oxalates and Hypertension

Oxalate is a metabolic end-product whose systemic concentrations are highly variable among individuals. Genetic (primary hyperoxaluria) and non-genetic (e.g., diet, microbiota, renal and metabolic disease) reasons underlie elevated plasma concentrations and tissue accumulation of oxalate, which is toxic to the body. A classic example is the triad of primary hyperoxaluria, nephrolithiasis, and kidney injury. Lessons learned from this example suggest further investigation of other putative factors associated with oxalate dysmetabolism, namely the identification of precursors (glyoxylate, aromatic amino acids, glyoxal and vitamin C), the regulation of the endogenous pathways that produce oxalate, or the microbiota's contribution to oxalate systemic availability. The association between secondary nephrolithiasis and cardiovascular and metabolic diseases (hypertension, type 2 diabetes, and obesity) inspired the authors to perform this comprehensive review about oxalate dysmetabolism and its relation to cardiometabolic toxicity. This perspective may offer something substantial that helps advance understanding of effective management and draws attention to the novel class of treatments available in clinical practice.

Topics: Diabetes Mellitus, Type 2; Humans; Hyperoxaluria, Primary; Hypertension; Kidney; Nephrolithiasis; Oxalates

Nephrolithiasis is the most common type of urinary system disease in developed countries, with high morbidity and recurrence rates. Nephrolithiasis is a serious health problem, which eventually leads to the loss of renal function and is closely related to hypertension. Modern medicine has adopted minimally invasive surgery for the management of kidney stones, but this does not resolve the root of the problem. Thus, nephrolithiasis remains a major public health issue, the causes of which remain largely unknown. Researchers have attempted to determine the causes and therapeutic targets of kidney stones and calculus‑related hypertension. Solute carrier family 26 member 6 (SLC26A6), a member of the well‑conserved solute carrier family 26, is highly expressed in the kidney and intestines, and it primarily mediates the transport of various anions, including OXa

Topics: Citrates; Dicarboxylic Acid Transporters; Hyperoxaluria; Hypertension; Intestines; Kidney; Kidney Calculi; Membrane Transport Proteins; Nephrolithiasis; Organic Anion Transporters, Sodium-Dependent; Oxalates; Sulfate Transporters; Symporters

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Anura; Aortic Valve Stenosis; Autoradiography; Biological Transport; Calcium; Calcium Isotopes; Cell Membrane; Electrophysiology; Guinea Pigs; Heart; Heart Failure; Hypertension; In Vitro Techniques; Methods; Muscle Contraction; Muscle Proteins; Muscle, Smooth; Muscles; Myocardium; Myofibrils; Oxalates; Phosphates; Physical Exertion; Rabbits; Sarcolemma; Sodium

To determine whether stone-formers have higher BP than controls drawn from the general population and matched for age, sex and ethnic origin and to compare the relationship between sodium and calcium excretion in the two groups.. Thirty-six patients [mean (+/-standard deviation, SD) = 49.0 +/- 11.7 years; range 27-70 years] with kidney or ureteric stones and 108 controls (mean age of 49.6 +/- 6.8 years; range 39-61 years), matched for gender, ethnic origin and age group were studied. Patients and controls underwent physical measurements, a venous blood sample and they were asked to collect a 24-h urine sample for sodium, potassium, calcium and creatinine.. Stone-formers were significantly heavier and had higher BP than age-, sex- and ethnic-matched population controls. Whilst the difference in systolic BP was independent of the difference in body mass index [16.8 mmHg (7.2-26.4 mmHg), p = 0.001), the difference in diastolic BP was attenuated after adjustment for body mass [1.8 (-3.4 to 7.1), p = 0.49]. Stone-formers passed less urine than controls [-438 ml/day (95% CI -852 to -25), p = 0.038]. They had higher urinary calcium than controls [+3.7 mmol/day (2.8-4.6 mmol/day), p < 0.001], even when expressed as ratio to creatinine [+0.20 (0.11-0.29), p < 0.001]. Sodium excretion was positively associated with urinary calcium in both stone-formers and in controls. The slopes were comparable (0.92 vs 0.98 mmol Ca/100 mmol Na) so that for any level of sodium excretion (or salt intake), stone-formers had a higher calcium excretion than controls.. In stone-formers, the BP is higher than in controls. Stone-formers excrete more calcium than controls do. In stone-formers and controls, the relationship between urinary sodium and calcium is similar. Since this relationship results from an effect of sodium on calcium, a reduction in salt intake may be a useful method of reducing urinary calcium excretion in stone-formers. However, the "relative" hypercalciuria seen in stone-formers is independent of salt intake and may well reflect an underlying genetic predisposition.

