Heparins and blood polymorphonuclear stimulation in haemodialysis: an expansion of the biocompatibility concept.

BACKGROUND: At the concentrations used in haemodialysis and in a dose-dependent way, unfractionated heparin (UFH) and, to a lesser degree, a low-molecular-weight heparin (LMWH) stimulate polymorphonuclear cells (PMN) in vitro, and could act in synergy with the stimulatory effect of dialysis membranes in vivo. To examine this hypothesis, we studied the effects of different heparin types and regimens on blood PMNs during haemodialysis sessions. METHODS: Ten haemodialysed patients were studied during regular dialysis sessions on a cellulose triacetate membrane (CT 110 G; 1.10 m(2); Baxter), with four different random heparin protocols: one high-UFH regimen (HHR) at 90 IU/kg body-weight (b.w.) and one low-UFH regimen (LHR) at 50 IU/kg b.w., and with a LMWH (nadroparin calcium) at 85 (HHR) or 45 (LHR) IU/kg b.w. Blood granulocytes, platelet counts, and plasma granulocyte degranulation products (elastase, lactoferrin) were measured serially during 4 h dialysis sessions. RESULTS: After 10 min, the reduction in PMNs with UFH was 29.5% for HHR (P<0.01) and 28.5% for LHR (P<0.01), and only 16.8 and 18.6% with LMWH (NS), significantly higher for HHR with UFH than with LMWH (P<0.01). At 60 min, the elastase increase with HHR was greater, 61% with UFH (P<0.01) and 37.8% with LMWH (P<0.01), significantly higher than LHR for UFH (P<0.05) or LMWH (P<0.05). The overall decrease in platelets (with LMWH P<0.01) and the overall increase in lactoferrin (P<0.001) were not different between heparinization procedures. CONCLUSION: Under a conventional heparin regimen, the PMN variation during the course of the dialysis session suggests a more biocompatible effect of LMWH over UFH. In addition, the variation of elastase favours the lower dose, whatever the type of heparin. Heparin type and dose should therefore be considered in studies addressing biocompatibility in haemodialysis: a low dose of LMWH may be viewed as a better biocompatible treatment with regard to leukocyte stimulation.

Twenty-five years of experience with out-center hemodialysis.

UNLABELLED: Twenty-five years of experience with out-center hemodialysis. BACKGROUND: Out-center hemodialysis (HD) offers patients a better quality of life, a greater independence, and a better rehabilitation opportunity. A lower mortality than with other modalities of dialysis has been reported. In addition, in France the charges paid depend on the modality of dialysis, out-center HD being the less expensive, and savings are also accomplished through fewer patient transports, which are additionally reimbursed. We present a 25-year experience of out-center HD. METHODS: We retrospectively studied the clinical records of 471 patients treated between 1974 and 1997 in a single nonprofit organization operating regional home HD (H-HD) and facilities for self-care HD (SC-HD). Survival results were analyzed according to: (a) causes of end-stage renal disease, (b) age at the start of HD, (c) period of start of HD, (d) modality of HD (H-HD, SC-HD), and (e) a subgroup of 174 patients defined at risk because they were contraindicated for transplantation. RESULTS: The mean age at the start of HD increased from 31.2 +/- 9.7 (mean +/- SD) years in 1974 to 52.6 +/- 13.5 years in 1997. Causes of the end of treatment were: (a) transplantation (63%), (b) transfer (20%), and (c) death (17%). The overall survival was 90% at 5 years, 77% at 10 years, 62% at 15 years, and 45% at 20 years, and, for the group at risk, 78%, 62%, 46%, and 31%, respectively. Cox proportional hazard analyses showed that risk factors were older age, diabetes, and renal vascular diseases. CONCLUSION: If adequate choice is given, out-center HD offers a reliable and safe modality of dialysis with better survival results than survival in full-care in-center HD. In addition, out-center HD ensures a striking financial benefit as compared with the higher costs if the same patients were treated with full-care in-center HD. These modalities should be encouraged for all HD patients who are able to be treated by out-center modalities.

The effects of high molecular weight- and low molecular weight-heparins on superoxide ion production and degranulation by human polymorphonuclear leukocytes.

High molecular weight (HMW) and low molecular weight (LMW) heparins affected superoxide ion production and degranulation by polymorphonuclear leukocytes (PMNL) isolated from either chronic hemodialyzed patients or healthy controls. Low concentrations in HMW-heparin, below 1.76 aXa IU/ml for patients and 1.34 aXa IU/ml for controls, increased O2- production started by phorbol myristate acetate. High concentrations above these values decreased it. Increasing LMW-heparin concentrations constantly decreased O2- production using the same stimulus. Myeloperoxidase (MPO) released by PMNL was found to be significantly HMW- and LMW-heparins dose-dependent. The addition of calcium chloride significantly increased MPO release. Lactoferrin release was not dose-dependent of HMW- or LMW-heparins. However, an increase of the percentage of positive responses for lactoferrin release was observed in the simultaneous presence of HMW-heparin and CaCl2 compared to HMW-heparin alone. Lysozyme release was also not dose-dependent of HMW- or LMW-heparins. An increase of the percentage of positive responses for lysozyme release was observed in the presence of CaCl2 alone compared to HMW-heparin.

