Continuous monitoring of plasma,interstitial, and intracellular fluid volumes in dialyzed patients by bioimpedance and hematocrit measurements

Bioimpedance spectroscopy (BIS) permits evaluation of extra- and intracellular fluid volumes in patients. We wished to examine whether this technique, used in combination with hematocrit measurement, can reliably monitor fluid transfers during dialysis. Ankle to wrist BIS measurements were collected during 21 dialysis runs while hematocrit was continuously monitored in the blood line by an optical device. Extracellular (ECW) and intracellular (ICW) water volumes were calculated using Hanai's electrical model of suspensions. Plasma volume variations were calculated from hematocrit, and changes in interstitial volume were calculated as the difference between ECW and plasma volume changes. Because accuracy of ICW was too low, changes in ICW were calculated as the difference between ultrafiltered volume and ECW changes. Total body water (TBW) volumes calculated pre- and postdialysis were, respectively, 3.25+/-3.2 and 1.95+/-2.5 liters lower on average than TBW given by Watson et al.'s correlation. Average decreases in fluid compartments expressed as percentage of ultrafiltered volume were as follows: plasma, 18%; interstitial, 28%, and ICW, 54%. When the ultrafiltered volume was increased in a patient in successive runs, the relative contributions of ICW and interstitial fluid were augmented so as to reduce the relative drop in plasma volume.     

Evidence of an endogenous digitalis-like factor in the plasma of patients with acromegaly

Evidence suggests that plasma-volume expansion leads to the release of a digitalis-like factor, which is thought to act on the renal tubular cells and cause natriuresis. We postulated that this factor might be present in patients with acromegaly (in whom plasma volume is elevated) and might return to normal levels when the disease was treated successfully. We measured the ability of plasma extracts from patients with acromegaly to inhibit the binding of ouabain to the sodium pump in normal red cells and to inhibit the enzymatic activity (sodium-potassium-ATPase) of the sodium pump in membrane preparations from normal kidneys. In 21 patients with active acromegaly, the mean (+/- SE) level of ouabain-binding inhibition (1.56 +/- 0.38) was higher (P less than 0.01) than that in either 11 successfully treated patients (0.18 +/- 0.05) or in 27 normal controls (0.19 +/- 0.03). The inhibition of sodium-potassium-ATPase activity by plasma was also greater in patients with active acromegaly (38.1 +/- 6.8 percent) than in successfully treated patients (18.4 +/- 5.6 percent, P less than 0.05) or controls (21.1 +/- 2.7 percent, P less than 0.05). Significant correlations were found between plasma volume and ouabain-binding inhibition in 23 patients (r = 0.72, P less than 0.01) and sodium-potassium-ATPase inhibition in 19 patients (r = 0.62, P less than 0.01). Pituitary adenomectomy decreased plasma volume and the inhibition by plasma of ouabain binding. We conclude that an endogenous digitalis-like factor is present in the plasma of patients with chronic volume expansion due to acromegaly. These results are consistent with the hypothesis that this natriuretic factor may have a physiologic role in water and sodium homeostasis.     

Alterations of vasoconstrictor and sodium-regulating hormone systems in vascularly decompensated liver cirrhosis

Plasma levels of atrial natriuretic peptide (ANP), aldosterone (PA), vasopressin (AVP), and the plasma renin activity (PRA) were examined in 15 vascularly decompensated patients suffering from liver cirrhosis, before and after administration of albumin and after a subsequent administration of furosemide. The initial ANP level was lower in 9 patients (group "A") and higher in 6 patients (group "B") than in healthy controls (Group "A": 19.5 +/- 3.0 fmol/ml; group "B": 36.7 +/- 3.9 fmol/ml; control: 25.8 +/- 2.4 fmol/ml). The initial PRA (4.4 +/- 1.0 ng AngI/ml/h) and AVP (8.5 +/- 1.5 pg/ml) activity in group "A" increased significantly compared to group "B" (PRA: 0.44 +/- 0.09; AVP: 4.1 +/- 0.5), indicating an intravascular volume depletion in group "A". Albumin infusion raised the urine and sodium excretion and the plasma concentration of ANP in group "A" but lowered in plasma levels of renin and vasopressin. The same parameters were not changed by albumin in group "B". Furosemide equally raised the urine flow rate and sodium excretion in both groups. Plasma ANP level depends on the intravascular volume, and the secondary change in its plasma concentration plays a considerable role in the retention of fluid and electrolytes in patients with cirrhosis. The increased intravascular volume in these patients depletes the fluid and electrolyte retention via the increase in ANP level.     

