Kidney Function and 24-Hour Proteinuria in Patients with Fabry Disease during 36 Months of Agalsidase Alfa Enzyme Replacement Therapy: A Brazilian Experience

Background. Prior to the introduction of enzyme replacement therapy (ERT), management of Fabry disease (FD) consisted of symptomatic and palliative measures. ERT has been available for several years using recombinant human agalsidase alfa, an analogue of alpha-galactosidase A (GALA). However, the limitations of ERT in improving kidney function have not been established. This study evaluates the safety and therapeutic effect of agalsidase alfa replacement in terms of kidney function and reduction in 24-hour proteinuria. Methods. During the period between January 1, 2002, and August 1, 2005, nine Fabry patients (7 male, 2 female) were treated according to protocol, receiving 0.2 mg/kg agalsidase alfa IV every two weeks. Kidney function was evaluated by measuring the glomerular filtration rate (GFR) using chromium ethylene diamine tetra-acetate clearance ((51)Cr-EDTA mL/min/1.73 m(2)) at baseline, 12, 24, and 36 months. 24-hour proteinuria was measured at baseline, 3, 6, 12, 18, 24, and 36 months of ERT. Kidney disease was classified according to National Kidney Foundation Disease Outcome Quality Initiative (NKF/DOQI) Advisory Board criteria, which define stage I chronic kidney disease (CKD) as GFR >= 90mL/min/1.73 m(2), stage II as 60-89 mL/min/1.73m(2), stage III as 30-59 mL/min/1.73 m(2), stage IV as 15-29 mL/min/1.73m(2), and stage V as < 15 mL/min/1.73m(2). Results. Six patients completed 36 months of therapy, 2 patients completed 18 months, and 1 patient completed 12 months. Mean patient age at baseline was 34.6 +/- 11.3 years. During the study period, kidney function remained stable in patients with stages I, II, or III CKD. One patient, who entered the study with stage IV CKD, progressed to end-stage chronic kidney disease, beginning hemodialysis after 7 months and receiving a kidney transplant after 12 months of ERT. Proteinuria also remained stable in the group of patients with pathologic proteinuria. The use of agalsidase alfa was well tolerated in 99.5% of the infusions administered. Conclusion. Over the course of 36 months of ERT, there was no change in kidney function and 24-hour proteinuria. This suggests thatagalsidase alfa may slow or halt the progression of kidney disease when used before extensive kidney damage occurs. No significant side effects were observed with ERT during the course of the study.

Early and 24-hour bond strength and degree of conversion of etch-and-rinse and self-etch adhesives

Purpose: To evaluate early and 24-hour microtensile bond strength (mu TBS) and the degree of conversion (DC) of one representative adhesive system from each of the four current bonding approaches. Methods: 40 human molars were sectioned occluso-gingivally into two halves. Resin composite was bonded incrementally to flat, mid-coronal dentin, using the adhesives Adper Scotchbond MP (MP); Adper Scotchbond 2 (SB); Clearfil SE Bond (SE); and Adper Prompt L-Pop (LP) according to the respective manufacturer`s instructions (n= 10). One half was immediately sectioned into sticks and subjected to mu TBS test. As the sectioning process took approximately 1 hour, the results were designated as 1-hour bond strengths. The other half was stored in distilled water at 37 degrees C for 24 hours before being sectioned and tested. The DC of these systems was measured using Fourier Transform-Raman spectroscopy in three periods: immediately, 1 and 24 hours after polymerization. Data were analyzed with ANOVA and Tukey`s tests. Results: There were no significant differences between the 1-hour and 24-hour bond strengths (P> 0.05), or among the DC measured immediately, 1 hour and 24 hours after polymerization (P> 0.05). However, significant differences were observed among adhesives (P< 0.05). mu TBS values obtained, in MPa (1 hour/24 hour), were: SB (48.6 + 1.3/48.4 + 3.5) = SE (51.9 + 4.7/53.3 +/- 2.9) > MP (35.3 +/- 10.9/38.6 + 6.7) > LP (25.5 + 1.1/26.0 + 1.5). The DC, in percentage (immediately/1 hour/24 hour), were: SE (81/82/87) > MP (79/77/81) > SB (60/63/65) > LP (39/37/42).

Factors associated with 24-hour urinary volume: the Swiss salt survey.