Topics: Adult; Aged; Antihypertensive Agents; Asian People; Black People; Blood Pressure; Body Mass Index; Calcium; Female; Humans; Hypertension; Lithotripsy; Male; Middle Aged; Nephrostomy, Percutaneous; Oxalates; Phosphates; Sodium Chloride, Dietary; Urinary Calculi; White People

Diet-induced models of chronic kidney disease (CKD) offer several advantages, including clinical relevance and animal welfare, compared with surgical models. Oxalate is a plant-based, terminal toxic metabolite that is eliminated by the kidneys through glomerular filtration and tubular secretion. An increased load of dietary oxalate leads to supersaturation, calcium oxalate crystal formation, renal tubular obstruction, and eventually CKD. Dahl-Salt-Sensitive (SS) rats are a common strain used to study hypertensive renal disease; however, the characterization of other diet-induced models on this background would allow for comparative studies of CKD within the same strain. In the present study, we hypothesized that SS rats on a low-salt, oxalate rich diet would have increased renal injury and serve as novel, clinically relevant and reproducible CKD rat models. Ten-week-old male SS rats were fed either 0.2% salt normal chow (SS-NC) or a 0.2% salt diet containing 0.67% sodium oxalate (SS-OX) for five weeks.Real-time PCR demonstrated an increased expression of inflammatory marker interleukin-6 (IL-6) (

Topics: Animals; Blood Pressure; Diet; Hypertension; Kidney; Oxalates; Rats; Rats, Inbred Dahl; Renal Insufficiency, Chronic; Sodium Chloride; Sodium Chloride, Dietary

The association of metabolic syndrome (MetS) traits with urinary calcium (UCE) or oxalate excretion (UOE) is uncertain in calcium stone formers (CSFs). Our aim was to investigate this association in a large group of Caucasian CSFs.. We retrospectively reviewed data of CSFs evaluated at our Kidney Stone Clinic from 1984 to 2015. Data on body mass index (BMI), MetS traits defined according to international consensus, family history of urolithiasis, anti-hypertensive treatments, calcemia, renal function, and 24-h urinary profile of lithogenic risk were collected. The association between MetS traits and UCE or UOE was tested with multivariate linear regression models accounting for a long list of potential confounders.. In a large group of Caucasian CSFs, hypertension was the only MetS trait significantly associated with UCE, while no MetS trait was associated with oxalate excretion.

Topics: Adult; Calcium; Comorbidity; Dyslipidemias; Female; Humans; Hypercalciuria; Hyperoxaluria; Hypertension; Italy; Kidney Calculi; Male; Middle Aged; Overweight; Oxalates; Prevalence; Retrospective Studies