Atrial natriuretic peptide plasma levels during hemodialysis and hemofiltration in patients with end-stage renal disease

Using a cross-over protocol we repeatedly measured the plasma levels of alpha-hANP (atrial natriuretic peptide) during one week by radio-immunoassay in eight patients with end-stage renal disease treated with chronic hemodialysis or hemofiltration. Before each hemodialysis or hemofiltration session mean plasma ANP levels (353 +/- 112, and 337 +/- 99 pg.ml-1, respectively) were significantly above normal (50 - 166 pg.ml-1). In all but one patient, the values fell significantly towards but not reaching the normal range. Plasma ANP concentrations returned to normal at the end of the treatment in only two of the eight subjects. There was a positive correlation between the increase in body weight from one treatment to the next and the plasma ANP concentration (r = +0.35, p less than 0.05). The net loss of fluid volume during each treatment did not correlate significantly with the change in plasma ANP levels. There was no difference between hemodialysis and hemofiltration. Plasma ANP measurement may be helpful in the judgement of volume status in patients with end-stage renal disease treated by hemodialysis or hemofiltration.     

The natriuretic peptides: universal volume controllers

Since the discovery of the natriuretic effect of atrial natriuretic peptide (ANP), a family of other natriuretic peptides similar to ANP were isolated, including atriopeptin, vessel dilator, long-acting natriuretic peptide, urodilatin, and brain natriuretic peptide (BNP) to name a few. ANP was noted to possess natriuretic and diuretic properties that controlled increases in intravascular volume. ANP was also found to be elevated in conditions of increased intraocular pressure and biliary obstruction. BNP was found to be elevated in conditions of increased intracranial pressure, pointing towards its role in controlling cerebrospinal fluid volume. While at the cellular level, ANP controlled individual cell size. This makes the natriuretic peptides not only controllers of intravascular volume, but also modulators of a myriad of cavity volumes down to the control of individual cell volume.     

Increase in plasma atrial natriuretic peptides during acute volume expansion in hypertensive man

A new hormonal system originating from cardiac atria has recently been discovered. These peptide hormones have important functions in the regulation of blood volume and fluid homeostasis. We have measured plasma concentrations of atrial natriuretic peptides (ANP) in two patients during acute volume expansion. ANP concentrations increased in relation to an increase in right atrial pressure, and significant diuresis/natriuresis was observed. We conclude that hormonal as well as neuronal mechanisms are activated by acute volume loading in man.     

Body fluid volumes measurements by impedance: A review of bioimpedance spectroscopy (BIS) and bioimpedance analysis (BIA) methods

