Advertisement

Topics

Prevention of Kidney Transplant Rejection

2014-08-27 03:58:06 | BioPortfolio

Summary

The purpose of this study is to see how effective 2 drugs, irbesartan and pravastatin, are at slowing kidney transplant failure.

Many kidney transplant patients have some type of chronic rejection. Chronic rejection is a disease that causes scarring and damage to the kidney. Over time, chronic rejection can lead to kidney failure, making it necessary for patients to start dialysis and possibly receive another kidney transplant. Doctors would like to see whether irbesartan and pravastatin can slow this damage and prevent kidney failure in patients with signs of chronic rejection.

Description

Renal graft failure due to chronic rejection, also known as chronic allograft nephropathy, is one of the leading causes for repeat renal transplantation. Chronic rejection is characterized by progressive fibrosis and scarring. Renal biopsies of patients undergoing chronic rejection show greater expression of profibrotic cytokines, including TGF-beta and PDGF, than normal kidney tissue. Moreover, the cytokine activity of chronic rejection resembles that of other fibrosing renal diseases. Angiotensin converting enzyme inhibitors (ACEinh) and HMG-CoA reductase inhibitors have been shown to protect effectively against other types of fibrotic disease. These drugs may protect against fibrosis and preserve renal function in renal transplant patients with chronic rejection, in part by blocking activation of TGF-beta and PDGF. This study evaluates the impact of irbesartan (an AII-RB which acts similar to an ACEinh) and pravastatin on the clinical progression of chronic rejection and on the expression of TGF-beta, PDGF, and connective tissue genes in the chronically rejecting kidney.

Prior to intervention, patients undergo a transplant renal biopsy to: 1) confirm the presence of chronic renal allograft nephropathy and 2) quantify baseline mRNA levels for TGF-beta, PDGF, and selected cytokines and connective tissue components. Patients are randomized to 4 arms: Group 1 receives pravastatin placebo plus irbesartan placebo; Group 2 receives pravastatin plus irbesartan placebo; Group 3 receives pravastatin placebo plus irbesartan; and Group 4 receives pravastatin plus irbesartan. Pravastatin is administered at a dose of 20 mg/day. Irbesartan is initiated at 150 mg/day and is titred to 300 mg/day after 2 weeks. Patients are evaluated routinely for serum creatinine and potassium levels, blood pressure, and other markers of kidney function. In addition, they are monitored for toxicities and adverse events, particularly an early rise in serum creatinine or muscle enzyme changes. At Month 6, or when serum creatinine has risen above 5.0 mg/dl if that is earlier, a repeat transplant kidney biopsy is obtained to compare to baseline. Changes in chronic allograft nephropathy and cytokine mRNA levels are evaluated to determine any correlation between clinical effect and changes in activity of profibrotic pathways. Study endpoints are death or renal failure manifested by initiation of dialysis or retransplantation.

Study Design

Primary Purpose: Treatment

Conditions

End-Stage Renal Disease

Intervention

Irbesartan, Pravastatin

Location

Ilene Blechman-Krom
Rockville
Maryland
United States
20850

Status

Completed

Source

National Institute of Allergy and Infectious Diseases (NIAID)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:58:06-0400

Clinical Trials [2525 Associated Clinical Trials listed on BioPortfolio]

Statin Therapy in Patients With Early Stage ADPKD

This study plans to learn if pravastatin is helpful in slowing down the progression of kidney disease in adults with autosomal dominant polycystic kidney disease (ADPKD). Pravastatin has b...

Irbesartan in Type 2 Diabetes

The aim of this multicenter, doubleblind, randomized study was to investigate the renoprotective effect of irbesartan treatment in patients with type 2 diabetes and microalbuminuria (a pre...

Saving Residual Renal Function Among Haemodialysis Patients Receiving Irbesartan

Angiotensin II receptor blockers (ARB) are known to preserve kidney function among patients with kidney diseases and reduced renal function, but not among haemodialysis patients. Haemodia...

Irbesartan in Hypertension

Study objectives: - To demonstrate the effect of irbesartan on the regulation of diastolic blood pressure, in case of missing one dose after a period of administration for 6 to 8 ...

Pravastatin Therapy in Patients With Active Crohn's Disease: A Pilot Study

The primary objective of this study is to provide data regarding clinical and immunologic activity of oral doses of pravastatin 80mg administered daily for 6 consecutive weeks, for the tre...

PubMed Articles [19729 Associated PubMed Articles listed on BioPortfolio]

The perspectives of patients with lithium-induced end-stage renal disease.

Lithium is the treatment of choice for patients suffering from bipolar disorder (BD) but prolonged use induces renal dysfunction in at least 20% of patient. Intensive monitoring of kidney functioning ...

History of Childhood Kidney Disease and Risk of Adult End-Stage Renal Disease.

The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease (...

Non-Proximal Renal Tubule-Derived Urinary Exosomal miR-200b as a Biomarker of Renal Fibrosis.

Renal fibrosis is a common outcome of nearly all kinds of chronic kidney disease (CKD) and eventually progresses to end-stage renal disease. The identification of an optimal biomarker of renal fibrosi...

Consumption of Coffee but Not of Other Caffeine-Containing Beverages Reduces the Risk of End-Stage Renal Disease in the Singapore Chinese Health Study.

Cross-sectional studies suggest that coffee drinking is associated with better renal function. However, to our knowledge, no prospective study has examined its relation with the risk of end-stage rena...

Effect of Hemodialysis on Global and Regional Cardiac Function in Children With End-stage Renal Disease.

Changes in cardiac structure and function are common among patients with end-stage renal disease. The aim of this study was to evaluate the effect of hemodialysis on global and segmental cardiac funct...

Medical and Biotech [MESH] Definitions

Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)

Functional KIDNEY FAILURE in patients with liver disease, usually LIVER CIRRHOSIS or portal hypertension (HYPERTENSION, PORTAL), and in the absence of intrinsic renal disease or kidney abnormality. It is characterized by intense renal vasculature constriction, reduced renal blood flow, OLIGURIA, and sodium retention.

Final stage of a liver disease when the liver failure is irreversible and LIVER TRANSPLANTATION is needed.

KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.

The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.

More From BioPortfolio on "Prevention of Kidney Transplant Rejection"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Nephrology - kidney function
Nephrology is a specialty of medicine and pediatrics that concerns itself with the study of normal kidney function, kidney problems, the treatment of kidney problems and renal replacement therapy (dialysis and kidney transplantation). Systemic conditions...

Endocrinology
Diabetes Diabetes Endocrine Obesity Oxycontin Renal Disease Thyroid Disorders Endocrinology is the study of the endocrine glands and the hormones that they secrete (Oxford Medical Dictionary). There are several groups of h...


Searches Linking to this Trial