A team of researchers, including Dr. Janos Peti-Peterdi and Dr. Alicia McDonough of the Keck School of Medicine of USC, has identified a new target for eliminating hypertension, which is a leading cause of kidney disease. The initial research was funded in part by a grant from UKRO.

The renin-angiotensin system or RAS regulates blood pressure and fluid balance in the body. If RAS becomes overactive, it can lead to consistently high blood pressure. Angiotensin-converting enzyme (ACE) and its product, angiotensin II (Ang II), play important roles in RAS. Ang II causes the blood vessels to constrict and blood pressure to rise. Many blood pressure medications, such as ACE inhibitor drugs, work by interfering with the actions of Ang II. Recently, lead researcher Dr. Romer Gonzalez-Villalobos of Cedars Sinai determined that Ang II is produced both outside the kidney in the systemic circulation and inside the kidney itself.

The new research study focuses on the renin-angiotensin system within the kidney, specifically exploring the the role of intrarenal ACE in response to hypertensive stimuli. The research team studied mice with no ACE activity in the kidneys as well as those with minimal activity. Introducing Ang II serum infusion produced full-blown hypertension in wild-type mice, but only a “blunted” hypertensive effect in altered mice, leading the scientists to conclude that the absence of ACE in the kidney protects against hypertension.

Further study showed that when intrarenal RAS is activated, kidney Ang II increases sodium and water reabsorption along the nephron, raising blood pressure. The finding highlights the specific way that intrarenal RAS can cause hypertension and paves the way for potential new hypertension treatments that could block or reduce renal ACE activity.

Source:

The Absence of Intrarenal ACE Protects Against Hypertension, Journal of Clinical Investigation, May 1, 2013

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Transplant Recipients International Organization (TRIO) Ventury County West Valley Chapter is hosting a free seminar open to all transplant recipients/candidates, dialysis patients waiting for a transplant, medical professionals and family members on Saturday, March 16, 2013 from 9 a.m. to 11 a.m at the Calabasas Tennis and Swim Center located at 23400 Park Sorrento in Calabasas, CA 91302. A continental breakfast will be served.

Anjay Rastogi, M.D., Ph.D., Department of Medicine, Division of Nephrology at the David Geffen School of Medicine UCLA will present “Blood Pressure: What You Can Do to Improve Outcomes.” About 1 in 5 U.S. adults with high blood pressure don’t know that they have it. Less than half of the people with high blood pressure (46%) have their condition under control. High blood pressure is a major risk factor for kidney disease.

Reservations are required and seating is limited to 65 attendees. If you would like to attend the seminar, please reserve your spot by contacting TRIO President, Ron Taubman at (818) 309-7919 or email him at taubmanappr@dslextreme.com.

Download the pdf file for this event.

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Researchers from Boston University School of Medicine have identified a link between the G alpha i-2 sub-unit protein pathway in the brain and renal excretion of sodium. They found that changes in salt intake affected changes in G alpha i-2 sub-unit protein levels and were able to prove that the protein pathway plays an important role in calming the renal sympathetic nervous system and facilitating the elimination of salt through the kidneys. The discovery points to a promising new target for treating salt-sensitive hypertension.

Source:

Researcher Finds Link Between Brain Signaling and Renal Function, Medical News Today, June 7, 2012

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A team of researchers from Baker IDI Heart and Diabetes Institute in Australia have shown that renal denervation, a new investigational technique to curb hard-to-treat blood pressure is safe in the short term for hypertensive patients with stage 3 to 4 CKD. Renal denervation uses radio frequency waves to deaden certain overactive sympathetic nerves in the kidneys, thereby disrupting signaling that can lead to high blood pressure.  Following the procedure, the patients in this study had lower blood pressure over a 12 month period. Estimated glomerular filtration rates remained the same after surgery.

Because overactivity of the sympathetic nervous system leads to worsening kidney disease as well as cardiovascular damage, the researchers believe renal denervation could protect the kidneys as well as the heart in some CKD patients. More studies, including those that explore the long term effects of the procedure will be needed to test their theories.

Sources:

Simple Procedure Lowers Blood Pressure in Kidney Disease Patients, Eureka Alert, May 17, 2012

Renal Denervation in Moderate to Severe CKD, Journal of the American Society of Nephrology, May 17, 2012

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Scientists studying the mechanisms behind cell adhesion have made some significant discoveries about the factors that influence podocyte survival. The kidney filter barrier is made up of podocyte cells with long foot-like projections that wrap around the capillaries of the glomerulus. The slits between these projections allow smaller molecules like salts, water and sugar to pass, while preventing larger molecules such as proteins from leaving the blood stream. Podocytes undergo significant physical stress as blood is pushed through the filter barrier. A receptor called integrin a3ß1 ensures that podocyte cells remain tightly bound to the glomerular basement membrane.