This paper reviews various bioimpedance methods permitting to measure non-invasively, extracellular, intracellular and total body water (TBW) and compares BIA methods based on empirical equations of the wrist-ankle resistance or impedance at 50 kHz, height and weight with BIS methods which rely on an electrical model of tissues and resistances measured at zero and infinite frequencies. In order to compare these methods, impedance measurements were made with a multifrequency Xitron 4200 impedancemeter on 57 healthy subjects which had undergone simultaneously a Dual X-ray absorptiometry examination (DXA), in order to estimate their TBW from their fat-free-mass. Extracellular (ECW) and TBW volumes were calculated for these subjects using the original BIS method and modifications of Matthie [Matthie JR. Second generation mixture theory equation for estimating intracellular water using bioimpedance spectroscopy. J Appl Physiol 2005;99:780–1], Jaffrin et al. [Jaffrin MY, Fenech M, Moreno MV, Kieffer R. Total body water measurement by a modification of the bioimpédance spectroscopy method. Med Bio Eng Comput 2006;44:873–82], Moissl et al. [Moissl UM, Wabel P, Chamney PW, Bosaeus I, Levin NW, et al. Body fluid volume determination via body composition spectroscopy in health and disease. Physiol Meas 2006;27:921–33] and their TBW resistivities were compared and discussed. ECW volumes were calculated by BIA methods of Sergi et al. [Sergi G, Bussolotto M, Perini P, Calliari I, et al. Accuracy of bioelectrical bioimpedance analysis for the assessment of extracellular space in healthy subjects and in fluid retention states. Ann Nutr Metab 1994;38(3):158–65] and Hannan et al. [Hannan WJ, Cowen SJ, Fearon KC, Plester CE, Falconer JS, Richardson RA. Evaluation of multi-frequency bio-impedance analysis for the assessment of extracellular and total body water in surgical patients. Clin Sci 1994;86:479–85] and TBW volumes by BIA methods of Kushner and Schoeller [Kushner RF, Schoeller DA. Estimation of total body water by bioelectrical impedance analysis. Am J Clin Nutr 1986;44(3):417–24], Lukaski et al. [Lukaski HC, Bolonchuk WW. Estimation of body fluid volumes using tetrapolar bioelectrical impedance measurements. Aviat Space Environ Med 1988;59:1163–9], Hannan et al. [Hannan WJ, Cowen SJ, Fearon KC, Plester CE, Falconer JS, Richardson RA. Evaluation of multi-frequency bio-impedance analysis for the assessment of extracellular and total body water in surgical patients. Clinical Science 1994;86:479–85], Deurenberg et al. [Deurenberg P, van der Koy K, Leenen R, Westrate JA, Seidell JC. Sex and age specific prediction formulas for estimating body composition from bioelectric impedance: a cross validation study. Int J Obesity 1991;15:17–25] These volumes were compared against those given by BIS method and, in the case of TBW, with those by DXA. For ECW, a good agreement was found between various BIS methods and that of Sergi while Hannan's values were higher. Both Matthie's and Moissl's methods gave mean TBW resistivities and volumes lower than those of Jaffrin's and DXA methods. Kushner et al. method gave values of TBW not significantly different from those of Jaffrin et al. and DXA, as Hannan's method in men, but Lukaski and Deurenberg methods led to an underestimation.     

Plasma arginine vasopressin, atrial natriuretic peptide and brain natriuretic peptide responses to long-term field training in the heat: effects of fluid ingestion and acclimatization

The maintenance of blood volume during exercise, especially in a hot environment, is of major importance for continued performance. In order to investigate the relationships between exercise, type and amount of fluid intake and the degree of acclimatization to heat stress and on responses of arginine vasopressin (AVP), atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), we studied 24 soldiers during and after jogging/walking exercise both before and after acclimatization to field training at [mean (SE)] 40 (0.7) °C and 32 (3)% relative humidity. The running exercise was carried out under three conditions, i.e., (1) without any fluid intake, (2) with intake of water or (3) with intake of a dextrose/electrolyte solution. Venous blood samples were drawn before exercise, at the end of exercise and at 15 min and 60 min afterwards. Acclimatization resulted in significant losses of body mass, total body water, plasma volume, ANP and increases in plasma osmolality, packed cell volume and AVP at rest but without any significant changes in BNP. During exercise with no fluid intake, there was a significant rise in plasma osmolality, Na⁺ and AVP, but no significant alterations in plasma ANP and BNP were observed. When subjects ingested water or dextrose/electrolyte solution during exercise, ANP rose by 234% and 431% respectively and BNP rose by 398% and 583% respectively without any significant increase in AVP. The results suggest that, during acclimatization, the subjects became slightly dehydrated. Alterations in response to changes in body water status appear to be greater for AVP than ANP or BNP at rest. During exercise in the heat ANP and BNP may play complementary roles.     

