Treatment of hyperphosphatemia, secondary hyperparathyroidism and hypocalcemia with calcium carbonate favorably modulates vaccination response in uremic rats.

AIMS: Immune dysfunction is characteristic of renal failure, leading to suboptimal antibody generation and increased susceptibility to infections. We tested whether the treatment of uremic phosphate retention by increased calcium carbonate intake will beneficially influence vaccination response in 5/6-nephrectomized rats. METHODS: The nephrectomized (uremic) and sham-operated (control) rats were either fed 0.3% calcium diet (NTX and Sham groups, respectively) or 3% high-calcium diet (Ca-NTX and Ca-Sham groups). All rats were immunized with tetanus toxoid 6 weeks after the operations, and antitoxin levels were measured 7 weeks later. RESULTS: Plasma creatinine was significantly elevated after the nephrectomy: the values (mean +/- SD) in the NTX (n = 16), Ca-NTX (n = 11), Sham (n = 14) and Ca-Sham (n = 8) groups were 97 +/- 14, 93 +/- 17, 66 +/- 7, and 69 +/- 8 micromol/l, respectively. The NTX group developed phosphate retention and secondary hyperparathyroidism, which were completely prevented by the high calcium diet. The mean tetanus antitoxin concentrations of the groups were: NTX 0.25 +/- 0.32; Ca-NTX 0.45 +/- 0.44; Sham 0.58 +/- 0.24 and Ca-Sham 0.64 +/- 0.25 IU/ml (log of geometric mean concentration). The antibody response in the NTX group was significantly lower, i.e. 43% of that in the Sham group (p = 0.003), while the response in the Ca-NTX group was not different from that in the Sham group. The tetanus response of all the uremic rats inversely correlated with the plasma levels of phosphate (r = 0.447, p = 0.02), parathormone (r = -0.409, p = 0.03) and creatinine (r = 0.578, p = 0.002). DISCUSSION: We conclude that renal failure impairs vaccination response in rats, the impairment of which can be favorably modulated by phosphate-binding and PTH-suppressing high-calcium diet.

Constant, but not pulsed calcitriol suppresses hemodialysis patients' antigen-induced lymphocyte proliferation.

BACKGROUND/AIMS: In vitro constant calcitriol [1,25-(OH)(2)D(3)] inhibits healthy individuals' T lymphocyte proliferation at supraphysiological concentrations. In contrast, among hemodialysis patients, intravenous 1,25-(OH)(2)D(3) pulse therapy of secondary hyperparathyroidism has been shown to be even immunostimulatory. We studied the effect of in vitro constant and intermittent 1, 25-(OH)(2)D(3) on lymphocyte antigen response of hemodialysis patients. METHODS: Twelve hemodialysis patients' peripheral blood mononuclear cells were stimulated with purified protein derivative of tuberculin (12.5, 25 and 50 mg/l) or tetanus toxoid (TT; 1,000, 5, 000 and 10,000 Lf/l, limit of flocculation) for 7 days. Constant 1, 25-(OH)(2)D(3) was added to all cultures at concentrations of 0, 10(-10) or 0.25 x 10(-9) mol/l (0, 42 and 105 ng/l) and to half of the cultures additionally as a 0.75 x 10(-9) mmol/l (315-ng/l) pulse on the 5th culture day. RESULTS: TT-induced lymphocyte proliferation was statistically related to a constant 1,25-(OH)(2)D(3) concentration (p = 0.001, analysis of variance). With constant 1, 25-(OH)(2)D(3) concentrations of 0, 42 and 105 ng/l, the TT-induced responses were 1.53, 1.44 and 1.40 log cpm, respectively (mean of TT concentrations). The responses of the (additionally) pulse-treated cells [1.65, 1.50 and 1.40 log cpm; concentrations of constant 1, 25-(OH)(2)D(3) as above] were similar to those of the nonpulsed cells. Thus constant, but not pulsed 1,25-(OH)(2)D(3) decreased the TT responses. On the purified protein derivative of tuberculin response, neither constant nor pulsed 1,25-(OH)(2)D(3) had any significant effect. CONCLUSIONS: The decline of TT response with constant 1,25-(OH)(2)D(3) corresponds with findings on immunosuppressive action of 1,25-(OH)(2)D(3) in previous studies done on normal subjects' cells. This was not seen with intermittently applied 1,25-(OH)(2)D(3). These results support the previous concept that intermittent 1,25(OH)(2)D(3) therapy is not immunosuppressive in hemodialysis patients.

Adequate seroresponse to influenza vaccination in dialysis patients.

BACKGROUND: Hemodialysis (HD) patients are immunocompromised, and they have been shown to react suboptimally to recommended vaccinations. Advances in dialysis therapy and other supportive measures may theoretically result in better immune system functions. Clinical evidence supporting this theory has, however, not been presented. With influenza vaccination response, we tried to address this question. METHODS: 42 HD and 15 continuous ambulatory peritoneal dialysis (CAPD) patients were vaccinated with a trivalent influenza vaccine, and the seroresponses at 5 weeks were measured. The results were compared with those of similarly vaccinated 20 nephrology outpatient clinic patients with varying degrees of renal insufficiency and those of 31 cardiac patients with normal renal function. RESULTS: The dialysis patients had higher prevaccination titers of hemagglutination-inhibiting (HI) antibodies to all three vaccine virus antigens than the other groups due to more frequent previous vaccinations. The dialysis patients exhibited lower antibody increases, but an almost comparable proportion of them reached a protective antibody level (HI titers > or =40) 5 weeks after vaccination [A/H3N2: 61% (cardiac patients), 35% (nephrology outpatient clinic patients), 67% (CAPD), and 36% (HD); A/H1N1: 71, 70, 80 and 60; B: 97, 90, 80, and 76%, respectively]. Among the HD group, all patients receiving parenteral calcitriol except 1 (83%), but only 50% of the other HD patients produced protective antibody titers at least to two out of three vaccine virus antigens. No other patient- or HD treatment-associated parameter was significantly related to the vaccination-induced antibody response. CONCLUSIONS: We conclude that influenza vaccination of dialysis patients according to current recommendations may be effective. Additionally, our results suggest that parenteral calcitriol treatment may augment the immune response of HD patients even in a clinically relevant way, an effect so far shown only in in vitro studies.