Blood transfusions in renal dialysis patients:

The effect of blood transfusions, given in low number (<5), on the immune response of renal dialysis patients was studied. A significantly lowered response of lymphocytes to mitogen stimulation was observed in patients after as few as one, two or three transfusions, depending on the patient. This led to an increased ▵48/▵0 ratio reflected by the enhanced response of the cells following delayed addition of sub-optimal dose of mitogen. There was no modification of the ratio of helper/inducer to suppressor/cytotoxic T cells subsets (OKT4/OKT8). The use of such simple in vitro tests in a strict protocol of transfusions could allow an adequate follow-up thereby limiting the risks of sensitization. These results demonstrate that important phenomena affecting patients' immune response are turned on following even a low number of transfusions in the majority of uremic patients. This could probably be related to the beneficial effects of blood transfusions on the kidney allograft survival already described.     

Antileukocyte antibodies in patients refractory to platelet transfusions

Sera from 12 multitransfused patients who were refractory to random-donor platelets were tested for lymphocytotoxic and leukoagglutinating antibodies using panel cells from various volunteers whose HLA-A and -B antigens were known. All sera contained leukoagglutinins reactive with cells from at least one panel member, whereas only 33% had lymphocytotoxic antibodies. Patients whose sera reacted frequently with panel cells using the microcapillary agglutination technic seldom responded to HLA-matched paltelets, whereas those whose sera reacted infrequently usually responded satisfactorily. It is concluded that non-HLA antibodies may play a significant role in determining the responses to platelet transfusions in multi-transfused patients.     

Association of HLA-DR antigens with the development of cytotoxic antibodies in patients on dialysis

Association between DR antigens and the occurrence of cytotoxic alloantibodies was studied in 251 patients on dialysis. Patients awaiting their first kidney graft were DR typed, and periodically investigated for the presence of alloantibodies. According to the observed peak panel reactive antibodies (PRA) the patients were divided into 3 groups: A, non-sensitized, B, moderately sensitized, and C, highly sensitized. The antigen DR3 was more frequent in sensitized (groups B + C) than in non-sensitized (group A) patients. This difference was significant on the level of P = 0.003, (Pcorr = 0.02). The antigen DR2 was more frequent in highly sensitized (group C) than in moderately sensitized (group B) patients with P = 0.002, not significant after correction for the number of investigated antigens.     

HTLV-III antibodies in hemodialysis patients — A consequence of blood transfusions?

Summary An investigation for HTLV-III antibodies in chronic hemodialysis patients revealed in four out of 276 patients a positive result using the ELISA and western blot techniques. All HTLV-III positive patients had received blood transfusions. As it has been shown that a needle stick could transmit the HTLV-III, it is suggested that hemodialysis patients who have received frequent blood transfusions should be screened.Abbreviations AIDS acquired immune deficiency syndrome - ELISA enzyme linked immunosorbent assay - HbSAg hepatitis surface antigen - HD hemodialysis - HTLV-III human T-cell lymphotropic virus type III     

The management of hypotension in dialyzed patients

Acute hypotension is a frequent hemodialysis complication. This intra-treatment vascular instability is a multifactorial process in which procedure-related and patient-related factors may influence the decrease in plasma volume and the impairment of cardiovascular regulatory mechanisms. Identification of the most susceptible patients and of the various risk factors may contribute to significantly improving cardiovascular stability during dialysis. In some high-risk patients, continuous monitoring of the various parameters can predict the appearance of symptomatic hypotension and help to prevent its onset.     

Significance of cytotoxic eye muscle antibodies in patients with thyroid-associated ophthalmopathy

We have studied the clinical significance of cytotoxic antibodies against human eye muscle cells in patients with thyroid-associated ophthalmopathy (TAO). Eye muscle reactive antibodies were measured in an antibody-dependent cell-mediated cytotoxicity (ADCC) assay. A positive test was defined as % specific lysis greater than the upper limit of normal, taken as the mean plus two standard deviations for normal subjects tested concurrently. As parameters of the severity of the ophthalmopathy we measured the degree of proptosis (mm), level of intraocular pressure (IOP) (mmHg) and American Thyroid Association classes (0-6). ADCC tests were positive in 21 out of 42 patients with TAO and in 8 out of 14 patients with Graves' disease without evident eye disease but in none of 12 normal subjects tested. In patients with TAO mean (+/- SE) IOP was significantly greater than that in patients with Graves' disease without apparent eye involvement for the primary position and for all gaze positions. There were significant positive correlations between levels of eye muscle reactive cytotoxic antibodies and the severity of the eye disease quantitated as American Thyroid Association classes 0-6, the IOP in the primary position and on downgaze, but not with the degree of proptosis. These results suggest that cytotoxic antibodies, as detected in ADCC, may play a role in the eye muscle damage of TAO and that their measurement may provide a useful clinical test.     

Ash Split Cath in geriatric dialyzed patients.

Vascular access is the essential step in performing hemodialysis in uremic patients. In the absence of a permanent and utilizable native arterio-venous fistula, the use of a tunnelled catheter makes dialysis therapy possible. The Ash Split Cath, a recently introduced chronic hemodialysis catheter, was inserted in five patients (7.1% of our prevalent dialysis population) because of repeated venous thrombosis in three patients and a poor venous tree in two. The mean age of patients was 78 years +/- 7. The average blood flow rate was 250+/-50 ml/minute and the mean venous pressure 140mm Hg +/- 35. Recirculation determined by low flux technique was less than 2%. KT/V calculated 3 months after the catheter placement was 1.2+/-0.02. During the follow-up we did not document any infection of the exit site or related to the catheter. This device is simple to place, gives adequate dialysis treatment and is useful in geriatric dialyzed patients in whom the arterio-venous fistula can no longer be used.     

