oxalates and Hypercalciuria

Kidney stone disease is a multifactorial condition influenced by both genetic predisposition and environmental factors such as lifestyle and dietary habits. Although different monogenic polymorphisms have been proposed as playing a causal role for calcium nephrolithiasis, the prevalence of these mutations in the general population and their complete pathogenetic pathway is yet to be determined. General dietary advice for kidney stone formers includes elevated fluid intake, dietary restriction of sodium and animal proteins, avoidance of a low calcium diet, maintenance of a normal body mass index, and elevated intake of vegetables and fibers. Thus, balanced calcium consumption protects against the risk for kidney stones by reducing intestinal oxalate availability and its urinary excretion. However, calcium supplementation given between meals might increase urinary calcium excretion without the beneficial effect on oxalate. In kidney stone formers, circulating active vitamin D has been found to be increased, whereas higher plasma 25-hydroxycholecalciferol seems to be present only in hypercalciuric patients. The association between nutritional vitamin D supplements and the risk for stone formation is currently not completely understood. However, taken together, available evidence might suggest that vitamin D administration worsens the risk for stone formation in patients predisposed to hypercalciuria. In this review, we analyzed and discussed available literature on the effect of calcium and vitamin D supplementation on the risk for kidney stone formation.

Topics: Bone and Bones; Calcium; Dietary Supplements; Humans; Hypercalciuria; Intestines; Kidney Calculi; Minerals; Oxalates; Risk; Vitamin D; Vitamin D3 24-Hydroxylase

Hypercalciuria is the most common metabolic abnormality that causes urolithiasis. The pathogenetic mechanisms responsible for hypercalciuria include enhanced gastrointestinal absorption of calcium, increased bone resorption and/or decreased renal reabsorption of calcium; the main dietary factors promoting hypercalciuria are high dietary sodium intake and protein-rich diet. The authors discuss pathophysiology of hypercalciuria and genetic factors behind 'idiopathic hypercalciuria'. The simplified diagnostic approach to hypercalciuria is outlined herein, and available therapeutic interventions of proven efficacy in idiopathic hypercalciuria are presented as well. Dietary intervention for hypercalciuria should include reduced sodium, protein and oxalate intake. Thiazide diuretics, in conjunction with a low-sodium diet, tend to reduce urinary calcium excretion and ameliorate idiopathic hypercalciuria. Potassium citrate acts as an inhibitor of calcium stone formation in the urinary tract. A low-calcium diet should generally be avoided, as it may increase urinary oxalate excretion and actually promote stone formation. In addition, a low-calcium diet may lead to negative calcium balance in subjects with hypercalciuria, and therefore increases the risk of osteopenia.

Topics: Bone Diseases, Metabolic; Bone Resorption; Calcium; Dietary Proteins; Humans; Hypercalciuria; Intestinal Absorption; Kidney; Oxalates; Sodium Chloride Symporter Inhibitors; Sodium, Dietary

Patients with urolithiasis have been increasing in the world, especially morbidity of calcium nephrolithiasis has been increasing in the advanced countries. The changes in the environmental factors including alternation of diet are said to be associated with the increment of morbidity of kidney stone. Idiopathic hypercalciuria is one of the most important risk factor of calcium nephrolithiasis and is classified into absorptive, resorptive, and renal leak. Though the origins of these three types of hypercalciuria are different, increased bone resorption and increased calcium absorption from gut tend to be observed simultaneously. Not only genetic abnormalities in the proteins which are involved in calcium metabolisms but environmental factors such as high sodium intake and chronic acid load caused by increased ingestion of animal protein have been considered to be associated with increased urinary calcium excretion. Renal metabolisms of oxalate and phosphate which are important compositions of calcium containing stone, uric acid as a promoter and citrate as a inhibitor of nephrolithiasis are also described.

Topics: Adenylyl Cyclases; Bone Resorption; Calcium; Citric Acid; Dietary Proteins; Humans; Hypercalciuria; Kidney; Kidney Calculi; Oxalates; Phosphates; Receptors, Calcium-Sensing; Risk Factors; Sodium Chloride, Dietary; Uric Acid

Topics: Calcium; Calcium Oxalate; Diet; Humans; Hypercalciuria; Kidney Calculi; Oxalates

