Summer spikes spotted online.

Google Insights for Search heat map displays relative volume of kidney stone searches from 2005 through 2009.

You might save yourself a lot of pain and trouble during the dog days of summer by drinking to your health – with a long, cool glass of water. The incidence of kidney stones – which can cause the kind of pain some women have compared to giving birth – peaks in summer months when temperatures soar and perspiration drips.

Now it turns out that these seasonal variations in kidney stone incidence are reflected in Google search engine queries, according to research by UCSF urologist Benjamin Breyer, M.D., and colleagues that is featured on the cover of this month’s issue of the scientific journal Urology.

“Kidney stones vary by season and region – they are more common in warmer places and during hotter times of the year,” Breyer says. Large kidney stones cause pain as they pass through the ureter, and many require surgery to remove. Keeping hydrated helps prevent the crystallization of stones.

Nationwide, about 13 percent of men and 7 percent of women in the United States suffer kidney stones during their lives, and half who experience one will develop another.

Not surprisingly, some people with pain or other symptoms of a kidney stone go online to see what more they can learn. As a UCSF clinical instructor in urology, Breyer, now a UCSF assistant professor, along with urology resident Michael Eisenberg, M.D., now an assistant professor at Stanford University, used an online tool called Google Insights for Search to see if the varying popularity of search terms would reflect seasonal and geographic differences in kidney stone prevalence.

“Kidney stones” was the best search term they found to mirror trends obtained from hospital data.

In addition to variations due to weather, genetics, diet and obesity also contribute to the likelihood that one develops kidney stones. The impact of kidney stones varies not only by season, but also by geographic location. A region where rates are high throughout the Southeast has been dubbed “the stone belt.”

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Sparing kidney helps prevent chronic kidney disease, reduces risk of osteoporosis.

Ithaar Derweesh (right), UC San Diego

Researchers at the University of California, San Diego, School of Medicine have shed new light on how surgery impacts both chronic kidney disease and bone health, particularly in women. For the first time, their findings point to the importance of pursuing kidney-sparing surgery in an effort to preserve kidney function and to reduce the risk of bone fractures later in life. The study was published in the July 19 edition of Urology and is now available online.

“When weighing the risks and benefits of partial versus radical nephrectomy, doctors and patients should take into account the impact on a patient’s bone health,” said Dr. Ithaar Derweesh, senior author and urologic oncologist at UC San Diego Moores Cancer Center. “This study illuminates the fact that preserving the kidney helps to prevent chronic kidney disease and significantly reduces bone fractures and risk of developing osteoporosis.”

Complete removal of a kidney has been found to be a significant risk factor for chronic kidney disease, which carries increased risk for metabolic complications, cardiovascular disease and death. With partial nephrectomy, functional kidney tissue and healthy cells are preserved and can help prevent or reduce the risk of development of chemical imbalances such as metabolic acidosis which may later lead to kidney dysfunction, muscle wasting and osteoporosis, a direct cause of bone loss and fractures.

“Women facing kidney surgery should investigate whether partial kidney removal is an option to treat their disease as it may help prevent bone brittleness,” said Dr. Christopher Kane, professor of surgery, C. Lowell and JoEllen Parsons Endowed Chair in Urology and chief of the Division of Urology, and paper co-author. “Too often urologists have done radical nephrectomies for patients who were candidates for partial nephrectomy. While partial nephrectomy is more complex for the surgeon to perform, it can offer better quality of life later in life.”

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New approach could potentially remove the need for a clinic-based dialysis process.

Shuvo Roy, UC San Francisco

UCSF researchers have designed a model filtration system that could offer a new approach to treating patients suffering from end-stage renal disease, potentially removing the need for a clinic-based dialysis process altogether.

Initial results of the research were presented as an abstract on June 10 by UCSF nanoengineer Shuvo Roy, Ph.D., during the annual conference of the American Society for Artificial Internal Organs in Washington, D.C. Roy also presented initial results of tests showing that silicon-based membranes are compatible with human blood and thus offer viable options as filters in implanted devices such as the team’s model for an implantable artificial kidney.

