Eric N. Taylor

Dietary Factors and the Risk of Incident Kidney Stones in Men: New Insights after 14 Years of Follow-up

Diet plays an important role in the pathogenesis of kidney stones. Because the metabolism of many dietary factors, such as calcium, may change with age, the relation between diet and kidney stones may be different in older adults. Uncertainty also remains about the association between many dietary factors, such as vitamin C, magnesium, and animal protein, and the risk of kidney stone formation. To examine the association between dietary factors and the risk of incident, symptomatic kidney stones in men and to determine whether these associations vary with age, a prospective cohort study was conducted of 45,619 men without a history of nephrolithiasis. Self-administered food frequency questionnaires were used to assess diet every 4 yr. A total of 1473 incident symptomatic kidney stones were documented during 477,700 person-years of follow-up. For men aged <60 yr, the multivariate relative risk (RR) for stone formation in the highest quintile of dietary calcium as compared with the lowest quintile was 0.69 (95% confidence interval [CI], 0.56 to 0.87; P = 0.01 for trend). By contrast, there was no association between dietary calcium and stone formation in men aged 60 yr or older. The multivariate RR for men who consumed 1000 mg or greater of vitamin C per day compared with those who consumed less than the recommended dietary allowance of 90 mg/d was 1.41 (95% CI, 1.11 to 1.80; P = 0.01 for trend). Other dietary factors showed the following multivariate RR among men in the highest quintile of intake compared with those in the lowest: magnesium, 0.71 (95% CI, 0.56 to 0.89; P = 0.01 for trend); potassium, 0.54 (95% CI, 0.42 to 0.68; P < 0.001 for trend); and fluid, 0.71 (95% CI, 0.59 to 0.85; P < 0.001 for trend). Animal protein was associated with risk only in men with a body mass index <25 kg/m(2) (RR, 1.38; 95% CI, 1.05 to 1.81; P = 0.03 for trend). Sodium, phosphorus, sucrose, phytate, vitamin B(6), vitamin D, and supplemental calcium were not independently associated with risk. In conclusion, the association between calcium intake and kidney stone formation varies with age. Magnesium intake decreases and total vitamin C intake seems to increase the risk of symptomatic nephrolithiasis. Because age and body size affect the relation between diet and kidney stones, dietary recommendations for stone prevention should be tailored to the individual patient.

Plasma 25-Hydroxyvitamin D Levels and Risk of Incident Hypertension Among Young Women

Numerous cross-sectional studies demonstrate an inverse association between plasma 25-hydroxyvitamin D [25(OH)D] and blood pressure or hypertension. Prospective data, however, are limited. Among 1484 women aged 32 to 52 years who did not have hypertension at baseline, we prospectively analyzed the association between plasma levels of 25(OH)D and the odds of incident hypertension using a nested case-control study design. We matched cases and controls on age, race, and month of blood collection and further adjusted for body mass index, physical activity, family history of hypertension, oral contraceptive use, and plasma levels of parathyroid hormone, calcium, phosphorous, creatinine, and uric acid. Median plasma 25(OH)D levels were lower in the cases (25.6 ng/mL) than in the controls (27.3 ng/mL; P<0.001). Women in the lowest compared with highest quartile of plasma 25(OH)D had an adjusted odds ratio for incident hypertension of 1.66 (95% CI: 1.11 to 2.48; P for trend=0.01). Compared with women with sufficient levels, those with vitamin D deficiency (<30 ng/mL; 65.7% of the study population) had a multivariable odds ratio of 1.47 (95% CI: 1.10 to 1.97). Plasma 25(OH)D levels are inversely and independently associated with the risk of developing hypertension.