Nephrocalcinosis is associated with conditions that cause hypercalcemia and the increased urinary excretion of calcium, phosphate, and/or oxalate. A monogenic etiology is found in almost 30% of childhood-onset nephrocalcinosis which is also a common manifestation of primary hyperparathyroidism. We discuss a child with nephrocalcinosis and features mimicking primary hyperparathyroidism.. A 7-year-old girl presented with nephrocalcinosis. Hypercalciuria, hyperphosphaturia, mild hypercalcemia, hypophosphatemia and elevated parathyroid hormone levels along with normal serum creatinine and absence of hypokalemic alkalosis suggested primary hyperparathyroidism. However, she was ultimately diagnosed with Bartter syndrome type 2 based on the presence of homozygous pathogenic variation in. This is the second reported case of late-onset Bartter syndrome type 2 without hypokalemic alkalosis. Patients with Bartter syndrome may present with high parathyroid hormone levels and hypercalcemia in addition to hypercalciuria. Thus, the present case suggests that the

Topics: Alkalosis; Bartter Syndrome; Calcium; Child; Creatinine; Female; Humans; Hypercalcemia; Hypercalciuria; Hyperparathyroidism, Primary; Nephrocalcinosis; Oxalates; Parathyroid Hormone; Phosphates

The pathophysiology of genetic hypercalciuric stone-forming rats parallels that of human idiopathic hypercalciuria. In this model, all animals form calcium phosphate stones. We previously found that chlorthalidone, but not potassium citrate, decreased stone formation in these rats.. To test whether chlorthalidone and potassium citrate combined would reduce calcium phosphate stone formation more than either medication alone, four groups of rats were fed a fixed amount of a normal calcium and phosphorus diet, supplemented with potassium chloride (as control), potassium citrate, chlorthalidone (with potassium chloride to equalize potassium intake), or potassium citrate plus chlorthalidone. We measured urine every 6 weeks and assessed stone formation and bone quality at 18 weeks.. Potassium citrate reduced urine calcium compared with controls, chlorthalidone reduced it further, and potassium citrate plus chlorthalidone reduced it even more. Chlorthalidone increased urine citrate and potassium citrate increased it even more; the combination did not increase it further. Potassium citrate, alone or with chlorthalidone, increased urine calcium phosphate supersaturation, but chlorthalidone did not. All control rats formed stones. Potassium citrate did not alter stone formation. No stones formed with chlorthalidone, and rats given potassium citrate plus chlorthalidone had some stones but fewer than controls. Rats given chlorthalidone with or without potassium citrate had higher bone mineral density and better mechanical properties than controls, whereas those given potassium citrate did not.. In genetic hypercalciuric stone-forming rats, chlorthalidone is superior to potassium citrate alone or combined with chlorthalidone in reducing calcium phosphate stone formation and improving bone quality.

Topics: Animals; Bone Density; Calcium Phosphates; Chlorthalidone; Hypercalciuria; Kidney Calculi; Male; Oxalates; Potassium Citrate; Rats

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

Nephrolithiasis is one of the most common urinary tract diseases. After the first episode of urinary calculus, the risk of recurrence is nearly 40% to 50% at 5 years. Nephrolithiasis is a systemic disease that is associated with some metabolic disorders. This study aimed to provide a picture of the frequency of metabolic abnormalities in patients with nephrolithiasis from west part of Iran.. Patients with recurrent urinary tract calculi referred to the Nephrology-Urology Clinics in Khorramabad city were recruited. After collection of demographic data of all the patients, 24-hour urine and blood samples were taken to measure biochemical factors.. Of the 232 participants, 125 were males and 107 were females. Hyperoxaluria was seen in 93 (40.1%) of the participants, hypercalciuria in 55 (23.7%), hypocitraturia in 58 (25%), and hyperuricosuria in 33 (14.9%). Hyperoxaluria in the males was significantly more frequent than in the female patients. There were no significant differences between the two groups in other urinary metabolic disorders.. Patients with nephrolithiasis from Lorestan province may have metabolic characteristics varying from those of regions; ethnicity may be a possible reason. Variation of dietary regimens, such as the amount of meat or vegetable in the diet that can change oxalate, calcium, or citrate of urine, might have influenced the results. Time of sampling is another factor. Population-specific studies are helpful to health care providers for preventive planning for nephrolithiasis.

