Decrease In Urinary Calcium Research Articles

Urinary Risk Profile, Impact of Diet, and Risk of Calcium Oxalate Urolithiasis in Idiopathic Uric Acid Stone Disease.

The role of diet in the pathogenesis of uric acid (UA) nephrolithiasis is incompletely understood. This study investigated the effect of dietary intervention on the risk of UA stone formation under standardized conditions. Twenty patients with idiopathic UA stone disease were included in the study. Dietary intake and 24 h urinary parameters were collected on the usual diet of the patients and a standardized balanced mixed diet. Although urinary UA excretion did not change, the relative supersaturation of UA decreased significantly by 47% under the balanced diet primarily due to the significant increase in urine volume and pH. Urinary pH was below 5.8 in 85% of patients under the usual diet, and in 60% of patients under the balanced diet. The supersaturation of calcium oxalate declined significantly under the balanced diet due to the significant decrease in urinary calcium and oxalate excretion and the increase in urine volume. Dietary intervention is a key component in the management of UA nephrolithiasis. Urinary calcium and oxalate excretion should also be monitored in patients with pure UA calculi to reduce the risk of mixed stone formation with calcium oxalate. Lower urinary pH in UA stone patients can only be partially explained by diet.

Changes in Urine Composition and Risk of Kidney Stone Disease Following Bariatric Surgery: A Systematic Review over Last 2 Decades

The association of kidney stone disease (KSD) and gastrointestinal (GI) surgery has been well established. With a rising obesity crisis, we wanted to see the correlation of urinary composition in patients undergoing bariatric surgery and their risk of KSD. The objective of this paper is to perform a systematic review and meta-analysis of literature to evaluate the changes in urinary composition and risk of KSD following bariatric surgery. A total of seven studies (2498 patients) underwent bariatric surgery with a mean age of 46.7years and a male:female ratio of 1:3. The most popular bariatric surgery was the Roux-en-Y procedure. Meta-analysis of the studies showed that significant decrease in urinary calcium, citrate, and urate, and increase in urinary oxalate. There was also a nonsignificant volume reduction in the post-operative cohort. The decrease in urinary citrate and increase in urinary oxalate are both predisposing factors of stone formation. There is strong evidence that bariatric surgery results in significant changes in urine composition in keeping with the increased risk of developing KSD. This identifies useful therapeutic targets in the prophylactic management of patients who have undergone bariatric surgery.

Bone and mineral metabolism in patients with primary aldosteronism: A systematic review and meta-analysis.

Patients with primary aldosteronism (PA) tend to exhibit a high prevalence of osteoporosis (OP) that may vary by whether PA is unilateral or bilateral, and responsive to PA treatment. To explore relationships between bone metabolism, PA subtypes, and treatment outcomes, we performed a systematic review and meta-analysis. The PubMed, Embase, and Cochrane databases were searched for clinical studies related to PA and bone metabolism markers. Articles that met the criteria were screened and included in the systematic review; the data were extracted after evaluating their quality. R software (ver. 2022-02-16, Intel Mac OS X 11.6.4) was used for the meta-analysis. A total of 28 articles were subjected to systematic review, of which 18 were included in the meta-analysis. We found that PA patients evidenced a lower serum calcium level (mean difference [MD] = -0.06 mmol/L, 95% confidence interval [CI]: -0.10 ~ -0.01), a higher urine calcium level (MD = 1.29 mmol/24h, 95% CI: 0.81 ~ 1.78), and a higher serum parathyroid hormone (PTH) level (MD = 2.16 pmol/L, 95% CI: 1.57 ~ 2.75) than did essential hypertension (EH) subjects. After medical treatment or adrenal surgery, PA patients exhibited a markedly increased serum calcium level (MD = -0.08 mmol/L, 95% CI: -0.11 ~ -0.05), a decreased urine calcium level (MD = 1.72 mmol/24h, 95% CI: 1.00 ~ 2.44), a decreased serum PTH level (MD = 2.67 pmol/L, 95% CI: 1.73 ~ 3.62), and an increased serum 25-hydroxyvitamin D (25-OHD) level (MD = -6.32 nmol/L, 95% CI: -11.94 ~ -0.70). The meta-analysis showed that the ser um PTH level of unilateral PA patients was significantly higher than that of bilateral PA patients (MD = 0.93 pmol/L, 95% CI: 0.36 ~ 1.49) and the serum 25-OHD lower than that of bilateral PA patients (MD = -4.68 nmol/L, 95% CI: -7.58 ~ 1.77). There were, however, no significant differences between PA and EH patients of 25-OHD, or BMD of femoral neck and lumbar spine. BMDs of the femoral neck or lumbar spine did not change significantly after treatment. The meta-analytical results were confirmed via sensitivity and subgroup analyses. Excess aldosterone was associated with decreased serum calcium, elevated urinary calcium, and elevated PTH levels; these effects may be enhanced by low serum 25-OHD levels. The risks of OP and fracture might be elevated in PA patients, especially unilateral PA patients, but could be reduced after medical treatment or adrenal surgery. In view, however, of the lack of BMD changes, such hypothesis needs to be tested in further studies.

