Erythrocyte membrane fluidity decreased in uremic hemodialyzed patients

Erythrocyte membrane fluidity was studied by means of electron spin resonance in 15 uremic, hemodialyzed patients and 14 normal subjects. Erythrocyte membrane fluidity determined using a 16-nitroxide stearic acid spin label probe was of a significantly lower level in the uremic patients, when compared with normal control subjects. Alterations in molar ratios of membrane free cholesterol to phospholipid are probably not a principal factor contributing to this change in fluidity. Significant decreases of phosphatidylcholine and molar ratios of phosphatidylcholine to sphingomyelin were noted in the erythrocyte membrane of uremic patients, and these alterations may relate to the fluidity change.     

Effect of dialysis on erythrocyte membrane of chronically hemodialyzed patients

The present work examines the role of uremia and the effect of dialysis treatment on red blood cells (RBCs) membrane properties of hemodialysis patients. The results showed that, the uremic patients had a lower values of erythrocyte deformability than that of healthy control subject. The median osmotic fragility (MOF) showed a significant increase in hemodialyzed patients than that for control group. The osmotic resistance to hemolysis was improved after dialysis. The solubilization process of the RBCs membrane showed that the detergent concentration needed to solubilize the RBCs membrane for uremic patient was much higher than that for control group. The abnormalities of the present results for RBCs membrane properties are mostly related to membrane fluidity, which are slightly improved after dialysis. Biochemical analysis showed a decreasing trend in RBCs count, urea nitrogen, creatinine, potassium,     

AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: a potential target for N-acetylcysteine treatment in dialysis patients

AOPP-induced activation of human neutrophil and monocyte oxidative metabolism: A potential target forN-acetylcysteine treatment in dialysis patients. BACKGROUND: Oxidative stress largely contributes to hemodialysis-associated lethal complications, thus explaining the urgent need of antioxidant-based therapeutic strategies in hemodialysis patients. We previously identified advanced oxidation protein products (AOPP) in the uremic plasma as exquisite markers of oxidative stress and potent mediators of monocyte activation. The present study was aimed at searching whether (1) AOPP can also trigger activation of polymorphonuclear neutrophils (PMN), and (2) whether AOPP-induced activation could be inhibited by N-acetylcysteine (NAC), a widely used compound which has been shown to prevent oxidative injury to kidney. METHODS: Both human serum albumin (HAS) AOPP (i.e., HOCl-modified HSA in vitro preparations and AOPP extracted from plasma of hemodialysis patients) were tested for their capacity to trigger phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase (MPO)-dependent activities as measured by lucigenin- and luminol-amplified chemiluminescence (CL), respectively, as compared to receptor-dependent [opsonized zymosan or receptor-independent phorbol myristate acetate (PMA)]. The effect of PMN priming by platelet-activating factor (PAF), and the effect of NAC on normal monocyte and on normal or hemodialysis patient's (N = 16) PMN oxidative responses were compared. RESULTS: HSA-AOPP triggered in a HOCl dose-dependent manner both NADPH-oxidase- and MPO-dependent CL of PMN. This latter was further enhanced by PAF priming. Plasma-derived AOPP obtained from hemodialysis patients also triggered PMN respiratory burst. NAC significantly reduced HSA-AOPP-mediated responses of normal monocyte and of normal and uremic PMN but had no significant effect on opsonized zymosan- or PMA-induced CL responses. CONCLUSION: This dual potential of NAC to inhibit phagocyte oxidative responses induced by HSA-AOPP without affecting those mediated by compounds mimicking pathogens supports the proposal of a therapeutic trial with NAC aimed at reducing oxidative stress-related inflammation in hemodialysis patients.     

