. In the final section we summarize the role and accomplishments of EUTox and the part it is likely to play in future action, which should be organized around focus points like biomarker and potential target identification, intestinal generation, toxicity mechanisms and their correction, kidney and extracorporeal removal, patient-oriented outcomes, and toxin characteristics in acute kidney injury and transplantation.

Parathyroid hormone metabolism and its potential as a uremic toxin

1980 ◽  
Vol 239 (1) ◽  
pp. F1-F12 ◽  
Author(s):  
E. Slatopolsky ◽  
K. Martin ◽  
K. Hruska
Keyword(s):  
Renal Failure ◽  
Parathyroid Hormone ◽  
Chronic Renal Failure ◽  
Biological Effects ◽  
Uremic Toxin ◽  
Terminal Portion ◽  
Single Chain ◽  
Biochemical Alterations ◽  
Amino Terminal ◽  
Carboxy Terminal

Secondary hyperparathyroidism is a universal complication of chronic renal failure. It has been proposed that the markedly elevated levels of immunoreactive parathyroid hormone (i-PTH) in uremia may represent a “uremic toxin” responsible for many of the abnormalities of the uremic state. Plasma i-PTH consists of a mixture of intact hormone, a single-chain polypeptide of 84 amino acids, and smaller molecular weight hormonal fragments from both the carboxy- and amino-terminal portion of the PTH molecule. The hormonal fragments arise from metabolism of intact PTH by peripheral organs as well as from secretion of fragments from the parathyroid glands. The structural requirements for the known biological actions of PTH reside in the amino-terminal portion of the PTH molecule. Carboxy-terminal fragments, biologically inactive at least in terms of adenylate cyclase activation, hypercalcemia, or phosphaturia, depend on the kidney for their removal from plasma, and thus accumulate in the circulation in chronic renal failure. It is unknown at the present time if other biological effects of these carboxy-terminal fragments may contribute to some of the biochemical alterations observed in uremia. The most significant consequence of increased PTH levels in uremia is the development of bone disease characterized by osteitis fibrosa. In addition, it would appear that PTH plays an important role in some of the abnormal electroencephalographic patterns observed in uremia. This may be due to a potential role of PTH in increasing calcium content of brain. Parathyroid hormone also has been implicated as a pathogenetic factor in many other alterations present in uremia, i.e., peripheral neuropathy, carbohydrate intolerance, hyperlipidemia, and other alterations. Unfortunately, outstanding clinical research is lacking in this field and conclusive experimental data are practically nonexistent. Further studies are necessary if one is to accept the concept of PTH being a significant “uremic toxin.”

scholarly journals ROLE OF CARDIAC MARKERS IN CHRONIC RENAL FAILURE PATIENTS.

2020 ◽  
pp. 81-82
Author(s):  
Ramesh Chandra Thanna ◽  
B K Agarwal ◽  
Rakesh Romday ◽  
Neha Sharma
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Positive Association ◽  
Morbidity And Mortality ◽  
Control Group ◽  
High Morbidity ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Hs Crp

Introduction: Cardiovascular diseases (CVD) are known as important reasons of the increased morbidity and mortality observed in patients with chronic renal failure (CRF). The association of serum Interlukin-6 , homocysteine as well as other cardiovascular risk factors in relation to existence and cause of CVD were investigated. Method: In this study 200 CRF patients were recruited and further stratified into group with Male and Female as case groups. Those without renal failure were assigned as control group (n=200). Results: The patients with CRF showed a significant increase in plasma levels of Cpk-MB homocysteine and C-reactive protein (CRP) compared to control. The positive association were observed between homocysteine, Urea and Hs-CRP, IL_6 . It shows a significant Association of parameters in CRF . Conclusion: The results demonstrated elevation in plasma values IL-6 , homocysteine and HS-CRP in patients with CRF . However, these modifications may be lead to atherosclerosis and consequence CVD event. These parameters may be important with respect to the high morbidity and mortality of CVD found in patients with CRF.

scholarly journals Impaired function of platelet membrane glycoprotein IIb-IIIa in end-stage renal disease.