BACKGROUND: Low 24-hour urine volume (24 UV) may be a significant risk factor for decline in kidney function. We therefore aimed to study associated markers and possible determinants of 24 UV in a sample of the Swiss population. METHODS: The cross-sectional Swiss Salt Study included a population-based sample of 1535 (746 men and 789 women) individuals from three linguistic regions of Switzerland. Data from 1300 subjects were available for the present analysis. 24 UV was measured using 24-hour urine collection. Determinants of 24 UV were identified using multivariable linear regression models. RESULTS: In bivariate analysis, 24 UV was higher in women compared to men (2000 ml/24 h [interquartile range (IQR): 1354, 2562] versus 1780 ml/24 h [IQR: 1244, 2360], p = 0.002). In multivariable regression analyses, independent associated markers of 24 UV were female sex (β = 280, 95% confidence interval [CI]: 174, 386, p < 0.0001), fluid intake (β = 604, 95% CI: 539, 670, p < 0.0001), sodium excretion (β = 4.2, 95% CI: 3.4, 4.9, p < 0.0001) age (β = 6.6, CI: 3.4, 9.7, p < .0001), creatinine clearance (β = 2.4, CI: 0.2, 4.6, p = 0.04), living in the German-speaking part of Switzerland (β = 124, CI: 29, 219, p = 0.01), alcohol consumption (β = 41, CI: 9, 73, p = 0.01 for increasing categories of alcohol consumption), body mass index (β = -32, CI: -45, -18, p < 0.0001), current smoking (β = -146, CI: -265, -26, p = 0.02), and consumption of meat and cold cut (β = -56, CI: -108, -5, p = 0.03). CONCLUSION: In this large population-based, cross-sectional study, we found several strong and independent correlates for 24 UV. These findings may be important to improve our understanding in the development of chronic kidney disease.

Increased 24-hour energy expenditure in cigarette smokers.

We studied the effect of smoking on energy expenditure in eight healthy cigarette smokers who spent 24 hours in a metabolic chamber on two occasions, once without smoking and once while smoking 24 cigarettes per day. Diet and physical exercise (30 minutes of treadmill walking) were standardized on both occasions. Physical activity in the chamber was measured by use of a radar system. Smoking caused an increase in total 24-hour energy expenditure (from a mean value [+/- SEM] of 2230 +/- 115 to 2445 +/- 120 kcal per 24 hours; P less than 0.001), although no changes were observed in physical activity or mean basal metabolic rate (1545 +/- 80 vs. 1570 +/- 70 kcal per 24 hours). During the smoking period, the mean diurnal urinary excretion of norepinephrine (+/- SEM) increased from 1.25 +/- 0.14 to 1.82 +/- 0.28 micrograms per hour (P less than 0.025), and mean nocturnal excretion increased from 0.73 +/- 0.07 to 0.91 +/- 0.08 micrograms per hour (P less than 0.001). These short-term observations demonstrate that cigarette smoking increases 24-hour energy expenditure by approximately 10 percent, and that this effect may be mediated in part by the sympathetic nervous system. The findings also indicate that energy expenditure can be expected to decrease when people stop smoking, thereby favoring the gain in body weight that often accompanies the cessation of smoking.

Sustained 24-hour blockade of the renin-angiotensin system: a high dose of a long-acting blocker is as effective as a lower dose combined with an angiotensin-converting enzyme inhibitor.

Whether a higher dose of a long-acting angiotensin II receptor blocker (ARB) can provide as much blockade of the renin-angiotensin system over a 24-hour period as the combination of an angiotensin-converting enzyme inhibitor and a lower dose of ARB has not been formally demonstrated so far. In this randomized double-blind study we investigated renin-angiotensin system blockade obtained with 3 doses of olmesartan medoxomil (20, 40, and 80 mg every day) in 30 normal subjects and compared it with that obtained with lisinopril alone (20 mg every day) or combined with olmesartan medoxomil (20 or 40 mg). Each subject received 2 dose regimens for 1 week according to a crossover design with a 1-week washout period between doses. The primary endpoint was the degree of blockade of the systolic blood pressure response to angiotensin I 24 hours after the last dose after 1 week of administration. At trough, the systolic blood pressure response to exogenous angiotensin I was 58% +/- 19% with 20 mg lisinopril (mean +/- SD), 58% +/- 11% with 20 mg olmesartan medoxomil, 62% +/- 16% with 40 mg olmesartan medoxomil, and 76% +/- 12% with the highest dose of olmesartan medoxomil (80 mg) (P = .016 versus 20 mg lisinopril and P = .0015 versus 20 mg olmesartan medoxomil). With the combinations, blockade was 80% +/- 22% with 20 mg lisinopril plus 20 mg olmesartan medoxomil and 83% +/- 9% with 20 mg lisinopril plus 40 mg olmesartan medoxomil (P = .3 versus 80 mg olmesartan medoxomil alone). These data demonstrate that a higher dose of the long-acting ARB olmesartan medoxomil can produce an almost complete 24-hour blockade of the blood pressure response to exogenous angiotensin in normal subjects. Hence, a higher dose of a long-acting ARB is as effective as a lower dose of the same compound combined with an angiotensin-converting enzyme inhibitor in terms of blockade of the vascular effects of angiotensin.

