Normotensive Hemodialysis Patients Research Articles

Comparative Evaluation of the Two Dimensional and Three Dimensional Echocardiography in the Assessment of the Right Ventricular Functions in Nondiabetic Normotensive Hemodialysis Patients

AbstractBackground: Cardiovascular diseases are one of the most important causes of death in hemodialysis patients. Few researches focused on the right ventricle functions in such patients. The rapid development of the 3D echocardiography gave a new dimension in the diagnosis and treatment plan.Aim of Study: To compare the two dimensional (2D) and three dimensional (3D) echocardiography in the assessment of right ventricular functions in nondiabetic, normotensive, hemodialysis patients.Patients and Methods: The study included 20 patients who were subjected to complete history tacking, full clinical examination, laboratory investigations and assessment of the right ventricular functions using 2D and 3D echocardiography.Results: The 3D echocardiography showed statistically significant differences compared to the 2D echocardiography in the assessment of the right ventricular functions. Fractional area change showed a mean of 33.25±9.21 compared to 38.05± 7.88 of the ejection fraction gained from the 3D echocardiog-raphy. The sensitivity and specificity of the 3D echocardiog-raphy were 100% and 80% compared to 73.3% and 60% for the 2D echocardiography. Moreover the degree of accuracy of the 3D echocardiography was 95% compared to 70% for the 2D echocardiography.Conclusion: The 3D echocardiography was more superior than the 2D echocardiography in the assessment of right ventricular functions in nondiabetic, normotensive, hemodi-alysis patients.

Echocardiographic assessment of right ventricular functions in nondiabetic normotensive hemodialysis patients.

Heart is affected structurally and functionally in end-stage renal disease (ESRD). However, the data available about adverse effects of ESRD on right ventricle (RV) is scarce. We aimed to evaluate echocardiographic parameters of RV in nondiabetic, normotensive patients with ESRD undergoing hemodialysis (HD). A total of 45 (24 women; mean age 52.4 ± 12.4 years) consecutive nondiabetic, normotensive patients with ESRD undergoing HD and 39 healthy age and sex-matched control subjects (22 women; mean age 50.3 ± 6.6 years) were enrolled in the study. M-mode and two dimensional images, color, pulsed and continuous wave Doppler, and tissue Doppler measurements were acquired from all subjects. Echocardiographic evaluation was performed in the days between HD dates of the patients. RV fractional area change, tricuspid annular plane systolic excursion, tricuspid E velocity, E/A ratio, tricuspid annular E´ velocity, and E´/A´ ratio were lower in patients than controls (p < 0.001, p = 0.003, p = 0.007, p = 0.005, p < 0.001, and p = 0.034, respectively). However, RV diastolic area, RV myocardial performance index, E/E´ ratio, and mean and systolic pulmonary artery pressure were higher in patients than controls (p < 0.001, p = 0.007, p = 0.005, p < 0.001, p = 0.006, respectively). RV systolic and diastolic functions of nondiabetic, normotensive HD patients are deteriorated as compared to healthy controls.

The Effects of a Single Dialysis Session on Atrial Electromechanical Conduction Times and Functions

Background/Aims: Abnormalities in atrial electromechanical delay (EMD) times and mechanical functions are considered as independent predictors of atrial fibrillation. However, to date, effects of a single hemodialysis (HD) session and acute volume-preload changes on atrial-EMD functions have not been investigated by Tissue Doppler Echocardiography (TDE). The aim of the present study was to evaluate atrial-EMD times and mechanical functions in HD patients. Methods: Thirty-five non-diabetic, normotensive HD patients and 35 healthy control subjects were enrolled in the study. Standard and TDE performed before mid-week dialysis session for hemodialysis group and on admission for control group. Results: Interatrial and left-right intraatrial-EMD intervals and left atrial mechanical volumes were significantly longer in hemodialysis group compared to controls (all p<0.01) and were reduced after HD session. Furthermore, removed ultrafiltration volume was associated with reduction in atrial-EMD intervals and functional volumes. LA-passive emptying volume, ultrafiltration volume, LV-E/E' ratio, and V_p were independent predictors of interatrial-EMD. Conclusions: The present study confirms negative effects in HD patients of structural remodeling and reveals negative effects of electrical remodeling. Prolonged inter and intraatrial-EMD intervals should be the underlying pathophysiological factors of increased rate of atrial fibrillation in the HD population.