1994 ◽  
Vol 5 (1) ◽  
pp. 36-46
Author(s):  
M P Gawaz ◽  
G Dobos ◽  
M Späth ◽  
P Schollmeyer ◽  
H J Gurland ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Uremic Toxin ◽  
Bleeding Tendency ◽  
Fibrinogen Receptor ◽  
Fibrinogen Binding ◽  
Uremic Patients ◽  
Stage Renal Disease

Impaired platelet function and a bleeding tendency are well-recognized complications of chronic renal failure. Because the fibrinogen receptor GPIIb-IIIa plays a central role in platelet aggregation and adhesion to the subendothelium, it was reasoned that a defect in this receptor may underlie the impaired platelet function in uremia. To test this hypothesis, the function of this receptor in the platelets of 11 uremic patients was studied. Aggregation studies were performed with flow cytometric techniques with anti-GPIIb-IIIa conformation-specific monoclonal antibodies (mAb) (anti-LIBS1 and anti-PMI-1). Antifibrinogen and antithrombospondin mAb were used to characterize fibrinogen binding to GPIIb-IIIa and the release of alpha-granules, respectively. Platelets from patients with chronic renal failure showed significantly decreased binding of conformation-dependent anti-LIBS1 mAb after ADP, phorbol myristate acetate, or RGD-peptide stimulation compared with normal controls, suggesting a defect related to the ability of the fibrinogen receptor to undergo a conformational change. Moreover, antifibrinogen and antithrombospondin binding to activated platelets were reduced in uremic patients, implying impairment of both ligand-binding and alpha-granule release. Hemodialysis partially restored GPIIb-IIIa function, which may account for the observed effects of this therapy in restoring platelet aggregation. These findings indicate that platelets of patients with chronic renal failure reveal an aggregation defect at least partially due to an intrinsic GPIIb-IIIa dysfunction and the presence of a putative uremic toxin that inhibits fibrinogen binding to GPIIb-IIIa.

scholarly journals Familial Atypical Hemolytic Uremic Syndrome with Positive pS1191L (c.3572C> T) Mutation in CFH A Single-Center Experience

2019 ◽  
Author(s):  
Fadime ERSOY DURSUN ◽  
Gözde YESIL ◽  
Hasan DURSUN ◽  
Gülşah SASAK
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Family History ◽  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Gene Mutations ◽  
Factor H ◽  
The Other ◽  
History Of ◽  
Uremic Syndrome

Abstract Background: Atypical hemolytic uremic syndrome is a condition characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, which can exhibit a poor prognosis. Gene mutations play a key role in this disease, which may be sporadic or familial. Methods: We studied, 13 people from the same family were investigated retrospectively for gene mutations of familial atypical hemolytic uremic syndrome after a patient presented to our emergency clinic with atypical hemolytic uremic syndrome and reported a family history of chronic renal failure. Results: The pS1191L mutation in the complement factor H gene was heterozygous in 6 people from the family of the patient with atypical hemolytic uremic syndrome. One of these people was our patient with acute renal failure and the other two are followed up by the Nephrology Clinic due to chronic renal failure. The other 3 persons showed no evidence of renal failure. The index case had a history of 6 sibling deaths; two of them died of chronic renal failure. Plasmapheresis and fresh frozen plasma treatment was given to our patient. When patient showed no response to this treatment, eculizumab therapy was started. Conclusions: The study demonstrated that a thorough family history should be taken in patients with atypical hemolytic uremic syndrome. These patients may have familial type of the disease and they should be screened genetically. Eculizumab should be the first choice in the treatment with plasmapheresis. It should be kept in mind that the use of eculizumab as prophylaxis in post-transplant therapy is extremely important for prevention of rejection.

scholarly journals CONDITION AFTER HEMOLYTIC-UREMIC SYNDROME IN A CHILD WITH 3RD STAGE CHRONIC KIDNEY DISEASE (case report)

2017 ◽  
Vol 4 (3) ◽  
pp. 136-138
Author(s):  
M.O. Gonchar ◽  
T.B. Ishenko ◽  
N.V. Orlova ◽  
G.R. Muratov ◽  
T.F. Kolibaeva ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Case Report ◽  
Chronic Renal Failure ◽  
Kidney Disease ◽  
Hemolytic Uremic Syndrome ◽  
Clinical Case ◽  
Disease Case ◽  
Uremic Syndrome ◽  
The Given

