oxalates and Cardiovascular-Diseases

Increased level of oxalates in urine and plasma can be attributed to endogenous overproduction, increased ingestion or excessive intestinal absorption. When a supersaturation status is reached, oxalates combine with calcium and crystallize to form 80% of the urinary stones. Several cardiovascular diseases such as coronary heart disease and stroke are thought to be associated with the formation of urinary stones via sharing the same pathogenesis and/or risk factors. This review investigated the evidence linking oxalates/urinary stones to cardiovascular diseases. Eventually, two theories can explain the possible association between urinary stones and cardiovascular diseases: the theory of common origin and the theory of common risk factors. While the first theory is based on the common vascular pathophysiology of urinary stones and cardiac events, the later suggests that metabolic syndrome traits increase the risk of urinary stones and cardiovascular diseases independently. A few cohort studies showed a higher risk of coronary heart disease and stroke among people with history of urinary stones than people without it while other cohort studies did not. These studies had different definitions for cardiovascular diseases, used various methods to assess urinary stones, and some of them did not control for potential confounders. When they were pooled together in meta-analyses, a significant heterogeneity across studies was observed. In conclusion, although there is some evidence indicating that urinary stones could increase the risk of cardiovascular diseases, a substantial causal relationship cannot be settled.

Topics: Cardiovascular Diseases; Humans; Kidney Calculi; Oxalates; Urinary Calculi; Urolithiasis

In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of death. Some uremic toxins are ingested with the diet, such as phosphate and star fruit-derived caramboxin. Others result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves. These nutrients include l-carnitine, choline/phosphatidylcholine, tryptophan and tyrosine, which are also sold over-the-counter as nutritional supplements. Physicians and patients alike should be aware that, in CKD patients, the use of these supplements may lead to potentially toxic effects. Unfortunately, most patients with CKD are not aware of their condition. Some of the dietary components may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins, such as trimethylamine N-Oxide (TMAO), p-cresyl sulfate, indoxyl sulfate and indole-3 acetic acid. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of death and cardiovascular disease and there is evidence that this association may be causal. Future developments may include maneuvers to modify gut processing or absorption of these nutrients or derivatives to improve CKD patient outcomes.

Topics: Cardiovascular Diseases; Carnitine; Choline; Diet; Gastrointestinal Microbiome; Humans; Methylamines; Micronutrients; Oxalates; Phosphates; Phosphatidylcholines; Renal Insufficiency, Chronic; Tryptophan; Tyrosine

The clinical significance of accumulating toxic terminal metabolites such as oxalate in patients with kidney failure is not well understood.. To evaluate serum oxalate concentrations and risk of all-cause mortality and cardiovascular events in a cohort of patients with kidney failure requiring chronic dialysis, we performed a. A total of 1108 patients had baseline oxalate measurements, with a median oxalate concentration of 42.4 µM. During follow-up, 548 patients died, including 139 (25.4%) from sudden cardiac death. A total of 413 patients reached the primary composite cardiovascular end point (cardiac death, nonfatal myocardial infarction, and fatal or nonfatal stroke). Patients in the highest oxalate quartile (≥59.7 µM) had a 40% increased risk for cardiovascular events (adjusted hazard ratio [aHR], 1.40; 95% confidence interval [95% CI], 1.08 to 1.81) and a 62% increased risk of sudden cardiac death (aHR, 1.62; 95% CI, 1.03 to 2.56), compared with those in the lowest quartile (≤29.6 µM). The associations remained when accounting for competing risks and with oxalate as a continuous variable.. Elevated serum oxalate is a novel risk factor for cardiovascular events and sudden cardiac death in patients on dialysis. Further studies are warranted to test whether oxalate-lowering strategies improve cardiovascular mortality in patients on dialysis.