Comparison of hemostasis with two high-flux hemocompatible dialysis membranes.

Eight adults with chronic renal failure were dialyzed using polyacrylonitrile (AN 69) or polysulfone (PS) membranes with a high (HHR) or low (LHR) continuous non-fractionated heparin regimen--a total of either 90 or 50 IU/kg body weight. With the HHR, for a mean anti-Xa (aXa) activity of around 0.40 IU/ml, no plasma activation of coagulation was observed; fibrinopeptide A (FPA) was in agreement with the residual blood volume (RBV) and the state of the bubble trap, especially with the PS membrane. With the LHR, for a mean aXa below 0.21 IU/ml, there was only moderate activation of coagulation. The PS membrane gave different results from the AN 69 membrane, RBV values on the HHR and aXa being lower on both the HHR and LHR, with FPA values being regularly lower on the LHR. The decrease in plasma beta-TG on the LHR was more marked with the PS than with the AN 69 membrane due to loss on dialysis or adsorption, as shown by the arterio-venous difference. The increase in plasma PF4 was related to the effect of heparin. However, there was no platelet activation. On the LHR, platelet count and intraplatelet beta-TG and PF4 levels remained very stable. The two high-flux membranes were very hemocompatible and require only low doses of heparin, but the dialyzer with AN 69 membrane need its geometry improving.

Complement C3 and C5 degradation products during hemodialysis treatment: study of an index of membrane bioincompatibility.

In 10 hemodialyses (HD) with cuprophan (CU) and 10 with polyacrylonitrile (PAN), signs of complement activation were investigated by following arterial and venous levels of C3a, C3d and C5a, in order to propose a marker of bioincompatibility. Despite large individual variabilities, significant increases of these molecules were detected at t 20 min, particularly with CU device in the artery and more marked in the vein except for C3d with PAN. During the later stage of HD, while C3a and C5a levels gradually declined, but remained significantly higher than t 0 in all the patients treated with CU, the C3d concentration reached a plateau suggesting a continuous complement activation throughout HD. HD using PAN membranes were associated with a lower C3a, C3d and C5a generation and fewer dialyses generating these products. In some dialyses the higher arterial level of these molecules suggests an extra-dialyzer complement activation especially with PAN membrane. Although C5a venous levels appeared to be the more significant index of complement activation, for clinical purposes we propose the C3d arterial measurement as a reliable, non-expensive and technically simple indicator of membrane intolerance.

[Lecithin cholesterol acyltransferase (LCAT) and lipid cardiovascular risk factors in hemodialysis patients]. / Lécithine cholestérol acyltransférase (LCAT) et facteurs lipidiques de risque cardiovasculaire chez les hémodialysés.

In order to study the reliability of plasma LCAT activity as a marker of cardiovascular risk, we compared 66 chronic hemodialysis patients with a control group (n = 72) and a coronary artery disease (CAD) patients group (n = 46). The decrease of LCAT activity (measured by the Nagasaki method) did not appear as a marker of CAD risk; if this activity was effectively lower in 51 of the hemodialysis patients (p less than 0.001) than in the patients of the control group, it was higher in CAD patients (p less than 0.001). In the remaining 15 hemodialysis patients, we found an almost undetectable LCAT activity, not accompanied by a change in esterification percentage when compared with the other hemodialysis patients; the mixing of these serums with control group restored an enzymatic activity and excludes the presence of an inhibitor. The only risk factors common to hemodialysis and CAD patients was the decrease of HDL cholesterol and the high frequency of combined hyperlipoproteinemia.

[An infrequent cause of acute renal failure]. / Une cause peu fréquente d'insuffisance rénale aiguë.

The clinical history of this patient was characterized by an acute localized then diffused pneumopathy, artificial respiratory assistance being necessary. At the same time, acute renal failure appeared with oligoanuria, the evolution of which being favorable after 15 days. The etiology of the pneumopathy was proved by the strongly positive ornithosis serodiagnosis: 1/512. The occupation of the patient, a country worker, correlated well with this diagnosis. The type and mechanism of the acute renal failure should be discussed. Renal biopsy disclosed a tubulo-interstitial nephritis. There was no shock during the whole clinical story. Very high CPK level in the blood was found early in the course of the disease. So, it seems probable that myolysis of viral origin, might be responsible of the renal defect.

The nephrotic syndrome in adults aged over 60: etiology, evolution and treatment of 76 cases.

A study of the clinical, etiological and histological features of the nephrotic syndrome occurring in 76 adults aged over 60 was performed. Membranous nephropathy was the most frequent type (40%). 32% of the cases of membranous nephropathy were associated with another disease which was a malignant one in 22% of the cases. In 2 cases a renal vein thrombosis was associated with the malignant disease. Amyloidosis appeared to be the most frequent cause of the secondary nephrotic syndrome (13%), and was often associated with plasma cell dyscrasia. The study also showed the importance of lipoid nephrosis among elderly patients with the nephrotic syndrome (20%). Amongst these cases it is necessary to consider the association of minimal changes with a systemic disease, and the histological diagnosis of focal hyalinosis. Indeed the presence in elderly patients of arteriolar, interstitial and glomerular lesions of hyalinosclerosis makes interpretation difficult. With corticosteroid therapy complete remission was frequent in patients with lipoid nephrosis.