Alkali Citrate Content of Common Over-the-Counter and Medical Food Supplements.

Objective: Potassium citrate effectively decreases kidney stone recurrence, but it is costly and associated with side effects. While several over-the-counter supplements and medical foods purport to provide sufficient citrate to prevent recurrent stones, corroborating data on their actual citrate content is limited. Materials and Methods: Nine common nonprescription products were purchased online. Reported citrate content was obtained from packaging, promotional materials, or ingredient labels. Using a single serving of each product, actual citrate, sodium, potassium, calcium, magnesium, and oxalate content was measured using spectrophotometry and chromatography. Total alkali citrate, cost, and amounts of each component per 10 mEq of alkali citrate were also calculated. Results: Nearly all products contained more citrate than advertised, except for Litholyte® powder, Litholyte® Coffee, and Horbäach® potassium citrate. Per serving, Moonstone® powder, LithoBalance™, and KSP tabs™ contained the most citrate (means of 63.9, 33.5, and 26.9 mEq, respectively). Moonstone and LithoBalance had the greatest discrepancy between total citrate and alkali citrate (15.7 and 11.8 mEq per serving, respectively). NOW® potassium citrate was least expensive ($0.04/10 mEq alkali citrate). KSP tabs delivered the most daily sodium (mean 158 mg/10 mEq alkali citrate, Litholyte Coffee provided the most potassium (mean of 13 mEq/10 mEq alkali citrate), and Kidney COP® provided the most calcium (mean 147 mg/10 mEq alkali citrate). Conclusion: Some common over-the-counter products contain sufficient alkali to potentially promote a citraturic response; Moonstone provides the most alkali citrate, but at a higher cost than other products. Sodium, potassium, and calcium from these products must also be considered in daily consumption.

Association of serum magnesium with all-cause mortality in patients with and without chronic kidney disease in the Dallas Heart Study.

Background: Low serum magnesium (SMg) has been linked to increased mortality and cardiovascular disease (CVD) in the general population. We examined whether this association is similar in participants with versus without prevalent chronic kidney disease (CKD) in the multiethnic Dallas Heart Study (DHS) cohort. Methods: SMg was analyzed as a continuous variable and divided into tertiles. Study outcomes were all-cause death, cardiovascular (CV) death or event, and CVD surrogate markers, evaluated using multivariable Cox regression models adjusted for demographics, comorbidity, anthropometric and biochemical parameters including albumin, phosphorus and parathyroid hormone, and diuretic use. Median follow-up was 12.3 years (11.9-12.8, 25th percentile-75th percentile). Results: Among 3551 participants, 306 (8.6%) had prevalent CKD. Mean SMg was 2.08 ± 0.19 mg/dL (0.85 ± 0.08 mM, mean ± SD) in the CKD and 2.07 ± 0.18 mg/dL (0.85 ± 0.07 mM) in the non-CKD subgroups. During the follow-up period, 329 all-cause deaths and 306 CV deaths or events occurred. In a fully adjusted model, every 0.2 mg/dL decrease in SMg was associated with ∼20-40% increased hazard for all-cause death in both CKD and non-CKD subgroups. In CKD participants, the lowest SMg tertile was also independently associated with all-cause death (adjusted hazard ratio 2.31; 95% confidence interval 1.23-4.36 versus 1.15; 0.55-2.41; for low versus high tertile, respectively). Conclusions: Low SMg levels (1.4-1.9 mg/dL; 0.58-0.78 mM) were independently associated with all-cause death in patients with prevalent CKD in the DHS cohort. Randomized clinical trials are important to determine whether Mg supplementation affects survival in CKD patients.

Longitudinal changes in serum 25-hydroxyvitamin D in the Dallas Heart Study.

