scholarly journals Cardiotoxicity of Uremic Toxins: A Driver of Cardiorenal Syndrome

Toxins ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 352 ◽  
Author(s):  
Suree Lekawanvijit
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Heart Rhythm ◽  
Cardiorenal Syndrome ◽  
Uremic Toxins ◽  
Excretory Function ◽  
Heart Rhythm Disorders ◽  
Increased Risk ◽  
Uremic Cardiomyopathy

Cardiovascular disease (CVD) is highly prevalent in the setting of chronic kidney disease (CKD). Such coexistence of CVD and CKD—the so-called “cardiorenal or renocardiac syndrome”—contributes to exponentially increased risk of cardiovascular (CV) mortality. Uremic cardiomyopathy is a characteristic cardiac pathology commonly found in CKD. CKD patients are also predisposed to heart rhythm disorders especially atrial fibrillation. Traditional CV risk factors as well as known CKD-associated CV risk factors such as anemia are insufficient to explain CV complications in the CKD population. Accumulation of uremic retention solutes is a hallmark of impaired renal excretory function. Many of them have been considered inert solutes until their biological toxicity is unraveled and they become accepted as “uremic toxins”. Direct cardiotoxicity of uremic toxins has been increasingly demonstrated in recent years. This review offers a mechanistic insight into the pathological cardiac remodeling and dysfunction contributed by uremic toxins with a main focus on fibroblastic growth factor-23, an emerging toxin playing a central role in the chronic kidney disease–mineral bone disorder, and the two most investigated non-dialyzable protein-bound uremic toxins, indoxyl sulfate and p-cresyl sulfate. Potential therapeutic strategies that could address these toxins and their relevant mediated pathways since pre-dialysis stages are also discussed.

Protein-bound uremic toxins: a long overlooked culprit in cardiorenal syndrome

2016 ◽  
Vol 311 (1) ◽  
pp. F52-F62 ◽  
Author(s):  
Suree Lekawanvijit ◽  
Andrew R. Kompa ◽  
Henry Krum
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Biological Effects ◽  
Cardiorenal Syndrome ◽  
Uremic Toxins ◽  
Kidney Transplant Recipients ◽  
Excretory Function ◽  
Dietary Amino Acid ◽  
Stage Renal Disease ◽  
End Stage

Protein-bound uremic toxins (PBUTs) accumulate once renal excretory function declines and are not cleared by dialysis. There is increasing evidence that PBUTs exert toxic effects on many vital organs, including the kidney, blood vessels, and heart. It has been suggested that PBUTs are likely to be a potential missing link in cardiorenal syndrome, based on the high incidence of cardiovascular events and mortality in the dialysis population, which are dramatically reduced in successful kidney transplant recipients. These data have led the call for more effective dialysis or additional adjunctive therapy to eradicate these toxins and their adverse biological effects. Indoxyl sulfate and p-cresyl sulfate are the two most problematic PBUTs, conferring renal and cardiovascular toxicity, and are derived from dietary amino acid metabolites by colonic microbial organisms. Therefore, targeting the colon where these toxins are initially produced appears to be a potential therapeutic alternative for patients with chronic kidney disease. This strategy, if approved, is likely to be applicable to predialysis patients, thereby potentially preventing progression of chronic kidney disease to end-stage renal disease as well as preventing the development of cardiorenal syndrome.

scholarly journals Effects of uremic toxins on hippocampal synaptic transmission: implication for neurodegeneration in chronic kidney disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Giuseppina Natale ◽  
Valeria Calabrese ◽  
Gioia Marino ◽  
Federica Campanelli ◽  
Federica Urciuolo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Disease Risk ◽  
Glutamate Release ◽  
Uremic Toxins ◽  
Synaptic Activity ◽  
Glutamatergic Transmission ◽  
Increased Risk ◽  
Multiple Drugs