Topics: Aged; Cardiovascular Diseases; Death, Sudden, Cardiac; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Oxalates; Proportional Hazards Models; Renal Dialysis; Retrospective Studies; Risk Factors

The potential cardiovascular impact of usual intakes of oxalate (Ox) is uninvestigated. We evaluated the effect of dietary Ox and its interaction with dietary calcium (Ca) on incident cardiovascular disease (CVD).. We included 2966 adult men and women aged 19-84 y without known CVD during baseline enrollment (2006-2008) of the Tehran Lipid and Glucose Study. Dietary intakes were assessed using a validated FFQ, and incident CVD (i.e., coronary heart disease, stroke, and CVD mortality) were documented through March 2018.. A 7.1% incident of CVD occurred during a median follow-up of 10.6 y. After multivariable adjustment for traditional risk factors and key dietary nutrients, including total fat and fiber, Ox intakes ≥220 mg/d increased incident CVD (HR T3 vs. T1 = 1.47, 95% CI = 1.02-2.12). This association was potentiated (HR T3 vs. T1 = 2.42, 95% CI = 1.19-4.89) in subjects who had a lower intake of Ca (< 981 mg/d); in a low-Ca diet, an even lower amount of dietary Ox (second tertile, 148-220 mg/d) was related to increased CVD events by 92% (HR = 1.92, 95% CI = 1.00-3.70). No association was observed between dietary Ox and CVD events in the presence of medium- and high levels of Ca intakes. The critical cut-off point of Ox-to-Ca for predicting CVD events was 0.14, which was related to an increased risk of CVD by 37% (HR = 1.37, 95% CI = 1.02-1.84).. Higher dietary Ox intake appeared to be associated with a modestly elevated risk of incident CVD, especially in a diet with a lower amount of Ca.

Topics: Adult; Aged; Aged, 80 and over; Calcium; Calcium, Dietary; Cardiovascular Diseases; Diet; Female; Follow-Up Studies; Humans; Iran; Male; Middle Aged; Oxalates; Prospective Studies; Young Adult

Topics: Acetic Acid; Animals; Cardiovascular Diseases; Citric Acid Cycle; Ethanol; Humans; Oxalates; Protective Factors; Risk Factors; Wine

Some in vitro and animal studies have shown endothelial dysfunction in hyperoxaluria models indicating its role in pathogenesis of urolithiasis and relation to CVD. The aim of this study was to investigate endothelial function in patients with urolithiasis in relation to urinary stone risk factors and metabolic parameters. A total of 120 subjects without any known CVD (60 with urolithiasis and 60 healthy subjects) were included into study. Fasting blood and 24-h urine samples were collected to study metabolic parameters (glucose and lipids) and urine stone risk factors (oxalate, citrate, uric acid, and calcium, pH). Endothelial function was assessed as flow-mediated dilation (FMD) at the brachial artery. Age, sex, and body mass index were similar in patients and controls. Of urine stone risk factors, oxalate and citrate were higher in patients than controls. Fasting blood glucose, total LDL cholesterol, and triglyceride were higher, and HDL cholesterol was lower in patients than controls. Although within normal limits systolic blood pressure was higher in patient group, patients with urolithiasis had a lower %FMD than controls. Percent FMD was negatively correlated with urinary oxalate/creatinine ratio (p = 0.019, r = -0.315), calcium/creatinine ratio (p = 0.0001, r = -0.505) age (p < 0.001, r = -0.694), BMI (p < 0.001, r = -0.838), total cholesterol (p < 0.001, r = -0.559), and triglyceride (p < 0.001, r = -0.529). Urine oxalate/creatinine ratio was positively correlated with age (p = 0.01, r = 0.327) and calcium/creatinine ratio with BMI (p = 0.001, r = 0.410). This is the first study demonstrating endothelial dysfunction in human subjects with urolithiasis. This indicates a possible predictive role of urolithiasis in future development of cardiovascular diseases.

Topics: Adult; Blood Circulation; Blood Glucose; Blood Pressure; Brachial Artery; Cardiovascular Diseases; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Citrates; Creatinine; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Oxalates; Risk Factors; Triglycerides; Urinary Calculi