Increased Water Viscosity Enhances Water Intake and Reduces Risk of Calcium Oxalate Stone Formation in Cats.

Simple SummaryIncreasing water intake and decreasing urine concentration are recommended for cats that form stony concretions in the bladder or urinary tract. The purpose of this study is to determine if water with increased viscosity results in increased water intake in cats by taking advantage of the unique anatomy of the cat’s tongue. Cats delicately dip their tongue into water, pull their tongues back up to their mouths, and capture the water that follows. Lapping occurs by fluid adhesion to the dorsal part of the tongue’s tip and by lifting a liquid column through the tongue’s upward motion before jaw closure. Cats have the ability to balance gravity and water surface tension to ingest the maximum amount of water per lap. This observation led us to question whether changing the properties of water in a way that allows cats to lift more water per lap is possible. Increasing the viscosity of water was accomplished with 1% methylcellulose, an ingredient that is palatable to cats. Cats consuming 1% methylcellulose water had increased water intake (25% and 21% higher at 28 and 56 days, respectively), and increased water intake reduces the risk for calcium oxalate stone formation. The benefit of giving cats viscous water is that they can increase water consumption without having to change their natural drinking behavior. The purpose of this study is to determine if water with increased viscosity results in increased water intake, thus lowering the risk of urolithiasis in cats. Twelve healthy adult cats were fed pre-trial standard dry maintenance food for 1 week and then randomized into two groups for the study phase. The cats continued to receive the same food but were provided either control (deionized) water or viscous (1% methylcellulose) water for two months and then switched to the other water type for two months in a cross-over study design with repeated measures. Complete blood counts, serum chemistry profiles, and urinalysis were performed at the initiation of the study and again at 1, 2, 3, and 4 months. Daily water consumption and energy intake for each cat were recorded. Body weights were assessed weekly. Cats consuming 1% methylcellulose water with increased viscosity had increased water intake (p < 0.001; 25% and 21% higher at 28 and 56 days, respectively). Increased consumption of water resulted in lower urine specific gravity (p = 0.04), serum creatinine (p = 0.02), and blood urea nitrogen (p = 0.002) concentrations (without changing serum albumin, glucose, and calcium concentrations or serum osmolality) and decreased urine calcium concentration (p = 0.01) compared with cats consuming control water. In addition, the increased water intake increased (p = 0.05) resistance to oxalate crystal formation.

Switching from conventional therapy to burosumab injection has the potential to prevent nephrocalcinosis in patients with X-linked hypophosphatemic rickets.

X-linked hypophosphatemic rickets (XLH) is a congenital fibroblast growth factor (FGF)23-related metabolic bone disease that is treated with active vitamin D and phosphate as conventional therapies. Complications of these therapies include nephrocalcinosis (NC) caused by excessive urine calcium and phosphate concentrations. Recently, an anti-FGF23 antibody, burosumab, was developed and reported to be effective in poorly-controlled or severe XLH patients. This study aimed to reveal the impact of switching treatments in relatively well-controlled XLH children with the Rickets Severity Scale less than 2.0. The effects of the two treatments in eight relatively well-controlled XLH children with a mean age of 10.4 ± 1.9 years were compared retrospectively for the same treatment duration (31 ± 11 months) before and after the baseline. Actual doses of alfacalcidol and phosphate as conventional therapy were 150.9 ± 43.9 ng/kg and 27.5 ± 6.3 mg/kg per day, respectively. Renal echography revealed spotty NC in 8/8 patients, but no aggravation of NC was detected by switching treatments. Switching treatments increased TmP/GFR (p=0.002) and %TRP (p<0.001), and improved the high urine calcium/creatinine ratio to the normal range (p<0.001) although both treatments controlled disease markers equally. Additionally, low intact parathyroid hormone during conventional therapy was increased within the normal range by switching treatments. Our results suggest that a high dose of alfacalcidol was needed to control the disease, but it caused hypercalciuria and NC. We concluded that switching treatments in relatively well-controlled XLH children improved renal phosphate reabsorption and decreased urine calcium extraction, and may have the potential to prevent NC.