Safety and feasibility of NeuroFlo use in eight- to 24-hour ischemic stroke patients.

BACKGROUND: Acute treatment of ischemic stroke patients presenting more than eight-hours after symptom onset remains limited and largely unproven. Partial aortic occlusion using the NeuroFlo catheter can augment cerebral perfusion in animals. We investigated the safety and feasibility of employing this novel catheter to treat ischemic stroke patients eight-hours to 24 h following symptom onset. METHODS: A multicenter, single-arm trial enrolled ischemic stroke patients at nine international academic medical centers. Eligibility included age 18-85 years old, National Institutes of Health stroke scale (NIHSS) score between four and 20, within eight-hours to 24 h after symptom onset, and perfusion-diffusion mismatch confirmed by magnetic resonance imaging. The primary outcome was all adverse events occurring from baseline to 30 days posttreatment. Secondary outcomes included stroke severity on neurological indices through 90 days. This study is registered with ClinicalTrials.gov, number NCT00436592. RESULTS: A total of 26 patients were enrolled. Of these, 25 received treatment (one excluded due to aortic morphology); five (20%) died. Favorable neurological outcome at 90 days (modified Rankin score 0-2 vs. 3-6) was associated with lower baseline NIHSS (P < 0·001) and with longer duration from symptom discovery to treatment. There were no symptomatic intracranial hemorrhages or parenchymal hematomas. Asymptomatic intracranial hemorrhage was visible on computed tomography in 32% and only on microbleed in another 20%. CONCLUSIONS: Partial aortic occlusion using the NeuroFlo catheter, a novel collateral therapeutic strategy, appears safe and feasible in stroke patients eight-hours to 24 h after symptom onset.

24-hour ambulatory electrocardiographic monitoring is unhelpful in the investigation of older persons with recurrent falls

Although frequently used in the assessment of patients with falls, it is unclear whether 24-hour ambulatory electrocardiography contributes to their assessment in older persons. The aim of this study is to identify electrocardiographic abnormalities in patients with recurrent falls and case controls, and determine whether 24-hour ambulatory electrocardiography identifies causal arrhythmias for falls. 24-hour ambulatory electrocardiography recordings were compared for the type and prevalence of arrhythmias and symptom correlation in consecutive older subjects with recurrent falls attending the accident and emergency department and in case controls (no previous falls or syncope).

Independent relations of left ventricular structure with the 24-hour urinary excretion of sodium and aldosterone.

Previous studies reported on the association of left ventricular mass index (LVMI) with urinary sodium or with circulating or urinary aldosterone. We investigated the independent associations of LVMI with the urinary excretion of both sodium and aldosterone. We randomly recruited 317 untreated subjects from a white population (45.1% women; mean age 48.2 years). Measurements included echocardiographic left ventricular (LV) properties, the 24-hour urinary excretion of sodium and aldosterone, plasma renin activity (PRA), and proximal (RNa(prox)) and distal (RNa(dist)) renal sodium reabsorption, assessed from the endogenous lithium clearance. In multivariable-adjusted models, we expressed changes in LVMI per 1-SD increase in the explanatory variables, while accounting for sex, age, systolic blood pressure, and the waist-to-hip ratio. LVMI increased independently with the urinary excretion of both sodium (+2.48 g/m(2); P=0.005) and aldosterone (+2.63 g/m(2); P=0.004). Higher sodium excretion was associated with increased mean wall thickness (MWT: +0.126 mm, P=0.054), but with no change in LV end-diastolic diameter (LVID: +0.12 mm, P=0.64). In contrast, higher aldosterone excretion was associated with higher LVID (+0.54 mm; P=0.017), but with no change in MWT (+0.070 mm; P=0.28). Higher RNa(dist) was associated with lower relative wall thickness (-0.81x10(-2), P=0.017), because of opposite trends in LVID (+0.33 mm; P=0.13) and MWT (-0.130 mm; P=0.040). LVMI was not associated with PRA or RNa(prox.) In conclusion, LVMI independently increased with both urinary sodium and aldosterone excretion. Increased MWT explained the association of LVMI with urinary sodium and increased LVID the association of LVMI with urinary aldosterone.