Urolithiasis is common and is becoming more prevalent worldwide. This study assessed the chronological trends in clinical and urinary metabolic features over 20 years in Korean urolithiasis patients. We performed a retrospective analysis of 4,076 patients treated at our clinic from 1996 to 2015. Urinary metabolic data and stone analysis data were available for 1,421 and 723 patients (34.9% and 17.7%), respectively. Patients were categorized into 4 groups according to the date of initial diagnosis: group 1 (1996-2000, n = 897), group 2 (2001-2005, n = 1,018), group 3 (2006-2010, n = 1,043), and group 4 (2011-2015, n = 1,118). Incidental detection of uric acid renal stones has become more prevalent in the past 10 years, accompanied by an increase in body mass index and age at diagnosis. Similarly, the prevalence of diabetes mellitus and of hypertension increased from one group to the next throughout the study period. Levels of 24-hour urinary excretion of sodium, calcium, uric acid, and oxalate have decreased significantly over the study period. The incidence of urinary metabolic abnormalities also showed an identical tendency. The proportion of stones composed of uric acid increased over the study period. In conclusion, incidental detection of uric acid renal stones has become more prevalent in Korea in the past 20 years. Urinary excretion of lithogenic constituents and the incidence of urinary metabolic abnormalities have decreased significantly over this period.

Topics: Age Factors; Body Mass Index; Calcium; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Incidence; Male; Middle Aged; Oxalates; Republic of Korea; Retrospective Studies; Risk Factors; Sodium; Uric Acid; Urolithiasis

Despite guidelines, routine 24-hour urine testing is completed in <10% of high-risk, recurrent stone formers. Using surrogates for metabolic testing, such as key patient characteristics, could obviate the cost and burden of this test while providing information needed for proper stone prevention counseling.. We performed a retrospective study of 392 consecutive patients from 2007 to 2014 with ≥2 lifetime stone episodes, >70% calcium oxalate by mineral analysis, and ≥1 24-hour urine collection. We compared mean 24-hour urine values by age in decades. We used logistic regression and receiver operating characteristic (ROC) curve analysis to assess the predictive ability of age, gender, body mass index (BMI), and comorbidities to detect abnormal 24-hour urine parameters.. The mean age of the cohort was 51 ± 16 years. Older age was associated with greater urinary oxalate (p-trend <0.001), lower urinary uric acid (UA) (p-trend = 0.007), and lower urinary pH (p-trend <0.001). A nonlinear association was noted between age and urinary calcium or citrate (calcium peaked at 40-49 years, p = 0.03; citrate nadired at 18-29 years, p = 0.001). ROC analysis of age, gender, and BMI to predict 24-hour urine abnormalities performed the best for hyperuricosuria (area under the curve [AUC] 0.816), hyperoxaluria (AUC 0.737), and hypocitraturia (AUC 0.740). Including diabetes mellitus or hypertension did not improve AUC significantly.. In our recurrent calcium oxalate cohort, age significantly impacted urinary calcium, oxalate, citrate, and pH. Along with gender and BMI, age can be used to predict key 24-hour urine stone risk results. These data lay the foundation for a risk prediction tool, which could be a surrogate for 24-hour urine results in recurrent stone formers, who are unwilling or unable to complete metabolic testing. Further validation of these findings is needed in other stone populations.

Topics: Adolescent; Adult; Age Factors; Aged; Body Mass Index; Calcium; Calcium Oxalate; Calcium Phosphates; Citrates; Citric Acid; Comorbidity; Diabetes Mellitus; Female; Humans; Hypercalciuria; Hyperoxaluria; Hypertension; Kidney Calculi; Male; Middle Aged; Nephrolithiasis; Obesity; Oxalates; Recurrence; Regression Analysis; Retrospective Studies; Sex Factors; Uric Acid; Urinalysis; Young Adult