EFFECT OF DIALYSIS ON ERYTHROCYTE MEMBRANE OF CHRONICALLY HEMODIALYZED PATIENTS

The present work examines the role of uremia and the effect of dialysis treatment on red blood cells (RBCs) membrane properties of hemodialysis patients. The results showed that, the uremic patients had a lower values of erythrocyte deformability than that of healthy control subject. The median osmotic fragility (MOF) showed a significant increase in hemodialyzed patients than that for control group. The osmotic resistance to hemolysis was improved after dialysis. The solubilization process of the RBCs membrane showed that the detergent concentration needed to solubilize the RBCs membrane for uremic patient was much higher than that for control group. The abnormalities of the present results for RBCs membrane properties are mostly related to membrane fluidity, which are slightly improved after dialysis. Biochemical analysis showed a decreasing trend in RBCs count, urea nitrogen, creatinine, potassium, phosphate, hemoglobin, and serum osmolarity after dialysis. Moreover, serum sodium, ionized calcium, total calcium, and blood sugar, showed a significant increase after dialysis.     

Hemodialysis membrane-induced activation of phagocyte oxidative metabolism detected in vivo and in vitro within microamounts of whole blood

The production of reactive oxygen species by phagocytes from uremic patients undergoing hemodialysis was monitored by chemiluminescence (CL) within microamounts of whole blood or isolated polymorphonuclear (PMN) cells, and compared on the basis of the dialysis membrane, cuprophane (CUP) or polyacrilonitrile (PAN). Compared to control subjects, resting and stimulated CL (with latex, zymosan, phorbol myristate acetate (PMA) but not formyl-methionyl-leucyl-phenylalanine (FMLP) were decreased in 10(-2) diluted blood sampled before dialysis. After 15 min of dialysis (ti), resting whole blood (10(-1) and 10(-2) diluted) CL increased sharply in patients dialyzed with the CUP but not the PAN membrane, while it returned to its predialysis level at the end of the session. This sharp resting CL increase found in whole blood at ti was not observed in isolated PMN cells except when tested with ti plasma from CUP dialyzed patients, suggesting that it was mediated via activated plasma compounds. In vitro treatment of normal blood, plasma, and isolated PMN cells with CUP membrane fragments reproduced this in vivo dialysis-induced activation of phagocyte oxidative metabolism strikingly and demonstrated additionally the requirement of complement for its induction. We propose this model as an effective means of evaluating dialysis membrane biocompatibility.     

Leukocyte rheology before and after chemotactic activation in some venous diseases.

OBJECTIVE: to evaluate leukocyte rheology, polymorphonuclear leukocyte (PMN) membrane fluidity and cytosolic Ca2+ concentration in subjects with post-phlebitic leg syndrome (PPS) and acute deep-venous leg thrombosis (DVT). SUBJECTS: twenty-two subjects with leg PPS and 14 subjects with leg DVT. METHODS: we evaluated the leukocyte filtration (unfractionated, mononuclear cells (MN) and PMN), the PMN membrane fluidity and the PMN cytosolic Ca2+ concentration. Subsequently, we evaluated the same PMN variables after in vitro chemotactic activation with 4-phorbol 12-myristate 13-acetate (PMA) and N -formyl-methionyl-leucyl-phenylalanine (fMLP). RESULTS: at baseline we observed a significant difference in the filtration variables of unfractionated and MN cells and in PMN cytosolic Ca2+ concentration. After activation, in normal subjects and subjects with PPS and DVT, a significant variation in PMN filtration at 5 and 15 minutes was evident. In normal subjects, no variation was present in PMN membrane fluidity or cytosolic Ca2+ concentration after activation. In subjects with PPS and DVT, we found a decrease in PMN membrane fluidity and an increase in PMN cytosolic Ca2+ concentration. After PMN activation (at 5 and 15 min) Delta% of IRFR distinguished normal subjects from subjects with PPS and DVT, while no difference was found in Delta% of membrane fluidity or cytosolic Ca2+ concentration. CONCLUSIONS: there is a functional alteration of leukocytes in these patients whose mechanisms are not yet clear.     

