CASE PRESENTATION
A 22-year-old African-American woman who has been dialysis dependent for four months due to hypertensive kidney disease is referred for kidney transplantation evaluation. Due to the recent occlusion of her left forearm arteriovenous graft, she is currently being dialyzed via a right internal jugular tunneled catheter. Her medications include methyldopa 250 mg bid, Tums 1000 mg with each meal and erythropoietin with dialysis. The patient is single without children, unemployed and lives with her 38 year old mother. She does not smoke or drink. Her review of systems is unremarkable. On physical exam, her weight is 284 pounds, height is 5 feet 2 inches and her body mass index is 51.9 kg/m2. The blood pressure is 130/80 and the cardiac and pulmonary exams are unremarkable. The surgeon feels she is otherwise a good candidate for transplantation except she must lose weight before being listed. What advice should she be given regarding weight loss?
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Raabe RD, Burr RB, Short R. One-year cognitive outcomes associated with carotid artery stent placement. J Vasc Interv Radiol 21:983-988;2010.
Purpose
To assess relatively long-term (ie, 1 year) neurocognitive outcomes of patients undergoing carotid artery stent (CAS) placement with cerebral protection.
Materials and Methods
Sixty-two patients (19 symptomatic; mean age, 73 years) with significant carotid stenosis (≥ 70% for symptomatic patients, ≥ 80% for asymptomatic patients) underwent CAS placement with embolic protection. Cognitive function was assessed prospectively with use of a battery of standardized tests administered at baseline (1-5 days before CAS endovascular therapy) and at 3, 6, and 12 months after CAS placement. Diffusion-weighted imaging (DWI) was performed before the procedure and within 24 hours after CAS placement.
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Oxidative Stress Mediates Protein Kinase C Activation and Advanced Glycation End Product Formation in a Mesangial Cell Model of Diabetes and High Protein Diet
Katherine R. Tuttle, Robert J. Anderberg, Sheryl K. Cooney, Rick L. Meek
American Journal of Nephrology 2009;29:171-180
Dr. Katherine Tuttle, Medical and Scientific Director at Providence Medical Research Center, was Co-Chair of the Work Group which developed new clinical practice guidelines for Diabetes and Chronic Kidney Disease. The Work Group included members from North America, Europe, and South America. As such, these guidelines for patient care will be widely adapted in the United States and throughout the world. The February supplement issue of The American Journal of Kidney Diseases (KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease.
Am J Kidney Dis. 2007 Feb;49(2 Suppl 2):S12-154) presents a complete version of the guidelines, which are a culmination of over 3 years of rigorous evidence review and synthesis.
The guidelines provide recommendations for diagnosis and staging of diabetic kidney disease. Medical management of diabetes and chronic kidney disease is clearly defined and the best treatment approaches are described based on current evidence. The guidelines also emphasize the importance of diabetes prevention to reduce the burden of diabetic kidney disease. Special populations with increased susceptibility and risks are also addressed. The Work Group defined key research areas where evidence is lacking.
[read full article ]Providence Medical Research Center is participating in a research project funded by the National Institute of Neurological Disorders and Stroke, a division of the National Institutes of Health. The Insulin Resistance Intervention after Stroke (IRIS) trial proposes an innovative therapy based on 20 years of accumulating evidence linking insulin resistance to increased risk for stroke and other blood vessel diseases.
Each year in the United States 700,000 persons suffer an ischemic stroke. An ischemic stroke is caused by a reduction in blood flow to the brain. This can be caused by a blockage or narrowing in a blood vessel that supplies blood to the brain or when the blood flow is reduced because of a heart or other condition. Of the 500,000 Americans who suffer this type of stroke, 100,000 will die. Among the 400,000 who survive an ischemic stroke each year, many will have another stroke or heart attack within five years.
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Providence Medical Research Center is one of approximately 15 research centers nationwide asked to participate in a new research project called CLEVER. This study, sponsored by National Institutes of Health, is for individuals who have blockages in their iliac artery(ies) from a medical condition called peripheral arterial disease.
The iliac arteries are in the lower abdomen leading to the legs. Blockages here cause symptoms like pain or cramping in leg or hip muscles when walking, called "claudication." Several treatment options are available, including:
- Vascular surgery (replacing a portion of your leg artery)
- Stent placement (a metal mesh tube placed through a small tube (catheter) temporarily put into your leg artery)
- Exercise therapy
- Medications
All the above procedures and treatments are accepted standard treatments. Each has been shown to be effective for improvement of claudication symptoms. The purpose of the CLEVER study is to compare treatment options, side-by-side, to learn which is the most effective and safe treatment for patients with claudication.