Fibroblast growth factor 23, cardiovascular disease risk factors, and phosphorus intake in the health professionals follow-up study

BACKGROUND AND OBJECTIVES Fibroblast growth factor 23 (FGF23) regulates phosphorus and vitamin D metabolism. Elevated FGF23 concentrations are associated with cardiovascular disease events and mortality across a broad range of kidney function, but the predictors of FGF23 concentrations in the general population are unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We examined cross-sectional associations of dietary and nondietary parameters with plasma FGF23 in 1261 participants of the Health Professionals Follow-up Study (mean age 64 ± 9, mean creatinine 0.9 ± 0.2 mg/dl, mean FGF23 64 ± 28 RU/ml). RESULTS In multivariable-adjusted analyses, each 5-year increase in age was associated with 2.1 RU/ml higher FGF23, each 500-mg increase in phosphorus intake was associated with 3.4 RU/ml higher FGF23, and each 0.1-mg/dl increase in creatinine was associated with 3.4 RU/ml higher FGF23. Participants in the highest category of body mass index had 9.5 RU/ml higher FGF23 than those in the lowest, smokers had 17.1 RU/ml higher FGF23 than nonsmokers, and participants with hypertension had 6.0 RU/ml higher FGF23 than those without hypertension. With respect to biochemical parameters, higher parathyroid hormone, phosphate, uric acid, and triglyceride levels all were associated independently with higher FGF23 in models adjusted for age, creatinine, and other factors. In a subset of 748 participants with available data, some inflammatory biomarkers were associated independently with higher FGF23. CONCLUSIONS In community-dwelling adults with largely preserved kidney function, established cardiovascular risk factors and higher phosphorus intake were associated with higher FGF23. These results might explain the link between FGF23 and cardiovascular disease.

Plasma fibroblast growth factor 23, parathyroid hormone, phosphorus, and risk of coronary heart disease

BACKGROUND Fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and phosphorus all have been proposed as plasma biomarkers for the development of coronary heart disease (CHD) in individuals with normal renal function. METHODS In a nested case-control study of men in the Health Professionals Follow-up Study, free of diagnosed cardiovascular disease at blood draw, we prospectively examined associations between plasma FGF23, PTH, and phosphorus and risk of CHD. During 10 years of follow-up, 422 men developed nonfatal myocardial infarction or fatal CHD. Controls were selected in a 2:1 ratio and matched for age, date of blood collection, and smoking status. RESULTS Mean estimated glomerular filtration rate was 86 mL/min per 1.73 m(2) in cases and controls. At baseline, there were no statistically significant differences between cases and controls in plasma levels of FGF23, PTH, or phosphorus. After adjusting for matching factors, family history of myocardial infarction, body mass index, alcohol consumption, physical activity, history of diabetes mellitus and hypertension, ethnicity, region, plasma 25-hydroxyvitamin D, and other factors, the odds ratios for incident CHD for participants in the highest, compared with lowest, quartiles were 1.03 (95% CI 0.70-1.52, P for trend 0.84) for FGF23, 1.20 (95% CI 0.82-1.76, P trend 0.99) for PTH, and 0.72 (95% CI 0.51-1.02, P trend 0.13) for phosphorus. CONCLUSIONS Plasma FGF23, PTH, and phosphorus are not associated with the development of incident CHD in men without chronic kidney disease.

Magnesium pemoline and dextroamphetamine: a controlled study in children with minimal brain dysfunction.

Eighty-one children with a diagnosis of minimal brain dysfunction were randomly assigned to receive magnesium pemoline (Cylert), dextroamphetamine or placebo. Parent, teacher and clinician ratings and a battery of psychological tests were measured before treatment and at the end of eight weeks. Significant improvement was found for both active drugs and few differences between drugs were obtained. Side effects were similar for the two drugs and a laboratory battery showed no toxic effects. It is concluded that magnesium pemoline offers a good alternative for treatment of this syndrome.

