Nhu Uyen Nguyen

No trend toward a spontaneous improvement of hyperparathyroidism and high bone turnover in normocalcemic long-term renal transplant recipients

Although hyperparathyroidism is a common feature in renal transplant recipients, the long-term course of parathyroid hormone (PTH) secretion in these patients is not well established, and the actual contribution of PTH to posttransplant bone disease remains incompletely understood. Therefore, we studied calcium-regulating hormones and serum osteocalcin, as a marker of bone remodeling, in 82 normocalcemic renal transplant recipients with good renal function who had received a graft 6 to 73 months previously and in 82 healthy subjects matched for age and sex. In all subjects, fasting serum and 24-hour urinary samples were collected. The transplant recipients had excessive PTH secretion (serum PTH, 6.9 +/- 0.5 pmol/L in recipients v 3.0 +/- 0.1 pmol/L in healthy subjects; P < 0.001) and high bone turnover (osteocalcin, 16.6 +/- 0.8 microg/L v 8.0 +/- 0.3 microg/L; P < 0.001). (Values are mean +/- SEM.) In addition, transplant recipients had a slightly higher ionized calcium than the healthy subjects, providing definite evidence of an inappropriate PTH secretion in renal transplant recipients. Furthermore, in subgroups of 25 recipients and 25 healthy controls matched for creatinine clearance, the results superimposed those obtained in the whole groups, suggesting that excessive PTH secretion and high bone turnover in renal transplant recipients did not merely reflect the moderately reduced renal function of some recipients. In the whole group of transplant recipients, PTH correlated positively with osteocalcin (r = 0.40; P < 0.001), suggesting that PTH contributes at least partly to posttransplant bone disease. Conversely, there was no correlation between serum PTH or osteocalcin and the delay from grafting. Therefore, our results provide no evidence for a spontaneous improvement of either persistent hyperparathyroidism or high bone turnover in normocalcemic long-term renal transplant recipients.

Lack of evidence that cyclosporine treatment impairs calcium-phosphorus homeostasis and bone remodeling in normocalcemic long-term renal transplant recipients.

Since the effects of cyclosporine on mineral and bone metabolism are controversial, we studied calcium regulating hormones, calcium-phosphorus (Ca-P) metabolism, and bone remodeling, assessed by serum osteocalcin, in long-term renal transplant recipients (RT). Forty-seven normocalcemic patients with good renal function receiving cyclosporine (CT, n = 27) or not (NC, n = 20) were studied at baseline and after an oral Ca load. CT and NC had similar age, daily dose of steroids, GFR level, and duration of transplantation. Baseline evaluation included 24-hr urinary Ca, P, TRP, TmP/GFR, fasting serum intact PTH, 1,25-(OH)2D, 25OHD, osteocalcin, Ca, and P. Subjects of the two groups had excessive secretion of PTH, tubular P wasting, and high serum osteocalcin level, as is usual in RT. However, there was no difference between CT and NC regarding any baseline variable. Ten CT and ten NC, matched for duration of transplantation and serum PTH level, ingested 1g Ca to achieve an acute dynamic study of PTH secretion and Ca-P metabolism. In both CT and NC, this Ca load caused the same decreases in serum PTH (P < 0.001), NcAMP (P < 0.05), and urinary P (P < 0.001) and the same increases in serum and urinary Ca (P < 0.001), and in both TmP/GFR and TRP (P < 0.001). These results strongly suggest that cyclosporine treatment had no significant effect on calcium-regulating hormone secretion, P-Ca metabolism, and bone remodeling level. We therefore consider that cyclosporine is unlikely to have any prominent role in the abnormalities of bone endocrine and mineral metabolism that are common in long-term kidney recipients.

