Summary of Annual Research

“The NKF supports ten institutional research fellowships into the causes and cures of kidney disease. Some of the current projects supported by our research grants are summarized here.”

Lay Progress Reports 1998-99

Institution: Harbor-UCLA Medical Center
Division of Nephrology
Title of Project: Tubular Cell Injury and Interstitial Fibrosis

The studies have discovered mechanisms through which the ultrafiltration of plasma proteins which occurs in many kidney diseases activates tubule cells. This activation of tubular cells initiates basolateral secretion of biologic signal molecules that interact with other cells in the peritubular environment in the kidney. In collaboration with these different cell types matrix proteins are made. The work demonstrates that tubular cells are vital in the transformation of biological signals received from the urine side. There is evidence that tubular cells become transformed, and this is the current focus in the laboratory.

Institution: Harbor-UCLA Medical Center
Division of Nephrology
Title of Project: Muscle Metabolism in Chronic Renal Failure

Malnutrition and debility of skeletal muscle occur commonly in individuals with chronic kidney failure. The researcher has conducted a series of experiments to examine the causes for this muscle wasting and methods for treating it. He has found that the level of calcium inside the cell often rises in kidney failure and that this may cause resistance to a hormone that stimulates protein synthesis. He has also found that reducing the level of acid may also stimulate protein synthesis in muscle cells. Furthermore, he has found that exercise training increases the formation of hormones and other proteins that may stimulate protein synthesis. Finally, he has found that a compound which is often abnormally low in kidney failure patients, carnitine, when given to animals before the administration of the powerful antibiotic, gentamicin, may actually protect against a type of kidney damage which occurs commonly with this antibiotic.

Institution: Harbor-UCLA Medical Center
Division of Nephrology
Title of Project: Regulation and Effects of Myostatin in Skeletal Muscle in Chronic Renal Failure

Patients with chronic kidney failure are often malnourished and have skeletal muscle wasting and debility. Recently a protein named myostatin was discovered that inhibits muscle protein synthesis and hypertrophy. The purpose of these studies is to examine whether myostatin levels in skeletal muscle are normal or increased in individuals with chronic kidney failure and whether they respond normally to such influences as exercise. In an initial study, research has shown that myostatin decreases in skeletal muscle of patients undergoing maintenance hemodialysis after they have exercise trained for three times per week for an average of 8.5 weeks. These findings suggest that the reduction in myostatin may be a factor that led to increased muscle strength and increased muscle mass in these MHD patients in response to their exercise training.

Institution: UC San Diego
Division of Nephrology
Title of Project: Intravascular Ultrasound Assessment of Hemodialysis Vascular Access

IVUS catheters are expensive, and at this time are intended for one-time use. We were able to demonstrate that catheters do not suffer any loss of image quality following repeat sterilization, and can be used at least five times. In a monitoring program with IVUS imaging every three months, a single catheter may last over one year for a single patient, thus greatly reducing the overall cost.

We have continued with IVUS imaging and are in the process of establishing a protocol for monitoring. We expect that with IVUS imaging, in addition to standard monitoring techniques (i.e., physical exam, recirculation rate, static venous pressures) we will be able to diagnose and treat access stenosis prior to the complete thrombosis. We have had no significant complications of the procedure, and procedure time (including set-up) has been reduced to less than 30 minutes. We are exploring the possibility of 3-D reconstruction of the IVUS images as well.

Institution: UC Irvine
Nephrology
Title of Project: Nitric Oxide Synthase Expression in the Course of the Evolution of Hypertension in Spontaneously Hypertensive Rats: Interrelationship with Angiotensin II and Oxygen Free Radical Activity

The completed portion of the study has produced highly promising results with regard to prevention of renal disease and cardiovascular complications in hypertensive animals. Specific treatment of hypertension for prolonged periods prevented development of renal failure, proteinuria and heart enlargement in animals with genetic hypertension. This has a major implication in humans since, after diabetes, hypertension is the second most common cause of renal failure in humans.

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