Total antioxidant capacity (TAC): is it an effective method to evaluate the oxidative stress in uraemia?

Lipoprotein abnormalities are common in uraemia and are considered important factors for development of atherosclerosis and progression of renal disease. Reduction of total antioxidant capacity (TAC) and lipid peroxidation (LP) probably play a major role in both processes. The aim of this study was to assess the effect of renal function, dietary manipulation and lipids on TAC of uraemic patients with different chronic renal failure (CRF). Sixty patients (36M, 24F), aged 60 +/- 12 years were divided into five groups according to serum creatinine levels (sCr,mg/dl)--CRFI, 1.5-3; CRFII, > 3-5.5; CRFIII, > 5.5; CRFIV, > 3 on vegetarian supplemented diet (SD); CRFV haemodialysis patients (HD)- and investigated for TAC by enhanced chemiluminescent assay, autoantibodies against oxidized LDL (oxLDLAb), lipids, apolipoprotein AI, B, Lp(a) and uric acid (UA). The results were compared to a control group of 19 people (8M, 11F), aged 52 +/- 11 years with sCr < 1.5. TAC increased significantly with the progression of CRF and was strongly related to both sCr and UA. Lipids and SD did not show any influence on TAC. Unexpectedly, lipid peroxidation did not correlate to TAC, neither to sCr or UA. HD accounted for a mild reduction of both TAC and LP. Patients on SD showed a marked reduction of LP as compared to patients with a similar degree of renal failure (CRF-III) but on conventional diet. Our results suggest that elevated TAC in uraemia is likely to be dependent on increased UA levels and does not seem to induce an effective protection in vivo from oxidative stress. In conclusion, TAC does not appear to be a reliable method for assessing the oxidative susceptibility of CRF patients.

Effects of zinc supplementation on the immune system and on antibody response to multivalent influenza vaccine in hemodialysis patients.

The depression of the immune system in chronic uremia is a well-known phenomenon but the role of serum zinc (Zn) levels on both cell-mediated and humoral immunity is still controversial. The aim of this study was to investigate the effect of Zn supplementation on the immune system and on antibody response to multivalent influenza vaccine (MIV) in hemodialysis patients (HP). Twenty-six HP and 11 healthy subjects (HS) were vaccinated with MIV. Hemodialysis patients were randomly divided into two groups. Group I (13 HP) was supplemented with 120 mg ZnSO4 after each dialysis session. Group II (13 HP) and Group III (11 HS) were given placebo. In all cases, the serum Zn levels, CD3, CD4, CD8, CD19, HLA-DR+ cell percentages, CD4/CD8 ratio and CD3+ HLA-DR+ cell percentages were determined before and 30 days after vaccination. Antibody levels to subgroups of MIV were also measured. All the baseline parameters studied were not statistically different between Group I and II. However, there was a significant difference between the basal parameters of Group III and the other two groups, except for CD3 and CD4 cell percentages. Serum Zn, CD19 cell percentage and antibody levels to MIV subgroups were significantly increased in Group I at the end of the first month of the study (p<0.01, p<0.05, p<0.001, p<0.001, and p<0.01, respectively), but the other parameters showed no significant changes. The only significant change observed in Groups II and III was an increase in antibody levels to MIV subgroups one month after vaccination. Antibody levels to MIV subgroups, were not statistically different between Groups I and II, but in Group III they were strikingly higher than those of HP (p<0.001). These results led us to conclude that Zn supplementation could not restore the immune parameters and enhance antibody response to MIV in HP.

Functional roles of phenylalanine(7) of thymic humoral factor-gamma 2 in the impaired blastogenic response of uremic T-lymphocytes.

The peptide analogs of thymic humoral factor-gamma 2 (THF-gamma 2) in which phenylalanine residue at the 7th position are replaced by phenylglycine (Phg), homophenylalanine (Hph), and 1-naphthylalanine (1-Nal) were synthesized by a solid-phase method and the immunological significance of the aromatic amino acid of this position was comparatively investigated. The in vitro restoring effect of the synthetic peptides on the impaired phytohemagglutinin (PHA) response of T-lymphocytes from uremic patients was tested. The observed activities of these peptides were in order (1-Nal7) thymic humoral factor [THF]-gamma 2 > 4-Fluoro (Phe7) THF-gamma 2 > THF-gamma 2. However, the other two analogs, [Phg7] THF-gamma 2 and [Hph7] THF-gamma 2, had no restoring effect even at a higher concentration.

