Monitoring Intracellular Concentration and Pharmacodynamic Effects of Tacrolimus in Peripheral Blood T CD4+ and B CD19+ Lymphocytes of Kidney Transplant Recipients
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Kidney Transplantation
- Sponsor
- University of Sao Paulo General Hospital
- Enrollment
- 45
- Locations
- 1
- Primary Endpoint
- Correlation between blood and intracellular levels of tacrolimus
- Last Updated
- 8 years ago
Overview
Brief Summary
Therapeutic drug monitoring (TDM) of immunosuppressive drugs is used to improve the immunosuppressive effect while minimizing the toxicity related to exposition to high serum levels. Although TDM is widely used in clinical practice, a significant number of kidney transplant recipients have acute allograft rejection in the first year after transplantation. To improve the use of immunosuppressive drugs, new approaches of TDM have been developed. Monitoring drug concentrations at lymphocytes of peripheral blood is considering promising because it indicates the availability of the drug directly in the target sites of immunosuppression. The present study intends to establish the concentration profile of tacrolimus in the peripheral blood in parallel with the concentration profile inside T and B lymphocytes of peripheral blood of kidney transplant recipients, and correlates them with the expected pharmacological effects. The pharmacological effects of tacrolimus in calcineurin dependent and calcineurin independent (mitogen-activated protein kinase (MAPK) dependent) activation pathways will be assessed by measuring activated nuclear factor of activated T cells (NFAT) and p38, respectively, by flow cytometry. The expression of interleukin (IL) - 2 and IL-10 by T and B lymphocytes, respectively, will be also used to monitoring the pharmacodynamic effects of tacrolimus.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Kidney transplant recipients with a well functioning graft (serum creatinine ≤ 2,0 mg/dL at inclusion)
- •Must be on tacrolimus therapy
- •Must be on short term follow up time (1 to 5 months) after surgery
Exclusion Criteria
- •A concomitant second solid organ transplant
- •Immunosuppression not containing tacrolimus
Outcomes
Primary Outcomes
Correlation between blood and intracellular levels of tacrolimus
Time Frame: From 1 up to 5 months post transplantation
The concentration of tacrolimus will be determined in the whole blood, in T CD4+ cell suspension and in B CD19+ cell suspension prepared from one blood sample per patient subject. The correlations among concentrations of tacrolimus in the 3 different cell matrices will be established.
Secondary Outcomes
- Correlation among intracellular levels of tacrolimus and its pharmacological effects(From 1 up to 5 months post transplantation)