Chronic Kidney Diseases, Heart Transplant
Conditions
Keywords
Immediate Release Tacrolimus, Extended Release Tacrolimus, IR Tacrolimus, XR Tacrolimus, Renal Tubular Injury, Heart Transplant Recipient, Chronic Kidney Disease
Brief summary
Immediate release (IR) tacrolimus peaks in the first two hours after administration. These peak levels are influenced by CYP3A5 expression with expressors requiring higher total daily doses with higher peak levels compared to non-expressors. Tacrolimus XR (Envarsus) is a once daily formulation with delayed absorption and lower peak levels while maintaining similar trough levels as seen with IR tacrolimus. A randomized trial of conversion from IR tacrolimus to tacrolimus XR in kidney transplant recipients have shown similar efficacy and adverse events between the two groups but no improvement in estimated GFR. However, urinary biomarkers of acute kidney injury associated with changes in tacrolimus dosing may be more sensitive then serum creatinine. The objective of this study is to assess renal tubular injury in heart transplant recipients who are converted from immediate release to tacrolimus XR. The hypothesis is that the delayed absorption and lower peak levels of tacrolimus XR will lead to less tubular injury and improved renal function without increased risk to the heart allograft.
Detailed description
The primary outcome is change in urinary NGAL expression with conversion from IR tacrolimus to tacrolimus XR. In aim 1, changes in urinary biomarkers of tubular injury at 4 weeks after conversion to tacrolimus XR with stable trough levels will be assessed. These changes will be assessed by CYP3A5 expressor category that will be determined by genotyping of a single gene for variants. The changes in GFR using the creatinine-cystatin C CKD-EPI equation will be assessed. In aim 2, the rate of rejection as defined as treated rejection within the last 30 days for any grade \> 1R or AMR or acute graft dysfunction (LV ejection fraction drop \> 10%) will be looked. The cardiac allograft vasculopathy based on coronary angiography +/- IVUS and right heart catheterization hemodynamics at baseline and 1 year post conversion will also be evaluated. In addition to changes in cardiac function, the changes in blood pressure, serum glucose, and cholesterol in the first year after conversion will be assessed.
Interventions
DRUGConversion from IR Tacrolimus to XR Tacrolimus
All participants will be consented to the study on IR Tacrolimus. After their baseline visit, they will be converted to XR Tacrolimus
Sponsors
Veloxis Pharmaceuticals
Loyola University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Stable, heart-only transplant recipient within 10 years of transplantation * 18 -80 years old * Currently taking IR Tacrolimus * Baseline eGFR\> 30mL/min/1.73m2
Exclusion criteria
* Multiple organ transplant recipients * Less than 18 years old * Greater than 80 years old * Heart-only transplants recipients with active malignancy, rejection, or greater than 10 years from transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary neutrophil gelatinase-associated lipocalin (NGAL) | 4 weeks | Change in Urinary NGAL level (ng/mL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Microalbuminuria | 4 weeks | Change in Urine albumin-creatinine ratio |
| CYP3A5 expressor category | Baseline | CYP3A5 genotyping to determine expressor category |
| Heart transplant rejection | 1 year | The rate of rejection as defined as treated rejection within the last 30 days for any grade\>1R, AMR, or acute graft dysfunction (LVEF drop greater than 10%) |
| Estimated Glomerular Filtration Rate (eGFR) | 4 weeks | Change in eGRF level by the Creatinine-Cystatin C CKD-EPI equation (mL/min/1.73m2) |
| Blood pressure | 1 year | Change in blood pressure (mmHg) |
| Serum glucose | 1 year | Change in serum glucose levels (mg/dL) |
| LDL Cholesterol | 1 year | Change in LDL cholesterol level (mg/dL) |
| Cardiac allograft vasculopathy | 1 year | The rate of cardiac allograft vasculopathy based on coronary angiography with or without IVUS and right heart catheterization hemodynamics |
Countries
United States
Contacts
Primary ContactSanjeev Akkina, MD
Outcome results
None listed