Alterations of granulopoiesis in chronic uremic patients treated with intermittent hemodialysis

Granulocyte-macrophage progenitor cells (CFU-GM), leukocyte colony-stimulating activity (CSA), granuloblast differentiation and proliferation and the effect of uremic serum on the in vitro growth of normal CFU-GM have been studied in 8 chronic uremic patients treated with intermittent hemodialysis three times a week. The studies were performed in the postabsorptive state twice in each patient, that is at the longest and shortest dialytic interval. CFU-GM growth in agar and leukocyte CSA did not differ significantly from the normal level in uremic subjects. The granulocytic and macrophagic differentiation in a liquid culture system was significantly reduced in uremic patients, notwithstanding the appearance of high numbers of undifferentiated blastic cells. The serum of uremic patients had no effect on normal CFU-GM and leukocyte CSA.     

Changes in the composition of plasma lipoproteins in the chronic uremic rat

The effect of chronic renal failure on the lipid and apolipoprotein concentrations of plasma, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) was studied in an experimental uremic rat model. Control rats were sham-operated and were divided into adlibitum-fed and pair-fed groups. The rats were studied (after an overnight fast) 32 days after the onset of uremia. The uremic rats had a 4-fold increase in plasma urea nitrogen and creatinine. The pair-fed and ad-lib-fed controls had similar levels of plasma urea nitrogen and lipid profiles. In the uremic rats, plasma triglyceride (TG) levels were increased 3.8-fold due to increased TG in the VLDL, IDL and HDL fractions. Their 2-3-fold increase in plasma free cholesterol (FC), esterified cholesterol (EC) and phospholipids (PL) were due to FC, EC and PL increases in VLDL, IDL, LDL and HDL. Their increase in plasma apo B (x 2.4) and apo E (x 1.5) were due to increases in VLDL, IDL and LDL. Their plasma apo A-I increased 2.4 fold due to increases in the LDL and HDL fractions. Uremic rats also had increases in the FC/PL molar ratio in VLDL, IDL and LDL. In their LDL, the apo B/total cholesterol (TC), apo B/PL and apo B/apo E molar ratios were decreased. In their HDL, the apo E/TC and apo E/PL molar ratios were decreased and the apo A-I/apo E molar ratio was increased. In conclusion, chronic uremia causes both quantitative changes in the levels and qualitative changes in the composition of the plasma lipoprotein particles. These results are compatible with the decreased hepatic lipase activities and impairment of remnant clearance observed in human chronic renal failure.     

Changes in heart rate variability in chronic uremic patients during ultrafiltration and hemodialysis

BACKGROUND: The analysis of heart rate variability (HRV) is a useful tool to evaluate cardiac autonomic modulation, which is frequently impaired in chronic uremia. AIMS: The aim of this study was to evaluate HRV in chronic uremics and to separately investigate the acute changes induced by volume depletion and solute removal during a hemodialysis session. METHODS: Fourteen uremic patients (8 males and 6 females, aged 50 +/- 15 years) on maintenance hemodialysis and 14 sex- and age-matched healthy controls were studied. Both groups underwent ambulatory electrocardiogram monitoring to evaluate the HRV time and frequency domain indices. The hemodialysis session was performed by 1 h of high-rate isolated ultrafiltration followed by 3 h of bicarbonate diffusive procedure. RESULTS: In uremic patients, the overall variability in the frequency [low-frequency power (LF): 505 +/- 473, vs. 1,446 +/- 654; high-frequency power (HF): 133 +/- 162 vs. 512 +/- 417; p < 0.001] and time domain indices (standard deviation of normal R-R intervals: 101.9 +/- 33.3 vs. 181.7 +/- 44.1 ms; p < 0.001) was markedly reduced compared to controls, whereas mean heart rate (83 +/- 12.4 vs. 60.9 +/- 8.8 bpm; p < 0.001) and LF/HF ratio (5.8 +/- 3.5 vs. 2.2 +/- 0.8; p < 0.001) were increased. Isolated ultrafiltration produced a marked further decrease in HRV indices, but the subsequent diffusive hemodialysis procedure, with a low ultrafiltration rate, made HRV increase again. CONCLUSIONS: Chronic uremics showed abnormal autonomic modulation with sympathetic-vagal imbalance. The unbalanced hypersympathetic response to body fluid depletion is related to the ultrafiltration rate. Low interdialytic weight gain and a low ultrafiltration rate, associated with adequate hemodialysis, should be the preferable strategy for uremic patients with autonomic dysfunction.     

Coronary revascularization in uremic diabetic patients under chronic hemodialysis

Coronary heart disease is the main cause of mortality among uremic patients on chronic hemodialysis (CHD) and is the determinant of the outcome in these cases after renal transplantation, especially in diabetics. In this study we report our experience with two uremic diabetics on CHD with severe coronary artery lesions in whom aortocoronary bypass was performed before renal transplantation. The outcome in the two patients, after 30 and 55 months respectively indicates successful results. We discuss the necessity to perform coronariography in all the high risk patients on CHD, such as diabetics and elderly before planning renal transplantation and achieve aortocoronary bypass surgery in those with severe coronary disease. The technics and difficulties of the surgery in uremics are also analized.     