Change of elastase and cathepsin G content in polymorphonuclear leukocytes during hemodialysis

Previous studies have demonstrated an increment of polymorphonuclear (PMN) elastase plasma levels during hemodialysis, suggesting release of this proteinase during dialysis treatment. In order to gain further evidence that proteinases are liberated from PMN leukocytes during dialysis both plasma levels of PMN elastase and the content of elastase and cathepsin G in neutrophils were determined during 3 hours of hemodialysis with cellulosic membranes (Cuprophan) in 10 patients. In blood smears, obtained at different times during dialysis, neutrophils were classified into 3 groups according to their proteinase content. Thus, group I neutrophils contained low, group II moderate, and group III leukocytes contained high amounts of both proteinases. With regard to their elastase content, prior to the onset of dialysis, 6% of the circulating PMN leukocytes were classified as fraction I, 58% as fraction II, and 36% as fraction III neutrophils. After 15 minutes of dialysis, at the nadir of leukopenia, all fractions of PMN leukocytes were significantly reduced (fraction I: -9%, fraction II: -60%, and fraction III: -83%) as compared to initial values. 30 minutes into hemodialysis, there was a significant increase in fraction I (+ 78%), whereas fraction II (-28%) and fraction III (-70%) remained diminished. At 180 times of hemodialysis the increment of fraction I neutrophils was even more pronounced (+ 187%), fraction II was also increased (+ 16%), and fraction III neutrophils had almost reached initial values. The cathepsin G content of PMN leukocytes displayed a rather similar pattern during dialysis. As to plasma levels of PMN elastase, there was a steady and significant increase from baseline values of 107.3 +/- 11.5 ng/ml up to 388.1 +/- 51.6 ng/ml after 3 hours of hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

An echocardiographic study of cardiac function in chronic hemodialysis patients

Echocardiography was studied in 83 uremic patients on maintenance hemodialysis and 18 normal subjects. Cardiac systolic and diastolic functions were evaluated according to Yamaguchi's method. Systolic functions such as ejection fraction and fractional shortening decreased in the patients receiving hemodialysis for less than 3 months. However, they remained within normal range in the patients under hemodialysis for more than 3 months. There were no significant correlations between systolic functions and mean blood pressure or various serum biochemical parameters such as urea nitrogen, creatinine, Na, K, Ca, P, hematocrit and PTH-C. Diastolic functions such as rapid filling rate/endosystolic volume, mean velocity of circumferential fiber lengthening during rapid filling, diastolic descent rate and diastolic posterior wall velocity also decreased in the patients receiving hemodialysis for less than 3 months. However, they increased slightly in the patients under hemodialysis for more than 3 months, although they were still lower than those in normal subjects. They were not related to mean blood pressure or various serum biochemical parameters. Hemodialysis patients had left ventricular hypertrophy regardless of duration of hemodialysis. Diastolic dysfunction in hemodialysis patients seemed to be due to systolic dysfunction, left ventricular hypertrophy and diminished ventricular compliance with myocardial degeneration. It was also suggested that increasing slow filling and atrial contraction in diastole might be related to diastolic dysfunction. These cardiac changes may be compensatory reactions of cardiac muscle to various uremic environments such as anemia, hypertension, fluid retention, electrolytes disturbance or uremic toxins.     

Polymorphonuclear leucocyte rheology and cytosolic Ca2+ content after activation in chronic renal failure

SUMMARY: We evaluated polymorphonuclear leucocyte (PMN) flow properties in patients with clinically stable chronic renal failure (CRF) and in control subjects at baseline and after activation with 4-phorbol 12-myristate 13-acetate (PMA) and N -formyl-methionyl-leucyl-phenylalanine (fMLP). Initial relative flow rate (IRFR) and clogging particles (CPs) were obtained using the St. George's Filtrometer, and PMN membrane fluidity was assessed by marking PMNs with 1-(4-(trimethylamino)phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). PMN cytosolic Ca²⁺ concentration was determined by marking PMNs with Fura 2-AM. At baseline, CRF patients showed a significant increase only in PMN cytosolic Ca²⁺ content. After activation with PMA and fMLP, a decrease in IRFR and an increase in CP were observed in both control subjects and CRF patients, although the variation in IRFR present in the group of CRF patients was greater than in the control group. After activation with PMA and fMLP, we found a decrease in PMN membrane fluidity only in CRF patients, but no variation in PMN cytosolic Ca²⁺ concentration in either group was observed. These results provide evidence for PMN dysfunction in chronic renal failure.     