Researchers from the Netherlands Cancer Institute in Amsterdam explored the link between a3ß1 and a protein called CD151, which is strongly expressed in podocytes.  They showed that CD151 and a3ß1 interact and that CD151 is involved in adhesion strengthening.  They studied mice lacking CD151 in podocytes and discovered that the mice developed glomerulosclerosis. They also suffered from kidney abnormalities, including unusually broad foot processes and irregular thickening of the glomerular basement membrane. They found that mice lacking global CD151 were not necessarily susceptible to renal disease unless they had a genetic predisposition. They reasoned that because the mice lacked CD151, their podocytes would be more loosely bound and unable to withstand increased mechanical stress. They proved the theory by increasing blood pressure and filtration pressure, which induced nephropathy in the mice.  Treating the mice with an ACE inhibitor drug reduced blood pressure as well as pressure within the glomerulus and prolonged their life span. The scientists determined that the reduction in glomerular pressure was key to preserving podocytes and slowing down glomerulosclerosis in the mice.

Source:

Blood Pressure Influences End Stage Renal Disease of CD151 Knockout Mice, Journal of Clinical Investigation, January 3, 2012

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The UN summit on non-communicable diseases taking place 17 days from now in New York may not be on every American’s radar, but it should be. The ambitious meeting aims to tackle the alarming rise of chronic diseases affecting the world’s population, particularly in developing nations – cancer, respiratory disease, cardiovascular disease, and diabetes. Everyone knows someone suffering from one of these diseases. Many argue that obesity should be included in this list, and it should be. Perhaps it deserves its own special high-level meeting. Chronic kidney disease should be listed, too, but if the world’s nations can manage to reduce the number of people developing high blood pressure and diabetes, they will prevent many cases of CKD.

This summit will be a start, but there is still a lot of work to be done. The proclamation outlining the details for preventing and controlling these diseases is still in draft form. And there have been no goals set for reducing the number of preventable deaths. Nations are at odds on the important issues of reducing tobacco and salt consumption. Norway’s proposal to set a salt reduction target of 5 grams per person per day worldwide by the year 2025 has been removed from the Outcome Document. This is disheartening. To get some perspective, the average American diet contains 12 to 14 grams of salt per day. Reducing salt to about a teaspoon a day would mean fewer strokes, fewer heart attacks, fewer deaths, fewer cases of hypertension, and by implication, fewer instances of chronic kidney disease. A recent study on salt published in the British Medical Journal showed that reducing salt intake by 3 grams per day in the U.S. “…would result in up to 120,000 fewer cases of coronary heart disease, up to 66,000 strokes and up to 99,000 heart attacks annually.” The NCD Alliance estimates that “…reducing global salt consumption by just 15% through mass-media campaigns and reformulation of processed foods and salt substitution could prevent an estimated 8.5 million deaths in just 10 years.”

The EU, Australia, Japan, the United States, and Canada currently oppose Norway’s salt target. The global group World Action on Salt and Health (WASH) recently issued a press release urging those nations to reconsider their position on salt reduction. News stories about the reasons behind the attempts to block reductions in salt, as well as sugar and fat have appeared in the Canadian press, but the media in the U.S. has yet to pick up on the story. It could be because Hurricane Irene and the unstable economy have dominated our recent news. However, one could argue that becoming a healthier nation in a healthier world would help our economy by saving money in the long run.

As this story evolves, we’ll keep you updated. Let’s hope the EU, Australia, Japan, the United States, and Canada reverse their position on salt. Stay tuned!

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Researchers at University of Tokyo Graduate School of Medicine have uncovered a new mechanism behind salt-sensitive hypertension. They found that a high-salt diet fed to salt-sensitive rats activates a gene called Rac1 in the kidneys; this leads to increased activity of the MR (Mineralocorticoid Receptor) protein and causes elevated blood pressure and kidney damage. Their study showed that Rac1 is regulated by both salt and aldosterone, a hormone that helps control blood pressure. They found that inhibiting Rac1 prevents high blood pressure as well as injury to the glomeruli of the kidney. Rac1 appears to be a major factor in determining salt sensitivity and could prove to be a beneficial target for preventing salt-sensitive hypertension and resultant kidney injury in humans.

Sources:

New Mechanistic Insight Into Salt-Induced High Blood Pressure, University of Tokyo Graduate School of Medicine, July 18, 2011

Abstract:

Rac1 GTPase in Rodent Kidneys Is Essential for Salt-Sensitive Hypertension Via a Mineralocorticoid Receptor-Dependent Pathway

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Recent stories about older living kidney donors, including some with medical issues, are truly inspiring and encouraging given the organ shortage. In an interesting article, Stephen Textor, M.D., Professor of Medicine at Mayo Clinic, describes his experience with donors with moderate essential hypertension, who would normally be excluded from donating. - Medical Abnormalities Need Not Exclude Middle-Aged Kidney Donors

In this amazing story, a 59-year-old man who once suffered from diabetes, was tested and cleared to donate a kidney to his brother. The two turned out to be identical twins, so there is no need for a lifetime of immunosuppressant drugs. – Diabetic Brothers Complete Triathlon