Increased dietary long-chain polyunsaturated fatty acids alter serum fatty acid concentrations and lower risk of urine stone formation in cats.

The lifespan of cats with non-obstructive kidney stones is shortened compared with healthy cats indicating a need to reduce stone formation and minimize chronic kidney disease. The purpose of this study was to investigate the effects of increasing dietary polyunsaturated fatty acids (PUFA) on urine characteristics. Domestic-short-hair cats (n = 12; mean age 5.6 years) were randomized into two groups and fed one of two dry-cat foods in a cross-over study design. For one week before study initiation, all cats consumed control food that contained 0.07% arachidonic acid (AA), but no eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). Group 1 continued eating control food for 56 days. Group 2 was fed test food for 56 days, which was control food plus fish oil and high-AA oil. Test food contained 0.17% AA, 0.09% EPA and 0.18% DHA. After 56 days, cats were fed the opposite food for another 56 days. At baseline and after each feeding period, serum was analyzed for fatty acid concentrations, and urine for specific gravity, calcium concentration, relative-super-saturation for struvite crystals, and a calcium-oxalate-titrimetric test was performed. After consuming test food, cats had increased (all P<0.001) serum concentrations of EPA (173%), DHA (61%), and AA (35%); decreased urine specific gravity (P = 0.02); decreased urine calcium concentration (P = 0.06); decreased relative-super-saturation for struvite crystals (P = 0.03); and increased resistance to oxalate crystal formation (P = 0.06) compared with cats consuming control food. Oxalate crystal formation was correlated with serum calcium concentration (r = 0.41; P<0.01). These data show benefits for reducing urine stone formation in cats by increasing dietary PUFA.

Urine Calcium and Bone Mineral Density in Calcium Stone-Forming Patients Treated with Alendronate and Hydrochlorothiazide

Introduction: The objective was to evaluate the effect of hydrochlorothiazide and alendronate on urine calcium and bone mineral density in calcium stone-forming patients. Material and Methods: A prospective, non-randomized, non-observational comparative study was performed; this study included 111 patients with recurrent calcium stones, divided into 3 groups according to the treatment received. Group 1: 36 patients were treated with alendronate, 70 mg/week; Group 2: 34 patients were treated with alendronate, 70 mg/week + hydrochlorothiazide, 50 mg/day; Group 3: 41 patients were treated with hydrochlorothiazide, 50 mg/day. All patients received recommendations on diet and fluid intake. Other variables of bone mineral density were studied and analyzed, including bone remodeling markers and urinary calcium before and after 2 years of treatment. The statistical analysis was performed using the SPSS 17.0 program, with a statistical significance of p < 0.05. Results: After 2 years of treatment, a significant difference was observed in the β-crosslaps and a bone mineral density improvement in Group 1, along with a decrease in urinary calcium. In Group 3, a statistically significant difference was found in urinary calcium and fasting calcium/creatinine ratio, as well as an improvement in bone mineral density after 2 years of medical treatment. In Group 2 patients treated with the combination, there was an improvement in bone mineral density and a decrease in the β-crosslaps marker similar to patients in Group 1, and a decrease in urinary calcium similar to those in Group 3. Conclusion: Combined alendronate + hydrochlorothiazide treatment offers the best results along with the improvement in bone mineral density and decrease in urine calcium in patients with recurrent calcium stones.