Carnitine and carnitine esters in plasma and adipose tissue of chronic uremic patients undergoing hemodialysis

carnitine concentrations were measured in the plasma and adipose tissue of seven chronically uremic and hyperlipidemic patients undergoing hemodialysis. Plasma levels of carnitine had dropped by the end of dialysis. The clearance of free carnitine was greater than that of acylcarnitine. Fasting plasma free carnitine, long-chain acylcarnitine, d-β-hydroxybutyrate and free fatty acid concentrations were normal but short-chain acylcarnitine values were elevated. In adipose tissue, total carnitine concentrations were normal but long-chain acylcarnitine concentrations were increased. These findings may indicate a hypermetabolic state in which the acute removal of carnitine during hemodialysis may lead to a critical shortage of this substance.     

Vascular stiffness in chronic renal failure patients treated by hemodialysis

Cardiovascular disease is a major cause of morbidity in patients with end-stage renal failure. Arterial stiffness measured by pulse wave velocity (PWV) is an independent risk factor for morbidity in end stage renal failure patients. The aim of our study was to evaluate the arterial stiffness in patients with chronic renal failure. In 20 chronic renal failure patients treated by hemodialysis (HD) we assessed the PWV of the carotic artery as well as artery diameter and distensibility, systolic pressure (SBP), diastolic pressure (DBP), pulse pressure (PP), and basal biochemical parameters and compared them with the values determined in 20 healthy controls of comparable age. PWV and PP are significantly (p < 0.001, p < 0.05) higher and distensibility of the carotic artery was significantly lower (p < 0.001) compared to a control group SBP and DBP were < 140/90 mmHg in HD patients (high normotensive range) but were significantly (p < 0.05) higher than in a control group. In HD patients PP was correlated with arterial distensibility r = -0.600 (p < 0.005), and systolic artery rice r = -0.408 (p < 0.05). SBP was correlated with PP r = 0.689 (p < 0.0007) and with arterial distensibility r = -0.476 (p < 0.03), arterial diameter to systolic artery rice r = -0.463 (p < 0.03), systolic artery rice to arterial distensibility r = 0.885 (p < 0.00001), intima media to arterial distensibility r = 0.815 (p < 0.00001), intima media to arterial compliance r = 0.893 (p < 0.00001). Our results suggest that not only established hypertension but also high normotensive pressure could cause arterial stiffness absened in chronic renal failure patients.     

Effect of erythropoietin on tissue factor and tissue factor pathway inhibitor in uremic hemodialysis patients

Some parameters of extrinsic coagulation pathway, including concentration and activity of tissue factor and concentration of tissue factor pathway inhibitor, have been estimated in uremic hemodialysis patients. The impact of erythropoietin treatment on the extrinsic coagulation pathway has also been the aim of the study. Increased concentration of tissue factor pathway inhibitor--TFPI has been found both in dialysed and non-dialysed uremic patients. This finding may be the evidence of endothelial damage as well as the protective factor against thrombotic complications. Erythropoietin treatment seemed not to induce statistically significant changes in extrinsic coagulation pathway. Some results indicate that estimation of "truncated' and "full length" forms of TFPI may be more useful comparing to complete TFPI concentration.     

Influence of hemodialysis, heparin and protamin on the pre-beta fraction of lipoproteins in patients with chronic kidney failure]

The spectrum of lipoproteins in the serum and the blood clotting time was examined in 19 dialyzed and 5 non-dialyzed patients with chronic renal failure. Compared were the values obtained in hemodialysis with intermittent and regional heparinization and the changes after the application of heparin in hemodialysis and beside it. In non-dialyzed and dialyzed patients in interdialyzation period were studied the changes of given parameters which occur after heparin and protamin application. Out of the results of this examination it follows that: 1. the most significant factor causing the changes of lipoprotein spectrum in the serum during hemodialysis is heparin. 2. the effect of protamin upon the lipoprotein spectrum during hemodialysis cannot be explained only by the neutralisation of heparin effect. 3. beside heparin and protamin in the spectrum changes of lipoproteins during hemodialysis also other factors are participant that are concerned with hemodialysis.     

Heart rate variability in patients with chronic renal failure treated by hemodialysis

Heart rate variability (HRV) is a non-invasive method used for the assessement of autonomic modulation of heart rate. Decreased HRV is an indicator of increased cardiovascular risk. The aim of this study was to evaluate the relationship between the heart rate variability and left ventricular hypertrophy and native parathormone (iPTH) serum concentration in patients with chronic renal failure (crf) treated by hemodialysis. 24-hours ECG recording with time domain HRV evaluation, resting, transthoracic echocardiography (ECHO), were measured in 59 crf patients and in 30 healthy volunteers. Creatinine, urea, total protein, albumin, electrolytes, hemoglobin, hematocrite and iPTH serum concentration as well as body mass index (BMI) were assessed in all patients. All crf patients had decreased lower values of HRV. The correlations between SDNN, pNN50, rMSSD and parameters of LVH and with PTH serum level indicated the disturbances of the autonomic function in chronic renal patients. Left ventricular hypertrophy (LVH) in all crf patients was observed. The correlations between iPTH serum level and parameters of LVH suggest the role of PTH in the development of uremic cardiomyopathy.     

