A Controlled Increase in Dietary Phosphate Elevates BP in Healthy Human Subjects.

Background Despite epidemiologic evidence for increased cardiovascular morbidity and mortality associated with both high dietary and serum phosphate in humans with normal renal function, no controlled phosphate intervention studies of systemic hemodynamics have been reported. Higher serum 25(OH) vitamin D levels are associated with better cardiovascular outcomes, but vitamin D increases intestinal phosphate absorption.Methods We conducted a prospective outpatient study with blinded assessment in 20 young adults with normal renal function randomized to high phosphate (regular diet plus 1 mmol/kg body wt per day of Na as neutral sodium phosphate) or low phosphate (regular diet plus lanthanum, 750 mg thrice/day, plus 0.7 mmol/kg body wt per day of Na as NaCl) for 11 weeks. After 6 weeks, all subjects received vitamin D3 (600,000 U) by intramuscular injection. Outcome parameters were 24-hour ambulatory systolic and diastolic BP (SBP and DBP), pulse rate (PR), biomarkers, and measures of endothelial and arterial function.Results Compared with the low-phosphate diet group, the high-phosphate diet group had a significant increase in mean±SEM fasting plasma phosphate concentration (0.23±0.11 mmol/L); 24-hour SBP and DBP (+4.1; 95% confidence interval [95% CI], 2.1 to 6.1; and +3.2; 95% CI, 1.2 to 5.2 mm Hg, respectively); mean 24-hour PR (+4.0; 95% CI, 2.0 to 6.0 beats/min); and urinary metanephrine and normetanephrine excretion (54; 95% CI, 50 to 70; and 122; 95% CI, 85 to 159 µg/24 hr, respectively). Vitamin D had no effect on any of these parameters. Neither high- nor low-phosphate diet nor vitamin D affected endothelial function or arterial elasticity.Conclusions Increased phosphate intake (controlled for sodium) significantly increases SBP, DBP, and PR in humans with normal renal function, in part, by increasing sympathoadrenergic activity

Effect of diet on plasma acid-base composition in normal humans

AbstractEffect of diet on plasma acid-base composition in normal humans. Steady-state plasma and urine acid-base composition was assessed in 19 studies of 16 normal subjects who ingested constant amounts of one of three diets that resulted in different rates of endogenous noncarbonic acid production (EAP) within the normal range. Renal net acid excretion (NAE) was used to quantify EAP since the two variables are positively correlated in normal subjects. A significant positive correlation was observed between plasma [H+] and plasma PCO2, and between plasma [HCO3-] and plasma PCO2, among the subjects. Multiple correlation analysis revealed a significant interrelationship among plasma [H+], plasma PCO2, and NAE (r = 0.71, P < 0.001), and among plasma [HCO3-], plasma PCO2, and NAE (r = 0.77, P < 0.001). The partial correlation coefficients indicated a significant positive correlation between plasma [H+] and NAE, and a significant negative correlation between plasma [HCO3-] and NAE, when plasma PCO2 was held constant. These findings indicate that two factors influence the level at which plasma [H+] is maintained in normal subjects: (1) the steadystate rate of endogenous noncarbonic acid production, and (2) the setpoint at which plasma PCO2 is regulated by the respiratory system. Plasma [HCO3-] is also co-determined by these two factors. In disease states, therefore, both factors must be known before a disturbance in acid-base homeostasis can be excluded.Effet du régime sur la composition acido-basique plasmatique chez des sujets humains normaux. La composition acido-basique plasmatique et urinaire à l'équilibre a été déterminée dans 19 études de 16 sujets normaux qui ingéraient des quantités constantes de l'un de trois régimes aboutissant à différents taux de production endogène d'acides non carboniques (EAP) à l'intérieur de la normale. L'excrétion rénale nette d'acides (NAE) a été utilisée pour quantifier l'EAP puisque les deux variables sont positivement corrélées chez des sujets normaux. Une corrélation significative positive a été observée entre le [H+] plasmatique et la PCO2 plasmatique, et entre le [HCO3-] plasmatique et PCO2 plasmatique, parmi ces sujets. Une analyse par corrélations multiples a révélé une interrelation significative entre [H+] plasmatique, PCO2 plasmatique et NAE (r = 0,71, P < 0,001), et entre [HCO3-] plasmatique, PCO2 plasmatique et NAE (r = 0,77, P < 0,001). Les coefficients de corrélation partielle ont indiqué une corrélation significative positive entre [H+] plasmatique et NAE, et une corrélation significative négative entre [HCO3-] plasmatique et NAE, lorsque PCO2 plasmatique était maintenue constante. Ces résultats indiquent que deux facteurs influencent le niveau auqeal [H+] plasmatique est maintenu chez des sujets normaux: (1) le taux de production à l'équilibre d'acides non carboniques endogènes, et (2) le point d'équilibre auquel PCO2 plasmatique est régulée par le système respiratoire. [HCO3-] plasmatique est également codéterminé par ces deux facteurs. Ainsi, dans les états pathologiques, les deux facteurs doivent être connus avant de pouvoir exclure une perturbation de l'homéostasie acido-basique