Effects of selenium supplementation on immune parameters in chronic uraemic patients on haemodialysis.

BACKGROUND: The involvement of selenium (Se) in immune response has been increasingly recognized, cell-mediated immunity being principally affected by Se deficiency. Blood Se levels in chronic uraemic patients are frequently lower than in controls, and in these patients cellular immunity in generally impaired. METHODS: The present study was designed to assess the effects of Se supplementation over 6 consecutive months on immune parameters in haemodialysis (HD) patients from Rostock (Germany) and Chieti (Italy). In both cities, five patients were supplemented with Se (500 micrograms thrice weekly for 3 months, then 200 micrograms thrice weekly for the next 3 months), whereas another five patients received placebo. All Se determinations were performed in a single laboratory. RESULTS: In both cities, basic plasma Se levels were significantly lower in patients than in their corresponding normal controls. After beginning Se supplementation, plasma Se concentration promptly normalized and levelled off in the normal range throughout the study. Se administration was well tolerated by all patients, and no side-effects attributable to Se toxicity were observed. Although no major change in immunocompetent cells (white blood count, total lymphocyte count, lymphocyte subpopulations) was observed during Se therapy, an improvement in T-cell response to phytohaemoagglutinin (as evaluated in Rostock patients) and a significant progressive increase in delayed-type hypersensitivity (as evaluated in Chieti patients) was observed in supplemented patients. After 6 months of Se therapy, the increase in delayed-type hypersensitivity of supplemented patients proved to be significantly higher when compared to both presupplementation values and to the results found in non-supplemented patients. Three months after suspension of Se supplementation, plasma Se levels and delayed hypersensitivity significantly decreased in Chieti patients, with both parameters returning similar to presupplementation values. CONCLUSIONS: In accordance with previous studies done in non-uraemic subjects, our investigation demonstrates for the first time the immunostimulatory properties of Se in HD patients. Though several problems on Se metabolism in uraemia remain unresolved, in our opinion moderate and safe Se supplementation can be beneficial in chronic uraemic patients.

Zinc supplementation stimulates tetanus antibody formation and soluble interleukin-2 receptor levels in chronic hemodialysis patients.

Immunodepression in end-stage renal disease has been associated with zinc deficiency. In a controlled study serum zinc levels, serum concentrations of soluble interleukin-2 receptor (sIL-2R), and tetanus IgG antibody titers were measured in 65 hemodialysis patients before and after intravenous zinc supplementation for 2 months. The hemodialysis patients had significantly lower predialysis serum zinc concentrations compared to healthy controls (63 +/- 1.65 versus 126 +/- 4.6 micrograms/dl, P < 0.001). Serum zinc concentrations increased to the normal range in the zinc-treated patients. After zinc substitution tetanus antibody titers rose significantly (0.81 +/- 0.12 versus 1.22 +/- 0.12 U/ml, P < 0.01). Pretreatment sIL-2R levels were elevated in 95% of examined patients. A further increase in sIL-2R was observed after zinc supplementation (234 +/- 14 versus 285 +/- 21 U/ml, P < 0.05). The results suggest that zinc induces the activation of T lymphocytes and T-cell dependent B lymphocytes in chronic uremic patients in vivo.

Hepatitis B vaccination in dialysis patients and nutritional status.

35 dialysis patients underwent anti-HBV vaccination. We classified patients in responders or non-responders using an anti-HBs titer of 50 UI/l as the discriminating serum level and tried to assess whether the antibody response bears any relationship with the nutritional status. 26 patients (74%) reached the target atb titer, which was maintained during follow-up (average 360 UI/l). The weak response in the other 9, with values never exceeding 20 UI/l, was short-lived. Anthropometric and impedenziometric parameters were higher in responders than in nonresponders, but the difference did not reach statistical significance. We conclude that the atb titer which discriminates uremics in responders or not must be greater than 50 UI/l and that the nutritional status may interfere with the seroconversion rate, but this conclusion needs to be validated in a wider population.