AbstractPatients affected by chronic kidney disease (CKD) have an increased risk of developing cognitive impairment. The cause of mental health disorders in CKD and in chronic hemodialysis patients is multifactorial, due to the interaction of classical cardiovascular disease risk factors, kidney- and dialysis-related risk factors with depression, and multiple drugs overuse. A large number of compounds, defined as uremic toxins that normally are excreted by healthy kidneys, accumulate in the circulations, in the tissues, and in the organs of CKD patients. Among the candidate uremic toxins are several guanidino compounds, such as Guanidine. Uremic toxins may also accumulate in the brain and may have detrimental effects on cerebral resident cells (neurons, astrocytes, microglia) and microcirculation. The present study aims to analyze the effect of Guanidine on hippocampal excitatory postsynaptic field potentials (fEPSPs) and in CA1 pyramidal neurons recorded intracellularly. Moreover, we compared these effects with the alterations induced in vitro by CKD patients derived serum samples. Our results show an increased, dose-dependent, synaptic activity in the CA1 area in response to both synthetic Guanidine and patient’s serum, through a mechanism involving glutamatergic transmission. In particular, the concomitant increase of both NMDA and AMPA component of the excitatory postsynaptic currents (EPSCs) suggests a presynaptic mechanism. Interestingly, in presence of the lower dose of guanidine, we measure a significant reduction of EPSCs, in fact the compound does not inhibit GABA receptors allowing their inhibitory effect of glutamate release. These findings suggest that cognitive symptoms induced by the increase of uremic compounds in the serum of CKD patients are caused, at least in part, by an increased glutamatergic transmission in the hippocampus.

Stroke in chronic renal failure

2008 ◽  
Vol 149 (15) ◽  
pp. 691-696
Author(s):  
Dániel Bereczki
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Chronic Renal Disease ◽  
Kidney Diseases ◽  
Cerebrovascular Diseases ◽  
Lipid Lowering ◽  
Increased Risk ◽  
Intracerebral Hemorrhages

Chronic kidney diseases and cardiovascular diseases have several common risk factors like hypertension and diabetes. In chronic renal disease stroke risk is several times higher than in the average population. The combination of classical risk factors and those characteristic of chronic kidney disease might explain this increased risk. Among acute cerebrovascular diseases intracerebral hemorrhages are more frequent than in those with normal kidney function. The outcome of stroke is worse in chronic kidney disease. The treatment of stroke (thrombolysis, antiplatelet and anticoagulant treatment, statins, etc.) is an area of clinical research in this patient group. There are no reliable data on the application of thrombolysis in acute stroke in patients with chronic renal disease. Aspirin might be administered. Carefulness, individual considerations and lower doses might be appropriate when using other treatments. The condition of the kidney as well as other associated diseases should be considered during administration of antihypertensive and lipid lowering medications.

Abstract MP74: Long Term Risk-Factor Profiles for Chronic Kidney Disease in the Framingham Heart Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Gearoid M McMahon ◽  
Sarah R Preis ◽  
Shih-Jen Hwang ◽  
Caroline S Fox
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Risk Factor ◽  
Kidney Disease ◽  
Framingham Heart Study ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Standard Deviation Increase ◽  
Heart Study ◽  
Increased Risk

Background: Chronic Kidney Disease (CKD) is an important public health issue and is associated with an increased risk of cardiovascular disease. Risk factors for CKD are well established, but most are typically assessed at or near the time of CKD diagnosis. Our hypothesis was that risk factors for CKD are present earlier in the course of the disease. We compared the prevalence of risk factors between CKD cases and controls at time points up to 30 years prior to CKD diagnosis. Methods: Participants were drawn from the Framingham Heart Study Offspring cohort. CKD was defined as an estimated glomerular filtration rate of ≤60ml/min/1.73m2. Incident CKD cases occurring at examination cycles 6, 7, and 8 were age- and sex-matched 1:2 to controls. Risk factors including systolic blood pressure (SBP), hypertension, lipids, diabetes, smoking status, body mass index (BMI) and dipstick proteinuria were measured at the time of CKD diagnosis and 10, 20 and 30 years prior. Logistic regression models, adjusted for age, sex, and time period, were constructed to compare risk factor profiles at each time point between cases and controls Results: During follow-up, 441 new cases of CKD were identified and these were matched to 882 controls (mean age 69.2 years, 52.4% women). Up to 30 years prior to CKD diagnosis, those who ultimately developed CKD were more likely to have hypertension (OR 1.74, CI 1.21-2.49), be obese (OR 1.74, CI 1.15-2.63) and have higher triglycerides (OR 1.43, CI 1.12-1.84, p=0.005 per 1 standard deviation increase). Each 10mmHg increase in SBP was associated with an OR of 1.22 for future CKD (95% CI 1.10-1.35) Additionally, cases were more likely to have diabetes (OR 2.90, CI 1.59-5.29) and be on antihypertensive therapy (OR 1.65, CI 1.14-2.40, p=0.009) up to 20 years prior to diagnosis. Increasing HDLc was associated with a lower risk of CKD (OR 0.84, CI 0.81-0.97 per 10mg/dl). Conclusions: As many as 30 years prior to diagnosis, risk factors for CKD are identifiable. In particular, modifiable risk factors such as obesity, hypertension and dyslipidemia are present early in the course of the disease. These findings demonstrate the importance of early identification of risk factors in patients at risk of CKD through a life-course approach.