On the mechanism of diminished urinary carbon dioxide tension caused by amiloride

On the mechanism of diminished urinary carbon dioxide tension caused by amiloride. We investigated under both in vivo and in vitro conditions the mechanism whereby amiloride administration, a model of distal renal tubular acidosis in dogs, decreases the urine-to-blood PCO2 gradient (U-B PCO2) in alkaline urine. The results demonstrate that U-B PCO2 is reduced in amiloride-treated dogs as previously reported in rats. The reduction in U-B PCO2 could not be attributed to amiloride-induced reductions in urinary HCO-3 concentration since the reduction in U-B PCO2 was observed over the same range of urinary HCO-3 concentrations (150 to 250 mEq per liter) as that achieved prior to amiloride administration. U-B PCO2 correlated positively and linearly with urinary HCO-3 concentration both prior to (P < 0.001) and during amiloride infusion (P < 0.001). Amiloride administration significantly decreased the slope (Δ[U-B PCO2]/Δ[HCO-3]u) of the regression line (P < 0.005). The possibility that amiloride might lower urine PCO2 by catalyzing intraluminal dehydration of H2CO3 was excluded by demonstrating that amiloride does not possess carbonic anhydrase activity. The additional possibility that amiloride might facilitate dissipation of carbon dioxide gradients through diffusion (as reported for carbonic anhydrase) was excluded by in vitro studies of the effect of amiloride on carbon dioxide diffusion. These findings suggest that the U-B PCO2 lowering effect of amiloride is not caused by alterations in urinary [HCO-3, CO2 diffusibility, or alterations in the dehydration rate of H2CO3 thereby providing strong support for the interpretation that reductions in U-B PCO2 during amiloride administration represent an impairment in distal nephron hydrogen ion secretion.Sur le méchanisme de la diminution de la pression partielle de carbonique dans l'urine déterminée par l'amiloride. Nous avons examiné in vivo et in vitro le mécanisme par lequel l'administration d'amiloride, un modèle d'acidose tubulaire distale chez le chien, diminue le gradient urinesang de PCO2 (U-B PCO2) en urine alcaline. Les résultats démontrent que U-B PCO2 est réduit chez le chien traité par l'amiloride comme cela a été antérieurement montré chez le rat. Le diminution de U-B PCO2 ne peut pas être attribuée à la diminution de la concentration urinaire de HCO-3 déterminée par l'amiloride puisque la diminution de U-B PCO2 a été observée pour le même éventail de concentrations urinaires de HCO-3 (150 à 250 mEq par litre) que celui réalisé avant l'administration d'amiloride. U-B PCO2 est corrélé linéairement et positivement à la concentration urinaire de HCO-3 aussi bien avant (P < 0,001) que pendant la perfusion d'amiloride (P < 0,001). L'administration d'amiloride diminue régulièrement la pente (Δ[U-B PCO2]/Δ[HCO-3]u) de la droite de régression (P < 0,005). La possibilité que l'amiloride puisse diminuer la PCO2 urinaire en catalysant la déshydratation intraluminal de H2CO3 a été exclue par la démonstration de l'absence d'activité de type anhydrase carbonique de l'amiloride. La possibilité que l'amiloride puisse faciliter la dissipation par diffusion des gradients de carbonique a été exclue par des études in vitro. Ces constatations suggèrent que l'effet de l'amiloride de diminution de U-B PCO2 n'est pas lié à des modifications de [HCO-3] de l'urine, de la diffusibilité du carbonique, ou du débit de déshydratation de H2CO3, et par conséquent constituent un argument fort en faveur d'une altération de la sécrétion distale d'ion hydrogène

Chronic respiratory alkalosis induces renal PTH-resistance, hyperphosphatemia and hypocalcemia in humans

