Impact of extracorporeal blood flow rate on blood pressure, pulse rate and cardiac output during haemodialysis.

Background: If blood pressure (BP) falls during haemodialysis (HD) [intradialytic hypotension (IDH)] a common clinical practice is to reduce the extracorporeal blood flow rate (EBFR). Consequently the efficacy of the HD (Kt/V) is reduced. However, only very limited knowledge on the effect of reducing EBFR on BP exists and data are conflicting.

A review of the immunosuppressive activity of cyclosporine metabolites: new insights into an old issue.

Cyclosporine A (CsA) is metabolized into a vast spectrum of metabolites. The potential immunosuppressive action of CsA's metabolites has been studied extensively in the early 1990's, with conflicting and inconclusive results. Since then, the pharmacological and clinical consensus guidelines recommend the use of specific monoclonal assays for measurement of CsA's concentrations thus avoiding metabolite interference.

The calcineurin activity profiles of cyclosporin and tacrolimus are different in stable renal transplant patients.

Cyclosporin and tacrolimus remain the cornerstone immunosuppressive drugs in organ transplantation. Dosing and monitoring these drugs is based on pharmacokinetic protocols, but measuring a pharmacodynamic parameter, calcineurin phosphatase (CaN) activity, could be a valuable supplement in determining optimal doses. Forty stable renal transplant patients were investigated three times in a 6-month period.

Correlations between calcineurin phosphatase inhibition and cyclosporine metabolites concentrations in kidney transplant recipients: implications for immunoassays.

Cyclosporine exhibits a wide spectrum of metabolites that vary considerably in the extent to which they interfere with the various parent drug monitoring immunoassays. There is no consensus regarding the clinical significance of metabolites. Cyclosporine exerts its immunosuppressive action by inhibiting the enzyme calcineurin phosphatase.

The hemodynamic effect of calcium ion concentration in the infusate during predilution hemofiltration in chronic renal failure.

Background: It is the prevailing view that convective dialysis techniques stabilize blood pressure. Calcium concentration in the substitution fluid may be important in this respect. The aim of this study is to investigate the influence of calcium ion concentration in the substitution fluid on hemodynamic stability during predilution hemofiltration (HF).

Predilution hemodiafiltration displays no hemodynamic advantage over low-flux hemodialysis under matched conditions.

Background: It is the prevailing view that convective dialysis techniques stabilize blood pressure. The aim of this study was to compare the intrasession hemodynamics during high-dose predilution hemodiafiltration (HDF) and low-flux hemodialsis, under strict controlled conditions.

Methods: Twelve stable hemodialysis patients were investigated in a randomized crossover blinded controlled trial.

Role of metabolites and calcineurin inhibition on C2 monitoring in renal transplant patients.

Background: Many transplantation centres have switched to C2 monitoring of cyclosporin-treated renal transplant patients. The rationale is that the C2 correlates best with AUC0-4 (area under the concentration-time curve), which again correlates with rejection and nephrotoxicity. It has also been demonstrated that calcineurin phosphatase is inhibited maximally 1-2 h after intake of cyclosporin in patients receiving their first dose.

Validation of the calcineurin phosphatase assay.

Background: The calcineurin inhibitors cyclosporine and tacrolimus are used as primary immunosuppressive drugs in transplant patients. Measuring calcineurin phosphatase (CaN) activity is a proposed pharmacodynamic approach to optimize dosing of these drugs.

Methods: Whole blood samples were obtained from 10 patients treated with calcineurin inhibitors and 20 healthy volunteers and frozen at -80 degrees C.