Evaluation of urinary calcium-creatinine ratio as a diagnostic tool in the management of preeclampsia

Background: Preeclampsia has a complex pathophysiology in which several studies have reported derangement in calcium metabolism. The decrease in urinary calcium and calcium–creatinine ratio (CCR) could be considered as a risk factor for development of preeclampsia. This ratio is easily measurable, most effective even with spot urine sample. Objective: To study the levels of urinary CCR and to correlate with proteinuria in preeclamptic patients and to assess the role of CCR in urine as a diagnostic marker in preeclampsia. Materials and Methods: This cross-sectional study was carried out in 30 cases of pregnant women diagnosed with preeclampsia and 30 age-matched controls in MS Ramaiah Teaching Hospital, Bangalore over a period of 2 months. Random urine samples were collected from the cases and controls, and urinary calcium, creatinine, and protein were measured using their corresponding methods. The urinary CCR was studied and correlated with proteinuria. All the quantitative variables were described in terms of mean and standard deviation. The differences in the mean values between cases and controls were tested through Student’s t-test or oblique propriate nonparametric test of significance. To test for differences in the proportion between cases and controls, X2 test of significance was employed. Result: It was found that urinary calcium was significantly increased in cases compared with the controls, whereas there was no significant difference in CCR. The CCR had a sensitivity and specificity of 40% and 86.67%, respectively. Conclusion: Although significant numbers of pregnant women with gestational hypertension and preeclampsia did not have decreased ratio, the urinary calcium levels had decreased in preeclamptic patients.

Increasing serotonin concentrations alter calcium and energy metabolism in dairy cows.

A 4×4 Latin square design in which varied doses (0, 0.5, 1.0, and 1.5 mg/kg) of 5-hydroxy-l-tryptophan (5-HTP, a serotonin precursor) were intravenously infused into late-lactation, non-pregnant Holstein dairy cows was used to determine the effects of serotonin on calcium and energy metabolism. Infusion periods lasted 4 days, with a 5-day washout between periods. Cows were infused at a constant rate for 1 h each day. Blood was collected pre- and 5, 10, 30, 60, 90, and 120 min post-infusion, urine was collected pre- and post-infusion, and milk was collected daily. All of the 5-HTP doses increased systemic serotonin as compared to the 0 mg/kg dose, and the 1.0 and 1.5 mg/kg doses increased circulating glucose and non-esterified fatty acids (NEFA) and decreased beta-hydroxybutyrate (βHBA) concentrations. Treatment of cows with either 1.0 or 1.5 mg/kg 5-HTP doses decreased urine calcium elimination, and the 1.5 mg/kg dose increased milk calcium concentrations. No differences were detected in the heart rates, respiration rates, or body temperatures of the cows; however, manure scores and defecation frequency were affected. Indeed, cows that received 5-HTP defecated more, and the consistency of their manure was softer. Treatment of late-lactation dairy cows with 5-HTP improved energy metabolism, decreased loss of calcium into urine, and increased calcium secretion into milk. Further research should target the effects of increasing serotonin during the transition period to determine any benefits for post-parturient calcium and glucose metabolism.

MP41-13 VITAMIN D REPLACEMENT IN RECURRENT RENAL STONE FORMERS WITH HYPERCALCIURIA DOES NOT INCREASE URINE CALCIUM EXCRETION OR RENAL STONE GROWTH