The filtration model is designed as a trap for mid-sized molecules that need to be filtered from the patient’s blood stream, with the upstream filter sized to leave large molecules such as proteins and blood cells in the blood, and the downstream filter sized to block urea and creatinine while allowing electrolytes and nutrients to return to the blood stream.

Ultimately, researchers say the system could provide an intermediary therapy for dialysis patients  awaiting a kidney transplant, thus untethering them from tri-weekly visits to dialysis centers. It also could be used in an interim device in developing an implantable bio-artificial kidney, in which cell therapy would augment the function of the downstream filter to replace most of the functions of a real kidney.

Abstracts are published in the March/April issue of the ASAIO journal.

Read a Q&A with Roy.

Blocking a specific receptor pathway may slow or prevent diabetic nephropathy, UC Davis investigators have shown.

Ishwarlal Jialal (left) and Sridevi Devaraj, UC Davis

UC Davis investigators have shown that blocking a specific receptor pathway could slow or even prevent diabetic nephropathy — an often fatal complication of diabetes for which there are few good treatment options. Published online today (May 26) in the journal Arteriosclerosis, Thrombosis and Vascular Biology, the study is the first to clarify the role of the receptor — toll-like receptor 2, or TLR2 — in diabetes-associated kidney disease.

“Diabetic nephropathy is one of the most serious outcomes of diabetes and the most common cause of renal failure,” said Ishwarlal Jialal, UC Davis professor of endocrinology, diabetes and metabolism and senior author of the study. “It is progressive and eventually requires chronic dialysis or transplant. But now we have a precise molecular target for treating this difficult disease.”

Nephropathy, which affects about 30 percent of diabetics, becomes apparent between five and 25 years following a diabetes diagnosis. It occurs when high glucose — often with hypertension — overworks the kidneys’ intricate blood filtration system, eventually causing that system to break down. It is typically diagnosed midway through the disease process, when the kidneys enlarge and protein appears in urine.

“We currently cannot fully predict why some people with diabetes, even some with well-controlled diabetes, get nephropathy while others do not,” said Jialal, whose lab specializes in studying the role of inflammation in heart disease and diabetic complications. “Our goal is to find a way to identify and stop it in its tracks at the earliest possible stages, well before dialysis is required.”

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UC San Diego’s Ravindra Mehta wins Shire Bywaters Award.

Ravindra Mehta, UC San Diego

Ravindra  L. Mehta, MD, FACP, professor of medicine at the University of California, San Diego School of Medicine’s Division of Nephrology and associate chair of clinical research at the UCSD Department of Medicine, has received the International Society of Nephrology (ISN) 2011 Shire Bywaters Award.

The award was established by the ISN to recognize lifetime achievement and outstanding contributions to the understanding of acute kidney injury in critically ill patients.  It was awarded to Mehta at the recent biannual Acute Renal Failure Satellite Symposia, held in conjunction with the World Congresses of Nephrology.

An internationally recognized expert in acute kidney injury, Mehta directs the Acute Dialysis Program at UC San Diego Health System.  His research has focused on the epidemiology and management of acute kidney injury (AKI) in critically ill patients.  His many contributions to the field have led to the development of citrate anticoagulation for continuous renal replacement therapies, formation of the Acute Kidney Injury Network (AKIN), diagnostic and staging criteria for AKI, and the development of guidelines for AKI management.  He also initiated an international registry project involving 15 institutions from around the world, all contributing epidemiological information on AKI to help guide the design of new clinical trials.

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The disease is characterized by the proliferation of cysts that eventually debilitate the kidneys.

Thomas Weimbs (left) and Jeffrey Talbot, UC Santa Barbara

Two discoveries at UC Santa Barbara point to potential new drug therapies for patients with kidney disease. The findings are published in this week’s issue of the Proceedings of the National Academy of Sciences.