Chronic respiratory alkalosis induces renal hyperphosphatemia and hypocalcemia in humans. The effects of chronic respiratory alkalosis on divalent ion homeostasis have not been reported in any species. We studied four normal male subjects during a four-day control period (residence at 500 m), during six days of chronic respiratory alkalosis induced by hypobaric hypoxia (residence at 3450 m), followed by a six-day eucapnic recovery period (500 m) under metabolic balance conditions. Chronic respiratory alkalosis (ΔPaCO2, -8.4mm Hg, Δ[H+] -3.2 nmol/liter) resulted in a sustained decrement in plasma ionized calcium concentration (Δ[IoCa++]p, -0.10 mmol/liter, P < 0.05) and a sustained increment in plasma phosphate concentration (Δ[PO4]p, +0.14 mmol/liter, P < 0.005) associated with increased fractional excretion of Ca++ (+0.5%, P < 0.005), decreased phosphate clearance (-6.1 ml/min, P < 0.025) and decreased excretion of nephrogenous cAMP (-1.5 nmol/100 ml GFR, P < 0.0025). Urinary phosphate excretion decreased by 15.4 mmol/24 hr on day 1 of chronic respiratory alkalosis (P < 0.0025), but returned to control values by day 6 despite hyperphosphatemia. Serum intact [PTH] did not change. Sustained hypomagnesuria (-0.8 mmol/24 hr, P < 0.05) occurred during chronic respiratory alkalosis and was accounted for, at least in part, by decreased fractional excretion of Mg++ (-0.7%, P < 0.05) in the absence of change in plasma magnesium concentration. Serum 1,25(OH)2D levels were unchanged by chronic respiratory alkalosis. In conclusion, the decrease in nephrogenous cAMP generation despite unchanged serum intact PTH concentration suggests that chronic respiratory alkalosis results in impaired renal responsiveness to PTH as manifested by alterations in PTH-dependent renal calcium and phosphate transport. Hypomagnesuria in chronic respiratory alkalosis may be due, at least in part, to hypocalcemia-induced enhancement of renal magnesium reabsorption. The failure of [PTH] to increase during hypocalcemia may reflect defective PTH secretion

Mental Health Care Professionals’ Appraisal of Patients’ Use of Web-Based Access to Their Electronic Health Record: Qualitative Study

BACKGROUND: Patients in a range of health care sectors can access their medical health records using a patient portal. In mental health care, the use of patient portals among mental health care professionals remains low. Mental health care professionals are concerned that patient access to electronic health records (EHRs) will negatively affect the patient’s well-being and privacy as well as the professional’s own workload. OBJECTIVE: This study aims to provide insights into the appraisal work of mental health care professionals to assess and understand patient access to their EHRs through a patient portal. METHODS: We conducted a qualitative study that included 10 semistructured interviews (n=11) and a focus group (n=10). Participants in both the interviews and the focus group were mental health care professionals from different professional backgrounds and staff employees (eg, team leaders and communication advisors). We collected data on their opinions and experiences with the recently implemented patient portal and their attempts to modify work practices. RESULTS: Our study provides insights into mental health care professionals’ appraisal work to assess and understand patient access to the EHR through a patient portal. A total of four topics emerged from our data analysis: appraising the effect on the patient-professional relationship, appraising the challenge of sharing and registering delicate information, appraising patient vulnerability, and redefining consultation routines and registration practices. CONCLUSIONS: Mental health care professionals struggle with the effects of web-based patient access and are searching for the best ways to modify their registration and consultation practices. Our participants seem to appraise the effects of web-based patient access individually. Our study signals the lack of systematization and communal appraisal. It also suggests various solutions to the challenges faced by mental health care professionals. To optimize the effects of web-based patient access to EHRs, mental health care professionals need to be involved in the process of developing, implementing, and embedding patient portals