CONTEXT: While the prevalence of vitamin D deficiency is well described in various populations, limited data are available regarding longitudinal variation in serum 25-hydroxyvitamin D concentrations. OBJECTIVES: To evaluate the temporal trends in serum 25(OH)D, prevalence of vitamin D deficiency and factors influencing these trends. PARTICIPANTS, DESIGN AND SETTING: Adults enrolled in the Dallas Heart Study, a longitudinal, probability-based, multiethnic, population study in Dallas, Texas, USA. MAIN OUTCOME MEASURES: Prevalence of vitamin D deficiency and predictors of change in serum 25(OH)D. RESULTS: A total of 2045 participants had serum 25(OH)D measured on two occasions (2000-2002 and 2007-2009) at a median interval of 7 years. Serum 25(OH)D decreased (42.7-39.4 nmol/L, P<.001) and the prevalence of vitamin D deficiency [25(OH)D <50 nmol/L] increased significantly (60.6%-66.4%, P<.0001) despite vitamin D supplementation increasing over the interval (7.2%-23.0%; P<.0001). In a multivariable model adjusting for sex, race, BMI, age, season of blood draw, smoking and exercise, a greater decline in serum 25(OH)D was noted in men compared with women (-8.0 vs -3.5 nmol/L, P<.0001), in participants of Hispanic ethnicity vs White and Black ethnicity (P<.0001), in nonobese vs obese participants (-7.2 vs -4.0 nmol/L, P=.005) and in nonusers vs users of vitamin D supplements (-5.7 vs -1.7 nmol/L, P=.032). CONCLUSIONS: Despite increased vitamin D supplementation, serum 25(OH)D decreased in an ethnically diverse cohort of Dallas County residents between 2000-2002 and 2007-2009. Features most predictive of a decline in serum 25(OH)D include male sex, Hispanic ethnicity and weight gain.

Effect of urine pH and magnesium on calcium oxalate saturation.

Hypomagnesiuria is a common biochemical finding in patients with calcium oxalate (CaOx) nephrolithiasis. Clinical trials using Mg supplements as therapy against CaOx stones have shown mixed results. We tested the effect of Mg administration in healthy subjects under conditions of controlled urine pH (UpH) on urinary Ca excretion rate (UCaV) and CaOx saturation. This is a 4-phase, double blind, placebo-controlled, metabolic crossover study performed in healthy volunteers. Mg lactate (MgLact2) was used as Mg supplement. High UpH and low UpH were achieved by administration of potassium citrate (K3Citrate) and ammonium chloride (NH4Cl), respectively, with potassium balance maintained by KCl. Eight participants completed 4 phases of study. The interventions successfully modulated 24-h UpH (7.0 ± 0.4 vs. 5.7 ± 0.6 in high vs low pH phases; P<0.001). Administration of MgLact2 increased UMgV [175.8 ± 40.2 vs 93.4 ± 39.7 mg/day (7.2 ± 1.7 vs 3.8 ± 1.6 mmol/day), high vs low Mg phase; P<0.001], and increased pH both at low (5.6 ± 0.5 to 5.8 ± 0.7; P = 0.02) and high UpH (6.9 ± 0.4 to 7.0 ± 0.3; P = 0.01). At a given urine pH, Mg supplementation marginally increased UCaV, but did not alter UOxV or CaOx saturation. Provision of an alkali load significantly lowered UCaV and saturation of CaOx at any level of UMgV. Compared to changes in UMgV, changes in UpH play a more significant role in determining urine CaOx saturation in healthy subjects. Mg supplements are likely to reduce CaOx saturation if they also raise urine pH.

Effects of sex and postmenopausal estrogen use on serum phosphorus levels: a cross-sectional study of the National Health and Nutrition Examination Survey (NHANES) 2003-2006.