维持性血液透析患者血浆ANP和BNP动态变化的意义

目的：探讨ANP、BNP评估维持性血液透析患者水平衡及干体重的价值。方法：40例血液透析龄≥1年的稳定的MHD患者为MHD组,40名健康志愿者为正常对照组。应用放免法检测稳定的MHD患者血液透析前后和透析间期ANP、BNP动态的变化;观察平均每日尿量对MHD患者血液透析前后和透析间期血浆ANP、BNP动态变化影响。结果：MHD患者血浆ANPOh、24h、48h高于-4h（Oh、24hP〈0．01,48hP〈0．05）,24h、48h低于Oh（P〈0．01）;48h低于24h（P〈0．05）;血浆BNP血液透析前后和透析间期无差异;MHD患者血浆ANP-4h、24h、48h均低于正常对照组（P〈0．01）,0h高于正常对照组（P〈0．05）;MHD患者血浆BNP-4h、0h、24h和48h均明显高于正常对照组（P〈0．01）。0h达干体重和未达干体重的MHD患者血浆ANP、BNP无差异;少无尿的MHD患者血浆ANP、BNP和有尿的MHD患者相比无统计学差异。结论：血浆ANP、BNP可以反映MHD患者的容量状况,BNP水平随容量的增加而增高,且对于容量的评价作用优于ANP,但二者评估干体重不敏感。提示严格控制血压,控制透析间期容量负荷增长,是预防MHD患者心脑血管事件发生的重要措施。     

Changes in blood pressure, fluid volumes and glomerular filtration rate during long-term treatment with prizidilol, an antihypertensive drug with combined vasodilatator and beta-adrenoceptor blocking actions

The long term effects on blood pressure, body fluid volumes, glomerular filtration rate and plasma renin concentration were studied in 11 patients with essential hypertension during treatment with prizidilol, which is an antihypertensive compound with combined vasodilatator and beta-adrenoceptor blocking actions. After the patients had been treated for four weeks with placebo, the active treatment was given for 12 weeks. Prizidilol reduced both supine and erect blood pressure by 26/14 mmHg (p less than 0.01) and 24/16 mmHg (p less than 0.01) respectively, without inducing significant changes in heart rate. Plasma volume increased significantly by eight percent (p less than 0.02), whereas the increase in extracellular fluid volume was insignificant. Glomerular filtration rate decreased by 4 ml/min./1.73 m2 (p less than 0.02). Plasma renin concentration was unchanged. Prizidilol was tolerated well, but six patients developed oedema and gained weight, which necessitated addition of diuretics in three patients.     

Effects of chronic salt loading on plasma atrial natriuretic peptide (ANP) in the spontaneously hypertensive rat

Plasma concentrations of immunoreactive atrial natriuretic peptide (ANP) was measured in spontaneously hypertensive rats (SHR) during chronic salt loading (1.5% NaCl in drinking water). During the 3-week experimental period mean arterial blood pressure, heart rate, urinary sodium excretion and body weight was assessed in salt-loaded as well as in control rats. The sodium excretion was more than 10-fold increased in the rats on the high salt diet. The plasma ANP concentration was significantly increased only 24 h after the start of the high salt intake. Thereafter plasma ANP concentrations were not significantly different from values obtained in control rats. The blood pressure was significantly increased after 3 weeks on the high salt diet. At the end of the 3-week experimental period the rats were subjected to a 10 and 20% acute volume expansion with homologous whole blood. During this intervention the increase in plasma ANP concentrations was blunted in the high salt rats compared to the control group. It is concluded that during chronic salt loading in SHR there is an initial rise in plasma ANP levels and that other hormonal and neuronal systems are more important in the long term maintenance of fluid and electrolyte balance.     

Correlation of blood pressure in end-stage renal disease with platelet cytosolic free calcium concentration during treatment of renal anemia with recombinant human erythropoietin.

