Researchers at Stanford School of Medicine have discovered that the podocyte cells that make up the kidney filter membrane may be able to regenerate during normal kidney function. Scientists have long believed that these cells, which suffer damage in more than 90 percent of chronic kidney diseases, such as FSGS and diabetic nephropathy, could not renew themselves. Researcher Steven Artandi, M.D., Ph.D., said, “It used to be thought that you were born with podocytes, and died with the same podocytes—you don’t make any more during your lifetime.”

In this study, Artandi and fellow scientists found that the over-expression of TERT, a protein component of the enzyme telomerase, causes podocytes to de-differentiate and divide, and the glomeruli to collapse as a result. A similar scenario occurs in patients with HIV-associated nephropathy or HIVAN. Interestingly, examination of the glomeruli of HIVAN patients revealed increased expression of TERT. Experiments in lab mice showed that increasing the expression of TERT produced the same result as in humans; once over-expression ceased, the cells stopped dividing and began acting like specialized podocyte cells again. The researchers also found that the Wnt signaling pathway is activated in patients with HIVAN. Wnt proteins are important to embryonic development and cell differentiation. The scientists were able to block Wnt signaling in mice with HIVAN to stop podocyte division and improve function. They now hope to discover if podocyte regeneration occurs during healthy kidney function. Dr. Artandi said, “If we can harness this regeneration, we may one day be able to treat people with chronic kidney disease.”

Source:

Regeneration of Specialized Cells Offers Hope for Treating Chronic Kidney Disease, Researchers Say, Stanford School of Medicine, December 4, 2011

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Researchers at University of Miami Miller School of Medicine and Harvard Medical School have discovered an important molecular mechanism behind worsening kidney disease. In a disease such as FSGS, for example, the kidney filter membrane (also known as the slit diaphragm) is damaged, allowing proteins to leak into the urine. The initial damage causes further injury to the podocyte cells, which make up the filter membrane. The podocytes die, resulting in more proteinuria and scarring of the kidneys.  The researchers found that when filter membrane injury occurs, CD2AP—a protein important for podocyte survival and proper signaling in the filter membrane—splits and releases the protein dendrin. This increases activity of protease cathepsin L, or Catl, which then degrades CD2AP, continuing the cycle of damage.

The study’s senior author, Jochen Reiser, M.D., Ph.D., explained, ““We knew that proteinuria is a risk for more and progressive renal disease, but now we understand a mechanism for how this is occurring. A healthy filter membrane regulates a healthy transcriptional program—both of which are altered in disease. The idea to improve not only proteinuria by rebuilding the slit diaphragm of podocytes, but also improve podocyte survival opens novel concepts for nephroprotection in otherwise progressive renal diseases, such as FSGS.”

Sources:

Nephrologists Discover Key to Kidney Disease Progression, University of Miami Miller School of Medicine, September 12, 2011

CD2AP in Mouse and Human Podocytes Controls a Proteolytic Program That Regulates Cytoskeletal Structure and Cellular Survival, JCI, The Journal of Clinical Investigation, October 3, 2011

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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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Metabolic syndrome describes a set of symptoms that increases the risk of Type 2 diabetes, heart disease, and stroke. Those risk factors are:

• high blood pressure
• obesity, particularly extra weight around the waist
• insulin resistance
• low good cholesterol
• higher levels of triglycerides

Patients are diagnosed with metabolic syndrome when they have 3 or more of these symptoms.

There have been a number of interesting discoveries about metabolic syndrome in the news lately. Scientists have found a link between metabolic syndrome and kidney disease which could lead to early interventions to prevent the syndrome as well as diabetes and kidney disease. – Metabolic Syndrome May Cause Kidney Disease

Researchers from the Gladstone Institutes have discovered how a gene called SIRT3 increases the risk of metabolic syndrome. – Gene That Exacerbates Risk Factors for Heart Disease and Diabetes Identified

Metabolic syndrome is also associated with increased incidence of kidney stones. An article from Internal Medicine News provides some insight into statistics and a possible cause for kidney stones in obese individuals. – Kidney Stones Linked to CVD, Metabolic Syndrome

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Researchers at Stanford University School of Medicine have identified a drug called STF-31 that starves and kills some kidney cancer cells by cutting off their energy supply of glucose. STF-31 works by binding to a particular glucose transporter. Testing in mice inhibited glucose transport by about half and resulted in slowed tumor growth with limited side effects and no negative impact on the brain, which also uses glucose for fuel. STF-31 may prove effective in fighting other cancers which require the same glucose transporter for energy production.

Source:

Potential Anti-Cancer Therapy That Starves Cancer Cells of Glucose Identified, ScienceDaily, August 4, 2011

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A team of nephrologists and researchers at University of Miami Miller School of Medicine have discovered a factor in the blood that may be responsible for up to two-thirds of the cases of focal segmental glomerulosclerosis or FSGS. They found that an excess of serum soluble urokinase receptor (suPAR) activates a protein in the kidney podocytes called ß3 integrin. The podocytes, which serve as a filtration barrier, begin to move and allow protein to pass into the urine. The process leads to breakdown and fusing of the podocytes, impaired filtration, and glomerular scarring. The scientists found that many patients with FSGS have elevated levels of suPAR in the blood. Therapies to reduce suPAR levels or stop the suPAR-ß3 interaction could prove beneficial. Tests for suPAR levels in the blood could also identify patients at risk of developing recurring FSGS after kidney transplantation.

Source:

Nephrologists Discover Cause of Common Kidney Disease, University of Miami Miller School of Medicine, July 31, 2011

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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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Researchers from Oregon Health and Science University Knight Cancer Institute have found that a gene called Src plays a role in helping some kidney cancers grow. The researchers are now looking at existing, approved drugs that may inhibit Src activity in cancer cells.  In addition, they have developed a method of identifying patients that could benefit from such drugs. This discovery could expand kidney cancer drug treatments beyond therapies that slow tumor growth, but fail to provide a cure, and don’t work for all patients.

Source:

Kidney Cancer Discovery Could Expand Treatment Options, Science Daily, July 7, 2011

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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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