Cardiovascular determinants of prognosis in normotensive hemodialysis patients

BackgroundNormotension has been hold to be the goal of hemodialysis. It remains obscure which cardiovascular parameter determines the prognosis in these normotensive hemodialysis patients.MethodsWe prospectively enrolled 145 hemodialysis patients, who had attained normotension without anti-hypertensive medications, and followed them for 72.6 ± 28.5 months. Important cardiovascular parameters were obtained at enrollment. Predictors for all-cause and cardiovascular mortalities were identified with the Cox model.ResultsThere were 45 (18 cardiovascular/27 non-cardiovascular) deaths occurred during follow-up. Age, diabetes, left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), carotid intima-media thickness (CIMT), and aortic pulse wave velocity (PWV) were significant predictors for all-cause and cardiovascular mortalities. After adjustment for age and diabetes, only LVEF was significantly associated with all-cause mortality. LVEF was significantly associated with cardiovascular mortality. LVEF remained as a significant independent predictor of cardiovascular death after adjusting for age, diabetes, LVMI, CIMT, or PWV, respectively.ConclusionLVEF is the independent predictor for all-cause and cardiovascular mortalities in the normotensive hemodialysis patients.

Chronic hypotension in hemodialysis patients: role of functional vascular changes and vasodilator agents

The aim of this study was to evaluate the hemodynamic pattern, vascular compliance, as well as the levels of vasoregulatory hormones and markers of inflammation and oxidative stress in a group of chronic hypotensive (CH) patients undergoing hemodialysis (HD) and to compare them with a group of normotensive HD patients. 14 normotensive and 10 CH hemodialysis patients were included in the study. Hemodynamic characteristics were evaluated by means of the pulse waveform analysis. Plasma levels of nitrites, interleukin-6 (IL-6), malondialdehyde (MDA), PTH-related peptide (PTHrp), catecholamines, angiotensin II and endothelin were measured. Blood pressure (BP) and peripheral vascular resistances (PVR) were lower in the hypotensive group (p < 0.001 and p = 0.005, respectively), whereas cardiac output was similar in both groups. Large (C1) (p = 0.001) and small (C2) (p = 0.022) artery elasticity indices were higher in hypotensive patients. In the whole group, C1 and C2 inversely correlated with mean BP (MBP). Plasma levels of nitrites (p = 0.011) were higher in hypotensive patients and inversely correlated with MBP (r = -0.516, p = 0.012). Time on HD correlated with plasma nitrites (r = 0.478, p = 0.024) and inversely with MBP (r = -0.598, p = 0.003). CH in HD patients is characterized by decreased PVR, a preserved cardiac output and greater vascular compliance. CH is associated with longer time on HD and higher plasma levels of nitrites/nitrates, suggesting that an enhanced production of nitric oxide induced by long-term HD, could be involved in CH. These findings suggest that functional vascular changes, likely related to an enhanced production of vasodilator agents, are responsible for CH in HD patients.

Effect of Ramipril on Left Ventricular Mass in Normotensive Hemodialysis Patients

Normotensive hemodialysis patients may still have left ventricular hypertrophy in the absence of significant pressure or volume overload. We examined the hypothesis that treatment with an angiotensin-converting enzyme inhibitor could be beneficial in the reversal of left ventricular hypertrophy in these patients. Forty-six normotensive patients with end-stage renal disease on regular hemodialysis therapy were randomly assigned to administration of ramipril, 2.5 mg 3 times/wk, or placebo for 1 year. Left ventricular mass index and parameters of cardiovascular structure and function were evaluated noninvasively by means of echocardiography and arterial tonometry at baseline, 6 and 12 months after treatment, and 1 month after washout. In the ramipril group, blood pressure decreased significantly at 6 and 12 months after treatment. There were no significant within-group or between-group differences in left ventricular mass index at entry, 6 and 12 months after treatment, and 1 month after washout. There were no significant differences in left atrial dimension, left ventricular size and wall thickness, left ventricular ejection fraction, aortic dimension, intima-media thickness, elastic modulus and augmentation index of the common carotid artery, and aortic pulse wave velocity between the ramipril and placebo groups at entry, 6 and 12 months after treatment, and 1 month after washout. A 12-month treatment with ramipril did not cause significant regression of left ventricular hypertrophy in normotensive hemodialysis patients. Results may suggest that the renin-angiotensin system has little role in the pathogenesis of mild left ventricular hypertrophy in these patients.