The hemodynamic hallmark of hypertension complicating the treatment of renal anemia with recombinant human erythropoietin (rHu-EPO) is increased total peripheral vascular resistance, but the mechanisms underlying the arteriolar vasoconstriction are still an enigma. We studied body fluid volumes, plasma renin activity, plasma norepinephrine, and calcium metabolism in platelets in 40 previously normotensive hemodialysis patients before and after 12 weeks of rHu-EPO treatment. Partial correction of anemia caused a rise in arterial pressure (94 +/- 6 mmHg vs 124 +/- 7 mmHg, p less than 0.05) and in platelet cytosolic calcium concentration (113 +/- 5 nM vs 171 +/- 18 nM, p less than 0.05) in eight patients. Hypertensive patients had significantly higher plasma noradrenaline concentrations, but they did not differ significantly in body fluid volumes and plasma renin activities. There was a close correlation between free calcium concentration in platelets and mean arterial pressure in patients developing rHu-EPO-induced-hypertension (r = 0.95). Short-term antihypertensive treatment resulted in a reduction of free calcium concentrations in platelets and a concomitant fall in blood pressure. The main results of the present studies suggest that rHu-EPO-induced hypertension might be associated with altered cellular calcium homeostasis and hyperactivity of the sympathetic nervous system. If rHu-EPO therapy induces alterations of pressor factors or the hormone itself raises the cytosolic calcium not only in platelets but also in vascular smooth muscle cells, altered cellular calcium influx may contribute to the arteriolar vasoconstriction.     

Gravitational stress and volume regulation.

During the past 3 decades, groundbased experiments have been performed in order to investigate the effects of increased and decreased gravitational stress, respectively, on the renal response in humans. Experiments that simulate an increase in gravitational load (+Gz) to the subjects (centrifugation, passive head-up titlt [HUT] or lower body negative pressure [LBNP] have clearly demonstrated a decrease in renal sodium and water excretion. Simultaneously, increases in plasma levels of arginine vasopressin (AVP), renin activity (PRA), aldosterone (PA), norepinephrine (NE) and decreases in ANP have been observed. Additionally, experiments that have utilized immersion of seated subjects to simulate a decreased gravitational stress (approximately 0 Gz) have demonstrated that renal water and sodium excretion increases by 100-400% and that plasma AVP, PRA, PA, and NE concentrations are reduced and ANP levels increased. Alternative experimental models conducted to simulate the effects of weightlessness in humans such as head-down tilt (HDT) and lower body positive pressure (LBPP) have yielded less consistent results than those of water immersion (WI) with respect to renal function. However, compared to a seated control HDT clearly induces an increased rate of renal fluid and sodium excretion. The demonstration that central volume expansion during WI is accompanied by an increase in renal fluid and electrolyte excretion and that central hypovolaemia during centrifugation, HUT, and LBNP is accompanied by the opposite effects indicate that changes in central blood volume is an important determinant of the renal functional changes. Results of experiments in humans during weightlessness in space are inconsistent and difficult to interpret. However, they have indicated that a cephalad redistribution of blood and fluid occurs and that this is accompanied by a decrease in total body fluid. Experimental models that, respectively, increase and decrease the gravitational stress in humans constitute promising tools in the investigation of the physiology and pathophysiology of volume regulation.     

Atrial natriuretic peptide attenuates pressor but enhances natriuretic responses to angiotensin II in pregnant conscious goats.

This study was designed to examine the actions of ANP in acute, ANGII-mediated hypertension during pregnancy. Effects on blood pressure, blood volume, and renal Na and K excretion were evaluated in conscious goats (n = 6). ANP (2 micrograms min-1), ANGII (0.5 microgram min-1), or ANGII+ANP (doses the same as for each peptide alone) was infused intravenously for 60 min. The pressor response to ANGII was reduced in pregnant goats. This reduction was seen in systolic, but not in diastolic pressure. ANP decreased pressure by 5-10 mmHg both in pregnancy and in non-pregnancy. When ANGII+ANP was infused, blood pressure initially rose as with ANGII but then declined. ANP suppressed only the elevated systolic pressure. Plasma protein concentration and haematocrit was reduced by ANGII but increased by ANP alone or together with ANGII, thereby implying fluid shift into the vasculature by ANGII and opposite movement by ANP. ANGII increased renal Na excretion to 1500 mumol min-1 in non-pregnancy, but only to half of that in pregnancy. ANP alone caused small natriuresis, but enhanced ANGII-induced natriuresis to near 3000 mumol min-1 in both non-pregnant and pregnant goats. In summary, ANP further attenuated the blunted blood-pressure rise due to ANGII in pregnant goats, and reduced plasma volume, but enhanced renal Na excretion as in non-pregnant goats. This implies that with the present combination ANP and ANGII caused a near maximal natriuretic response that was not modified by the systemic cardiovascular changes occurring in pregnant goats.     