BACKGROUND: Elevation of serum phosphorus concentrations has been associated with cardiovascular events in older women and men. Whether age, sex, or estrogen therapy is associated with different phosphorus levels is unknown. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 7,005 participants in the National Health and Nutrition Examination Survey (NHANES) 2003-2006. PREDICTORS: Demographic data; body measurement indexes; dietary intake by 24-hour dietary recall and food-frequency questionnaire; data for reproductive health, prescription medication, cardiovascular disease, osteoporosis, and diabetes mellitus obtained by questionnaire; and blood chemistry indexes. OUTCOMES & MEASUREMENTS: Serum phosphorus concentrations. RESULTS: In both males and premenopausal females, serum phosphorus levels decline progressively with age. In males, the decline continues over the entire age range of 21-85 years. In contrast, in females, serum phosphorus levels increase between ages 46-60 years (sex×age interaction; P<0.001). The increase in serum phosphorus levels in older women is independent of changes in serum parathyroid hormone levels, daily dietary phosphorus intake, and estimated glomerular filtration rate. In analysis of covariance, we show that postmenopausal women receiving estrogen therapy have significantly lower serum phosphorus levels than non-estrogen users after adjusting for age, race, body mass index, daily dietary phosphorus intake, and serum albumin, serum parathyroid hormone, and 25-hydroxyvitamin D levels (3.83 vs 3.98mg/dL; P<0.001). LIMITATIONS: The study was cross-sectional in design and estrogen therapy was not randomly assigned or concealed. Important phosphorus regulatory factors such as serum fibroblast growth factor 23 and klotho were not available in the study. CONCLUSIONS: Estrogen status may account for the difference in serum phosphorus levels in postmenopausal women.

Comparison of insulin action on glucose versus potassium uptake in humans.

BACKGROUND AND OBJECTIVES: Insulin has several physiologic actions that include stimulation of cellular glucose and potassium uptake. The ability of insulin to induce glucose uptake by cells is impaired in type 2 diabetes mellitus, but whether potassium uptake is similarly impaired is not known. This study examines whether the cellular uptake of these molecules is regulated in concert or independently. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Thirty-two nondiabetic and 13 type 2 diabetic subjects with normal GFR were given a similar, constant metabolic diet for 8 days. On day 9, they were subjected to a hyperinsulinemic euglycemic clamp for 2 hours. Serum and urinary chemistry were obtained before and during the clamp. Glucose disposal rate was calculated from glucose infusion rate during hyperinsulinemic euglycemia. Intracellular potassium and phosphate uptake were calculated by the reduction of extracellular potassium or phosphate content corrected for urinary excretion. RESULTS: Although glucose disposal rate tended to be lower in type 2 diabetics, cellular potassium uptake was similar between diabetics and nondiabetics. Additionally, although glucose disposal rate was lower with increasing body mass index (R² = 0.362), cellular potassium (R² = 0.052), and phosphate (R² = 0.002), uptake rates did not correlate with body mass index. There was also no correlation between glucose disposal rate and potassium (R² = 0.016) or phosphate uptake (R² = 0.053). Conclusions Insulin-stimulated intracellular uptake of glucose and potassium are independent of each other. In type 2 diabetes, potassium uptake is preserved despite impaired glucose disposal.

Significance of elevated parathyroid hormone after parathyroidectomy for primary hyperparathyroidism.

OBJECTIVE: To provide a clinical update on persistent parathyroid hormone (PTH) elevation after surgical resection for primary hyperparathyroidism (PHPT) and to suggest a schedule for follow-up monitoring and strategies for future study. METHODS: We reviewed the literature targeting studies with detailed analysis of biochemical parameters before and after parathyroidectomy for PHPT. We focused on potential etiologies and currently available outcome data. RESULTS: PTH elevation with eucalcemia after parathyroidectomy for PHPT occurs in 12% to 43% of patients. Underlying etiology is probably multifactorial, and possible causes include bone hunger, vitamin D deficiency, inadequate calcium intake or absorption, reduced peripheral sensitivity to PTH, underlying chronic kidney disease, and/or a renal leak of calcium. No consensus exists on how to follow-up and treat these patients. CONCLUSIONS: Although most patients with PTH elevation after parathyroidectomy will have normalization of PTH levels with time and/or calcium and vitamin D supplementation, this finding may be an early indicator of autonomous parathyroid secretion in a small number of patients. Patients with persistent PTH elevation should be monitored over time for recurrence of PHPT and other possible complications. A standardized follow-up protocol is needed to better study and elucidate the clinical significance of elevated PTH after parathyroidectomy.

Metabolic basis for low urine pH in type 2 diabetes.

