Advanced glycation end products (AGEs) are proinflammatory mediators implicated in the pathogenesis of diabetic kidney disease (DKD). In this study, dose-dependent effects of angiotensin receptor blockade on urinary AGEs were evaluated in patients with DKD. Patients with type 2 diabetes and proteinuria >=500 mg/d (n = 11) were compared with diabetic controls without DKD (n = 10) and normal controls (n = 11). After a 2-week washout period, DKD participants were treated with candesartan doses progressively increasing from 8, 16, 32, to 64 mg/d every 3 weeks for a total of 12 weeks. Other antihypertensive agents were adjusted to maintain stable blood pressure.
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)
Comprehensive lifestyle change can impact health favorably in many domains, from prevention and treatment of various diseases to improved functional status and quality of life. Although habitual behaviors clearly influence chronic kidney disease (CKD), lifestyle change often is not stressed in the clinical setting. The purpose of this review is to provide a critical appraisal of the scientific basis for effects of lifestyle on CKD and practical strategies that promote healthy behaviors. This review begins with a clinical case presentation to provide context for the scientific discussion. Dietary composition of macronutrients, particularly protein intake, is highlighted. Clinical evidence is presented for avoiding protein excess, a contemporary problem in the typical overeating environment of the developed world.
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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.
Katherine R. Tuttle, MD; Joan E. Milton, MS, RD, CD Arch Intern Med. 2009;169(11):1027
Dr. M. Shane McNevin is the Principal Investigator for several research trials at Providence Sacred Heart Medical Center and Children's Hospital (SHMC). Dr. McNevin is a leading physician at the Providence Continence Center, as well as the program director for the gastrointestinal section of Providence Cancer Center. Board certified in general surgery, along with colon and rectal surgery, he is an expert in the diagnosis, medical management and surgical treatment of colorectal and anal tumors, inflammatory bowel disease and pelvic floor disorders. Dr. McNevin is also highly respected by his peers across the nation. In the last year alone, he has been invited to share his expertise at four major professional conferences.
Dr. Mc Nevin has been selected as an investigator for new treatments for fecal incontinence (FI). These research trials examine the effectiveness and safety of new treatment methods and are being run in only a handful of locations in the United States. Dr. Mc Nevin was chosen as an investigator by the companies sponsoring these trials because he is a leader in the field of colon and rectal surgery. In addition to his work on these ground breaking trials, Dr. McNevin also conducts his own original research through his office at Surgical Specialists of Spokane.
SHMC is currently participating in a research trial for the treatment of FI. This study, sponsored by Torax Medical, Inc., is investigating the safety and effectiveness of a revolutionary new device to treat FI. This is a study being done in only four locations across the United States. Current treatment options for FI are limited. These include standard treatment with sphincteroplasty (surgical repair of the rectal sphincter), bulking agents (adding fiber to the diet), or Radio Frequency delivery to the anal canal which can cause tissue shrinkage and tightening of muscle tissue.
This current study will evaluate a novel device called the Magnetic Anal Sphincter (MAS).The MAS is an implantable device made up of a series of magnetic beads. The beads are attached with little wires to create a "necklace" shape. The device is implanted around the muscles that control continence. The attractive force of the magnetic beads provides additional strength to these muscles.
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.
There are 26 million American adults with Chronic Kidney Disease (CKD). Often there are no symptoms with early kidney disease so most people aren't even aware that they have CKD. Millions of others are not aware that they are at risk. High risk groups include those with diabetes, hypertension and family history of kidney disease.
African Americans, Hispanics, Pacific Islanders, Native Americans and Seniors are also at increased risk. The key to preventing the progression of kidney disease is early detection.
The National Kidney Foundation's Kidney Early Evaluation Program (KEEP®) offers free screening for those with certain risk factors including anyone 18 years and older with high blood pressure, diabetes or a family history of kidney disease. KEEP is designed to raise awareness about kidney disease among high risk individuals and provide free testing and educational information so that kidney disease and its complications can be prevented or delayed.
There are three simple tests that can be done to detect CKD. These tests are: blood pressure check, a urine test for urine albumin (protein in the urine) and a blood test for serum creatinine (a blood protein byproduct).
To help raise awareness, and appreciation for all the vital functions the kidneys perform, the National Kidney Foundation is encouraging Americans to learn more and take steps now to preserve kidney health. March 12 is World Kidney Day, the perfect time to get to know your kidneys and find out if you're at risk.
To find out more Click Here
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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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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Katherine R. Tuttle , Am J Kidney Dis, 2009 Jan; 53(1): 12-15. (Commentary on the ACCORD Study Group: Effects of intensive Glucose lowering in type 2 diabetes. N Engl J Med 358: 2545-2559, 2008 and the ADVANCE Collaborative Group: Intensive blood glucose control and vascular outcomes in patients with type 2 daibetes. N Engl J Med 358: 2560-2572, 2008 )
The effects of intensive glycemic control on cardiovascular disease (CVD) outcomes in "high risk" type 2 diabetes are the subject of much debate. The New England Journal of Medicine recently published results of two landmark clinical trials in patients with type 2 diabetes and CVD or multiple risk factors, ACCORD (Action to Control Cardiovascular Risk in Diabetes, n=10,521) and ADVANCE (Action in Diabetes and Cardiovascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation, n=11,140).1,2
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.