Restoration of hemorrhaged plasma volume by gastrointestinal fluid in the dog

Conscious, intact and splenectomized, male dogs were hemorrhaged 35 percent of their blood volumes (23 +/- 3 and 25 +/- 4 ml/kg, respectively) from carotid loop cannulas. Isotonic saline or glucose solutions were administered by gastric tube in volumes equal to the blood volume hemorrhaged. Plasma volume, mean arterial blood pressure, venous hematocrit, plasma protein concentration, and interstitial fluid pressure were monitored after hemorrhage and after fluid treatment. The magnitudes of plasma volume restoration 8 h after hemorrhage in the nontreated dogs averaged 56 +/- 9 percent of the hemorrhaged volume and did not differ significantly between intact and splenectomized dogs. Plasma volumes, however, were increased significantly by enterally administered fluids. The maximum rates of plasma volume restoration occurred within the 1st h after fluid treatment. Approximately 46 percent and 28 percent of the hemorrhaged plasma volume was replaced by saline and glucose solutions, respectively, during this period. Results support the hypothesis that fluid is absorbed from the gastrointestinal tract following hemorrhage, and that enterally administered fluids restore plasma volume at a rate and to an extent exceeding that provided by net interstitial fluid exchange alone.     

Attenuated release of atrial natriuretic peptide and vasorelaxation in streptozotocin-induced diabetic rats.

The present study was aimed at investigating the atrial natriuretic peptide (ANP) and urinary responses to acute perturbations in fluid balance and the vascular function in diabetes mellitus (DM). DM was induced in rats by treatment with streptozotocin (50 mg/kg, i.p.). Ten weeks later, the plasma ANP concentration measured in the conscious state was significantly higher in DM group (27.5 +/- 3.9 pg/mL) than in the control (15.4 +/- 2.6 pg/mL), while the atrial tissue contents of ANP were lower. In response to acute extracellular volume expansion (VE), amounting up to 5% of body weight over 45 min, under thiopental anesthesia (50 mg/kg, i.p.), the magnitude of increase in plasma ANP was lower in the DM group than in the control (56.8 +/- 25.2 vs. 189.1 +/- 53.6% increases over the basal). Urinary sodium excretion during VE was also lower in the DM group. Acetylcholine-induced relaxation of the isolated aortic rings was attenuated in the DM group, which was partially restored by L-arginine-supplementation (2 g/L in drinking water). These results suggest that body fluid homeostasis and vascular functions are unfavorably altered in DM.     

Redistribution of body fluids during postural manipulations

Inter-compartmental body-fluid distribution is contingent upon posture, exercise state and environmental temperature. This investigation aimed at quantifying the distribution of intra- and extravascular fluid volumes during postural manipulations. Fluid shifts were measured in eight males utilizing a simultaneous, radionuclide dilution technique, in which radioiodinated serum fibrinogen, radiochromated crythrocytes, radiobromine and tritiated water were used to measure plasma, red cell, extracellular and total body water volumes. Subjects were exposed to three postural changes [seated (control), supine and standing] for 30 min at an air temperature of 22.0 d?C, with each posture separated by 30 min seated rest. Total body water content remained stable throughout postural changes (P= 0.842). Relative to seated volumes, BV increased by 89 mL when supine, and decreased by 406 mL while standing (P= 0.003), with such shifts being primarily a result of plasma movement (P= 0.011). Red cell volume changes were not significant. Vascular fluid lost during standing was filtered into the interstitial compartment (P= 0.014), with the extracellular and intracellular volumes remaining unaffected (P= 0.271 and P= 0.800, respectively). These observations confirmed the influence of posture on inter-compartmental body-fluid distribution. The intravascular fluid loss when standing was caused by the filtration of plasma into the interstitium, while, during supine rest, intravascular volume increased, reflecting fluid flux from the interstitium to the circulation.     