The impact of the Dietary Approaches to Stop Hypertension (DASH) diet on kidney stone formation is unknown. We prospectively examined the relation between a DASH-style diet and incident kidney stones in the Health Professionals Follow-up Study (n = 45,821 men; 18 yr of follow-up), Nurses' Health Study I (n = 94,108 older women; 18 yr of follow-up), and Nurses' Health Study II (n = 101,837 younger women; 14 yr of follow-up). We constructed a DASH score based on eight components: high intake of fruits, vegetables, nuts and legumes, low-fat dairy products, and whole grains and low intake of sodium, sweetened beverages, and red and processed meats. We used Cox hazards regression to adjust for factors that included age, BMI, and fluid intake. Over a combined 50 yr of follow-up, we documented 5645 incident kidney stones. Participants with higher DASH scores had higher intakes of calcium, potassium, magnesium, oxalate, and vitamin C and had lower intakes of sodium. For participants in the highest compared with the lowest quintile of DASH score, the multivariate relative risks for kidney stones were 0.55 (95% CI, 0.46 to 0.65) for men, 0.58 (95% CI, 0.49 to 0.68) for older women, and 0.60 (95% CI, 0.52 to 0.70) for younger women. Higher DASH scores were associated with reduced risk even in participants with lower calcium intake. Exclusion of participants with hypertension did not change the results. In conclusion, consumption of a DASH-style diet is associated with a marked decrease in kidney stone risk.

Topics: Adult; Age Factors; Aged; Diet; Female; Humans; Hypertension; Kidney Calculi; Male; Middle Aged; Oxalates; Proportional Hazards Models; Prospective Studies; Risk Factors

Greater body mass index (BMI) is a risk factor for kidney stones. However, the relation between BMI and the urinary excretion of many lithogenic factors remains unclear.. We studied urine pH, urine volume, and 24-hour urinary excretion of calcium, oxalate, citrate, uric acid, sodium, magnesium, potassium, phosphate, and creatinine in stone-forming and non-stone-forming participants in the Health Professionals Follow-Up Study (599 stone-forming and 404 non-stone-forming men), Nurses' Health Study (888 stone-forming and 398 non-stone-forming older women), and Nurses' Health Study II (689 stone-forming and 295 non-stone-forming younger women). Each cohort was divided into quintiles of BMI. Tests of linear trend were conducted by 1-way analysis of variance. Linear regression models were adjusted for age, history of stone disease, dietary intake, and urinary factors.. Participants with greater BMIs excreted more urinary oxalate (P for trend

Topics: Adult; Body Mass Index; Calcium; Calcium Oxalate; Citrates; Comorbidity; Creatinine; Diabetes Mellitus; Female; Humans; Hydrogen-Ion Concentration; Hypertension; Kidney Calculi; Linear Models; Magnesium; Middle Aged; Obesity; Oxalates; Phosphates; Potassium; Risk Factors; Sodium; Urine

Transport activities of cardiac sodium-calcium exchange and sarcoplasmic reticulum calcium ATPase were measured biochemically in spontaneously hypertensive rats (SHR) with hypertrophied myocardium and in normotensive Wistar-Kyoto (WKY) rats and it was tested whether possible differences have consequences for the contractile properties of papillary muscle.. Sarcolemmal sodium-dependent calcium transport via sodium-calcium exchange and oxalate-supported sarcoplasmic reticulum calcium uptake were measured in left ventricular membranes of 22-week-old rats. Postextrastimulatory potentiated contractions, postrest potentiated contractions, the twitch-to-twitch decay of those potentiations and the response to increasing stimulation frequency of left ventricular papillary muscles were analysed.. Compared with WKY rats we found in SHR: a significant increase in sodium-calcium exchange (65%) and in sarcoplasmic reticulum calcium uptake (24%); a steeper twitch-to-twitch decay in postextrastimulatory potentiated contractions and postrest potentiated contractions, suggesting a lower calcium fraction recirculating between myofilaments and sarcoplasmic reticulum and, consequently, a relatively higher calcium efflux via sodium-calcium exchange; a stronger rest-dependent decrease in recirculating calcium fraction in postrest potentiated contractions accompanied by accelerated relaxation, suggesting an increasing driving force for calcium extrusion via sodium-calcium exchange, probably caused by decreasing intracellular sodium during rest; a greater transient decrease in peak force of subsequent twitches after postrest potentiated contractions below pre-interventional level, indicating higher cellular calcium loss; and a smaller negative inotropic effect in response to doubling of stimulation rate as a manoeuvre to increase the intracellular sodium level.. In SHR, the contractile properties suggest an increased contribution of sodium-calcium exchange to cellular calcium removal, which is strongly supported by the enhanced sodium-calcium exchange activity in cardiac membrane vesicles.