Left ventricular mass and hemodynamic overload in normotensive hemodialysis patients

It remains uncertain whether the hemodynamic parameters are important determinants of left ventricular mass (LVM) in normotensive chronic hemodialysis (NTHD) patients, as has been found in their hypertensive counterparts. Forty NTHD patients (mean age, 53.7 +/- 14.4 years; male/female, 18/22) without the requirement of antihypertensive drugs for at least six months were studied. Controls were 41 hypertensive hemodialysis patients (HTHD) and 46 normotensive subjects with normal renal function (NTNR). The influence of anthropometrics, cardiovascular structure and function, and volume status on LVM (by two-dimensional echocardiography) was analyzed by steps of multiple linear regression. As compared with the NTNR and NTHD group, the HTHD group had obvious pressure and volume/flow overload, and greater LV wall thickness, chamber size and mass. In contrast, NTHD subjects had similar blood pressure, large artery function, LV chamber size and stroke volume as the NTNR subjects. However, the NTHD patients still had greater wall thickness and LVM, along with greater cardiac output, lower total peripheral resistance and lower end-systolic meridional stress to volume ratio (ESSV) than the NTNR group. LVM in the NTHD group was significantly positively related to averaged systolic blood pressure (SBPavg), body surface area, extracellular fluid (ECF), carotid intima-media thickness (IMT), aortic pulse wave velocity (PWV), and negatively related to ESSV and Kt/V. The independent significant noncardiac structural determinants of LVM in NTHD subjects were ESSV, SBPavg, PWV and SV (model r2 = 0.617, P < 0.001). The NTHD patients, without significant pressure and volume overload, still had increased LVM that was partially explained by the persistent flow overload and subclinical LV dysfunction.

The vascular endothelin system is not overactive in normotensive hemodialysis patients

The hemodynamic significance of elevated endothelin-1 (ET) plasma levels in hemodialysis (HD) patients is unknown. Therefore, we studied the role of ET in the regulation of vascular tone in normotensive HD patients and matched healthy controls (C). The forearm blood flow (FBF) responses to adenosine, norepinephrine, the ET-A receptor antagonist BQ-123 (40 nmol/min), the ET-B receptor antagonist BQ-788 (1 and 50 nmol/min), and ET (5 pmol/min) were measured. Results are percent of baseline change +/- SEM (baseline = 100%). Responses to adenosine and norepinephrine were both unchanged in HD. In HD, BQ-123 increased FBF less than in C (133 +/- 9 vs. 178 +/- 27%; P = 0.02). BQ-788 failed to change FBF in C but decreased FBF to 83 +/- 4% in HD. Compared to BQ-123 alone, BQ-123 plus BQ-788 (50 nmol/min) caused an additional increase of FBF (234 +/- 32%, P < 0.001) in C, but not in HD (139 +/- 14%). This additional increase was absent when BQ-788 was co-infused at 1 nmol/min. ET reduced FBF comparably in both groups. Resistance vessels of HD patients have unremarkable contractile properties, as shown by responses to adenosine and norepinephrine. In HD, the basal vascular ET-mediated tone is reduced. The main action of the ET-B receptor in C is vasoconstrictive, which also is blunted in HD. The intact response to exogenous ET indicates the normal function of ET receptors in HD. Our results could be explained by a reduced generation or reduced metabolic clearance rate of ET in normotensive HD patients. Controversy remains concerning the role of the ET-B receptor when comparing the present data with previously published literature.