BACKGROUND AND OBJECTIVES: Type 2 diabetes is associated with excessively low urine pH, which increases the risk for uric acid nephrolithiasis. This study was conducted to assess the metabolic basis responsible for the excessive urinary acidity of individuals with type 2 diabetes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Nine non-stone-forming patients who had type 2 diabetes and low urine pH and 16 age- and body mass index-matched non-stone-forming volunteers without type 2 diabetes were maintained on a constant metabolic diet for 7 days, and 24-hour urine was collected on the last 2 days of the diet. RESULTS: Urine dietary markers (potassium, sulfate, phosphorus, and urea nitrogen) were not different between the two groups. Patients with type 2 diabetes exhibited a significantly lower 24-hour urine pH (5.45+/-0.27 versus 5.90+/-0.42; P<0.01) and higher net acid excretion (NAE; 57+/-12 versus 38+/-18 mEq/d; P<0.01) compared with control subjects. The proportion of NAE excreted as ammonium (NH4+/NAE) was significantly lower in patients with type 2 diabetes than in control subjects (0.70+/-0.12 versus 0.94+/-0.36; P<0.01); however, the greater NAE in patients with type 2 diabetes was not accounted for by the differences in unmeasured urinary anions. CONCLUSIONS: The overly acidic urine in patients with type 2 diabetes persists after controlling for dietary factors, body size, and age. The lower pH is due to a combination of greater NAE and lower use of ammonia buffers in patients with diabetes, which predisposes them to uric acid urolithiasis.

Effects of potassium alkali and calcium supplementation on bone turnover in postmenopausal women.

Potassium citrate may improve calcium balance by conferring an alkali load. Calcium supplementation slows postmenopausal bone loss by inhibiting PTH secretion. This study explores whether combined treatment with potassium citrate and calcium citrate is more effective than either agent alone in inhibiting bone loss. In a crossover study involving 18 postmenopausal women, the following treatments were compared: potassium citrate (4.3 g or 40 mmol/d), calcium citrate (800 mg or 20 mmol/d), combined treatment, and placebo. During the last 2 d of each 2-wk phase, serum and 24-h urine were collected for assessment of calcium metabolism, alkali load, and bone turnover markers. Compared with placebo, potassium citrate provided an alkali load and significantly decreased urinary calcium without changing serum PTH (sPTH) or bone turnover markers. Calcium citrate significantly increased absorbed calcium, marginally decreased sPTH, and significantly reduced bone resorption markers. Combined treatment retained key features of potassium citrate and calcium citrate. However, more alkali was delivered than with potassium citrate alone, and absorbed calcium did not differ from calcium citrate alone. Compared with placebo, combined treatment increased urinary calcium, marginally reduced sPTH, provided a clear alkali load, and reduced the bone resorption markers serum type I collagen C-telopeptide and urinary N-telopeptide by 20.4% (P < 0.0001) and 18.2% (P = 0.005), respectively. A significant trend was noted for the decrease in bone resorption markers as treatment changed from placebo to potassium citrate to calcium citrate to combined treatment. In postmenopausal women, combined treatment with potassium citrate and calcium citrate inhibits bone resorption by providing an alkali load and increasing absorbed calcium.

Novel insights into the pathogenesis of uric acid nephrolithiasis.

PURPOSE OF REVIEW: The factors involved in the pathogenesis of uric acid nephrolithiasis are well known. A low urinary pH is the most significant element in the generation of stones, with hyperuricosuria being a less common finding. The underlying mechanism(s) responsible for these disturbances remain poorly characterized. This review summarizes previous knowledge and highlights some recent developments in the pathophysiology of low urine pH and hyperuricosuria. RECENT FINDINGS: Epidemiological and metabolic studies have indicated an association between uric acid nephrolithiasis and insulin resistance. Some potential mechanisms include impaired ammoniagenesis caused by resistance to insulin action in the renal proximal tubule, or substrate competition by free fatty acids. The evaluation of a large Sicilian kindred recently revealed a putative genetic locus linked to uric acid stone disease. The identification of novel complementary DNA has provided an interesting insight into the renal handling of uric acid, including one genetic cause of renal uric acid wasting. SUMMARY: The recognition of metabolic, molecular, and genetic factors that influence urinary pH, and uric acid metabolism and excretion, will provide novel insights into the pathogenesis of uric acid stones, and open the way for new therapeutic strategies.