You have accessJournal of UrologyStone Disease: Medical Therapy1 Apr 2015MP41-13 VITAMIN D REPLACEMENT IN RECURRENT RENAL STONE FORMERS WITH HYPERCALCIURIA DOES NOT INCREASE URINE CALCIUM EXCRETION OR RENAL STONE GROWTH Luke McGuinness, Robert Calvert, and Vinita Mishra Luke McGuinnessLuke McGuinness More articles by this author , Robert CalvertRobert Calvert More articles by this author , and Vinita MishraVinita Mishra More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1641AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Reduced vitamin D levels are found in up to 50% of recurrent renal stone patients. Reluctance to replace vitamin D in these patients exists due to a theoretical risk of increased intestinal calcium absorption and subsequent renal excretion. Recent evidence suggests that increased absorption might be offset by increased bone deposition with no effect on urine excretion. We aim to assess the effect of pharmacological correction of low vitamin D in hypercalciuric renal stone formers compared to those with adequate vitamin D in a metabolic stone clinic. METHODS Retrospective review of 30 recurrent renal stone formers with hypercalciuria was undertaken. Serum 25 hydroxyvitamin D (25OHD) and 24hr urine biochemistry were measured in all patients at baseline and during follow-up. Renal stone growth was assessed with abdominal x-rays. Hypercalciuria was treated with diet and diuresis advice and pharmacotherapy (thiazide/ potassium citrate/allopurinol). Those with low 25OHD levels (¡Ü50nmol/L) were prescribed vitamin D replacement (VDR). Outcomes of 24hr urine biochemistry and new stone growth were compared between those on VDR (n= 17) and those with adequate 25OHD levels (n= 13). RESULTS Nine patients (30%) had vitamin D deficiency (¡Ü30nmol/L), 8 (27%) had insufficiency (>30 and ¡Ü50nmol/L) and 13 (43%) had adequate levels (>50nmol/L). 17 patients were prescribed vitamin D replacement (mean duration 14 months). 13 patients with adequate levels had mean follow-up of 22 months. No significant difference in baseline 24hr urine biochemistry was seen. Patients on VDR had an increase in 25OHD (33.6 to 74.7nmol/L, p<0.001) whilst 24hr urine calcium levels reduced non-significantly (9.33 to 8.78mmol/24hr, p>0.1). Patients with adequate 25OHD level (64.7nmol/L) had a significant decrease in urinary calcium (10.6 to 8.28mmol/24hr, p=0.003). No other significant changes were seen on urine biochemistry. The mean decrease in urine calcium in those on VDR (0.43mmol/24hr) compared to those with adequate 25OHD (2.28mmol/24hr) was not significant (p=0.15). 10 patients had new stone growth; 6 patients (35%) on VDR and 4 patients (31%) with adequate 25OHD (p>0.5). CONCLUSIONS Low vitamin D levels are present in more than half of hypercalciuric stone formers. Vitamin D replacement does not adversely affect urine calcium levels in patients with low vitamin D status or increase renal stone risk compared to those with adequate levels. Furthermore a beneficial effect may exist due to increased bone mineralisation but further evaluation is required. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e505 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luke McGuinness More articles by this author Robert Calvert More articles by this author Vinita Mishra More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Combination therapy of Chinese herbal medicine Fructus Ligustri Lucidi with high calcium diet on calcium imbalance induced by ovariectomy in mice

Context: Our previous biological study demonstrated that Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait. (Oleaceae), could be used to maintain calcium balance and prevent age-related osteoporosis since it effectively decreased calcium loss and increased calcium retention in rats.Objective: This study investigates the combination effect of the Chinese herbal medicine FLL and a high calcium diet on calcium imbalance induced by ovariectomy in mice.Materials and methods: The ovariectomized (OVX) mice were orally treated with vehicle, FLL extract (700 mg/kg), milk powder (5 g/mice) fortified with calcium (1.0% Ca) and the combination of FLL with milk powder. After 6 weeks of treatment, urine, serum, and tibia were preserved for biochemical analysis and kidneys were taken for gene expression analysis.Results: The combination treatment of FLL and a high calcium diet significantly increased bone calcium content (6.80 ± 0.34 mg) by 22% (p < 0.05) and decreased urine calcium excretion (0.099 ± 0.009 mg/mg) by 62% (p < 0.01) as compared with those of the OVX group (bone Ca, 5.57 ± 0.31 mg; urine Ca/Cr, 0.261 ± 0.017 mg/mg). The mRNA expression of renal calcium-binding protein-9k (CaBP-9k) and calcium-sensing receptor (CaSR) in combination treatment group was significantly up-regulated and down-regulated, respectively, as compared with those of the OVX group.Conclusion: The beneficial effects of this combination therapy on calcium balance of OVX mice were, at least partially, attributed to its regulation on mRNA expression of CaBP-9k and CaSR in kidney.

Relationship Between Glomerular Filtration Rate and 24-Hour Urine Composition in Patients With Nephrolithiasis

To examine the relationship between GFR and 24-hour urine composition in patients with nephrolithiasis to understand how renal function may affect stone risk. Alterations in glomerular filtration rate (GFR) are associated with a number of physiological changes. A retrospective, institutional review board-approved review of patients from 2 metabolic stone clinics was performed. One-way analysis of variance and multivariate linear regression models were used to evaluate the relationship between GFR quintile and 24-hour urine composition. A total of 403 patients (241 male, 162 female) with a mean age of 52.6 ± 14.2 years were included in the study. On univariate analysis, decreasing GFR by quintile was associated with significant reductions in urine calcium, citrate, supersaturation of calcium oxalate, and supersaturation of calcium phosphate (P < .05 for each). In multivariate linear regression models, decreasing GFR by quintile was associated with significant decreases in urine calcium (β = -11.2, 95% CI = -18.3 to 4.01), urine citrate (β = -32.4, 95% CI = -54.1 to 10.8), oxalate (β = -1.83, 95% CI = -2.85 to 0.81), supersaturation of calcium oxalate (β = -0.58, 95% CI = 0.84 to 0.33) and supersaturation of calcium phosphate (β = -0.09, 95% CI = 0.17 to 0.02), as well as an increase in urine magnesium (β = 3.40, 95% CI = 0.7 to 6.1). Reduction in GFR is associated with decreased urine calcium, oxalate, and citrate, and increased urine magnesium. These findings have implications for treatment of patients with stone disease and impaired renal function.