Elevated Adiponectin Serum Levels in Women with Systemic Autoimmune Diseases

Adipose tissue produces a wide range of proteins that may influence the immune system. In this study, we assessed the serum levels of leptin, adiponectin, and ghrelin, in association with the measurements of body composition, in 15 female patients with various autoimmune diseases (systemic lupus erythematosus, primary Sjögrens syndrome, sarcoidosis, mixed connective tissue disease, vasculitis, CREST syndrome, and polymyositis) and in 15 healthy female controls. There were no statistically significant differences between the patients and controls with regard to serum leptin, serum ghrelin, global fat mass, adiposity, and fat mass in the android or gynoid regions, whereas serum adiponectin levels were higher in patients than controls (16.3 ± 1.6 μg/mL versus 9.7 ± 0.6 μg/mL; P = .01). As adiponectin is known to exhibit potent anti-inflammatory properties, a high adiponectinemia in patients with systemic autoimmune disease may mitigate the inflammatory response. However, the precise consequences of these elevated serum adiponectin levels on the metabolic syndrome development and atherosclerotic cardiovascular risk in this patient population still needs to be determined.

Conditions of autonomic reciprocal interplay versus autonomic co-activation : Effects on non-linear heart rate dynamics

The present study was aimed at investigating the autonomic nervous system influences on the fractal organization of human heart rate during sympathovagal interactions, with special emphasize on the short-term fractal organization in heart rate variability (HRV), as assessed by the scaling exponent (alpha(1)) of the detrended fluctuation analysis. Linear and non-linear HRV analyses were used to study the sympathetic and vagal modulation of heart rate in ten healthy men (mean +/- SEM; age 26 +/- 1 years) during conditions of 1) increased sympathetic activity and vagal withdrawal (head-up tilt), 2) decreased sympathetic activity and increased vagal outflow (thermoneutral upright head-out water immersion, WIn), and 3) simultaneous activation of the two arms of the autonomic nervous activity (upright head-out immersion in cold water, WIc). Hemodynamic and linear HRV results were consistent with previous reports during similar physiological conditions. alpha(1) increased significantly during head-up tilt (from 0.71 +/- 0.13 supine to 0.90 +/- 0.15 upright) and WIn (0.86 +/- 0.10) and was significantly decreased during WIc (0.61 +/- 0.15). Thus, alpha(1) increased when the cardiac autonomic interplay was altered in a reciprocal fashion, whatever the direction of the balance change. Conversely, alpha(1) decreased during the concomitant activation of both vagal and sympathetic activities. The results of linear analysis were necessary to precisely define the direction of change in autonomic control revealed by an increase in alpha(1), while the direction of change in alpha(1) indicated whether an increased vagal activity is coupled with a decreased or increased sympathetic activation. Using both linear and non-linear analysis of HRV may increase the understanding of changes in cardiac autonomic status.

Plasma renin and aldosterone changes during twenty minutes' moderate exercise

SummaryThe influence of posture on plasma renin and aldosterone changes during exercise performed at a constant relative work load (40%–50% maximal oxygen uptake) was studied in eight healthy men. Each subject carried out two 20-min exercises on an ergocycle at an interval of 8 days; the first exercise was performed in the normal sitting position (upright exercise), the second in a comfortable supine position (supine exercise). In both cases, heart rate and blood pressure were measured as well as plasma renin activity (PRA), aldosterone (ALDO) and osmolality, before and immediately after exercise, and 15 min following the end of exercise. An increase in heart rate, blood pressure, PRA, ALDO and osmolality was noted at the end of each exercise. This increase was greater in the supine exercise than when upright for PRA and ALDO; plasma osmolality and blood pressure showed identical increases for both types of exercise; increase in heart rate was greater when supine than when upright. PRA and ALDO were still elevated 15 min after the upright activity, but had regained their base values in that time after the supine exercise. Our results show that moderate, relatively brief periods of exercise stimulate the production of renin and aldosterone, but the response is less when supine than in the normal upright position.