Comparisons of serum vitamin d levels, status, and determinants in populations with and without chronic kidney disease not requiring renal dialysis: a 24-hour urine collection population-based study.

OBJECTIVE: Vitamin D deficiency is frequent in the general population and might be even more prevalent among populations with kidney failure. We compared serum vitamin D levels, vitamin D insufficiency/deficiency status, and vitamin D level determinants in populations without chronic kidney disease (CKD) and with CKD not requiring renal dialysis. DESIGN AND METHODS: This was a cross-sectional, multicenter, population-based study conducted from 2010 to 2011. Participants were from 10 centers that represent the geographical and cultural diversity of the Swiss adult population (≥15 years old). INTERVENTION: CKD was defined using estimated glomerular filtration rate and 24-hour albuminuria. Serum vitamin D was measured by liquid chromatography-tandem mass spectrometry. Statistical procedures adapted for survey data were used. MAIN OUTCOME MEASURE: We compared 25-hydroxy-vitamin D (25(OH)D) levels and the prevalence of vitamin D insufficiency/deficiency (serum 25(OH)D < 30 ng/mL) in participants with and without CKD. We tested the interaction of CKD status with 6 a priori defined attributes (age, sex, body mass index, walking activity, serum albumin-corrected calcium, and altitude) on serum vitamin D level or insufficiency/deficiency status taking into account potential confounders. RESULTS: Overall, 11.8% (135 of 1,145) participants had CKD. The 25(OH)D adjusted means (95% confidence interval [CI]) were 23.1 (22.6-23.7) and 23.5 (21.7-25.3) ng/mL in participants without and with CKD, respectively (P = .70). Vitamin D insufficiency or deficiency was frequent among participants without and with CKD (75.3% [95% CI 69.3-81.5] and 69.1 [95% CI 53.9-86.1], P = .054). CKD status did not interact with major determinants of vitamin D, including age, sex, BMI, walking minutes, serum albumin-corrected calcium, or altitude for its effect on vitamin D status or levels. CONCLUSION: Vitamin D concentration and insufficiency/deficiency status are similar in people with or without CKD not requiring renal dialysis.

Transcutaneous carbon dioxide tension in newborn infants: reliability and safety of continuous 24-hour measurement at 42 degrees C.

In 58 newborn infants a new iridium oxide sensor was evaluated for transcutaneous carbon dioxide (tcPCO2) monitoring at 42 degrees C with a prolonged fixation time of 24 hours. The correlation of tcPCO2 (y; mm Hg) v PaCO2 (x; mm Hg) for 586 paired values was: y = 4.6 + 1.45x; r = .89; syx = 6.1 mm Hg. The correlation was not influenced by the duration of fixation. The transcutaneous sensor detected hypocapnia (PaCO2 less than 35 mm Hg) in 74% and hypercapnia (PCO2 greater than 45 mm Hg) in 74% of all cases. After 24 hours, calibration shifts were less than 4 mm Hg in 90% of the measuring periods. In 86% of the infants, no skin changes were observed; in 12% of infants, there were transitional skin erythemas and in 2% a blister which disappeared without scarring. In newborn infants with normal BPs, continuous tcPCO2 monitoring at 42 degrees C can be extended for as many as 24 hours without loss of reliability or increased risk for skin burns.

New anthropometry-based age- and sex-specific reference values for urinary 24-hour creatinine excretion based on the adult Swiss population (epublish)

BACKGROUND: Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. METHODS: We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. RESULTS: The mean urinary creatinine excretion was 193 ± 41 μmol/kg/24 hours in men and 151 ± 38 μmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). CONCLUSIONS: We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.