PARATHORMON, CALCIUM, PHOSPHORUS, AND LEFT VENTRICULAR STRUCTURE AND FUNCTION IN NORMOTENSIVE HEMODIALYSIS PATIENTS

Clinical and experimental data suggest that Parathormon (PTH), calcium, and phosphorus participate in left ventricular hypertrophy (LVH) and affect myocardial contractility in end-stage renal disease. Cellular calcium overload and interstitial fibrosis induced by PTH may lead to impairment of left ventricular diastolic function. Hyperphosphatemia is an independent risk of cardiovascular mortality in dialysis patients. The aim of the study was to estimate the influence of PTH and calcium-phosphorus metabolism on left ventricular structure and function in hemodialysis patients, without hypertension and antihypertensive drug therapy (SBP = 126.2 ± 11.1 DBP = 75.8 ± 6.5 mmHg). Echocardiographic findings in a group of 22 normotensive HD patients had been compared to 43 hypertensive HD patients. Relationships between PTH, calcium-phosphorus metabolism and echocardiography in normotensive group were then evaluated. Left ventricular mass index (LVMI) was lower in normotensive patients: 128.3 ± 46.2 versus 165.8 ± 46.7 (p < 0.01). The prevalence of LVH was 55% in normotensive HD patients compared to 86% in hypertensive group (p < 0.01). In normotensive group we found correlation between PTH and LVMI (r = 0.44; p < 0.05). There were also significant relationships between calcium and posterior wall thickness (r = −0.44; p < 0.05), phosphorus and LVMI (r = 0.47; p < 0.05). A significant correlation was observed between both phosphorus, calcium × phosphorus product and E/A ratio: r = −0.47 and r = −0.43, respectively (p < 0.05 both). Disturbances of calcium-phosphorus metabolism and secondary hyperparathyroidism contributes to left ventricular hypertrophy, and impaired left ventricular diastolic function in normotensive hemodialysis patients.

No Association between Deletion-Type Angiotensin-Converting Enzyme Gene Polymorphism and Left-Ventricular Hypertrophy in Hemodialysis Patients

Left-ventricular hypertrophy (LVH), a bad prognostic sign, is a common finding in hemodialysis patients. The aim of the study was to analyze factors, including angiotensin-converting enzyme (ACE) genotype that may have an effect on the development of LVH in hemodialysis patients. Seventy-nine hemodialysis patients (42 males, 37 females, mean age 37.7 ± 13.1 years) and 82 age- and sex-matched normotensive healthy controls (40 males, 42 females, mean age 35.6 ± 5.7 years) were included. Left-ventricular mass index (LVMI) was higher in the hemodialysis group compared to controls (170.1 ± 69.3 versus 84.9 ± 15.7 g/m², p < 0.001). Fourty-three hypertensive patients in the hemodialysis group had an increased LVMI compared to 36 normotensive hemodialysis patients (194.2 ± 75.5 versus 141.2 ± 48.0 g/m², p < 0.001). On univariate analysis, LVMI was found to be correlated with blood pressure (r = 0.38, p < 0.001), time spent on dialysis (r = 0.22, p = 0.02) and hemoglobin levels (r = –0.21, p = 0.03). No correlation was found between LVMI and age (r = 0.09, p = 0.22), predialytic creatinine (r = 0.09, p = 0.21) and albumin (r = –0.10, p = 0.18). On multivariate analysis for the predictors of LVMI, blood pressure, time spent on dialysis and hemoglobin levels were also found to be significant. LVMI in DD, ID and II genotypes were 155.0 ± 71.2, 181.6 ± 60.6, and 163.6 ± 83.4 g/m², respectively (p > 0.05). No association between LVMI and DD genotype was found. ACE genotype distribution was similar in hemodialysis patients and healthy controls. It was concluded that LVH in hemodialysis patients was mainly related to hypertension, anemia and time spent on dialysis and the DD genotype had no effect on LVMI in hemodialysis patients.