Production and kinetics of interleukin-1 in hemodialysis. In vivo and in vitro study

Interleukin-1-beta (IL-1-beta) was measured in the plasma and peripheral blood mononuclear cell lysates of uremic patients undergoing maintenance hemodialysis by means of either cuprophane or polysulfone membranes. Basal plasma levels of IL-1-beta in hemodialyzed patients were strikingly higher than those of uremic patients on conservative treatment or of healthy subjects. Plasma levels of IL-1-beta in uremic patients increased significantly after 3 and 6 months of hemodialysis. The study of the kinetics of IL-1-beta concentration during a single hemodialysis session revealed that the concentration of IL-1-beta fell to 21 and 22% of the predialysis level with cuprophane and polysulfone, respectively. Hemodialysis patients also had a significantly higher intracellular IL-1-beta level than normal controls. During the hemodialysis session, an increase in cell-associated IL-1-beta was seen regardless of the membrane employed. In a parallel study, normal mononuclear cells were subjected to closed-loop in vitro dialysis with either cuprophane or polysulfone membranes, with or without acetate buffer. After 120 min of recirculation, an increase in cell-associated IL-1-beta was detected, but no changes were seen in the circulating medium. IL-1-beta production was not significantly influenced by either membrane or the dialysate composition. Hemodialysis has been associated with high plasma- and cell-associated IL-1 levels. The kinetics of intradialytic changes of IL-1-beta levels make IL-1 an unlikely cause of acute complications in hemodialysis. On the other hand, a chronic elevation of IL-1 in plasma of patients on maintenance hemodialysis may contribute to the development of some of the long-term complications of this treatment.     

Abnormal cytoplasmic pH regulation during activation in uremic neutrophils.

Neutrophils isolated from ESRF patients demonstrated abnormal cytoplasmic pH changes after FMLP stimulation; the initial cytoplasmic acidification was absent (P less than 0.001 compared to controls) and the degree of alkalinization enhanced (P less than 0.05 compared to controls). This effect was not due to the absence of any of the factors associated with acidification in normal PMN since superoxide production was enhanced (P less than 0.05 compared to controls) and intracellular calcium release was normal. Our observations are not explicable by alterations in the function of the Na:H antiport since the kinetics of antiport activation by cytoplasmic pH were not different in uremic and control cells. Other factors must therefore be important in generating the abnormal pH response to chemotactic factors in uremic PMN. Cells from CAPD patients had some degree of initial acidification (P less than 0.001 compared to controls and P less than 0.05 compared to ESRF) and enhanced alkalinization (P less than 0.05 compared to controls). Preincubation of normal PMN in four-hour dwell PDE reproduced the responses of uremic PMN with absent acidification, enhanced alkalinization and enhanced superoxide generation after FMLP stimulation (P less than 0.05 compared to controls). Changes in the control of cytoplasmic pH in stimulated PMN may influence PMN function, and our observations may be relevant to the susceptibility of uremic patients to infection.     