Omega-3 Fatty Acids Eicosapentaenoic Acid and Docosahexaenoic Acid in the Management of Hypercalciuric Stone Formers

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.

Phosphate decreases urine calcium and increases calcium balance: A meta-analysis of the osteoporosis acid-ash diet hypothesis

BackgroundThe acid-ash hypothesis posits that increased excretion of "acidic" ions derived from the diet, such as phosphate, contributes to net acidic ion excretion, urine calcium excretion, demineralization of bone, and osteoporosis. The public is advised by various media to follow an alkaline diet to lower their acidic ion intakes. The objectives of this meta-analysis were to quantify the contribution of phosphate to bone loss in healthy adult subjects; specifically, a) to assess the effect of supplemental dietary phosphate on urine calcium, calcium balance, and markers of bone metabolism; and to assess whether these affects are altered by the b) level of calcium intake, c) the degree of protonation of the phosphate.MethodsLiterature was identified through computerized searches regarding phosphate with surrogate and/or direct markers of bone health, and was assessed for methodological quality. Multiple linear regression analyses, weighted for sample size, were used to combine the study results. Tests of interaction included stratification by calcium intake and degree of protonation of the phosphate supplement.ResultsTwelve studies including 30 intervention arms manipulated 269 subjects' phosphate intakes. Three studies reported net acid excretion. All of the meta-analyses demonstrated significant decreases in urine calcium excretion in response to phosphate supplements whether the calcium intake was high or low, regardless of the degree of protonation of the phosphate supplement. None of the meta-analyses revealed lower calcium balance in response to increased phosphate intakes, whether the calcium intake was high or low, or the composition of the phosphate supplement.ConclusionAll of the findings from this meta-analysis were contrary to the acid ash hypothesis. Higher phosphate intakes were associated with decreased urine calcium and increased calcium retention. This meta-analysis did not find evidence that phosphate intake contributes to demineralization of bone or to bone calcium excretion in the urine. Dietary advice that dairy products, meats, and grains are detrimental to bone health due to "acidic" phosphate content needs reassessment. There is no evidence that higher phosphate intakes are detrimental to bone health.

Somatostatin and primary hyperparathyroidism.

No satisfactory medical therapy exists for the treatment of primary hyperparathyroidism. Calcitonin and diphosphonates do not give good long-term control. This work examines the efficacy of the somatostatin analogue octreotide in the management of hyperparathyroidism. Twenty-one patients were admitted before parathyroid surgery and were treated for 6 days with subcutaneous octreotide 100 micrograms twice daily. Fasting blood samples were taken for determination of serum levels of calcium and parathyroid hormone, and 24-h urinary calcium excretion was measured before and after treatment. A significant decrease in urinary calcium was demonstrated, but the reduction in serum calcium level was not statistically significant and there was no change in serum parathyroid hormone concentration. Octreotide may provide therapy for patients with hyperparathyroidism and for those who have undergone unsuccessful neck exploration or who are unfit for operation. It may ameliorate hypercalciuria and reduce stone formation. The octapeptide may also have a potential role as a diagnostic test in primary hyperparathyroidism by determining the symptomatic effect of reducing raised levels of serum and urinary calcium.