Prevention of Diabetic Kidney Disease: Negative Clinical Trials With Renin-Angiotensin System Inhibitors , Robert G. Nelson, Katherine R. Tuttle. American Journal of Kidney Diseases March 2010 (Vol. 55, Issue 3, Pages 426-430)
The onset of diabetic kidney disease typically is marked by the development of increased urinary albumin excretion. Microalbuminuria, the earliest detectable increase in urinary albumin levels, is defined as an albumin-creatinine ratio in the range of 30-300 mg/g.1 Although there presently is a debate about whether albuminuria is an adequate biomarker of diabetic kidney disease, it remains the test most commonly used by clinicians and researchers alike to screen for diabetic kidney disease. Because angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are proven therapies for diabetic kidney disease characterized by macroalbuminuria (albumin-creatinine ratio > 300 mg/g), by logical extension, these agents might also prevent the development of microalbuminuria. The DIRECT (Diabetic Retinopathy Candesartan Trials)-Renal Program, published in 2009 in the Annals of Internal Medicine,2 and RASS (Renin-Angiotensin System Study), published in 2009 in the New England Journal of Medicine,3 test this hypothesis. (full article on line)
Tuttle KR. Protein kinase C-beta inhibition for diabetic kidney disease. Diabetic Res & Clin Practice 13:S70-S74,2008.
Amid the rapidly rising number of people with diabetes worldwide, the prevalence of diabetic kidney disease (DKD) is expected to increase considerably despite available treatments. Consequently, novel therapeutic agents are urgently needed. Ruboxistaurin mesylate is a bisindolylmaleimide that specifically inhibits the β isoform of protein kinase C (PKC). In experimental models of DKD, ruboxistaurin normalized glomerular hyperfiltration, decreased urinary albumin excretion, preserved kidney function, and reduced mesangial expansion, glomerulosclerosis, and tubulointerstitial fibrosis. These beneficial effects of ruboxistaurin, both alone and combined with renin-angiotensin system inhibition, have been observed in a variety of experimental models of DKD. A phase 2 study of PKC-β inhibition in persons with type 2 diabetes and DKD already treated with angiotensin converting enzyme inhibition and/or angiotensin receptor blockade has been conducted. Addition of ruboxistaurin for 1 year reduced urinary albumin, prevented an increase in urinary transforming growth factor-β, and stabilized estimated glomerular filtration rate. Based on secondary analyses of clinical trials in patients with diabetic retinopathy or neuropathy, ruboxistaurin appears safe and may also prevent onset of DKD. PKC-β inhibition holds promise as a new strategy to improve kidney disease outcomes in diabetes. Large-scale clinical trials will be required to confirm safety and to validate prospective benefits of ruboxistaurin on relevant clinical endpoints in DKD.
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Andrew S. Levey, MD, Daniel Cattran, MD, Aaron Friedman, MD, W. Greg Miller, PhD, John Sedor, MD, Katherine Tuttle, MD, Bertram Kasiske, MD, Thomas Hostetter, MD
American Journal of Kidney Diseases Volume 54, Issue 2, Pages 205-226
Changes in proteinuria have been suggested as a surrogate outcome for kidney disease progression to facilitate the conduct of clinical trials. This report summarizes a workshop sponsored by the National Kidney Foundation and US Food and Drug Administration (FDA) with the following goals: (1) to evaluate the strengths and limitations of criteria for assessment of proteinuria as a potential surrogate end point for clinical trials in chronic kidney disease (CKD), (2) to explore the strengths and limitations of available data for proteinuria as a potential surrogate end point, and (3) to delineate what more needs to be done to evaluate proteinuria as a potential surrogate end point. We review the importance of proteinuria in CKD, including the conceptual model for CKD, measurement of proteinuria and albuminuria, and epidemiological characteristics of albuminuria in the United States.
The American Diabetes Association (ADA) reports there are currently 20.8 million people with diabetes mellitus (DM) in the United States, or 7-8% of the population, and approximately 1.5 million new cases are diagnosed each year. Approximately 44% of people who are newly diagnosed as having chronic kidney disease are individuals with DM.
Providence Medical Research Center (PMRC) is one of approximately 50-80 centers in North America who will be participating in a research study of an investigational drug for patients with Type 2 Diabetes Mellitus (T2DM). Management with current medications that treat the complications of T2DM, such as diabetic kidney disease, may not sufficiently reduce the rate and onset of damage to the kidneys. The consequence of this damage is improper filtering by the kidneys and excess protein in the urine or "proteinuria". Previous research has shown that treatments that reduce proteinuria, which is a common sign of T2DM related to declining kidney function, can slow progression of diabetic kidney disease. This study is designed to determine the effect of the investigational drug on proteinuria and also on kidney function.
There are many factors known to lead to the decline in renal function for people who have T2DM. High blood pressure, high blood sugar levels, and potentially high cholesterol levels all play a role in the loss of kidney function. Recent research has found another contributor to a decline in renal function is an increase in Connective Tissue Growth Factor (CTGF), a protein the body normally produces. CTGF acts along with many other proteins to regulate the production of fibrous tissues in the body. It is thought that when CTGF is too high, growth of this fibrous or scar-like tissue occurs in the kidney. This results in loss of kidney function and proteinuria. Previous studies have found that current medications that treat hypertension and diabetes may help to protect the kidneys from damage, but they do not completely normalize CTGF levels. This study will also examine the effects of an investigational drug on CTGF levels. We at Providence Medical Research Center are proud to be a part of this important study.