Hemodialysis and red cell cation transport in uremia: role of membrane free fatty acids

Active and facilitated cation transport in erythrocytes of uremic patients may be improved acutely by hemodialysis, although the mechanisms remain unknown. As nonesterified fatty acids (NEFA) can affect Na+ pump activity in vitro, changes in plasma and red cell membrane NEFA content following a single hemodialysis procedure were examined and compared with acute changes in erythrocyte cation flux rates in 34 hemodialysis patients. In nonsodium-loaded cells, small changes in Na+ pump flux with dialysis did correlate with changes in intracellular Na+ content (r = 0.59; N = 17; P less than 0.01). On average, neither maximal Na+ pump activity nor Na+/Li+ counter-transport flux improved with dialysis, but Na+/K+/Cl- cotransport rates rose 25% post-dialysis (P less than 0.02). Plasma NEFA levels rose 87% following hemodialysis but erythrocyte membrane NEFA content declined by 23% (P less than 0.001). Importantly, 24 of the 34 subjects studied had a decrease in erythrocyte membrane NEFA content of greater than 10%, and in these patients, the fall in membrane NEFA correlated with an increase in ouabain-sensitive Na+ efflux (r = 0.564; P less than 0.01). The effects of hemodialysis on both erythrocyte NEFA content and Na+ pump flux could be reproduced by incubating pre-dialysis cells in fatty acid-free albumin. We conclude that acute changes in membrane NEFA may modulate active cation transport in uremic erythrocytes.     

Studies on the relationship between serum albumin concentration and lipid peroxidation in the erythrocyte membrane of maintenance hemodialysis patients

We conducted a study on the long-term prognosis of maintenance hemodialysis patients with and without diabetes mellitus(144 cases). As a result, significant differences were observed in the long-term prognosis over a 15-year period between those with a serum albumin concentration of more than 3.8 g/dl and those with a serum albumin concentration of less than 3.8 g/dl. The group with a serum albumin concentration of more than 3.8 g/dl showed a better prognosis than the group with a concentration of less than 3.8 g/dl. We investigated the levels of thiobarbituric acid-reactive substances (TBA-RS) in the erythrocyte membrane of maintenance hemodialysis patients(23 cases), pre-dialysis uremic phase patients(12 cases) and healthy controls(7 cases). TBA-RS in the erythrocyte membrane of pre-dialysis uremic phase patients was higher than that observed in the other groups. The TBA-RS in the erythrocyte membrane in the maintenance hemodialysis without diabetes mellitus group was lower than that in the pre-dialysis uremic phase group. The TBA-RS in the erythrocyte membrane in the maintenance hemodialysis without diabetes mellitus group thus indicated an inverse relationship with the serum albumin concentration, Kt/V and erythrocyte tocopherol contents. These results suggested that serum albumin protects against erythrocyte membrane lipid peroxidation, and that this function is related to hemodialysis. We thus conclude that hypoalbuminemia appears to increase the oxidative damage and acceleration of arteriosclerosis, while it also worsens the long-term prognosis of maintenance hemodialysis patients.     

Electron paramagnetic resonance study of erythrocyte membrane fluidity in renal transplant recipients

Renal transplantation (KTx) patients receiving calcineurin inhibitors-cyclosporine (CsA) or tacrolimus (TAC)-are known to be at risk for the development of posttransplant hemolytic uremic syndrome. The syndrome has been reported to occur more often with CsA than TAC treatment. It has also been noted that CsA affects erythrocyte membrane fluidity. The aim of this study was to investigate whether the impairment of erythrocyte membrane fluidity is similar among patients under treatment with different calcineurin inhibitors (CsA or TAC). Venous blood was collected from 29 KTx patients and from nine healthy volunteers. To investigate the fluidity of intact erythrocyte membranes spin label electron paramagnetic resonance spectroscopy was applied. Comparison of values for controls versus CsA-treated patients demonstrated a significant decrease in membrane viscosity in the hydrophobic region of the lipid bilayer among CsA-treated patients, whereas there was no significant difference between control and patients treated with TAC. There was no significant difference in the molecular order close to the polar heads of lipid molecules among all groups. The observed changes in erythrocyte membrane fluidity among CsA-treated patients and the lack of this phenomenon in the TAC group may correlate with more frequent prevalence of hemolytic anemia among CsA than TAC-treated patients.     