Left ventricular hypertrophy in patients with chronic renal failure treated by hemodialysis

Left ventricular hypertrophy (LVH) is common and important predictor of risk of death in end-stage renal failure. In the present study we have analysed echocardiographically the left ventricular hypertrophy and some possible risk factors continuing to its development in patients with chronic renal failure (crf) treated by hemodialysis (HD). From a cohort of 85 patients with crf we selected for analysis 59 clinically stable patients. Echocardiography (ECHO), body mass index (BMI), serum creatinine, urea, total protein, albumin, hemoglobin, hematocrit, electrolytes and parathyroid hormone (PTH) concentrations were evaluated in all patients at the next hours after HD session. LVH was common in HD patients: concentric LVH was detected by ECHO in 46 patients and in 13 patients eccentric LVH was observed. Mean serum concentrations of urea, creatinine, PTH and phosphate differed from normal values while hemoglobin, total protein, albumin, sodium kalium, calcium serum concentration were in the normal range. Positive correlation was found between PTH serum concentration and LVM r = 0.704 (p < 0.001), between PTH serum concentration and IVS r = 0.267 (p < 0.04), between PTH serum concentration and PW t = 0.238 (p < 0.04), and negative correlation between BMI and LVMI r = -0.451 (p < 0.05). The correlations between serum PTH concentration and LVH and between BMI and LVH confirmed that both hyperparathyroidism and malnutrition are important factors influencing the development of LVH in HD patients.     

Intravenous methylcobalamin treatment for uremic and diabetic neuropathy in chronic hemodialysis patients.

OBJECT: To study the effects of the intravenous administration of methylcobalamin, an analogue of vitamin B12, for uremic or uremic-diabetic polyneuropathy in patients who are receiving maintenance hemodialysis. An ultra-high dose of vitamin B12 has been reported to promote peripheral nerve regeneration in experimental neuropathy. METHODS: Nine patients received a 500 microg methylcobalamin injection 3 times a week for 6 months. The effects were evaluated using neuropathic pain grading and a nerve conduction study. RESULTS: Serum concentrations of vitamin B12 were ultra-high during treatment due to the lack of urinary excretion. After 6 months of treatment, the patients' pain or paresthesia had lessened, and the ulnar motor and median sensory nerve conduction velocities showed significant improvement. There were no side effects. CONCLUSION: Intravenous methycobalamin treatment is a safe and potentially beneficial therapy for neuropathy in chronic hemodialysis patients.     

Platelet reactivity in patients with chronic kidney disease and hemodialysis

Journal of Thrombosis and Thrombolysis - End stage renal disease requiring hemodialysis (HD) is frequent and coronary artery disease (CAD) is a common comorbidity. It is associated with bleeding...     

Labile plasma iron levels in chronic hemodialysis patients treated by intravenous iron supplementation

The increased usage of intravenous iron in hemodialysis patients during recent years has led to increasing concern over the potential development of iron overload. Current methods for detecting iron overload, transferrin saturation, and serum ferritin are neither sensitive nor specific. Labile plasma iron (LPI) represents a component of nontransferrin‐bound iron and may be a more accurate indicator of impending iron overload. We studied whether LPI measured can serve as an early indicator of impending iron overload and mortality in hemodialysis patients. Chronic hemodialysis patients from two medical centers in Israel and Poland who received intravenous iron were included. Baseline clinical and laboratory parameters were recorded. LPI was measured before and 48 hours after a single IV administration. Correlation of positive LPI with laboratory parameters and 2‐year mortality was evaluated. One hundred and one hemodialysis patients were included in the study. LPI became positive post‐administration in 18 (17.8%) patients. Ferritin levels >526 ng/mL and monthly iron doses >250 mg were associated with positive LPI after intravenous iron. At a 2‐year follow‐up, higher mortality was observed in the positive LPI group (61.1% compared to 25.3%, P ≤ .05), although this effect was not statistically significant after multivariate adjustment. A substantial number of hemodialysis patients have positive LPI after intravenous iron administration. LPI positively correlates with laboratory parameters that are currently in routine clinical use for detecting iron overload and with higher intravenous iron dose. Further studies should be conducted to establish the clinical implications of LPI monitoring in hemodialysis patients.     

血液透析患者冠心病介入治疗可行性初探

目的　探讨尿毒症血液透析患者进行冠状动脉造影及介入治疗的可行性及近期疗效。方法　对 3例频发心绞痛的血液透析患者在适当水化和强化透析基础上 ,应用非离子型造影剂行冠状动脉造影术。结果　单支病变 2例 ,双支 (多处 )病变 1例。分别于造影后 4～ 7日行支架置入术 ,成功置入 1～ 4个支架。术后临床随访 12～ 18个月 ,患者心绞痛症状明显缓解或消失 ,肾功能无恶化。结论　对血液透析患者行冠状动脉造影及介入治疗是安全可行的。