Extracellular fluid volume and composition changes during sodium pentobarbitone anaesthesia in the dog

Serial measurements of extracellular fluid (ECF), and plasma volumes were evaluated in dogs before and during general anaesthesia with sodium pentobarbitone and under controlled conditions of arterial pH, pO2, pCO2, and blood pressure. Sodium pentobarbitone anaesthesia caused an early, significant rise in ECF volume with a fall in haematocrit, plasma protein, and plasma potassium concentrations. Plasma osmolality and sodium concentrations were unchanged. The lack of change in ECF sodium concentration suggests that the total ECF sodium content increased in parallel with the expansion of this compartment. Sodium bound to macromolecules in the interstitial space or to bone is suggested as a possible source of sodium ions. It is unlikely that intracellular sodium stores contribute to a significant extent in these changes. During prolonged anaesthesia plasma volume progressively increased while total ECF volume returned towards control values. This work clarifies previous observations and suggests that major fluid movements occur during sodium pentobarbitone anaesthesia primarily associated with altered cell membrane properties and generalised haemodynamic changes.     

Plasma concentrations of atrial natriuretic peptide, arginine vasopressin and hormones of the renin-angiotensin system in patients with end-stage renal disease

Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), plasma renin activity (PRA) and aldosterone, were measured before and after 3 h of hemodialysis in 9 patients with end-stage renal disease on maintenance hemodialysis. Hormone concentrations were also determined in the same patients on a separate occasion after 1 h of ultrafiltration (UF). Plasma concentrations of ANP were significantly higher in the patients with ESRD than in a normal reference population and declined after both 1 h and 3 h of hemodialysis. Plasma concentrations of ANP failed to exhibit a significant decline after 1 h of UF. Plasma AVP concentrations were not significantly different after either hemodialysis or UF, while plasma aldosterone concentrations fell with hemodialysis. The decline in plasma aldosterone concentrations paralleled the decrease in dialysis-induced fall in serum potassium concentrations. There was no correlation between the blood pressures, heart rate, interdialytic weight gain and estimated fluid overload and any of the hormones measured except for the plasma renin activity (PRA) which correlated significantly with the systolic blood pressure. The data suggest that ANP may not be a major factor in blood pressure regulation in normotensive patients with ESRD and its elevation in patients with ESRD is most likely due to fluid overload and atrial distention as well as a possible reduction in its metabolic clearance in renal insufficiency. The fall in plasma ANP following hemodialysis is not due to its removal by dialysis but is most likely due to a reduction in ANP production caused by dialysis-induced correction of hypervolemia.     

Study of genotype frequencies of ANP 664G/A polymorphism in normal subjects and CVD patients, and its association with plasma ANP levels

Atrial natriuretic peptide (ANP) plays a crucial role in regulating body fluid volume and blood pressure, by promoting natriuresis and vasodilatation and by inhibiting the renin-angiotensin system. Plasma levels of ANP are elevated in heart failure and hypertension, and ANP is thus believed to be involved in the pathogenesis of cardiovascular disorders. Previous case-control studies have shown that a single nucleotide polymorphism in the first exon of ANP gene, 664G/A, is associated with a risk of cerebrovascular disease (CVD) in white populations. Plasma ANP levels, however, were not evaluated in these studies in relation to the 664G/A, although the nucleotide substitution causes an amino-acid change in the propeptide of ANP. In this study, we analyzed the genotype frequencies of the 664G/A in Japanese patients with CVD (n = 199) and age- and gender-matched control subjects(n = 176). Genotypes with the 664A allele in the Japanese control subjects (G/A and A/A 12.5%) were apparently more frequent compared to the published frequency of the white control population (G/A and A/A 6.6%, p = 0.0437). Genotypes with the 664A allele, however, were not significantly different between our CVD patients(15.1%) and controls (12.5% p = 0.4714). In the control group (n = 137), the mean plasma ANP levels were not different between the 664G/G (15.7 +/- 10.7 pg/ml) and 664G/A genotypes (15.6 +/- 6.8 pg/ml, p = 0.9708). These results suggest that there is a racial difference in the allele frequency of 664G/A, and that this polymorphism may not be a major risk factor for CVD in the Japanese, nor is it a major determinant of plasma ANP level.