Acute Oral Calcium Load Decreases Parathyroid Secretion and Suppresses Tubular Phosphate Loss in Long-Term Renal Transplant Recipients

Persistent hyperparathyroidism and impaired tubular reabsorption of phosphate (P) are common after kidney transplantation. In order to assess the suppressibility of these abnormalities, we studied the effects of a single oral calcium (Ca) load (1 g) in 7 healthy subjects (HS) and in 14 normocalcemic long-term renal transplant recipients with good renal function (RT). In HS and RT, serum and urinary Ca were similar at baseline, and increased (p < 0.001) to the same extent after Ca ingestion. Serum parathyroid hormone (PTH) and nephrogenic cAMP (NcAMP) levels were higher at baseline in RT than HS (mean +/- SEM; respectively, PTH 7.8 +/- 0.8 vs. 3.5 +/- 0.6 pmol/l, p < 0.001, and NcAMP 24.8 +/- 2.3 vs. 13.9 +/- 2.3 nmol/l GFR, p < 0.01). After Ca, PTH (p < 0.001) and NcAMP (p < 0.01) decreased markedly in both RT and HS. Maximal changes in PTH and NcAMP were larger in RT than HS (PTH - 3.3 +/- 0.4 vs. -2.1 +/- 0.03 pmol/l, p < 0.01, and NcAMP -18.2 +/- 3.3 vs. -8.1 +/- 2.6 nmol/l GFR, p < 0.05). Although PTH levels remained significantly higher in RT than HS from baseline to the end of the study (p < 0.001), PTH decreased to the normal range in RT after Ca load. Moreover, NcAMP reached similar values in RT and HS after Ca (16.0 +/- 3.3 vs. 13.2 +/- 2.8 nmol/l GFR at the end of the survey, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The role of posture on the changes in plasma atrial natriuretic factor and arginine vasopressin levels during immersion

SummaryIn seven healthy male volunteers we investigated changes in plasma atrial natriuretic factor ([ANF]), arginine vasopressin ([AVP]) and plasma volume (PV) during supine immersion. Twenty minutes head-out water immersion in a supine position in a thermo-neutral water bath attenuated the increase in PV induced by 20 min in a supine position in air, but increased the mean plasma [ANF] from 32.0 pg · ml−1, SEM 5.1 to 53.3 pg · m−1, SEM 3.6 and decreased the mean plasma [AVP] from 1.4 pg · ml −1, SEM 0.1 to 0.9 pg · ml−1, SEM 0.04. Simultaneously, diuresis and natriuresis increased markedly. During a 20-min control period in the supine posture without immersion, PV, plasma [ANF] and [AVP] remained unaffected while diuresis and natriuresis did not increase to the same extent. These data suggest that an increase in the central blood volume induced by a weak external hydrostatic pressure during supine immersion triggered the changes in plasma [ANF] and [AVP] and that the increase was probably due to a shift of blood volume from peripheral to central vessels. The changes in plasma [ANF] contributed to the changes in natriuresis.

Relative effects of the supine posture and of immersion on the renin aldosterone system at rest and during exercise

SummaryThe relative influences of the supine posture and of immersion on the renin-aldosterone system (RAS) were studied at rest and during moderate exercise in five healthy men.When supine, resting or immersion to the neck for 20 min in a thermoneutral environment both induced a decrease in plasma renin activity (PRA) when compared with the levels measured after 15 min sitting at rest (resting: −44%,p<0.05. Immersion: −45%,p<0.05). There was no significant difference in PRA decrease between the two situations. Aldosterone (ALDO) values were lower after supine rest or immersion than those observed after sitting at rest, but the difference was not significant. Two types of exercise at a constant relative work load (40–50% maximal oxygen uptake), namely cycling on an ergocycle in the supine position and free-style swimming, induced increases in PRA and ALDO when compared with the levels measured after 15 min rest when sitting (respectively, PRA=+35%,p<0.05, and +45%,p<0.05, ALDO=+32%,p<0.01 and +35%,p<0.05). Increases in PRA and ALDO did not differ between the two exercises.Thus inhibitory effects on RAS of change in external pressure are negligible during water immersion to the neck in the supine position and during swimming at moderate intensity.