The obese patient (metabolic syndrome)

2015 ◽  
Author(s):  
Maarit Korkeila ◽  
Bengt Lindholm ◽  
Peter Stenvinkel
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Overweight And Obesity ◽  
Blood Cholesterol ◽  
Long Term Effects ◽  
Reverse Epidemiology ◽  
Increased Risk

Overweight and obesity cause pathophysiological changes in renal function and increase the risk for chronic kidney disease in otherwise healthy subjects. This should not be a surprise as the risk factors for metabolic syndrome largely overlap with those for chronic kidney disease. Intentional weight loss has beneficial effects on risk factors, but long term effects are less clear. Bariatric surgery does seem to achieve rapid benefits on blood pressure and proteinuria as well as on other aspects of metabolic syndrome, but its long term implications for kidney function are less clear cut as there may be an increased risk of nephrolithiasis, and possibly AKI and other complications.Obesity in haemodialysis patients is one of those paradoxical examples of reverse epidemiology where a factor associated with negative outcomes in the general population is associated with better outcomes in dialysis patients. The same is true for high blood cholesterol values. Interpretation is complicated by complex competing outcomes and confounders.

scholarly journals The first consecutive 5000 patients with Coronavirus Disease 2019 from Qatar; a nation-wide cohort study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ali S. Omrani ◽  
Muna A. Almaslamani ◽  
Joanne Daghfal ◽  
Rand A. Alattar ◽  
Mohamed Elgara ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Cohort Study ◽  
Kidney Disease ◽  
Older Age ◽  
Icu Admission ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Male Sex

Abstract Background There are limited data on Coronavirus Disease 2019 (COVID-19) outcomes at a national level, and none after 60 days of follow up. The aim of this study was to describe national, 60-day all-cause mortality associated with COVID-19, and to identify risk factors associated with admission to an intensive care unit (ICU). Methods This was a retrospective cohort study including the first consecutive 5000 patients with COVID-19 in Qatar who completed 60 days of follow up by June 17, 2020. The primary outcome was all-cause mortality at 60 days after COVID-19 diagnosis. In addition, we explored risk factors for admission to ICU. Results Included patients were diagnosed with COVID-19 between February 28 and April 17, 2020. The majority (4436, 88.7%) were males and the median age was 35 years [interquartile range (IQR) 28–43]. By 60 days after COVID-19 diagnosis, 14 patients (0.28%) had died, 10 (0.2%) were still in hospital, and two (0.04%) were still in ICU. Fatal COVID-19 cases had a median age of 59.5 years (IQR 55.8–68), and were mostly males (13, 92.9%). All included pregnant women (26, 0.5%), children (131, 2.6%), and healthcare workers (135, 2.7%) were alive and not hospitalized at the end of follow up. A total of 1424 patients (28.5%) required hospitalization, out of which 108 (7.6%) were admitted to ICU. Most frequent co-morbidities in hospitalized adults were diabetes (23.2%), and hypertension (20.7%). Multivariable logistic regression showed that older age [adjusted odds ratio (aOR) 1.041, 95% confidence interval (CI) 1.022–1.061 per year increase; P < 0.001], male sex (aOR 4.375, 95% CI 1.964–9.744; P < 0.001), diabetes (aOR 1.698, 95% CI 1.050–2.746; P 0.031), chronic kidney disease (aOR 3.590, 95% CI 1.596–8.079, P 0.002), and higher BMI (aOR 1.067, 95% CI 1.027–1.108 per unit increase; P 0.001), were all independently associated with increased risk of ICU admission. Conclusions In a relatively younger national cohort with a low co-morbidity burden, COVID-19 was associated with low all-cause mortality. Independent risk factors for ICU admission included older age, male sex, higher BMI, and co-existing diabetes or chronic kidney disease.

