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Granulocyte activation during haemodialysis in the absence of complement activation: inhibition by calcium channel
M Haag-Weber1, P Schollmeyer, W H Hörl
1Department of Medicine, University of Freiburg, FRG.
Insights
Calcium channel blockers reduce granulocyte activation during hemodialysis with PMMA and PAN dialyzers, but not cuprophane. This suggests calcium ions mediate granulocyte activation when complement activation is absent.
Area of Science:
- Nephrology
- Pharmacology
- Immunology
Background:
- Hemodialysis can activate granulocytes and complement.
- The role of calcium ions in this activation is not fully understood.
Purpose of the Study:
- To investigate the effect of calcium channel blockers (nifedipine, diltiazem, verapamil) on hemodialysis-induced granulocyte and complement activation.
- To determine if calcium ions mediate granulocyte activation during hemodialysis.
Main Methods:
- Continuous infusion of calcium channel blockers during hemodialysis.
- Measurement of plasma lactoferrin, elastase-alpha 1-proteinase inhibitor (E-alpha 1PI), and C3a levels.
- Use of dialyzers made of cuprophane, polymethylmethacrylate (PMMA), and polyacrylonitrile (PAN).
Main Results:
- Calcium channel blockers did not alter blood pressure.
- No significant changes in lactoferrin, E-alpha 1PI, or C3a were observed with cuprophane dialyzers.
- All tested calcium channel blockers significantly reduced lactoferrin and E-alpha 1PI with PMMA dialyzers.
- Nifedipine and verapamil reduced lactoferrin and E-alpha 1PI with PAN dialyzers.
Conclusions:
- Calcium channel blockers inhibit granulocyte activation with minimal anaphylatoxin formation during hemodialysis using PMMA and PAN dialyzers.
- These drugs are ineffective when complement activation occurs with cuprophane dialyzers.
- Granulocyte activation during hemodialysis, in the absence of complement activation, appears to be mediated by calcium ions.
Abstract:
The effect of the calcium channel blockers nifedipine (9 and 18 micrograms kg-1 h-1), diltiazem (100 and 200 micrograms kg-1 h-1) and verapamil (19 micrograms kg-1 h-1) continuously infused during haemodialysis on granulocyte and complement activation was investigated. Plasma levels of lactoferrin, elastase in complex with alpha 1-proteinase inhibitor (E-alpha 1PI) and C3a were measured in patients dialysed with dialysers made of cuprophane, polymethylmethacrylate (PMMA) and polyacrylonitrile (PAN). Calcium channel blockers caused no change of blood pressure during haemodialysis in all patients. There was no effect of nifedipine, diltiazem or verapamil on plasma lactoferrin, E-alpha 1PI or C3a levels in patients dialysed with cuprophane. However, plasma lactoferrin and E-alpha 1PI values were significantly reduced by all calcium channel blockers in patients dialysed with PMMA, and also by nifedipine and verapamil in patients dialysed with PAN. Our data indicate that calcium channel blockers inhibit granulocyte activation occurring in dialysers with very little anaphylatoxin formation. These drugs, however, are ineffective in patients dialysed with cuprophane where complement activation takes place. Therefore, granulocyte activation during haemodialysis in the absence of complement activation seems to be mediated by calcium ions.