Both the prevalence of cardiovascular risk factors and event rate are increased in patients with urolithiasis. Screening is recommended to all patients who have high cardiovascular risk. The aim of this study was to document 10-year risk of cardiovascular disease and mortality in asymptomatic patients with urolithiasis. Consecutive 200 patients with calcium oxalate urolithiasis were compared with 200 age- and sex-matched healthy controls. Ten-year cardiovascular disease risk was calculated with the Framingham Risk Score and mortality risk with SCORE risk score. Calcium, oxalate, and citrate excretion were studied as urinary stone risk factors. The results indicate that patients with urolithiasis had higher total cholesterol (p < 0.0001), lower HDL-cholesterol (p < 0.0001), and higher systolic blood pressure (p < 0.0001) and hsCRP (p < 0.0001) compared with controls. Patients with urolithiasis had a higher Framingham Risk Scores [OR 8.36 (95% CI 3.81-18.65), p = 0.0001] and SCORE risk score [OR 3.02 (95% CI 1.30-7.02), p = 0.0006] compared with controls. The Framingham and SCORE risk score were significantly correlated with urinary calcium (p = 0.0001, r = 0.460, and p = 0.005, r = 0.223, respectively) and oxalate excretion (p = 0.0001, r = 0.516, p = 0.001, r = 0.290, respectively). In multiple linear regression analysis, urinary calcium and oxalate excretion, age, sex, total cholesterol, HDL-cholesterol, hsCRP and smoking were the independent predictors of 10-year cardiovascular disease risk and urinary calcium and oxalate excretion, age, sex, total cholesterol, fasting blood glucose for 10-year cardiovascular mortality. In conclusion, patients with calcium oxalate urolithiasis carry high risk of cardiovascular disease and mortality. All patients should be screened at the initial diagnosis of urolithiasis for the risk factors.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calcium; Calcium Oxalate; Cardiovascular Diseases; Case-Control Studies; Citric Acid; Cross-Sectional Studies; Female; Humans; Linear Models; Longitudinal Studies; Male; Middle Aged; Oxalates; Retrospective Studies; Risk Factors; Urolithiasis; Young Adult

Pre-dialysis plasma oxalate concentration was measured in a cross-sectional study of 75 patients receiving maintenance haemodialysis. The aims of this study were to enable formulation of hypotheses regarding the determinants of plasma oxalate concentration and to allow preliminary examination of the possibility that hyperoxalaemia confers an increased risk of cardiac and vascular disease even in the absence of primary hyperoxaluria. Plasma oxalate concentration ranged between 7 and 76 mumol/l, mean (SD) 34.6 (18.1) mumol/l (normal range less than 0.8-2.0 mumol/l). Significant correlations were found between plasma oxalate concentration and plasma creatinine, duration of dialysis, current dose of ascorbic acid, and serum phosphate, and each of these variables retained significance on multiple linear regression. Oxalate clearance across a 1 m2 hollow-fibre Cuprophan dialyser, at 500 ml/min dialysate flow and blood flow between 175 and 225 ml/min, was measured 1 h after commencement of dialysis (n = 19). Mean (SD) clearance was 96.5 (27.0) ml/min. No significant association was found between self-reported maximum walking distance or the occurrence of symptoms of cardiac failure and plasma oxalate concentration. No relationship was found between plasma oxalate concentration and electrocardiographic conduction disturbances (n = 8) 'major' ST/T wave changes (n = 22), 'minor' ST/T wave changes (n = 49). Plasma oxalate was significantly greater in patients with radiologically detectable calcification of medium-sized arteries than in those without calcification, but duration of dialysis was also significantly longer in these patients. Routine haemodialysis results in marked hyperoxalaemia, which may be exacerbated by ascorbate supplementation. Oxalate clearance is similar to that of other small molecules such as creatinine and phosphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Creatinine; Cross-Sectional Studies; Electrocardiography; Female; Humans; Male; Metabolic Clearance Rate; Middle Aged; Oxalates; Renal Dialysis; Risk Factors

Plasma oxalate has been measured in 125 patients maintained on continuous ambulatory peritoneal dialysis using an enzyme/bioluminescent assay. Values ranged between 6 and 134 mumol/l, with a positively skewed distribution. Multiple linear regression analysis with plasma oxalate as the dependent variable showed highly significant associations with the dose of ascorbic acid, dose of alfacalcidol, and plasma creatinine, and weaker associations with serum phosphate, serum calcium, and body weight. When the presence of other potential risk factors was taken into account, no significant relationship could be found between the presence of clinically evident cardiac or vascular disease and plasma oxalate.

Topics: Ascorbic Acid; Cardiovascular Diseases; Female; Humans; Male; Oxalates; Oxalic Acid; Peritoneal Dialysis, Continuous Ambulatory