Retrospective evaluation of risk factors and treatment outcome predictors in cats presenting to the emergency room for constipation

2019 ◽  
Vol 22 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Sarah E Benjamin ◽  
Kenneth J Drobatz
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Physical Examination ◽  
Emergency Room ◽  
Treatment Protocol ◽  
Urgent Care ◽  
Hospital Data ◽  
Increased Risk ◽  
Clinicopathologic Findings

Objectives Constipation is a common complaint in cats presenting to the emergency room and can become a frustrating recurrent condition. Despite widespread anecdotal reports of risk factors for constipation, at the time of writing there have been no studies supporting these associations or assessing treatment outcomes. The aim of this study was to identify risk factors in the signalment, history, physical examination and clinicopathologic findings of cats presenting to the emergency room for constipation. In addition, we aimed to assess factors contributing to the success or failure of enemas administered to these cats. Methods A medical record search identified 189 cats with a diagnosis of constipation/obstipation that were treated and discharged by the emergency service at an academic veterinary hospital. Data regarding signalment, medical history, physical examination and clinicopathologic findings, as well as treatments performed, were recorded. Ninety-nine cats presenting to the emergency room for other reasons were identified as controls. Statistical analysis was performed to assess risk factors for constipation, as well as success/failure of enema treatments. Results Older, overweight cats and cats with chronic kidney disease or previous episodes of constipation were found to be at increased risk of constipation ( P <0.0001, P = 0.0004, P = 0.0046 and P <0.0001, respectively). Ionized calcium levels were significantly higher in constipated cats, though varied significantly within the cohort ( P = 0.0133). Cats noted to be painful on abdominal palpation were less likely to defecate following an enema. Adjunctive treatments (fluids, laxatives) increased the likelihood of a successful enema but were not statistically significant. Conclusions and relevance Older, overweight cats with a history of constipation or chronic kidney disease are more likely to present for constipation. Further studies are needed to determine the most appropriate treatment protocol in an urgent care setting.

Prevalence of Impaired Kidney Function in the German Elderly: Results from the Berlin Aging Study II (BASE-II)

Gerontology ◽  
2017 ◽  
Vol 63 (3) ◽  
pp. 201-209 ◽  
Author(s):  
Maximilian König ◽  
Maik Gollasch ◽  
Ilja Demuth ◽  
Elisabeth Steinhagen-Thiessen
Keyword(s):  
Risk Factors ◽  
Older Adults ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
The Elderly ◽  
Community Dwelling ◽  
Structured Interviews ◽  
Cross Sectional ◽  
Increased Risk ◽  
Aging Study

Background: In aging populations with an ever-growing burden of risk factors such as obesity, diabetes, and hypertension, chronic kidney disease (CKD) is on the rise. However, little is known about its exact prevalence among elderly adults, and often albuminuria is not included in the definition of CKD. Moreover, novel equations for the estimated glomerular filtration rate (eGFR) have recently emerged, which have not been applied comprehensively to older adults. Data on CKD awareness among the elderly are sparse. Objectives: To determine the prevalence of CKD among older adults by eGFR and albumin/creatinine ratio (ACR), compare the performance of 6 established and novel eGFR formulas, explore risk factors, and determine the awareness of CKD in a large cohort of community-dwelling elderly from Germany. Methods: A total of 1,628 subjects from the Berlin Aging Study II (BASE-II) were included in this analysis (mean age 68.7 years; 51.2% female). Extensive cross-sectional data on sociodemographics, lifestyle, medication, and diagnoses were inquired during structured interviews and a medical examination, and blood and urine parameters were measured. Results: In all, 77.1% of the subjects had hypertension, 12.4% had diabetes, and 18.3% were obese. The prevalence of CKD strongly depended on the eGFR equations used: 25.4% (full age spectrum [FAS] equation), 24.6% (Berlin Initiative Study), 23.1% (Lund-Malmö revised), 19.3% (Cockcroft-Gault), 16.4% (Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI]), and 14.7% (Modification of Diet in Renal Disease [MDRD]). Of the subjects with an eGFRFAS <60 mL/min/1.73 m2 and/or an ACR >30 mg/g, only 3.9% were aware of having CKD. Polypharmacy, age, BMI, coronary artery disease, non-HDL cholesterol, and female sex were independently associated with CKD. Conclusions: CKD is prevalent among older adults in Germany, but awareness is low. The FAS equation detects higher rates of CKD than MDRD and CKD-EPI, which are most widely used at present. Also, when CKD is defined based on eGFR and albuminuria, considerably more people are identified than by eGFR alone. Finally, polypharmacy is associated with an increased risk for CKD in the elderly.