Soda and Other Beverages and the Risk of Kidney Stones

BACKGROUND AND OBJECTIVES Not all fluids may be equally beneficial for reducing the risk of kidney stones. In particular, it is not clear whether sugar and artificially sweetened soda increase the risk. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We prospectively analyzed the association between intake of several types of beverages and incidence of kidney stones in three large ongoing cohort studies. Information on consumption of beverages and development of kidney stones was collected by validated questionnaires. RESULTS The analysis involved 194,095 participants; over a median follow-up of more than 8 years, 4462 incident cases occurred. There was a 23% higher risk of developing kidney stones in the highest category of consumption of sugar-sweetened cola compared with the lowest category (P for trend=0.02) and a 33% higher risk of developing kidney stones for sugar-sweetened noncola (P for trend=0.003); there was a marginally significant higher risk of developing kidney stones for artificially sweetened noncola (P for trend=0.05). Also, there was an 18% higher risk for punch (P for trend=0.04) and lower risks of 26% for caffeinated coffee (P for trend<0.001), 16% for decaffeinated coffee (P for trend=0.01), 11% for tea (P for trend=0.02), 31%-33% for wine (P for trend<0.005), 41% for beer (P for trend<0.001), and 12% for orange juice (P for trend=0.004). CONCLUSIONS Consumption of sugar-sweetened soda and punch is associated with a higher risk of stone formation, whereas consumption of coffee, tea, beer, wine, and orange juice is associated with a lower risk.

Parathyroid hormone and the risk of incident hypertension.

Objective The presence of parathyroid hormone receptor mRNA in a wide variety of tissues, including the endothelium, suggests that parathyroid hormone has potentially important effects in addition to the maintenance of calcium and phosphate homeostasis. We conducted a prospective study to examine the association between plasma intact parathyroid hormone levels and the subsequent risk of developing hypertension. Methods We measured intact parathyroid hormone in 481 men without hypertension from the Health Professionals Follow-up Study. During 10 years of follow-up, we observed 142 cases of incident hypertension. Cox proportional hazards regression was used to adjust for age, race, body mass index, alcohol use, smoking, physical activity, predicted plasma 25-hydroxyvitamin D level, and other factors. Results Median baseline levels of intact parathyroid hormone were 40.1 pg/ml in individuals who developed hypertension and 36.3 pg/ml in those who did not (P = 0.01). After multivariate adjustment, the relative risk for incident hypertension in men in the highest quartile of parathyroid hormone (median 56.0 pg/ml) compared with the lowest quartile of parathyroid hormone (median 26.3 pg/ml) was 1.83 (95% confidence interval 1.10–3.03; P for trend = 0.01). Analyses restricted to men in the lowest 90th percentage of the parathyroid hormone distribution (≤58 pg/ml) yielded similar results. Further adjustment for the intake of calcium and sodium, as well as for season and fasting status at time of blood draw, did not materially change the results. Conclusion Plasma levels of intact parathyroid hormone, even within ranges considered normal, are positively and independently associated with a higher risk of incident hypertension.

Effect of Vitamin D Repletion on Urinary Calcium Excretion among Kidney Stone Formers

BACKGROUND AND OBJECTIVES Despite the important role of vitamin D in maintaining bone health, many clinicians are reluctant to treat vitamin D deficiency in kidney stone formers because of the theoretical risk of increasing urinary calcium excretion. This study examined the effect of vitamin D repletion on urinary calcium excretion among stone formers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Participants (n=29) were recruited from urology clinics affiliated with New York Presbyterian Hospital. Enrollment criteria included a history of nephrolithiasis, urinary calcium excretion between 150 and 400 mg/d, and a serum 25-hydroxyvitamin D level <30 ng/ml. Participants were given oral ergocalciferol (50,000 IU/wk) for 8 weeks. Serum and 24-hour urine tests were repeated after 8 weeks. RESULTS Levels of 25-hydroxyvitamin D increased significantly after vitamin D repletion (17±6 and 35±10 ng/ml, P<0.001), but mean 24-hour urinary calcium excretion did not change (257±54 and 255±88 mg/d at baseline and follow-up, respectively, P=0.91). However, 11 participants had an increase in urinary calcium excretion ≥20 mg/d; these participants also had an increase in urine sodium excretion, likely reflecting dietary variability. No participant experienced adverse effects from vitamin D, including hypercalcemia. CONCLUSIONS Among stone formers with vitamin D deficiency, a limited course of vitamin D repletion does not seem to increase mean urinary calcium excretion, although a subset of individuals may have an increase. These data suggest that vitamin D therapy, if indicated, should not be withheld solely on the basis of stone disease, but 24-hour urinary calcium excretion should be monitored after repletion.