Pharmacology Review

After completing this article, readers should be able to: 1. Review the actions of the diuretic agents commonly used in neonates. 2. Delineate the adverse effects of diuretic therapy. 3. Determine the roles of diuretics in therapy. Diuretics represent one of the most common classes of drugs administered to sick neonates and infants. Unwanted fluid retention arising from myriad neonatal disorders can and does complicate the optimal care of sick infants. To appreciate the many factors that influence a patient’s response to diuretic therapy and clinical and laboratory monitoring, we direct readers to the article “The Ontogeny of Human Kidney Development: Influence on Neonatal Diuretic Therapy” in this issue. All the clinically relevant diuretics, with the exception of aldosterone receptor antagonists (eg, spironolactone), must achieve sufficient free drug concentrations within the renal tubular lumen to reach their sites of action. Thus, diuretic effectiveness ultimately is guided by the functional capacity of the kidney, which clearly is influenced by infants’ gestational and postnatal ages. This article addresses the most common diuretics used in the neonate and young infant, focusing on the pharmacokinetic and pharmacodynamic characteristics of each drug relative to the infant’s postconceptional age and other factors that influence the infant’s overall response to therapy. ### “Loop” or “High Ceiling” Diuretics All diuretics, with the exception of spironolactone, must reach the renal tubular lumen to exert their pharmacologic effect. A lower renal blood flow (RBF) in preterm infants reduces the amount of drug delivered to the kidney, potentially limiting diuretic effectiveness. Highly protein-bound, loop diuretics (Table 1) are filtered minimally at the glomerulus. Instead, these agents are carried to the proximal tubule where they are actively secreted into the lumen via the organic acid transport pump. Luminal flow then carries the loop diuretics to their sites of action. | Loop Diuretics | || | •Bumetanide | | •Furosemide | | •Torsemide | | Thiazide Diuretics | | •Chlorothiazide | | •Chlorthalidone | | •Hydrochlorothiazide | | •Indapamide | | •Metolazone | | Aldosterone Antagonists | | •Eplerenone | | •Spironolactone | Table 1. Commonly Used Diuretic Drugs in Preterm and Newborn Infants Loop diuretics bind …

THE EFFICACY OF DIETARY INTERVENTION ON URINARY RISK FACTORS FOR STONE FORMATION IN RECURRENT CALCIUM OXALATE STONE PATIENTS

Nutrition is suggested to be the major environmental risk factor in idiopathic calcium oxalate stone disease. The study was designed to evaluate the effect of dietary intervention on urinary risk factors for recurrence in calcium oxalate stone formers. A total of 76 men and 31 women with idiopathic calcium oxalate stone disease collected 24-hour urine on their habitual, self-selected diets and after 7 days on a balanced standardized diet according to the recommendations for calcium oxalate stone formers. On the usual diet, a urine volume of less than 2.0 l per 24 hours was present in 57.9%, hypercalciuria in 25.2%, hypomagnesuria in 18.7%, hyperoxaluria in 14.0%, hyperuricosuria in 41.3% and hypocitraturia in 57.0% of patients. The frequency of metabolic abnormalities and the risk of calcium oxalate stone formation decreased significantly on the ingestion of the balanced diet, due to the significant increase in urinary volume, pH and citrate excretion and the significant decrease in urinary calcium and uric acid excretion. No change occurred in urinary oxalate and magnesium excretion. The evaluation of urinary risk profiles of the patients on their usual dietary habits revealed a high risk for calcium oxalate stone formation. A low fluid intake and an increased intake of protein and alcohol were identified as the most important dietary risk factors. The shift to a nutritionally balanced diet according to the recommendations for calcium oxalate stone formers significantly reduced the stone forming potential.

Additional beneficial effect of tamarind ingestion over defluoridated water supply to adolescent boys in a fluorotic area

Objective We evaluated the effect of tamarind ( Tamarindus indicus) on ingestion and whether it provides additional beneficial effects on mobilization of fluoride from the bone after children are provided defluoridated water. Methods A randomized, diet control study was conducted in 30 subjects from a fluoride endemic area after significantly decreasing urinary fluoride excretion by supplying defluoridated water for 2 wk. Subjects were then assigned to one of two groups, with 15 in each group. One group was supplemented with tamarind (experimental group) for 3 wk and the other (control) group was given only defluoridated water for the same period. Results The mean changes in urinary components after tamarind ingestion (volume, pH, fluoride calcium, copper, and magnesium) in the control and experimental groups were compared. There was a significant increase ( P < 0.01) in fluoride excretion and urinary pH and a significant decrease in urinary calcium ( P < 0.01) and copper ( P < 0.05) excretion in the experimental group as compared with the control group. There was no change in urinary volume between groups. Conclusions Tamarind intake appears to have an additional beneficial effect on the mobilization of deposited fluoride from bone, by enhancing urinary excretion of fluoride.