Role of volume overload in dialysis-refractory hypertension

It has been observed that while most hypertensive hemodialysis patients normalize their blood pressure with volume removal, there is a population of hemodialysis patients whose hypertension is refractory to volume removal. Our hypothesis is that such patients are still volume overloaded posthemodialysis and are not at a “true” dry weight. This study used atrial natriuretic peptide (ANP) assays (as a marker of hydration status) to study this hypothesis. Three groups of patients were studied: normotensive hemodialysis patients (n = 12; group 1), hypertensive hemodialysis patients who consistently normalize their blood pressure with fluid removal (n = 12; group 2), and hypertensive hemodialysis patients whose hypertension is refractory to fluid removal (n = 9; group 3). Plasma ANP levels were measured before and after hemodialysis by radioimmunoassay after extraction on Sep-Pac (Penninsula Laboratories, Belmont). On the day of study the predialysis mean arterial pressures in the three groups were 94.9 ± 1.9 mm Hg in the normotensive group, 119.5 ± 2.7 mm Hg in the dialysis-sensitive hypertension group, and 134.4 ± 3.8 mm Hg in the dialysis-refractory hypertension group ( P < 0.05 for comparisons between all groups). Mean arterial pressure did not change predialysis and postdialysis in the normotensive group (94.9 ± 1.9 mm Hg to 93.1 ± 1.8 mm Hg, respectively; P = 0.24), decreased in the dialysis-sensitive hypertension group (119.5 ± 2.7 mm Hg to 100.8 ± 3.7 mm Hg, respectively; P < 0.0001), and did not change in the dialysis-refractory hypertension group (134.4 ± 3.8 mm Hg to 133.8 ± 2.9 mm Hg, respectively; P = 0.77). Predialysis and postdialysis serum ANP levels were, respectively, 235.8 ± 27.7 pg/mL and 237.8 ± 36.2 pg/mL ( P = 0.92) in the normotensive group, 809.2 ± 295.5 pg/mL and 161.1 ± 48.6 pg/mL ( P = 0.03) in the dialysis-sensitive hypertension group, and 1,728.3 ± 309.9 pg/mL and 1,936.1 ± 359.1 pg/mL ( P = 0.22) in the dialysis-refractory hypertension group. Mean predialysis ANP levels were higher in the dialysis-refractory hypertension group than in the dialysis-sensitive hypertension group (1,728.3 ± 309.9 pg/mL v 809 ± 359.1 pg/mL; P = 0.048). Mean prehemodialysis ANP in all hypertensive patients (n = 21) was higher (1,203.1 ± 232.9) than in the normotensive patients (235.8 ± 27.7) ( P = 0.004). In conclusion, our findings are consistent with a hypothesis that inadequate removal of excess volume during hemodialysis plays a major role in dialysis-refractory hypertension.

Studies of the vessel wall properties in hemodialysis patients

Compliance is an important property of the arterial system and abnormalities in compliance can greatly affect cardiovascular function. The elastic properties of the common carotid artery were therefore studied in 24 normotensive hemodialysis patients and 24 healthy normotensives using a noninvasive technique. The hemodialysis patients and the control subjects were matched for blood pressure. Arterial distension was measured by Doppler analysis of the vessel wall movements and blood pressure was recorded by finger-phlethysmography (Finapres). The vessel wall distensibility (DC: 2.49 +/- 0.23 10(-3)/mm Hg; mean +/- SEM) was significantly reduced and the end diastolic diameter (d: 7.3 +/- 0.3 mm) was significantly increased in younger hemodialysis patients (36.3 +/- 2.0 years) when compared with age-related controls (DC: 3.44 +/- 0.24 10(-3)/mm Hg; d: 6.3 +/- 0.3 mm; mean +/- SEM). In older hemodialysis patients (60.2 +/- 2.3 years), there was no significant difference in vessel wall distensibility (DC: 1.55 +/- 0.15 10(-3)/mm Hg) and vessel diameter (d: 7.8 +/- 0.3 mm) as compared with age-matched controls (DC: 1.77 +/- 0.14 10(-3)/mm Hg; d: 7.2 +/- 0.3 mm). The results show that vessel wall distensibility of the common carotid artery is decreased in younger hemodialysis patients as compared with age-matched healthy subjects. The volume expanded state in hemodialysis patients cannot account for the decreased arterial distensibility, since volume depletion by hemodialysis was not associated with a significant change of arterial distensibility (DC 2.14 +/- 0.44 10(-3)/mm Hg before, DC 2.26 +/- 0.45 10(-3)/mm Hg after ultrafiltration, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Hemodialysis on Plasma Levels of Vasoactive Peptides: Endothelin, Calcitonin Gene-Related Peptide and Human Atrial Natriuretic Peptide

To determine the role of vasoactive peptides such as endothelin (ET), calcitonin gene-related peptide (CGRP) and human atrial natriuretic peptide (hANP) in the regulation of blood pressure in uremic patients, and to determine the effect of various types of dialyzer membranes on hemodialysis (HD)-induced changes in plasma levels of such peptides, plasma ET, CGRP and hANP were measured in HD patients and patients on continuous ambulatory peritoneal dialysis (CAPD). Plasma levels of ET, CGRP, and hANP were significantly higher in HD and CAPD patients than in healthy subjects. There were no significant differences in plasma levels of ET, CGRP, and hANP between hypertensive and normotensive HD patients, and no significant correlation was observed between HD-induced changes in plasma levels and changes in blood pressure. Plasma levels of ET decreased when HD was performed using high-flux membranes, such as polyacrylonitrile (PAN), polymethyl methacrylate (PMMA) and cellulose triacetate (CTA), but did not decrease using a saponified cellulose (SC) membrane. Plasma levels of CGRP decreased in the case of PAN, but increased significantly with PMMA and showed no change with SC and CTA. Plasma levels of hANP decreased in all types of dialyzer membranes due to decreased secretion. These results indicate that the effect of HD on plasma levels of ET and CGRP, but not hANP, depends on the type of dialyzer membrane used.