Serum Anion Gap and Blood Pressure in the National Health and Nutrition Examination Survey

Increased production of organic acid can result in an elevated serum anion gap and may play a role in the development of hypertension. We studied the cross-sectional associations between anion gap and blood pressure and between serum bicarbonate and blood pressure in the 1999-2000 and 2001-2002 National Health and Nutrition Examination Surveys. We included 5043 adult participants who were not taking antihypertensive medications or diuretics and who denied hypertension, cardiovascular disease, diabetes, and other diseases. Linear regression was used to adjust for age, race, body mass index, creatinine, albumin, and other factors. Sample weights were used to produce weighted regression parameters. In the lowest quintile of anion gap, mean values of sodium, chloride, and bicarbonate were 139 mEq/L, 105 mEq/L, and 25 mEq/L, respectively. In the highest quintile, mean values of sodium, chloride, and bicarbonate were 140 mEq/L, 101 mEq/L, and 22 mEq/L, respectively. Mean blood pressure was 118/72 mm Hg. After multivariable adjustment, participants in the highest quintile of anion gap had systolic blood pressure 3.73 mm Hg higher (95% CI: 1.83 to 5.63 mm Hg; P for trend: <0.01) than participants in the lowest quintile. Participants in the highest quintile of bicarbonate had systolic blood pressure 2.73 mm Hg lower (95% CI: 1.26 to 4.20 mm Hg; P for trend: <0.01) than participants in the lowest quintile. No associations were observed between anion gap or bicarbonate and diastolic blood pressure. The results were unchanged after excluding participants with estimated glomerular filtration rate <60 cc/min per 1.73 m2. The anion gap is independently associated with higher blood pressure. Further research is needed to elucidate the relation between organic acid and hypertension.

Plasma bicarbonate and risk of type 2 diabetes mellitus

Background: Several biomarkers of metabolic acidosis, including lower plasma bicarbonate and higher anion gap, have been associated with greater insulin resistance in cross-sectional studies. We sought to examine whether lower plasma bicarbonate is associated with the development of type 2 diabetes mellitus in a prospective study. Methods: We conducted a prospective, nested case–control study within the Nurses’ Health Study. Plasma bicarbonate was measured in 630 women who did not have type 2 diabetes mellitus at the time of blood draw in 1989–1990 but developed type 2 diabetes mellitus during 10 years of follow-up. Controls were matched according to age, ethnic background, fasting status and date of blood draw. We used logistic regression to calculate odds ratios (ORs) for diabetes by category of baseline plasma bicarbonate. Results: After adjustment for matching factors, body mass index, plasma creatinine level and history of hypertension, women with plasma bicarbonate above the median level had lower odds of diabetes (OR 0.76, 95% confidence interval [CI] 0.60–0.96) compared with women below the median level. Those in the second (OR 0.92, 95% CI 0.67–1.25), third (OR 0.70, 95% CI 0.51–0.97) and fourth (OR 0.75, 95% CI 0.54–1.05) quartiles of plasma bicarbonate had lower odds of diabetes compared with those in the lowest quartile (p for trend = 0.04). Further adjustment for C-reactive protein did not alter these findings. Interpretation: Higher plasma bicarbonate levels were associated with lower odds of incident type 2 diabetes mellitus among women in the Nurses’ Health Study. Further studies are needed to confirm this finding in different populations and to elucidate the mechanism for this relation.