Topics: Adult; Biomarkers; Calcium; Citrates; Cross-Sectional Studies; Female; Humans; Hypercalciuria; Hyperoxaluria; Iran; Male; Middle Aged; Nephrolithiasis; Oxalates; Recurrence; Risk Factors; Sex Distribution; Uric Acid; Urinalysis

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 aim of this study was to show the presence of phosphorus and calcium metabolism disorders and the presence of urine lithogenic factors in women with osteoporotic fracture without previous urinary lithiasis.. We conducted a cross-sectional study including 55 women with osteoporotic fracture surgically treated in the Trauma Department. We included women with osteoporotic fracture demonstrated by the fracture area, fracture mechanism and the presence of osteoporosis by bone densitometry. We analyzed phospho-calcium metabolism as well as the calciuria, oxaluria, citraturia and uricosuria levels with fasting and 24-hour urine study. The presence of abnormal calcium and phosphorus metabolism was compared between women with hypercalciuria and normocalciuria.. The 55 women had a mean age of 70.1±13.8 years and a mean body mass index of 27.9±3.8 kg/m2. Forty-percent of the patients showed hypercalciuria, 36.4% hyperoxaluria, 36.4% hypocitraturia, and 5.3% hyperuricosuria. When comparing patients with hypercalciuria and normocalciuria, the only statistically significant difference was fasting urinary calcium/creatinine levels (0.16 versus 0.08, respectively; P<0.0001).. Women with osteoporotic fracture showed several lithogenic factors in the urine studies, mainly fasting hypercalciuria. Although in this study hypercalciuria did not involve the presence of lithiasis, it can favor the appearance of lithiasis with other predisposing conditions. Therefore, an accurate assessment of urine calcium levels with other lithogenic factors, such as citrate and oxalate levels, may facilitate individualized management and treatment of osteoporosis without increasing the risk of nephrolithiasis.

Topics: Aged; Aged, 80 and over; Citrates; Cross-Sectional Studies; Female; Humans; Hypercalciuria; Middle Aged; Osteoporotic Fractures; Oxalates; Postmenopause; Urolithiasis

Hypercalciuria is a common poorly understood abnormality among stone formers. We aimed to identify hypercalciuric male stone formers with a primary defect in renal calcium reabsorption and to look for associated risk factors.. A retrospective cross-sectional database study of 623 male idiopathic calcium stone formers with normal plasma ultrafilterable calcium levels attending the Southampton stone clinic. Filtered calcium was estimated from plasma ultrafilterable calcium (60% of total plasma calcium) and 24 h creatinine clearance. Reabsorbed calcium was the difference between filtered and excreted calcium.. 276 men had hypercalciuria (urine calcium >7.50 mmol/24 h); 347 had normocalciuria. Hypercalciuric men filtered more calcium than normocalciuric men: median values 247 and 227 mmol/24 h, but the ranges overlapped (175-371 and 153-316 mmol/24 h). However, across the entire filtration range, hypercalciuric men reabsorbed less of the filtered calcium. Among the hypercalciuric men, we noticed differences between those with high and low filtration. We therefore compared data for hypercalciuric men in the highest and lowest filtration quintiles (n=55). Men with high filtration were younger at their first stone episode and had significantly higher plasma ultrafilterable calcium and calcium reabsorption, urinary calcium, oxalate, urate and creatinine excretion and creatinine clearance. 35% with high filtration and 40% with low filtration had recurrent stones; 27% and 20%, respectively, had an affected first-degree relative.. Hypercalciuric men reabsorbed proportionately less filtered calcium than normocalciuric men. Among hypercalciuric men, the risks for stones were higher in those with a high than a low filtered calcium load and presentation was earlier.

Topics: Absorption; Adult; Aged; Calcium; Cohort Studies; Creatinine; Cross-Sectional Studies; Demography; Humans; Hypercalciuria; Kidney; Male; Middle Aged; Oxalates; Retrospective Studies; Risk Factors; Urolithiasis; Young Adult

To investigate the use of fish oil in the dietary management of hypercalciuric stone formers. Prostaglandins have been linked to urinary calcium excretion, suggesting a role for omega-3 fatty acids in the treatment of hypercalciuric urolithiasis.. We retrospectively studied a cohort of patients treated at our stone clinics from July 2007 to February 2009. Patients' urinary risk factors for stone disease were evaluated with pre- and post-intervention 24-hour urine collections. All patients received empiric dietary recommendations for intake of fluids, sodium, protein, and citric juices. All subjects with hypercalciuria (urinary calcium>250 mg/d for males or >200 mg/d for females) on at least two 24-hour urine collections were counseled to supplement their diet with fish oil (1200 mg/d).. Twenty-nine patients were followed for 9.86±8.96 months. The mean age was 43.38±13.78 years. Urinary calcium levels decreased in 52% of patients, with 24% converting to normocalciuria. The average urinary calcium (mg/d) decreased significantly from baseline (329.27±96.23 to 247.47±84.53, P<.0001). Urinary oxalate excretion decreased in 34% of patients. The average urinary oxalate (mg/d) decreased significantly from baseline (45.40±9.90 to 32.9±8.21, P=.0004). Urinary citrate (mg/d) increased in 62% of subjects from baseline (731.67±279.09 to 940.22±437.54, P=.0005). Calcium oxalate supersaturation decreased in 38% of the subjects significantly from baseline (9.73±4.48 to 3.68±1.76, P=.001).. Omega-3 fatty acids combined with empiric dietary counseling results in a measurable decrease in urinary calcium and oxalate excretion and an increase in urinary citrate in hypercalciuric stone formers.