Effects of dexamethasone on renal and systemic acid-base metabolism

Effects of dexamethasone on renal and systemic acid-base metabolism. We carried out long-term balance studies in adrenalectomized (ADX) dogs to evaluate the effects of small amounts of a glucocorticoid steroid with minimal mineralocorticoid potency (dexamethasone; DEX) on renal and systemic acid-base metabolism under conditions of constant mineralocorticoid replacement and both normal and increased systemic acid loads. We investigated the effects of low and high dosages of dexamethasone (0.2 mg/day [normal-DEX] vs. 0.8 mg/day [high-DEX]) before and during hydrochloric acid feeding (5 mmol/kg/day) in paired studies on ADX dogs (N = 7) maintained on constant mineralocorticoid replacement (deoxycorticosterone, corticosterone, aldosterone). Prior to hydrochloric acid feeding, no differences in plasma acid-base composition were observed between the two dosages despite greater endogenous acid production with the higher dosage of DEX, evidenced by greater rates of both net acid excretion (NAE) and the excretion of urinary anions other than chloride, bicarbonate, and phosphate (urine anion gap). During hydrochloric acid feeding, mean plasma bicarbonate (PHCO3) decreased from 21.2 ± 0.4 to 13.7 ± 0.5 (normal-DEX) and from 21.1 ± 0.4 to 15.8 ± 0.4 mEq/liter (high-DEX). The difference in the decrements in PHCO3 between groups was significant (P < 0.05). With continued hydrochloric acid feeding in both groups, increasing the DEX dosage from 0.2 to 0.8 mg/day in the normal-DEX group resulted in a. significant increase in NAE (ΣΔNAE, +161 mEq, P < 0.02) and in PHCO3 (+3.6 ± 0.5 mEq/liter, P < 0.01) to steady-state levels by day 10, which were values not significantly different from those in high-DEX. The DEX dose-related increase in NAE was greater than the corresponding increase in endogenous acid production estimated from the change in urine anion gap, and was due largely to an increase in ammonium excretion, which, because urine pH did not decrease, could not be attributed to increased intraluminal trapping of ammonia as a result of more acidic tubular fluid. These studies indicate that the severity of hydrochloric acid-induced metabolic acidosis in mineralocorticoid-replete ADX dogs can be mitigated by increasing the dosage of exogenous glucocorticoid and suggest that this acidosis mitigating effect is mediated in part by the increased NAE associated with the stimulation of renal ammonia production. These studies further indicate that the rate of production of fixed acids of metabolism increases with an increased dosage of exogenous glucocorticoid, but that this acidosis-producing effect is more than offset by independent stimulation of renal net acid excretion, such that metabolic acidosis is prevented (basal condition) or if present (hydrochloric acid feeding) is significantly ameliorated.Effets de la dexaméthasone sur le métabolisme acido-basique rénal et systémique. Les études de bilan qui sont rapportées ont été réalisées chez des chiens surrénalectomisés (ADX) pour évaluer les effets de faibles quantités d'un stéroïde glucocorticoïde, ayant une activité minéralocorticoïde faible (dexaméthasone; DEX), sur le métabolisme acido-basique rénal et systémique dans des conditions de traitement substitutif permanent de minéralocorticoïdes et de charge acide soit normale soit élevée. Nous avons étudié les effets de doses de dexaméthasone (0,2 mg/jour; normale-DEX) ou 0,8 mg/jour (élevée-DEX) avant et pendant l'administration d'acide chlorhydrique à raison de 5 mmol/kg/jour dans des études appariées chez des chiens ADX (N = 7) recevant un traitement substitutif par les minéralocorticoïdes (deoxycorticosterone acetate, corticosterone, aldosterone). Avant l'administration d'acide chlorhydrique, il n'y avait pas de différence dans la composition acido-basique du plasma selon les doses de DEX malgré l'augmentation de production endogène d'acide sous l'effet de la dose la plus élevée de DEX, augmentation traduite par une élévation de l'état stationnaire d'excrétion nette d'acide (NAE) et de la somme des débits d'excrétion des anions urinaires autres que le chlore, le bicarbonate et le phosphate (trou anionique urinaire). Au cours de l'administration d'acide chlorhydrique la concentration plasmatique moyenne de bicarbonate (PHCO3) a diminué de 21,2 ± 0,4 à 13,7 ± 0,5 (normale-DEX) et de 21,1 ± 0,4 à 15,8 ± 0,4 mEq/litre (élevée-DEX). La différence des diminutions de bicarbonate était significative (P < 0,05). Au cours de l'administration prolongée d'acide chlorhydrique aux deux groupes l'augmentation de la dose de DEX de 0,2 à 0,8 mg/jour dans le groupe normale-DEX a eu pour résultat une augmentation significative de NAE (ΣΔNAE, +161 mEq, P < 0,02) et de PHCO3 (+ 3,6 ± 0,5 mEq/litre, P < 0,01), jusqu'à de nouveaux états stationnaires, le jour 10, non sigmficativement différents de ceux observés dans le groupe élevée-DEX. L'augmentation de NAE dépendant de la dose de DEX a été plus grande que l'augmentation correspondante de la production endogène d'acide estimée à partir de la modification du trou anionique urinaire, elle était principalement due à une augmentation de l'excrétion d'ammonium qui, du fait que le pH de l'urine n'a pas diminué, ne peut pas être attribuée à une augmentation de la captation intraluminale d'ammonia. Ces résultats indiquent que la sévérité de l'acidose métabolique déterminée par acide chlorhydrique chez les chiens ADX recevant des minéralocorticoïdes peut être atténuée par l'augmentation de la dose de glucocorticoïdes exogènes et suggère que cet effet d'atténuation a pour médiateur partiel l'augmentation de NAE associée à la stimulation de la production rénale d'ammonia. Ces résultats indiquent, de plus, que le débit de production des acides fixes augmente en même temps que la dose de glucocorticoïdes exogènes mais que cet effet de production d'acidose est plus que compensé par la stimulation indépendante de l'excrétion rénale nette d'acide, de telle sorte que l'acidose métabolique est empêchée (conditions basales) ou significativement améliorée au cours de l'administration acide chlorhydrique