Immunologic factors determining survival of cadaver-kidney transplants. The effect of HLA serotyping, cytotoxic antibodies and blood transfusions on graft survival.

We assessed immunologic factors determining graft survival in 510 recipients of primary cadaver allografts at one center. The degree of HLA match grade did not directly affect graft survival (54 per cent in no-antigen match, and 42 per cent in three-antigen match, at two years). There was no correlation between the HLA match grade and the degree of stimulation of the mixed lymphocyte culture. Patients receiving more than five blood transfusions had a significantly better graft survival than nontransfused recipients (52 versus 23 per cent, respectively, at two years, P less than 0.001). The beneficial effect of transfusions was noted whether or not lymphocytotoxic antibodies were produced, provided adequate screening was performed before transplantation. Transfusions did not alter the degree of stimulation in the mixed lymphocyte culture. More liberal use of transfusions and frequent screening for cytotoxic antibodies would probably result in more effective cadaver-kidney transplantation.     

Neutralisation of cytotoxic vacuolating activity by serum antibodies of Helicobacter pylori-infected patients

The study involved 196 H. pylori strains and 196 serum samples taken from the same patients. H. pylori strains were investigated for the production of vacuolating cytotoxin. Antibodies to the vacuolating cytotoxin produced by H. pylori were detected in the sera samples by neutralisation assay (on Intestine 407 cells) and ELISA. Of the 196 H. pylori strains tested, 80 (40.8%) were found to express vacuolating cytotoxic activity. The titres of cytotoxic nonconcentrated broth culture filtrates ranged from 1:2 to 1:128. The vacuolating assay was positive in 37.1% strains isolated from children, and in 50% strains isolated from adults. Cytotoxin-positive H. pylori strains were found more frequently in duodenal ulcer (71%) than in chronic gastritis (35.2%) patients, and this difference was statistically significant p < 0.05. Neutralising antibodies to vacuolating cytotoxin were present in 51% and 49% of the serum samples tested by neutralisation and ELISA, respectively. Duodenal ulcer patients had antibodies to vacuolating cytotoxin more frequently (p < 0.05) than chronic gastritis patients. Antibodies to cytotoxin were detected in the serum samples from patients infected by cytotoxic (100%) and noncytotoxic (18%) H. pylori strains.     

Role of blood transfusions on the induction of antibodies against recognition sites on T lymphocytes in renal transplant patients

We have tested sera from 23 renal allograft recipients to study the effects of blood transfusions on the induction of antibodies directed against recognition sites on T lymphocytes. The results demonstrate that antibodies capable of inhibiting responses in MLC could be induced by blood transfusion. This inhibition in MLC is observed by treatment of responder lymphocytes with serum plus rabbit complement and is mediated by IgG antibodies. Also, the inhibitory effect is specific for certain responder cells and is not mediated by antibodies against common surface antigens of either the responder or the stimulator lymphocytes. The antibodies inhibiting proliferative responses in MLC against antigens present on the kidney donor were demonstrable in renal transplant recipients with functional allografts, but not in patients who had rejected the graft. The data suggest that antibodies directed against recognition sites on T lymphocytes could be induced by blood transfusions and these antibodies may be associated with prolonged graft survival.     

Plasma calprotectin in chronically dialyzed end-stage renal disease patients

Objective  

The current study aimed to evaluate plasma calprotectin levels and clearance end-stage renal disease (ESRD) patients with and without acute infection undergoing chronic hemodialysis (HD).     

The cardio-renal-anaemia syndrome predicts survival in peritoneally dialyzed patients

Introduction

Anaemia is one of the arms of the cardio-renal-anaemia syndrome (CRA) in chronic kidney disease (CKD) patients. The correction of anaemia was effective in the amelioration of both cardiac and renal failure. We studied the relationship between the severity of CRA syndrome in peritoneally dialyzed patients and their survival probability.

Material and methods

Fifty-six patients on peritoneal dialysis were followed for 1 year. Definition of the severity of the CRA in dialysis patients: cardiac arm – NYHA class I-IV = 1-4 points, renal arm – non-diabetic patients age < 65 =1 point, non-diabetic patients age>65 = 2 points, diabetic patients age < 65 = 3 points, diabetic patients age>65 = 4 points, anaemia arm – Hb 11-13 g/dl (male), 11-12 g/dl (female) = 1 point, Hb 10-11 g/dl = 2 points, Hb 9-10 g/dl = 3 points, Hb < 9 g/dl = 4 points. The severity score = cardiac + renal + anaemia arms score divided by 3 (maximum 4 points).

Results

A total of 10/56 patients (18%) died during the study. The median value for the severity score of the whole group was 1.69. In Kaplan-Meier analysis CRA severity score was strongly associated with mortality (p < 0.001). It also correlated with albumin, CRP, erythropoietin treatment, Hb and fasting glucose. In the multivariate regression analysis age, Hb, albumin, and presence of diabetes remained significant predictors of death.

Conclusions

The severity score of CRA syndrome in peritoneally dialyzed patients is an independent and very significant predictor of death. The patients with a high severity score had more hypoalbuminaemia, higher inflammation markers and higher prevalence of diabetes and chronic heart failure. Cardio-renal-anaemia syndrome severity scoring as defined by us could be an easy tool to predict outcome of dialysis patients.     

Granulocyte specific cytotoxic antibodies in pregnancy and multitransfused sera

The myeloid cell line K562 was used to screen for specific antibodies in sera obtained from pregnant women and multitransfused patients. The alloantisera thus procured reacted with random granulocytes in a pattern suggestive of a polymorphic system. Some antibodies were found to react only in the cold. A simple reproducible method for the simultaneous separation of granulocytes and lymphocytes for microcytotoxicity is described.