Topics: Adult; Calcium; Citrates; Combined Modality Therapy; Cyclooxygenase Inhibitors; Dietary Supplements; Docosahexaenoic Acids; Drug Evaluation; Eicosapentaenoic Acid; Female; Fish Oils; Follow-Up Studies; Humans; Hypercalciuria; Male; Middle Aged; Oxalates; Prostaglandins; Retrospective Studies; Urolithiasis

Little is known about the renal handling of oxalate in patients with idiopathic hypercalciuria (IH). To explore the role of tubular oxalate handling in IH and to evaluate whether differences exist between IH and normal controls, we studied 19 IH subjects, 8 normal subjects, and 2 bariatric stone formers (BSF) during a 1-day General Clinical Research Center protocol utilizing a low-oxalate diet. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, oxalate, and calories. Plasma oxalate concentrations and oxalate-filtered loads were similar between patients (includes IH and BSF) and controls in both the fasting and fed states. Urinary oxalate excretion was significantly higher in patients vs. controls regardless of feeding state. Fractional excretion of oxalate (FEOx) was >1, suggesting tubular secretion of oxalate, in 6 of 19 IH and both BSF, compared with none of the controls (P < 0.00001). Adjusted for water extraction along the nephron, urine oxalate rose more rapidly among patients than normal subjects with increases in plasma oxalate. Our findings identify tubular secretion of oxalate as a key mediator of hyperoxaluria in calcium stone formers, potentially as a means of maintaining plasma oxalate in a tight range.

Topics: Adult; Calcium; Diet; Female; Humans; Hypercalciuria; Kidney Calculi; Kidney Tubules; Male; Middle Aged; Oxalates

Elevated sodium excretion in urine resulting from excessive sodium intake can lead to hypercalciuria and contribute to the formation of urinary stones. The aim of this study was to evaluate salt intake in patients with urinary lithiasis and idiopathic hypercalciuria (IH).. Between August 2007 and June 2008, 105 lithiasic patients were distributed into 2 groups: Group 1 (n = 55): patients with IH (urinary calcium excretion > 250 mg in women and 300 mg in men with normal serum calcium); Group 2 (n = 50): normocalciuric patients (NC). Inclusion criteria were: age over 18 years, normal renal function (creatinine clearance ≥ 60 ml/min), absent proteinuria and negative urinary culture. Pregnant women, patients with intestinal pathologies, chronic diarrhea or using corticoids were excluded. The protocol of metabolic investigation was based on non-consecutive collection of two 24-hour samples for dosages of: calcium, sodium, uric acid, citrate, oxalate, magnesium and urinary volume. Food intake was evaluated by the three-day dietary record quantitative method, and the Body Mass Index (BMI) was calculated and classified according to the World Health Organization (WHO). Sodium intake was evaluated based on 24-hour urinary sodium excretion.. The distribution in both groups as regards mean age (42.11 ± 10.61 vs. 46.14 ± 11.52), weight (77.14 ± 16.03 vs. 75.99 ± 15.80), height (1.64 ± 0.10 vs. 1.64 ± plusorminus 0.08) and BMI (28.78 ± 5.81 vs. 28.07 ± 5.27) was homogeneous. Urinary excretion of calcium (433.33 ± 141.92 vs. 188.93 ± 53.09), sodium (280.08 ± 100.94 vs. 200.44.93 ± 65.81), uric acid (880.63 ± 281.50 vs. 646.74 ± 182.76) and magnesium (88.78 ± 37.53 vs. 64.34 ± 31.84) was significantly higher in the IH group (p < 0.05). There was no statistical difference in calcium intake between the groups, and there was significantly higher salt intake in patients with IH than in NC.. This study showed that salt intake was higher in patients with IH as compared to NC.