Immune deficiency in uremia: interleukin-2 production and responsiveness and interleukin-2 receptor expression and release

We have studied the role of interleukin-2 (IL-2) and its receptors in the impaired in vitro lymphocyte response characteristic of hemodialysis patients treated by means of cuprophane membranes. The proliferative response of T lymphocytes as well as T-cell-dependent B cell proliferation after stimulation with mitogens was significantly reduced in hemodialysis patients. The in vitro production of IL-2 after such stimulation in parallel cultures was found to be similar in patients and in controls. The expression of IL-2 receptor on the lymphocyte cellular membrane in the hemodialysis group was also similar to controls. The in vitro proliferative response of uremic lymphocytes to exogenous IL-2, however, was significantly depressed suggesting a reduced availability of biologically active IL-2 receptor. The release of soluble IL-2 receptor by lectin-stimulated lymphocytes in culture was also significantly lower in the patient group; yet, hemodialysis patients has a strikingly elevated level of plasma soluble IL-2 receptor, and similar high levels were also found in three other groups of end-stage renal disease patients dialyzed by means of cellulose acetate, polysulfone and polyacrylonitrile membranes, as well as in a group of uremic patients on conservative treatment. In the hemodialysis patient group a significant positive correlation between levels of soluble IL-2 receptor and the duration of hemodialysis was found. Since soluble IL-2 receptor has been reported to down-regulate lymphocyte responses, the elevation in plasma levels of soluble IL-2 receptor in hemodialysis patients may be a pathogenetic factor in the progressive development of impaired immunity associated with end-stage renal disease.     

Clinical Aspects of Hemofiltration

We report on clinical experiences obtained in 7 uremic patients treated since January 1976 3 times weekly by chronic hemofiltration. The observations which we collected in more than 300 treatments suggest that hemofiltration might be superior to conventional hemodialysis.

The main advantages of this treatment are characterized by its better control of hypertension, hyperhydration, and possibly of uremic bone disease. Furthermore, the applied acrylonitrile membrane allows the removal of substances with a molecular weight up to 60, 000, similar to the glomerular basement membrane. Additionally, we report on methodological problems, on the compatibility of hemofiltration, and finally on its efficiency for removal of different uremic solutes.     

Red blood cell membrane lipid peroxidation in continuous ambulatory peritoneal dialysis patients

We have recently described that in the erythrocytes from uremic patients on chronic hemodialysis, the pentose-phosphate shunt is defective, the membrane concentrations of malonyldialdehyde, resulting from peroxidation of polyunsaturated fatty acids in the membranes themselves, are increased, and the concentrations of vitamin E, an antioxidizing agent, are reduced. In the present study we have analyzed these same metabolic aspects in a group of uremic patients in continuous ambulatory peritoneal dialysis. We have found normal function of the pentose-phosphate shunt, slightly elevated concentrations of malonyldialdehyde compared to controls, but definitely lower than in chronic hemodialysis patients, and higher tocopherol concentrations than in both controls and chronic hemodialysis patients.     

Nonenzymatic glycosylation of hemoglobin and total plasmatic proteins in end-stage renal disease

In order to ascertain whether there are abnormalities of nonenzymatic glycosylation in uremia, the levels of nonenzymatically glycosylated hemoglobin (GHb), and total plasmatic glycosylated proteins (PGP) were studied using the thiobarbituric acid (TBA) method, a procedure not interfered with by carbamylation. Total hemoglobin A1 (HbA1) and the A1c fraction were also determined by ion exchange chromatographic methods. Sixty-six end-stage renal disease patients (29 nondiabetic and 8 diabetic uremic patients on conservative treatment, 29 nondiabetic hemodialysis patients) and 56 controls (32 nonuremic diabetic patients and 24 healthy controls) were studied. High levels of GHb and total PGP were found in the nondiabetic uremic group on conservative treatment with all the methods used, but the persistence of high chromatographically determined HbA1 levels in hemodialysis patients contrasts with the results obtained with the other techniques, which showed lower values on hemodialysis. Nondiabetic uremic patients with abnormal oral glucose tolerance curves had significantly higher levels of TBA-determined GHb and PGP. Uremic diabetic patients had the highest glycosylation levels of all the studied groups. We conclude that there is an abnormal nonenzymatic glycosylation of proteins in uremia, independent of carbamylation reactions and partially corrected by hemodialysis.     