A 66-year-old-donor participates in a new robot-assisted transplant operation in this video report. – Robot Assists AGH Surgeon During Kidney Transplant

And here are two wonderful stories about healthy donors in their 60′s. – Tampa Nuns Say It’s a Miracle Kidney Donation Fit and Paired Kidney Donations Save Two Lives, Enrich Two Others

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Dopamine, an important neurotransmitter that helps to control the brain’s reward and pleasure centers, is often studied in connection with neurological disorders like Parkinson’s disease.  Now researchers at Vanderbilt University Medical Center have discovered that dopamine produced within the kidneys, rather than the brain, is critical to maintaining normal blood pressure and salt and water balance. They showed that mice with impaired kidney dopamine production developed hypertension and died sooner than ordinary mice, despite having normal brain and plasma dopamine levels. Although dopamine has previously been associated with hypertension, this study pinpoints the important role of dopamine made in the kidneys.

Sources:

Long Live Dopamine Production by the Kidneys, Vanderbilt University Medical Center, June 23, 2011

Intrarenal Dopamine Deficiency Leads to Hypertension and Decreased Longevity in Mice, Journal of Clinical Investigation, June 23, 2011

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Dear diary, it’s been too long! So much has happened since my last entry back in October and it’s a bit complicated to explain. Maintaining a healthy body can be a difficult balancing act. After a complete physical, including an artery scan and blood vessel flexibility test, my doctor found anomalies that pointed to elevated blood pressure – some thickening in the neck arteries and small blood vessels that tested “abnormal”. (Interestingly, I have since read a Science Daily article that explained that vegans and strict vegetarians are at risk for hardened arteries if they don’t get enough of the vitamins and nutrients that can prevent it, namely B12 and Omega 3′s.) My cholesterol levels weren’t an issue, but my vegetarian diet, which didn’t include eggs or milk, clearly needed improvement. I was very low in vitamins B12 and D. At that point, I was feeling pretty lousy from the lack of B12 – nervous, unfocused, plagued with painful and annoying sores on my tongue, constantly sick with colds and a wicked throat ailment that delayed one of my doctor visits. Before this, I was hardly ever sick. I was glad there was a reason and a solution for my ill health, and the vitamin D deficiency actually gave me hope. I had just read about a study linking low vitamin D to high blood pressure. I told my doctor cheerfully and he was full of genuine sympathy. “Maybe we’ll get lucky,” he said.

Because I’m fairly young and my blood pressure readings taken in the doctor’s office tend to hover in the pre-hypertension to stage 1 range, he was inclined to put me on medication to bring it down right away, but I didn’t want that. I convinced him to let me monitor myself morning and night and follow a regular exercise routine – a 2 mile walk a day at least 5 days a week. He knew the walking would be good for my heart, but he wasn’t sure it would help my blood pressure that much. Again, I had read about another study that showed that exercise can lower blood pressure in the short term as well as the long term. Plus exercise is a great stress reliever. Although I accept that my high blood pressure is at least partly hereditary, I know stress has something to do with it. After 2 weeks of walking, the doctor could see that my blood pressure numbers were dropping. He knew how determined I was, so he agreed to give me a few months to see what exercise, relaxation, and vitamin D could do.

So that’s what I’ve been up to – doctoring (and slowly paying off the doctor bill), taking my vitamins, exercising like crazy, working hard, and attempting to de-stress. There have been setbacks. The B12 didn’t kick in until I took a potent liquid version. And I lost a little too much body fat from walking, which left me exhausted and threw my hormones out of whack. I’m back in the swing now, eating sockeye salmon, drinking milk, eating eggs, and everything under the sun reputed to lower blood pressure – oranges, orange juice, blueberries, strawberries, walnuts, dark chocolate, green tea.

I have days when my blood pressure gets me down, when I don’t want to test myself. The beeping sound when the test begins makes me nervous and I hate it when the cuff squeezes my arm, sometimes so tight that it leaves a red mark. Even if I have 8 out of 10 good blood pressure readings, the perfectionist in me seizes on the higher ones (even when they aren’t that high at all).  I wonder what I did wrong.

Sometimes this whole health regimen overwhelms me. I’ve started practicing a relaxing breathing technique described by Dr. Andrew Weil. It seems to be helping, but I know I have more to do. In the last few months, I’ve read about so many activities that are said to lower blood pressure that I feel I need to make a list and create a schedule for myself to fit everything in – tai chi, yoga, meditation, singing, music therapy, tap dancing (I made this last one up myself; if I could dance in front of the TV watching Fred Astaire and Ginger Rogers, I’m convinced I’d tap the high blood pressure away.)

It’s nearly April 15. Last night I couldn’t help thinking about my taxes as the blood pressure cuff squeezed tighter and tighter. Needless to say, the reading was a little high. Maybe that “to do” list isn’t such a crazy idea after all.

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