Topics: Adult; Calcium; Case-Control Studies; Creatinine; Female; Humans; Hypercalciuria; Logistic Models; Magnesium; Male; Middle Aged; Oxalates; Prospective Studies; Risk Factors; Sodium; Sodium Chloride, Dietary; Uric Acid; Urinary Calculi

Topics: Female; Humans; Hypercalciuria; Kidney Calculi; Kidney Tubules; Male; Oxalates

We evaluated the metabolic and the nutritional aspects of 134 urolithiasic children, in order to outline the risk factors that contribute to idiopathic stone formation in children.. In this prospective study 134 children (56 females, 78 males) with renal calculi were evaluated. The age of the patients ranged 6 months to 16 years. A dietary survey was performed on every child. All patients were investigated with respect to stone localization, serum and urine risk factors. Statistical analysis of data was carried out using software SPSS 11.0 for Windows. Statistical significance was determined using chi-square test.. Hypercalciuria was the commonest risk factor detected in this group (28.3%). A decrease of water intake was noted in all age group specially in the rural area (549.6 vs 1150.6 ml/day), and an increase in animal protein intake in 17 cases (mean 1.9 g/kg). In addition, increased intake of starchy foods and food with high oxalate content (sorgum) was observed in our 10-16 years group (51%). Calcium oxalate monohydrate represents the principal component of idiopathic stone (58.2%), which is more frequent in children (68%) than infants (51.7%) (P < 0.02).. The high frequency of idiopathic urolithiasis highlights the influence of dietary habit in stone formers in our country. The increase in calcium oxalate stones in school-age children confirms the change in the etiology of urolithiasis according to age.

Topics: Adolescent; Child; Child, Preschool; Diet; Diet Surveys; Drinking; Feeding Behavior; Female; Humans; Hypercalciuria; Infant; Male; Meat; Nephrolithiasis; Oxalates; Prevalence; Prospective Studies; Risk Factors; Tunisia

We evaluated the clinical, radiological and metabolic features of 162 children with urolithiasis or microlithiasis who had been referred to our pediatric nephrology clinics between 1998 and 2008 with suspected urolithiasis. The medical histories of these children (78 girls, 84 boys), who ranged in age from 2 months to 16 years (mean age 5.59 +/- 0.35 years), were reviewed retrospectively for clinical and metabolic features of urinary tract calculi. Urinary tract infections (UTI) were present in 45.9% of the cases. The most common presenting symptoms were flank pain or restlessness (25.3%) and hematuria (21.6%), followed by UTI (16%), whereas 23.5% of the cases were detected incidentally during evaluation for other medical conditions. Other symptoms at presentation included dysuria, passing stones, penile edema, enuresis, vomiting and anorexia. Urine analysis revealed metabolic abnormalities in 87% of the cases, including hypercalciuria (33.8%), hypocitraturia (33.1%), hyperoxaluria (26.5%), hyperuricosuria (25.4%), hypocitraturia + hypercalciuria (21.1%), hyperphosphaturia (20.8%) and cystinuria (5.7%). Almost 50% of the patients had a positive family history for urolithiasis. The most frequently involved site was in the kidneys (86%). Ureters and bladder were involved in 12 and 2% of the cases, respectively. A family history of urolithiasis, presenting symptoms and underlying metabolic abnormalities were similar for microlithiasis and the patients with larger stones. However, in our study population, microlithiasis was mainly a disease of young infants, with a greater chance for remission and often not associated with structural changes. The presenting symptoms of urolithiasis show a wide spectrum, so that a high index of suspicion is important for early detection. A metabolic abnormality can be identified in 87% of cases of urolithiasis. Detection of microlithiasis may explain a number of symptoms, thus reducing invasive diagnostic procedures and allowing early recognition of metabolic abnormalities. These results draw attention to the importance of screening for UTIs in patients with urolithiasis.

Topics: Calcium; Child; Child, Preschool; Citric Acid; Cystinuria; Female; Humans; Hypercalciuria; Hyperoxaluria; Hypophosphatemia, Familial; Infant; Male; Metabolic Diseases; Oxalates; Phosphates; Retrospective Studies; Uric Acid; Urinary Calculi; Urinary Tract Infections; Urolithiasis

Topics: Calcium; Humans; Hypercalciuria; Lithiasis; Male; Nephrolithiasis; Oxalates; Urinary Calculi; Water-Electrolyte Balance