Assessing the Functionality and Biocompatibility of a Wireless Contact Lens Sensor for 24 hour-intraocular Pressure Monitoring in Volunteers: Preliminary Results

Purpose: In vitro studies in porcine eyes have demonstrated a good correlation between induced intraocular pressure variations and corneal curvature changes, using a contact lens with an embedded microfabricated strain gauge. Continuous 24 hour-intraocular pressure (IOP) monitoring to detect large diurnal fluctuation is currently an unmet clinical need. The aims of this study is to evaluate precision of signal transmission and biocompatibility of 24 hour contact lens sensor wear (SENSIMED Triggerfish®) in humans. Methods: After full eye examination in 10 healthy volunteers, a 8.7 mm radius contact lens sensor and an orbital bandage containing a loop antenna were applied and connected to a portable recorder. Best corrected visual acuity and position, lubrication status and mobility of the sensor were assessed after 5 and 30 minutes, 4, 7 and 24 hours. Subjective comfort was scored and activities documented in a logbook. After sensor removal full eye examination was repeated, and the registration signal studied. Results: The comfort score was high and did not fluctuate significantly, except at the 7 hour-visit. The mobility of the contact lens was minimal but its lubrication remained good. Best corrected visual acuity was significantly reduced during the sensor wear and immediately after its removal. Three patients developed mild corneal staining. In all but one participant we obtained a registration IOP curve with visible ocular pulse amplitude. Conclusions: This 24 hour-trial confirmed the functionality and biocompatibility of SENSIMED Triggerfish® wireless contact lens sensor for IOP-fluctuation monitoring in volunteers. Further studies with a range of different contact lens sensor radii are indicated.

Sustained 24-hour blockade of the renin-angiotensin system: a high dose of a long-acting blocker is as effective as a lower dose combined with an angiotensin-converting enzyme inhibitor

Résumé en français Jusqu'alors, il n'avait jamais été formellement démontré qu'une forte dose d'un antagoniste de l'angiotensine II à longue durée d'action pouvait être aussi efficace sur le blocage du système rénine-angiotensine que l'association d'un inhibiteur de l'enzyme de conversion avec le même antagoniste de l'angiotensine II à des doses plus faibles. Dans cette étude randomisée en double aveugle, nous avons étudié le blocage du système rénine-angiotensine obtenu avec trois doses d'olmesartan medoxomil (20, 40 et 80 mg) chez 30 volontaires sains que nous avons comparé au blocage obtenu par du lisinopril (20 mg), seul ou associé à de l'olmesartan medoxomil (20 et 40 mg). L'étude s'est déroulée en deux phases selon un design par crossover. A deux reprises, chaque volontaire à reçu durant une semaine l'un des six traitements possibles. Un intervalle d'une semaine a été respecté entre les deux phases (période de washout). L'objectif principal était d'étudier, 24 heures après la dernière dose, le blocage de l'élévation de la pression systolique en réponse à l'administration d'angiotensine I. Ce blocage était de 58% ± 19% (moyenne ± déviation standard) avec 20 mg de lisinopril, de 58% ± 11% avec 20 mg d'olmesartan medoxomil, de 62% ± 16% avec 40 mg d'olmesartan medoxomil, et de 76% ± 12% avec la plus forte dose d'olmesartan medoxomil (80 mg) (P=.016 versus 20 mg de lisinopril et P=.0015 versus 20 mg d'olmesartan medoxomil). Le blocage était de 80% ± 22% avec 20 mg de lisinopril associé à 20 mg d'olmesartan medoxomil et de 83% ± 9% avec 20 mg de lisinopril associé à 40 mg d'olmesartan medoxomil (P= .3 versus 80 mg d'olmesartan medoxomil). Ces résultats montrent, que chez les volontaires sains, une dose suffisamment élevée d'olmesartan medoxomil peut induire un blocage à 24 heures quasi complet de l'élévation de la pression artérielle en réponse à l'administration d'angiotensine I. De même, en terme de blocage de l'effet vasculaire de l'angiotensine I, une dose suffisamment élevée d'un antagoniste de l'angiotensine II de longue durée d'action est tout aussi efficace que ce même antagoniste à des doses plus faibles associé avec à un inhibiteur de l'enzyme de conversion.