Increased dietary oxalate does not increase urinary calcium oxalate saturation in hypercalciuric rats

Human calcium oxalate (CaOx) nephrolithiasis may occur if urine is supersaturated with respect to the solid-phase CaOx. In these patients, dietary oxalate is often restricted to reduce its absorption and subsequent excretion in an effort to lower supersaturation and to decrease stone formation. However, dietary oxalate also binds intestinal calcium which lowers calcium absorption and excretion. The effect of increasing dietary oxalate on urinary CaOx supersaturation is difficult to predict. To determine the effect of dietary oxalate intake on urinary supersaturation with respect to CaOx and brushite (CaHPO4), we fed 36th and 37th generation genetic hypercalciuric rats a normal Ca diet (1.2% Ca) alone or with sodium oxalate added at 0.5%, 1.0%, or 2.0% for a total of 18 weeks. We measured urinary ion excretion and calculated supersaturation with respect to the CaOx and CaHPO4 solid phases and determined the type of stones formed. Increasing dietary oxalate from 0% to 2.0% significantly increased urinary oxalate and decreased urinary calcium excretion, the latter presumably due to increased dietary oxalate-binding intestinal calcium. Increasing dietary oxalate from 0% to 2.0% decreased CaOx supersaturation due to the decrease in urinary calcium offsetting the increase in urinary oxalate and the decreased CaHPO4 supersaturation. Each rat in each group formed stones. Scanning electron microscopy revealed discrete stones and not nephrocalcinosis. X-ray and electron diffraction and x-ray microanalysis revealed that the stones were composed of calcium and phosphate; there were no CaOx stones. Thus, increasing dietary oxalate led to a decrease in CaOx and CaHPO4 supersaturation and did not alter the universal stone formation found in these rats, nor the type of stones formed. These results suggest the necessity for human studies aimed at determining the role, if any, of limiting oxalate intake to prevent recurrence of CaOx nephrolithiasis.

Alendronate decreases urine calcium and supersaturation in genetic hypercalciuric rats

The mechanism of excess urine calcium excretion in human idiopathic hypercalciuria (IH) has not been determined but may be secondary to enhanced intestinal calcium absorption, decreased renal calcium reabsorption, and/or enhanced bone demineralization. We have developed a strain of genetic hypercalciuric stone-forming (GHS) rats as an animal model of human IH. When these GHS rats are placed on a low-calcium diet (LCD), urinary calcium (UCa) excretion exceeds dietary calcium intake, suggesting that bone may contribute to the excess UCa excretion. We used the GHS rats to test the hypothesis that bone contributes to the persistent IH when they are fed an LCD by determining if alendronate (Aln), which inhibits bone resorption, would decrease UCa excretion. GHS rats (N = 16) and the parent strain (Ctl, N = 16) were fed 13 g/day of a normal (1.2%) calcium diet (NCD) for seven days and were then switched to a LCD (0. 02%) for seven days. Ctl and GHS rats in each group were then continued on LCD for an additional seven days, with or without injection of Aln (50 micrograms/kg/24 hrs). UCa excretion was measured daily during the last five days of each seven-day period. To determine the effects of Aln on urine supersaturation, the experiment was repeated. All relevant ions were measured, and supersaturation with respect to calcium oxalate and calcium hydrogen phosphate was determined at the end of each period. UCa was greater in GHS than in Ctl on NCD (7.4 +/- 0.5 mg/24 hrs vs. 1.2 +/- 0.1, GHS vs. Ctl, P < 0.01) and on LCD (3.9 +/- 0.2 mg/24 hrs vs. 0. 7 +/- 0.1, GHS vs. Ctl, P < 0.01). LCD provides 2.6 mg of calcium/24 hrs, indicating that GHS rats are excreting more calcium than they are consuming. On LCD, Aln caused a significant decrease in UCa in GHS rats and brought GHS UCa well below calcium intake. Aln caused a marked decrease in calcium oxalate and calcium hydrogen phosphate supersaturation. Thus, on a LCD, there is a significant contribution of bone calcium to the increased UCa in this model of IH. Aln is effective in decreasing both UCa and supersaturation. The Aln-induced decrease in urine supersaturation should be beneficial in preventing stone formation in humans, if these results, observed in a short-term study using the hypercalciuric stone-forming rat can be confirmed in longer term human studies.