Leukocyte C5a receptor modulation during hemodialysis

Exposure of blood to hemodialysis (HD) membranes results in the activation of the complement system. In this study, flow cytometry was used to analyze the binding of fluoresceinated chemotactic factors (C5a, f-Met-Leu-Phe-Lys [fMLPL], and casein) and aggregated IgG to PMN and monocytes isolated from normal whole blood following passage through a hemodialyzer. Analysis of ligand binding by these PMN and monocytes showed no difference in the binding of casein, fMLPL, or aggregated IgG throughout the 45 minute procedure. In contrast, a progressive decrease in the binding of C5a by PMN and monocytes occurred. By 45 minutes, the average percentage of PMN binding C5a had dropped from 95 to 61% and monocytes from 73 to 40%. In additional studies, blood samples were obtained from chronic renal failure patients undergoing hemodialysis at four different time intervals during dialysis. Total white blood cell (WBC) counts showed that the mean WBC count at 30 minutes dropped to 60.9% of the predialysis WBC count, and rebounded to 133.8% by two hours and 128.2% by four hours. Analysis of the binding of C5a, casein, fMLPL, or aggregated IgG by PMN or monocytes from HD patients indicated there were no significant differences at the four time intervals studied. When blood samples from normal subjects or chronic hemodialysis patients were incubated in vitro with dialysis membrane fibers, a loss of identifiable C5a receptors was observed on PMN from normal blood, while PMN from HD patients showed no significant change in the percentage of C5a-receptor-positive cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sympathetic skin response in hemodialysis patients: correlation with nerve conduction studies and adequacy of dialysis

A sympathetic skin response (SSR) test was performed in diabetic and nondiabetic patients undergoing regular hemodialysis and the results correlated with nerve conduction studies (NCS): sensory conduction velocity (SCV) and motor conduction velocity (MCV). Comparisons were made between diabetic and nondiabetic patients and between cuprophane and polyacrylonitrile membrane dialyzed patients. Six nondiabetic uremic patients (30%) and all diabetic patients had no SSR. Eight nondiabetic uremic patients (40%) had a mildly impaired response. Nondiabetic patients with a normal response were younger (31.1+/-16.4 years) than the patients with abnormal SSR, whether mildly impaired response (58.3+/-20.3 years; p<0.05, Anova) or absent response (65.3+/-13.8 years; p<0.01, Anova). SCV, MCV, and SSR values were reduced (p<0.01) in uremic patients with respect to normal subjects. Severity and frequencies of sensory NCS abnormalities in nondiabetic patients were: normal 20%, mildly impaired 75%, and severely impaired 5%. Severity and frequencies of motor conduction abnormalities were: normal 80%, mildly impaired 20%, severely impaired 0%. The SSR abnormality incidence in patients with a normal NCS was similar to that in patients with either mildly or severely impaired NCS (chi-square test). There was a positive linear correlation between the SSR amplitude and SCV (r = 0.52, p<0.01) and MCV (r = 0.49, p<0.01). The SSR latency was also significantly related to SCV (r = 0.66, p<0.01) and MCV (r = 0.61, p<0.01). A significant negative correlation was found between age and SSR parameters, amplitude (r = -0.56, p<0.01) and latency (r = -0.66, p<0.01). No correlation was found between duration of hemodialysis or Kt/V and SSR. No differences were found in SSR, NCS, or Kt/V values between cuprophane membrane and polyacrylonitrile membrane dialyzed patients (Student's t test). The relationship between NCS and SSR in uremic patients was confirmed. Old age and diabetes mellitus, but not the dialysis membrane used, were confirmed as synergistic factors of neuropathic impairment. It appeared that SSR is more sensitive than NCS in detecting polyneuropathy in uremic patients on hemodialysis.