Angiotensin II Blockade for Chronic Allograft Nephropathy
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Purpose
Chronic allograft nephropathy continues to be a major cause of kidney transplant loss and return to dialysis. Treatment options are limited and the course of the disease tends to be progressive. This trial is designed to prevent a major mediator of this process, namely the expansion of the cortical interstitial compartment of the kidney where most of the scarring occurs. The drug being studied, Losartan, has proven efficacious in a number of kidney diseases.
| Condition | Intervention | Phase |
|---|---|---|
|
Kidney Disease Proteinuria |
Drug: Losartan |
Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Prevention |
| Official Title: | Angiotensin II Blockade for the Prevention of Cortical Interstitial Expansion and Graft Loss in Kidney Transplant Recipients |
- GFR studies [ Time Frame: Yearly ] [ Designated as safety issue: Yes ]
| Enrollment: | 153 |
| Study Start Date: | December 2002 |
| Study Completion Date: | June 2011 |
| Primary Completion Date: | June 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Losartin |
Drug: Losartan
For the first 14 days after subject is randomized they will take 50mg of losartan. After the 14 days the dose will be increased to 100mg of losartan daily.
|
Detailed Description:
Renal transplant loss due to chronic allograft nephropathy (CAN) is widely acknowledged as a major problem that has increased in relative importance as the incidence of early graft loss from acute rejection has declined. Studies from various centers, including the University of Minnesota, suggest that, after excluding patients dying with a functioning graft, as many as 80% of patients who will return to dialysis do so because of CAN. At the present time there are no therapeutic options once the clinical manifestations of CAN have developed. Testing measures to prevent CAN have not been addressed.
The overall purpose of this project is to investigate the role of the renin-angiotensin-aldosterone system (RAAS) in the development of CAN. This system plays an important role in the progression of many experimental and clinical renal diseases. Furthermore, blockade of this system with angiotensin converting enzyme inhibitors and angiotensin II receptor blockers has yielded beneficial results in retarding injury and progression in numerous intrinsic renal diseases. This study specifically investigates the long term benefit of the angiotensin II receptor blocker, losartan, in the prevention of cortical interstitial volume expansion (an accurate predictor of long term graft function) and graft loss from biopsy proven CAN in a 5 year, randomized, double masked, placebo controlled study of kidney transplant recipients. This clinical trial will directly test the hypothesis that blockade of the renin angiotensin aldosterone system will provide a substantial benefit through blood pressure lowering independent mechanisms, namely, interruption of fibrogenic pathways, anti-proteinuric actions, amelioration of hyperfiltration and possibly some immunomodulatory effects.
The proposed studies will also characterize the interstitial ultrastructural compositional changes that occur in the renal allografts with CAN, the effects of treatment on these changes and provide a complete description of the incidence and predictors for the development of transplant glomerulopathy. These studies will also determine the impact of angiotensin II receptor blockade on the rate of decline of glomerular filtration rate, as well as the impact of glomerular size on the rate of graft loss from CAN, the incidence and the progression of post transplant proteinuria, the nature of the permselectivity defects responsible for the proteinuria and will also explore the association of proteinuria with graft loss from CAN. This trial will also help construct a profile for the RAAS in the transplant recipients and explore the relationship between two genes polymorphisms, ACE and TGF-Beta, and CAN.
These studies should help to describe the natural history, nature and pathogenesis of CAN, elucidate early markers and predictors of this important disorder and, perhaps, define a safe and useful preventative strategy.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age > 18 years.
- Recipients of a first or a second renal transplant alone or in combination with a pancreas transplantation.
- Informed consent
- Adequate baseline biopsy; at least 10 cortical projection fields.
Exclusion Criteria:
- Age < 18 years.
- Serum creatinine 2.5mg/dL.
- Persistent hyperkalemia; potassium > 5.4 mEq/L.
- Known hypersensitivity to losartan or iodine allergy.
- Documented renal artery stenosis by duplex ultrasonography.
- Recipients of grafts from an HLA-identical sibling.
- Recipients whose primary renal disease is primary hyperoxaluria,dense-deposit disease, focal segmental glomerulosclerosis or hemolytic uremic syndrome.
- Women of childbearing age who wish to become pregnant and/or are unwilling to use contraceptive measures or who are pregnant.
- Recipients requiring ACE inhibitors or AII blockers for a cardiovascular indication (e.g. systolic dysfunction).
- Recipients who are > 55 years old and had a history of cardiovascular disease (coronary artery disease, stroke or peripheral vascular disease).
Contacts and Locations| United States, Minnesota | |
| University of Minnesota | |
| Minneapolis, Minnesota, United States, 55455 | |
| Hennepin County Medical Center | |
| Minneapolis, Minnesota, United States, 55415 | |
| Principal Investigator: | Hassan N. Ibrahim, M.D., M.S. | University of Minnesota - Clinical and Translational Science Institute |
| Principal Investigator: | Bertram Kasiske, M.D. | Hennepin County Medical Center, Minneapolis |
More Information
No publications provided
| Responsible Party: | Hassan Ibrahim, M.D., University of Minnesota - Clinical and Translational Science Institute |
| ClinicalTrials.gov Identifier: | NCT00067990 History of Changes |
| Obsolete Identifiers: | NCT01467895 |
| Other Study ID Numbers: | ANGIOB, R01DK060706, DK60706 |
| Study First Received: | September 3, 2003 |
| Last Updated: | January 30, 2012 |
| Health Authority: | United States: Federal Government |
Keywords provided by University of Minnesota - Clinical and Translational Science Institute:
|
chronic allograft nephropathy post transplant proteinuria |
Additional relevant MeSH terms:
|
Kidney Diseases Proteinuria Urologic Diseases Urination Disorders Urological Manifestations Signs and Symptoms Angiotensin II Losartan Vasoconstrictor Agents |
Cardiovascular Agents Therapeutic Uses Pharmacologic Actions Anti-Arrhythmia Agents Antihypertensive Agents Angiotensin II Type 1 Receptor Blockers Angiotensin Receptor Antagonists Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 16, 2013