The Center for Maternal Fetal Medicine at Providence Sacred Heart Medical Center and Children's Hospital provides a wide spectrum of highly specialized diagnostic and therapeutic procedures to monitor pregnancy from conception through delivery. As part of their efforts to stay on the cutting edge of practice, our physicians participate in research trials.
Sacred Heart Perinatologists Dr. Reinaldo Acosta and Dr. Jorge Tolosa have been chosen as investigators in perinatal research by the National Institute of Child Health and Human Development (NICHD) Maternal Fetal Medicine Units (MFMU) Network.
The NICHD is one of the Institutes within the National Institutes of Health (NIH). In 1986, the NICHD created the MFMU Network to focus on clinical questions in maternal fetal medicine, particularly with respect to the continuing problems of preterm birth, low birth weight, and medical problems of pregnancy. Operating under cooperative agreements, the current Network is comprised of fourteen university-based clinical centers and a data coordinating center. Since its creation, the MFMU Network has been a driving influence for introducing new scientific discoveries into the field of perinatology. More than 30 randomized clinical trials, cohort studies and registries have been completed or are in progress. The studies to date have not only identified new therapies and evaluated technologies used in maternal-fetal medicine, but also have helped to abolish practices that are not useful.
Click here to visit the Center for Maternal Fetal Medicine Web page.
- Multi-center clinical trials in multiple specialties
- Original, investigator-initiated studies
- Pharmacokinetic and pharmacodynamic studies
- Physiology studies
- Cellular and molecular biology
Providence Sacred Heart Medical Center and Providence Medial Research Center have been selected as one of about 50 sites for a National Institutes of Health study to determine if aggressive treatment of stroke victims for high blood pressure and cholesterol-along with placing a stent to widen a narrowed artery in a patient's brain-can reduce their risk of having a second stroke.
"People who suffer an ischemic stroke, the most common kind of stroke, have a 30 percent to 50 percent chance of having another stroke," says Dr. Chris Zylak, a neurointerventional radiologist and the lead researcher for the study here. Drs. Zylak and Madeleine Geraghty, director of Sacred Heart's Primary Stroke Center, will treat study patients.
The best treatment for prevention of another stroke or TIA (transitory ischemic attack or mini stroke) in patients with narrowing of one of the arteries in the brain is uncertain. A common treatment is the use of anti-clotting medications to prevent blood clots from forming in the narrowed vessel. There are a variety of medicines used for this purpose. These medications are usually taken for the rest of a patient's life.
The SAMMPRIS trial is a study funded by The National Institutes of Health (NIH). It is being done to determine whether intracranial stenting (a device inserted in a blood vessel in the brain) combined with intensive medical therapy is better than intensive medical therapy alone for preventing stroke or death in individuals who have had a stroke or TIA caused by a narrowing in one of the arteries in the brain.
Radica Z. Alicic, MD, Sandeep A. Saha, MD, Robert A. Short, PhD, and Katherine R. Tuttle, MD
Current Hypertension Reports 2009, 11:354-362
Albuminuria has been recognized as a risk marker for both chronic kidney disease and cardiovascular disease in large observational cohorts. In addition, post hoc analyses of many large randomized trials have found a positive relationship between albuminuria and adverse renal and cardiovascular outcomes, leading some to suggest that albuminuria may be a potential therapeutic target for antihypertensive treatment. However, direct clinical evidence linking albuminuria reduction to reduction in adverse renal and cardiovascular events is scarce. (Abstract on line)
It's a simple premise, but it's the foundation of the "Start!" movement, from the American Heart Association (AHA). Research has shown that you can gain about two hours of life for every hour of regular vigorous exercise you do. You couldn't find a better two-for-one deal if you tried!
It's a good thing, too. The American workforce is becoming more and more sedentary. As a result, our waistbands are growing. So are our healthcare costs and the number of preventable illnesses.
Start! is here to stop the trend. Walking is simply the first step toward a healthier lifestyle.
So join the Start! Movement. Check out the AHA free tools on-line to motivate more Americans to Start! walking:
The Start! movement is here to motivate and encourage all Americans to take up walking and other healthy habits as part of their daily routine all year round, and to live longer, stronger, heart-healthy lives.
April 8th is National Start! Walking Day, we challenge you to join the nationwide campaign to get Americans walking! The goal of The American Heart Association is to walk a million steps and raise $1 million.
The AHA Challenge for You!
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Start! by getting out and taking a WALK
- Then take 30 minutes to inspire your friends and family by sending them an email.
- Encorage them to take a WALK and join you in raising funds to fight our nation's No. 1 and No. 3 killers -heart disease and stroke.
Katherine R. Tuttle, MD; Joan E. Milton, MS, RD, CD Arch Intern Med. 2009;169(11):1027
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