Monitoring Concentration and Pharmacodynamic Effects of Tacrolimus in Peripheral Blood Lymphocytes of Kidney Transplant Recipients

University of Sao Paulo General Hospital

Status: Unknown

Conditions: Kidney Transplantation; Rejection

Study type: Observational

Funder types: Other

Identifiers

NCT03425071

CAAE 41558915900000068

Details and patient eligibility

About

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.

Enrollment: 45 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

45 participants in 3 patient groups

Healthy volunteers

Description:

Healthy volunteers - subjects without exposure to tacrolimus. Blood samples from these subjects will be used in "in vitro" experiments.

kidney transplant (KTx) months 1-2

Description:

Kidney transplant recipients recruited during the months 1 to 2 of follow up after kidney transplantation surgery. These are subjects expected to be exposed to high blood levels of tacrolimus. Blood samples from these subjects will be used in "ex vivo" experiments.

KTx months 4-5

Description:

Kidney transplant recipients recruited during the months 4 to 5 of follow up after kidney transplantation surgery. These are subjects expected to be exposed to standard blood levels of tacrolimus. Blood samples from these subjects will be used in "ex vivo" experiments.