Gonchar M.O., Ishchenko T.B., Orlova N.V., Muratov G., Kolibaeva T., Khmara N., Podvalnaya N.Currently, hemolytic-uremic syndrome is one of the frequent causes of acute kidney failure in children, so the timeliness of diagnosis and treatment determines the outcome of the disease. In the given clinical case, a set of certain factors that lead to an unfavorable outcome of the disease and the progression of chronic renal failure are presented. Clinical case of a 14-year-old child K., who was admitted to the nephrology department of the Regional Children's Clinical Hospital with the diagnosis: 3rd stage CKD, subcompensated stage of chronic renal failure and condition after hemolytic-uremic syndrome.KeyWords: hemolytic-uremic syndrome in children, chronic kidney disease. СТАН ПЫСЛЯ ПЕРЕНЕСЕНОГО ГЕМОЛІТИКО-УРЕМІЧНОГО СИНДРОМУ У ДИТИНИ З III СТАДІЄЮ ХРОНІЧНОГО ЗАХВОРЮВАННЯ НИРОК (КЛІНІЧНЕ СПОСТЕРЕЖЕННЯ)Гончарь М.О., Іщенко Т.Б., Орлова Н.В., Муратов Г.Р., Колібаєва Т.Ф., Хмара Н.В., Підвальна Н.А. В даний час гемолітико-уремічний синдром є однією з найчастіших причин гострої ниркової недостатності у дітей, тому своєчасність постановки діагнозу і лікування визначає результат захворювання. На наведеному клінічному випадку, представлено сукупність певних факторів, які привели до несприятливого результату захворювання і прогресування хронічної ниркової недостатності. Клінічний випадок дитини К. 14 років, який знаходився в нефрологічному відділенні Обласної дитячої клінічної лікарні з діагноз: ХХН III ст. Хронічна ниркова недостатність субкомпенсированная стадія. Стан після перенесеного гемолітико-уремічного синдрому.Ключові слова: гемолітико-уремічний синдром, діти, клінічний випадок, хронічне захворювання нирок. СОСТОЯНИЕ ПОСЛЕ ПЕРЕНЕСЕННОГО ГЕМОЛИТИКО-УРЕМИЧЕСКОГО СИНДРОМА У РЕБЕНКА С III СТАДИЕЙ ХРОНИЧЕСКОГО ЗАБОЛЕВАНИЯ ПОЧЕК (КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ)Гончарь М.А., Ищенко Т.Б., Орлова Н.В., Муратов Г.Р., Колибаева Т.Ф., Хмара Н.В., Подвальная Н.А. В настоящее время гемолитико-уремический синдром является одной из частых причин острой почечной недостаточности у детей, поэтому своевременность постановки диагноза и лечения определяет исход заболевания. На приведенном клиническом случае, представлено совокупность определенных факторов, которые привели к неблагоприятному исходу заболевания и прогрессированию хронической почечной недостаточности. Клинический случай ребенка К. 14 лет, который находился в нефрологическом отделении Областной детской клинической больнице с диагноз: ХБП III ст. Хроническая почечная недостаточность субкомпенсированная стадия. Состояние после перенесенного гемолитико-уремического синдрома.Ключевые слова: гемолитико-уремический синдром, дети, клинический случай, хроническое заболевание почек.

scholarly journals Impacts of Indoxyl Sulfate and p-Cresol Sulfate on Chronic Kidney Disease and Mitigating Effects of AST-120

Toxins ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 367 ◽  
Author(s):  
Wen-Chih Liu ◽  
Yasuhiko Tomino ◽  
Kuo-Cheng Lu
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Large Scale ◽  
Interstitial Fibrosis ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Renal Diseases ◽  
Glomerular Sclerosis ◽  
Inflammatory Reactions

Uremic toxins, such as indoxyl sulfate (IS) and p-cresol, or p-cresyl sulfate (PCS), are markedly accumulated in the organs of chronic kidney disease (CKD) patients. These toxins can induce inflammatory reactions and enhance oxidative stress, prompting glomerular sclerosis and interstitial fibrosis, to aggravate the decline of renal function. Consequently, uremic toxins play an important role in the worsening of renal and cardiovascular functions. Furthermore, they destroy the quantity and quality of bone. Oral sorbent AST-120 reduces serum levels of uremic toxins in CKD patients by adsorbing the precursors of IS and PCS generated by amino acid metabolism in the intestine. Accordingly, AST-120 decreases the serum IS levels and reduces the production of reactive oxygen species by endothelial cells, to impede the subsequent oxidative stress. This slows the progression of cardiovascular and renal diseases and improves bone metabolism in CKD patients. Although large-scale studies showed no obvious benefits from adding AST-120 to the standard therapy for CKD patients, subsequent sporadic studies may support its use. This article summarizes the mechanisms of the uremic toxins, IS, and PCS, and discusses the multiple effects of AST-120 in CKD patients.

Sign in / Sign up

Export Citation Format

Share Document