The current standard-of-care is inadequate to stem the rising tide of kidney failure, cardiovascular disease, and death attributable to diabetic kidney disease (DKD). Improved treatment approaches for DKD are, therefore, urgently needed. In this Practice Point commentary, I discuss a randomized, placebo-controlled clinical trial performed by Parving et al., which evaluated the effects of a renin inhibitor, aliskiren, on albuminuria in patients with type 2 diabetes mellitus and macroalbuminuria. The investigators administered aliskiren combined with losartan, an angiotensin-receptor blocker that represents current standard-of-care treatment for DKD. The primary outcome measure of the study-a 20% reduction in the mean urinary albumin-to-creatinine ratio in aliskiren-treated participants as compared with the placebo group-was achieved after 6 months' treatment. Although aliskiren holds promise, large, long-term studies are necessary to confirm its safety and to demonstrate its beneficial effect on clinical end points before renin inhibition is embraced as the next step forward in the treatment of DKD.
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. Michael Ring, recently presented a poster session on behalf of his co-authors: Ken Daratha, Robert Short, Denise Dominik, Lynn Shuler and Katherine Tuttle, for the 2008 American College of Cardiology (ACC) Conference in Chicago, Il. His topic was "Two Year Safety and Revascularization Outcomes Following Coronary Artery Intervention with Bare Metal Stents Versus Strategies of Selective or Predominant Drug Eluting Stents in a Community Setting".
The poster presentation represented the work of their current study completed at Providence Medical Research Center and Sacred Heart Medical Center. The study compared the outcome of individuals who had received a bare metal stent with those who had received drug eluting stents. Patients were tracked for a minimum of 2 years following the placement of the stent, using a regional hospital electronic record.
In the state of Washington, the Fraternal Order of Eagles have donated thousands of dollars to the Max Baer Heart Fund, which in turn has provided grants to the local heart health programs at area hospitals and health centers. Over the past decade, they have generously supported medical research, first at The Heart Institute of Spokane, then at PMRC. The Eagles have made donations tor research every year beginning in 1998 and continuing today. Funds provided have helped to further research in the fields of heart disease, diabetes, and diabetic kidney disease. Through these generous donations, we have been able to purchase equipment and perform specialized analyses for a number of studies.
PMRC is grateful to the donations from the Spokane Aerie #2, Valley Eagle's Aerie # 3433 and Deer Park Aerie #3564. The Mission of the Eagles, to provide hope and lessen ills, is being well served as we reach beyond what is known in science and medicine.
Current Hypertens Reports 9:393-402, 2007.
Radica Alicic and Katherine R. Tuttle
The National Institutes of Health (NIH) is an agency of the U.S. Department of Health and Human Services. The NIH is composed of 27 Institutes and Centers, providing leadership and financial support to researchers in every state and throughout the world.
It is the primary Federal agency for conducting and supporting medical research. The research conducted or funded by the NIH is helping to lead the way toward important medical discoveries that improve people's health and save lives. NIH scientists investigate ways to prevent disease as well as the causes, treatments, and even cures for common and rare diseases. Many of the studies funded by the NIH are conducted at multiple research facilities across the country. This allows for access to research studies to a greater number of participants. Only sites with a proven record for excellence in clinical trial conduct are selected to be participating centers for NIH funded trials. Providence Medical Research Center (PMRC) is a participating center for 6 trials being funded by the NIH. It is a privilege to have been selected for participation in these noteworthy research studies.
PMRC is currently enrolling participants in two type 1 diabetes trials. Both trials are sponsored by the National Institutes of Health and are being conducted at various sites around the United States and the world. Local Pediatric Endocrinologist, Dr. Jeanne Hassing, is the primary investigator for these studies at Sacred Heart Medical Center.
Type 1 diabetes is a significant health problem that affects many people. It is estimated that 5-10% of Americans who are diagnosed with diabetes have type 1 diabetes. Type 1 diabetes is usually diagnosed in children and young adults, and was previously known as juvenile diabetes. In type 1 diabetes, the body does not produce enough insulin. Insulin is a hormone that is needed to convert sugar (glucose), starches and other food into energy needed for daily life.
These trials are designed to find out more about how type 1 diabetes occurs. Relatives of people with type 1 diabetes have a 10 to 15 times greater risk of the disease than people without a family history. Because of this, we are screening close blood relatives of people with type 1 diabetes. Brothers, sisters, parents, children, cousins, aunts, uncles, and grandchildren of people with type 1 diabetes may be eligible.
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