Response of vasoactive substances to intermittent ultrafiltration in normotensive hemodialysis patients.

The changes in blood volume (BV), atrial natriuretic peptide (ANP), plasma renin activity (PRA), aldosterone (Aldo), norepinephrine (NE), epinephrine (Epi), parathyroid hormone (PTH), arginine vasopressin (AVP) and the cyclic nucleotides cAMP and cGMP were measured during a fluctuating BV cycle in 15 patients with end-stage renal failure maintained on chronic hemodialysis (HD). HD consisted of 4 periods of about 60 min each. The first half of each HD period consisted of ultrafiltration (UF) greater than 1,000 ml/h, and the second half consisted of no UF. Changes in relative BV were measured using continuous hemoglobinometry. Total BV at the end of treatment was 74.3 +/- 6.9% of the pretreatment volume. A significant positive correlation between BV and the levels of ANP, PTH, Epi and cGMP and an inverse correlation between BV and PRA, Aldo, AVP and NE were demonstrated. While mean values of NE and AVP levels were directly related to actual changes in BV, individual values did not homogeneously reflect this relationship. The cyclic nucleotides cGMP and cAMP did not follow immediate BV changes, but showed a significant decrease correlated with diminished BV. Based on a pre-postdialysis analysis, significant changes in PRA and Aldo were missing. It seems possible that vascular stability in dialysis patients may be maintained by the response of NE and AVP, and not by the renin-aldosterone system. The changes in ANP and cGMP values correlated most significantly (r = 0.38 and r = 0.51, p < 0.005) with the changes in BV, but no single variable could explain the blood pressure regulation during HD with intermittent rapid UF.

Follow-Up of Cardiac Changes Induced by Anemia Compensation in Normotensive Hemodialysis Patients with Left-Ventricular Hypertrophy

28 anemic [hematocrit (Hct) < 25%] and normotensive patients on maintenance hemodialysis with uremia-associated left-ventricular (LV) hypertrophy were treated with recombinant human erythropoietin. Before correction of anemia, after 4 months at a target Hct of 35% and 16 months (Hct still 35%) patients were assessed by echocardiography and physical stress testing. Partial correction of anemia resulted in a decrease in the LV end-diastolic diameter from 52.6 +/- 3.4 SD mm to 49.6 +/- 3.4 mm at 4 months (p < 0.01) and 47.9 +/- 2.9 mm at 16 months (p < 0.001). Concomitantly there was a slight decrease of LV end-systolic diameter (30.4 +/- 3.1 vs. 32.6 +/- 3.5 mm, p < 0.05) and LV posterior wall thickness (12.1 +/- 0.9 vs. 12.8 +/- 0.8 mm, p < 0.05) at 16 months. The calculated LV muscle mass index was reduced from 199 +/- 35 g/m2 to 173 +/- 34 g/m2 at 4 months (p < 0.01) and 160 +/- 28 g/m2 at 16 months (p < 0.001). Heart rate at rest was reduced significantly from 80 +/- 12 to 73 +/- 11 min (p < 0.01) at 4 and 16 months. LV ejection fraction, thickness of LV septum and blood pressure did not change. Partial correction of anemia led to an increase of maximal physical stress tolerance from 1.4 +/- 0.4 to 1.85 +/- 0.5 W/kg b.w. at 4 months (p < 0.01), which was maintained at 16 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-Term Effects of Recombinant Human Erythropoietin on Macro-and Microcirculation in Chronic Hemodialysis Patients

Recombinant human erythropoietin therapy (ReHuEpo) at short term leads to an increase in systemic vascular resistance and to a decrease in cardiac index and skin microcirculatory flow. Long-term adaptive changes might occur. We studied the effects of ReHuEpo therapy on macrocirculation and skin microcirculation in 8 normotensive and normovolemic hemodialysis patients before and after, respectively, 4 and 14 months of treatment. The reported macrocirculatory changes at short term were at long term not significantly different as compared with the initial values. The mean arterial pressure remained unaltered, as might be explained by the slow correction of the hematocrit and the decrease in cardiac output in all initially long-lasting normotensive patients who were maintained normovolemic. Left ventricular end-diastolic dimensions decreased, and also the left ventricular muscle mass decreased, depending on the initial left ventricular muscle mass. The skin oxygenation improved, whereas the maximal capillary flow decreased both at short- and long-term ReHuEpo treatment. The number of capillaries in the nail fold remained unchanged. However, the percentage of tortuosity decreased significantly during ReHuEpo therapy.

