Acute Renal Failure, Heart Transplantation
Conditions
Keywords
cyclosporine, metabolites, metabolic pattern, genotypes
Brief summary
Following heart transplantation many patients develop acute renal failure in the early posttransplant phase and some are in need of renal replacement therapy for shorter or longer time. The cause of this acute renal failure is most probably multi factorial but many reports indicate that cyclosporine has a central role in the pathophysiology and it is generally recommended to lower the cyclosporine load to patients developing acute renal failure in this population. Several in vitro studies on renal cells in culture indicate that the primary metabolites of cyclosporine (AM1, AM9, AM4N) are less toxic to the kidney than cyclosporine itself. However, the secondary metabolite AM19 as well as the cyclic metabolites AM1c and AM1c9 has been associated with decreased renal function and nephrotoxicity renal transplant recipients. The primary objective of this pilot study is to investigate if the concentrations of secondary- and cyclic metabolites of cyclosporine (AM19, AM1c, AM1c9) is related to development of acute renal failure in the early posttransplant phase following heart transplantation. Secondary objectives are to investigate associations between genotypes of P-glycoprotein and CYP3A5 and the metabolic pattern of cyclosporine.
Interventions
DRUGcyclosporine A
Sponsors
University of Oslo School of Pharmacy
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Heart transplant recipients receiving CsA as part of their immunosuppressive therapy. * 18 years of age or older. * Signed informed consent.
Exclusion criteria
* None
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary analysis of cyclosporine and metabolite concentrations and ratios will be compared between the patients developing acute renal failure and those who do not | — |
Secondary
| Measure | Time frame |
|---|---|
| Regression analysis comparing concentrations/ratios and actual renal function (continuously parameter) | — |
| Descriptive listing of cyclosporine and metabolites concentrations in CYP3A5*3/*3 patients compared to the other patients. It is anticipated that an exploratory analysis will be performed to compare the two groups. | — |
| Descriptive listing of CsA and metabolites concentrations in patients with different combinations of MDR-1 genotypes compared to the other patients. It is anticipated that an exploratory analysis will be performed to compare the two groups. | — |
Countries
Norway
Outcome results
None listed