scholarly journals Cardiorenal syndrome in patients with chronic kidney disease and diabetes mellitus

2013 ◽  
Vol 16 (3) ◽  
pp. 90-96
Author(s):  
Irina Mikhailovna Kutyrina ◽  
Tatiana Evgen'evna Rudenko ◽  
Svetlana Alekseevna Savel'eva ◽  
Mikhail Yur'evich Shvetsov ◽  
Marina Vladimirovna Shestakova
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiorenal Syndrome ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Related Factors ◽  
Myocardial Remodelling ◽  
History Of

AIM: Combination of cardiovascular and renal disease is currently viewed as a unified cardiorenal syndrome (CRS). The aim of our study was to assess the CRS prevalence and risk factors associated with left ventricular hypertrophy (LVH) in patients with pre-dialysis stages of chronic kidney disease (CKD) of various etiology. MATERIALS AND METHODS: We enrolled 172 patients with CKD to participate in this study. First group consisted of 83 patients with nondiabetic CKD at 2nd through 4th stage (mean age 46-15 years, 51% male and 29% female). Mean glomerular filtration rate (GFR) was 37.2 ml/min (33.9-41.4 with 95% CI); creatinine plasma clearance was 2.9 mg/dl (2.6-3.2). Second group consisted of 89 patients with type 2 diabetes mellitus (T2DM) and CKD at 1st?2nd stage (40% male and 60% female) with albuminuria (mean age 57.3-7.1 years). Duration of diabetes in this sampling was 10.4-7.1 years. All patients underwent standard clinical examination, supplemented with echocardiography to evaluate the influence of general and CKD-related risk factors for LVH. RESULTS: LVH was diagnosed in 37.3% of non-diabetic patients with CKD at 2nd through 4th stage. Aside from classic cardiovascular riskfactors (including age, gender, arterial hypertension, family history of cardiovascular diseases, hypercholesterolemia), we observed theimpact of kidney-related factors (anemia, plasma creatinine, disturbance of calcium-phosphorus metabolism). CKD progression wasassociated with elevation in the incidence of concentric and eccentric LVH). Patients with T2DM were diagnosed with LVH in 36% ofcases. Increased myocardial mass correlated with plasma levels of uric acid, HbA1c, obesity and albuminuria. There was also a firmassociation between diabetic nephropathy, left ventricular myocardial remodelling and a history of cardiovascular events. CONCLUSION: In patients with diabetes mellitus and CKD cardiorenal syndrome develops at pre-dialysis stages due to both classic and kidney-related cardiovascular risk factors.

Epidemiology of gout

2016 ◽  
Author(s):  
Samantha Hider ◽  
Edward Roddy
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Beta Blockers ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Epidemiological Studies ◽  
Dietary Factors ◽  
Angiotensin Ii Receptor ◽  
Converting Enzyme Inhibitors ◽  
Increased Risk

Gout is the most prevalent inflammatory arthritis in men. Data from epidemiological studies conducted in several countries suggest that the prevalence and incidence of gout have risen over the last few decades, although incidence may have stabilized recently. Dietary factors (animal purines, alcohol, and fructose), co-morbid medical conditions (obesity, metabolic syndrome, hypertension, and chronic kidney disease), and medications (diuretics, aspirin, beta blockers, angiotensin converting-enzyme inhibitors, and non-losartan angiotensin II receptor blockers) have been confirmed to be risk factors for both hyperuricaemia and gout. In contrast, low-fat dairy products, coffee, vitamin C, calcium channel antagonists, and losartan appear to reduce the risk of developing gout. People with gout are themselves at increased risk of developing cardiovascular disease and chronic kidney disease, independent of traditional risk factors for these conditions.

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