Topics: Animals; Biological Transport; Calcium; Electric Stimulation; Hypertension; Male; Membranes; Myocardial Contraction; Oxalates; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sodium

Topics: Creatinine; Graft Rejection; Humans; Hypertension; Kidney Calculi; Kidney Transplantation; Male; Middle Aged; Oxalates; Prednisone; Pyelonephritis

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Citrates; Coronary Disease; Female; Humans; Hypertension; Male; Middle Aged; Oxalates

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Alkaline Phosphatase; Animals; Azides; Calcium; Cell Membrane; Diazoxide; Hypertension; Ionophores; Leucyl Aminopeptidase; Male; Mesenteric Arteries; Nucleotidases; Oxalates; Phosphoric Diester Hydrolases; Proadifen; Propranolol; Rats; Subcellular Fractions

Energy-dependent calcium uptake activity of microsomes isolated from the rat aorta has been characterized. The microsomes consist of smooth membrane vesicles which in the presence of MG-ATP as an energy source continuously sequester calcium over a 60-min period. This calcium uptake is greatly stimulated by oxalate anion which serves as a calcium trapping agent. Unlike the calcium uptake of mitochondria this uptake is not inhibited by sodium azide. Sucrose density gradient analysis of the microsomal calcium uptake suggests that the system is associated with the sarcoplasmic reticulum. In presence of 5 mM Mg-ATP and 20 muM calcium approximately 38 nmol of calcium per mg of microsomal protein are taken up in 20 min. In the absence of ATP, less than 2 nmol of calcium per mg of protein are taken up in the first 2 min with no further uptake of calcium in subsequent time periods. When calcium uptake activity is plotted against calcium or ATP concentration of the medium, half maximal activity is calculated for 24.3 muM calcium and for 1.6 mM ATP. The calcium uptake characteristics of the rat aorta microsomes are compatible with a postulated role in the relaxation of the vascular smooth muscle and the provision of an intracellular calcium store for muscle contraction. Aorta microsomes from SHR rats (a genetic strain that is spontaneously hypertensive) have a significantly reduced uptake when compared with the corresponding nonhypertensive control strain. The level of calcium and ATP for half maximal activity of the rat aorta microsomal calcium uptake system is approximately the same in the SHR and the control strain. The rate of release of calcium from rat aorta microsomes is apparently identical in SHR strain and control. The calcium uptake activity of kidney and liver microsomes isolated from the SHR strain and control. The calcium uptake activity of kidney and liver microsomes isolated from the SHR rat appears to be identical to that found in the control strain.

Topics: Adenosine Triphosphate; Animals; Aorta; Azides; Biological Transport, Active; Calcium; Hypertension; Kidney; Kinetics; Magnesium; Male; Membranes; Microsomes; Oxalates; Rats

Topics: Adult; Creatinine; Humans; Hypertension; Male; Metabolism, Inborn Errors; Oxalates; Proteinuria

Topics: Ascorbic Acid; Aspirin; Asthma; Calcium; Citrates; Coronary Disease; Depression, Chemical; Diabetes Mellitus; Duodenal Ulcer; Dwarfism, Pituitary; Emphysema; Facial Paralysis; Gluconates; Histamine H1 Antagonists; Humans; Hypertension; Hyperthyroidism; Kidney Calculi; Liver Diseases, Parasitic; Magnesium; Oxalates; Phosphates; Pyridoxine; Schistosomiasis; Stimulation, Chemical; Terpenes; Tuberculosis, Pulmonary

Topics: Adult; Aged; Arteriosclerosis; Cholesterol; Female; Humans; Hypertension; Male; Middle Aged; Oxalates; Uric Acid