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Background: In chronic kidney disease (CKD), left ventricular hypertrophy (LVH) is prevalent and is associated with increased cardiovascular morbidity and mortality. Vitamin D receptor (VDR) activation attenuates LVH progression in animal models., Methods: PRIMO is a multinational, randomized, double-blinded trial with oral paricalcitol in subjects with stages 3-4 CKD, mild-to-moderate LVH and an LV ejection fraction >50%. The primary endpoint is change in the left ventricular mass index (LVMI) compared with placebo after 48 weeks of treatment. The main secondary endpoints are changes in diastolic function parameters. In this paper, we report baseline characteristics from this study., Results: LVMI was 33.0 ± 7.5 g/m(2.7) for males and 30.8 ± 7.2 g/m(2.7) for females (p = 0.04). LVMI correlated with systolic blood pressure (r = 0.24), urine albumin creatinine ratio (r = 0.39), troponin T (r = 0.29), high-sensitivity C-reactive protein (r = 0.25) and plasma levels of B-type brain natriuretic peptide (r = 0.22); all p < 0.01. In multiple linear regression, each remained independently associated with LVMI. The early diastolic velocity of the lateral mitral annulus (E') was 8.1 ± 2.4 cm/s. E' was inversely correlated with age in univariate (r = -0.14, p = 0.04) and multivariable (p = 0.02) analysis., Conclusion: Among 227 multinational subjects with stages 3-4 CKD, baseline LVMI correlates with baseline blood pressure, urine albumin creatinine ratio and cardiac biomarkers, and baseline diastolic function correlates with age. This research was funded by Abbott Laboratories; ClinicalTrials.gov No. NCT00497146., (Copyright © 2011 S. Karger AG, Basel.)

Several factors have been blamed for increasing gastrointestinal absorption of aluminum. The likely role of iron metabolism was suggested some years ago. As iron and aluminum share many chemical properties, it is reasonable to think they also share biological pathways. The aim of this study was: (a) to evaluate serum aluminum transport and its relationship with iron-binding capacity, and (b) to investigate aluminum hydroxide absorption as a function of iron and aluminum. We investigated 127 patients with chronic renal failure undergoing hemodialysis in a study divided into two phases: phase 1, a basal study to investigate serum iron and aluminum status, and phase 2 in which an aluminum absorption test was performed. In phase 1, we found that the lower basal serum iron and iron transferrin saturation the greater serum aluminum (p < 0.001). In phase 2, we found a negative relationship between serum aluminum increments after the test and basal levels of serum aluminum and iron (r = -0.70; p < 0.001). These results suggest that the amount of either aluminum or iron carried by transferrin may influence the transferrin capacity to bind the other element and also may modulate, together with other factors, the gastrointestinal absorption of iron and aluminum.

The immediate transient baroreceptor sensitivity was measured in 9 conscious fetal and 7 conscious newborn lambs for periods of at least 35 days following bolus injections of phenylephrine (20-50 mug/kg). Mean sensitivities were unchanged throughout gestation from 105 days at 6.7 +/- 0.4 msec/cm H2O (n = 45) and were insignificantly different from those in the newborn period, 5.9 +/- 0.4 msec/cm H2O (n = 78). In contrast, baroreflex sensitivities were less in 2 fetuses and 2 newborn lambs when pressures were increased by chronically implanted thoracic aortic balloon cuff; they were 3.03 +/- 0.11 (n = 127) and 0.91 +/- 0.11 msec/cm H2O (n =61), respectively. "Steady-state" heart period-arterial pressure curves indicate that the baroreflex operates down to levels of 40 cm H2O in the fetus which is lower than that achieved in the adult of other species, rabbit and man.

Autonomic nervous control of heart rate (HR) during hypoxia was studied longitudinally using 9 chronically catheterized fetal lambs (109 day to term) and 10 newborn lambs (2--28 days old). Changes in heart rate (deltaHR) during hypoxia were age-dependent. Before 120 days of gestation deltaHR was insignificant, but between 120 days to term bradycardia occurred. The newborn response was marked tachycardia. Autonomic influences on HR were quantified using atropine and propranolol blockade. In fetal lambs, antagonistic increases in parasympathetic and sympathetic outflows were evident during hypoxia. In hypoxic lambs 120 days to term, net bradycardia reflected predominant parasympathetic cardio-deceleration; before 120 days of gestation both the parasympathetic and sympathetic outflows increased, but no net deltaHR occurred. In hypoxic newborn lambs, sympathetic and parasympathetic changes contributed synergistically to the net tachycardia. Thus the pattern of autonomic control of HR during hypoxia differs in fetal and newborn lambs. Changes in sympathetic and parasympathetic influences are antagonistic in the fetus, but synergistic in the newborn.

Reflex heart rate (HR) responses to hypotension were studied in chronically instrumented fetal and newborn lambs. Studies spanned 106-141 days of gestation and 1-22 days after birth. Brief hypotensive stimuli (10 s) were produced by inflation of a cuff implanted around the inferior vena cava; HR and mean arterial pressure (MAP) were recorded from a carotid arterial catheter. Autonomic nervous control of HR was examined using selective sympathetic beta-adrenergic blockade (propranolol 1 mg/kg), cholinergic blockade (atropine 0.2-0.3 mg/kg), and total autonomic blockade (propranolol plus atropine). In newborn lambs (n = 4) HR increased progressively as MAP was reduced in the range 5-50%. Tachycardia during mild hypotension (less than 15% MAP fall) was due to sympathetic activation as it was abolished by propranolol. During severe hypotension (greater than 30% MAP fall) tachycardia was reduced by selective beta-adrenergic blockade and by cholinergic blockade, and totally abolished by total autonomic blockade; thus withdrawal of vagal tone plus augmentation of sympathetic activity contribute to the increase of HR in response to large MAP falls in the newborn. Fetal lambs (n = 4) responded with tachycardia in mild hypotension (less than 15% MAP fall) but this was reversed when hypotension was severe (greater than 30% MAP fall). The primary tachycardia was due to sympathetic activation and was indistinguishable from the newborn response.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of autonomic nervous control of basal heart rate was studied in unanesthetized fetal lambs (93 days to term) and newborn lambs (2--29 days), using atropine and/or propranolol blockade. Fetal lambs showed a progressive increase in parasympathetic restraint of heart rate; vagal influence in the newborn lamb was similar to the term fetus. Sympathetic stimulation of fetal heart rate declined toward term, possibly due to the strongly increasing parasympathetic influence. Sympathetic influence in the newborn was similar to the early-gestation fetus. Intrinsic heart rate was about 185 beats/min throughout the fetal and newborn life span studied. Thus changes in basal heart rate resulted from a different balance of the sympathetic and parasympathetic components of the autonomic nervous outflow.