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.

Correlation of blood pressure in end-stage renal disease with platelet cytosolic free-calcium concentration

The fluorescent probe Quin-2 showed the cytosolic free-calcium concentration in platelets to be elevated in 12 hypertensive hemodialysis patients, who were compared with 12 normotensive hemodialysis patients. There was a close correlation between the free-calcium level of platelets and mean arterial pressure (r = 0.88). Short-term antihypertensive treatment resulted in a reduction of free-calcium concentration and a concomitant fall in blood pressure. These results suggest an integrative contributory role for calcium in the pathophysiology of hypertension accompanying end-stage renal disease.

Uremic cardiomyopathy: An inadequate left ventricular hypertrophy

Echocardiographic study of the left ventricle was performed in 57 selected, normotensive hemodialysis patients in comparison to 40 healthy controls matched for sex, age and blood pressure. The statistically significant abnormalities in uremic patients were an enlargement of the left ventricular end-diastolic diameter (LVEDiD) (5.58 +/- 0.60 vs. 5.05 +/- 0.5 cm; P less than 0.001) and an increase in the left ventricular radius to posterior wall-thickness ratio (r/Th) (3.65 +/- 0.68 vs. 3.27 +/- 0.44; P less than 0.001). Enlargement of the ventricle was related to anemia (P less than 0.001) and the hemodynamic effect of arteriovenous fistula. Ventricular radius to wall thickness ratio was inversely related to systolic arterial pressure in controls (P less than 0.001) and patients (P less than 0.01) with a significant upward shift of the regression in dialysis patients (P less than 0.001). In dialysis patients, the left ventricular posterior wall thickness (LVPWT) was inversely correlated to serum parathormone (PTH) level (P less than 0.001), and r/Th ratio was positively correlated to serum PTH (P less than 0.001). Bone biopsy was performed in 28 patients. Histomorphometric indexes of osteitis fibrosa were in dialysis patients, correlated to echocardiographic abnormalities; osteoclasts number was inversely correlated to LVPWT (P less than 0.001) and positively related to r/Th ratio (P less than 0.001). Osteoclastic resorption surfaces and LVPWT were inversely correlated (P less than 0.001), while a positive correlation between r/Th ratio and osteoclastic resorption surfaces was observed (P less than 0.001). Osteoblastic surfaces and tetracycline double-labeled surfaces were also correlated to LVPWT (P less than 0.001) and r/Th ratio (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Norepinephrine-related mechanism in hypertension accompanying renal failure

Various blood pressure (BP)-regulating factors were assessed before and after 4 weeks of selective norepinephrine (NE) inhibition with the sympathetic neurone blocker, debrisoquine, in nine hypertensive, nine normotensive hemodialysis patients (HDP), and 11 normal subjects. On placebo, hypertensive HDP had an increased total blood volume (P less than 0.05) and exchangeable sodium (P less than 0.001), while both HDP groups had increased (P less than 0.05) plasma clearances of NE and angiotensin II (AII), and tended to have higher basal plasma NE, renin, and AII levels, and lower BP responses to NE or AII than normal subjects. Plasma epinephrine and the chronotropic dose of isoproterenol (CDI) did not differ significantly among groups. Debrisoquine lowered supine BP markedly in hypertensive HDP (on average from 181/107 to 148/88 mm Hg) and slightly in normotensive HDP (143/78 to 131/76 mm Hg), but not in normal subjects (116/74 to 120/79 mm Hg). In all groups, plasma NE, CDI, and NE pressor dose were reduced in parallel (by 35 to 75%; P less than 0.05 to less than 0.001), and the relation between stepwise increasing plasma NE and BP changes during NE infusion was commensurably displaced to the left (P less than 0.01). The remaining parameters were not changed consistently. HDP, as normal subjects, respond to decreased sympathetic outflow with increased alpha- and beta-receptor sensitivity. Hypertension in HDP depends strongly on a NE-related mechanism. The latter seems to complement renin-angiotensin, sodium and fluid volume in the pathogenesis of high BP.