Effects of zinc supplementation on zinc status and immunity in haemodialysis patients.

The depression of immunity to various antigens in chronic uremia is a frequently encountered phenomenon. Zinc deficiency might well be an important factor in its genesis. The aim of this study was to investigate the role of zinc deficiency in this reduced immune response. Two groups of 7 patients on haemodialysis who had failed to respond with seroconversion to an earlier vaccination against hepatitis B were revaccinated. One group received zinc by the addition of zinc chloride to the dialysate. Before initiation of the study zinc in plasma and leucocytes was measured. No difference in plasma and leucocyte zinc was observed between the two groups. Zinc in leucocytes was lower in patients than in a group of healthy volunteers (61.5 pmol/10E6 cells +/- 4.6 versus 73.8 +/- 5.6, p less than 0.005). Plasma zinc showed no difference between patients and healthy volunteers. During zinc supplementation zinc in plasma rose in the patient group receiving zinc (10.4 mmol/L +/- 1.5 to 14.2 +/- 1.9, p less than 0.005). However, no rise in leucocyte zinc was seen. At the end of the trial seroconversion had occurred in 2 patients in each group. It is concluded that zinc supplementation in haemodialysis patients does not lead to the restoration of leucocyte zinc to normal levels. Neither did it lead to an enhanced antibody response in our population after revaccination of haemodialysis patients against hepatitis B.

Effect of a low-protein diet on chemiluminescence production by leukocytes from uremic patients.

Chemiluminescence (CL) emission from leukocytes was studied in 20 uremic patients after ingestion of opsonized zymosan. CL production was impaired when compared with control groups. Six months after a low-protein, low-phosphorus diet supplemented with essential amino acids and ketoanalogues (SD) was started, a significant improvement in CL production was observed. SD may be expected to decrease the susceptibility of uremic patients to bacterial infections.

Isoprinosine enhances PHA responses and has potential effect on natural killer cell (NK) activity of uremic patients in vitro.

We studied the effect of an immuno-stimulating agent, isoprinosine, which is being marketed as an antiviral drug, on some immune functions in vitro in 14 uremic patients treated by hemodialysis and in 10 healthy controls. PHA and PPD induced stimulations of DNA synthesis and interleukin-2 (Il-2) production and NK cell activity were measured from peripheral blood mononuclear cells cultured with and without isoprinosine. PHA responses were enhanced by isoprinosine (100 micrograms/ml) both in the patient group (p less than 0.001) and in the control group (p less than 0.05) but PPD responses in neither. The enhancement of PHA responses was not due to an increased production of Il-2(T-cell growth factor). Isoprinosine augmented NK activity in those patients whose NK activity was initially low. No enhancement could be seen in the controls or in those patients whose NK activity was comparable to that of the controls. Our results motivate a clinical study with isoprinosine in uremic patients at the risk of virus infection.

Immunosuppressive effect of intra-lymphatic irradiation.

The effect of intra-lymphatic administration of Lipiodol-l131 on the number of T and B lymphocytes, and on the in vivo response to common antigens and to DNCB, was investigated in uremic patients in the pre-transplant period. T lymphocytes have been detected by rosette formation with sheep erythrocytes (E) and B lymphocytes by rosette formation with erythrocytes sensitized with antibody and complement (EAC). After irradiation it was observed a lymphopenia due to a statistically significant decrease in the number of both T and B peripheral blood lymphocytes and a depletion of these cells in the irradiated lymph nodes. Their ability to give delayed hypersensitivity response to common antigens in vivo was lost after intralymphatic irradiation. Two patients were able to develop sensitization to DNCB and this reaction was supressed in one of them by irradiation. These effects of intralymphatic irradiation on the immune system favours further study of this method in clinical renal transplantation.