Over 600,000 people in the United States and 12 million worldwide are affected by the inherited kidney disease known as autosomal-dominant polycystic kidney disease, or ADPKD. The disease is characterized by the proliferation of cysts that eventually debilitate the kidneys, causing kidney failure in half of all patients by the time they reach age 50.

Currently, no treatment exists to prevent or slow cyst formation, and most ADPKD patients require kidney transplants or lifelong dialysis for survival, explained Thomas Weimbs, director of the laboratory where the discoveries were made. Weimbs is an associate professor in the Department of Molecular, Cellular and Developmental Biology and the Neuroscience Research Institute at UCSB.

First, Weimbs and his research team discovered a molecular mechanism that sheds light on the disease. The mechanism concerns polycystin-1, a protein that is mutated in ADPKD patients. The team discovered how this protein regulates a well-known transcription factor called STAT3. Transcription factors transcribe information from DNA to RNA, from specific genes. Second, the team discovered that STAT3 is strongly, and aberrantly, activated in polycystic kidneys.

“The clinical significance of these discoveries lies in the fact that STAT3 is also known to be aberrantly activated in many forms of cancer and is considered an important drug target for cancer therapy,” said Weimbs. “Numerous STAT3 inhibitors are currently being developed and tested, and several experimental drugs are already available. Our results suggest that STAT3 activation is a driving force for the cyst growth that leads to polycystic kidneys in ADPKD. Therefore, STAT3 may be a highly promising drug target for the treatment of ADPKD.”

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Promising results from study using pirfenidone.

Kumar Sharma, UC San Diego

Researchers at the UC San Diego School of Medicine, the National Institutes of Health (NIH) and the Mayo Clinic have published promising results of a clinical study using an experimental anti-fibrotic and anti-inflammatory drug called pirfenidone to treat patients with diabetic nephropathy. Their study will be published in today’s (April 21) issue of the Journal of the American Society of Nephrology (JASN).

Diabetic nephropathy remains the leading cause of end-stage kidney disease (ESKD) in the United States. It is a common complication of diabetes, in which kidney cells are damaged as a result of high blood sugar levels.

“The dramatic finding of this exploratory study is that an appropriate dose of pirfenidone not only halted decline but actually improved kidney function in these patients,” said Dr. Kumar Sharma, FAHA, professor of medicine in the UC San Diego division of nephrology and director of the Center for Renal Translational Medicine, who headed the study.

The principal process underlying the progression of chronic kidney disease to ESKD — where dialysis is required to keep a patient alive — is called renal (kidney) fibrosis. The fibrosis, or scarring, damages tiny blood vessels in the glomerulus, structures that filter and remove waste from the blood, and in between tubular cells.

Transforming growth factor beta (TGF-β) is a protein that controls many cellular functions, including extracellular matrix accumulation. TGF-β is stimulated in the diabetic kidney due to uncontrolled blood sugar and elevated blood pressure and can promote renal fibrosis.

“To date, therapies for diabetic nephropathy have been limited to drugs that improve blood pressure or control blood sugar levels,” said Sharma. Instead, pirfenidone seems to work by blocking TGF-β; in effect, shutting down the growth factors that cause renal fibrosis.

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UCLA’s kidney and pancreas program now performs about 300 transplants each year.

Alan Wilkinson, UCLA

Patients who received kidney transplants through the UCLA Kidney and Pancreas Transplant Program had the highest three-year transplant survival rate among patients who underwent the procedure at U.S. centers that perform 80 or more transplants a year, according to new government data.

More than 6,000 kidney transplants have been performed at UCLA since 1964; these include combined kidney-liver, heart-liver and multi-organ transplants. The kidney and pancreas program now performs about 300 transplants each year, said Dr. Alan Wilkinson, director of the program.

“We achieve these results in spite of taking on very high-risk patients — some with complex medical problems and others at high risk of having rejection,” he said.

About 92 percent of patients who received kidneys at Ronald Reagan UCLA Medical Center had functioning transplants three years after their surgeries, according to data compiled by the Scientific Registry for Transplant Recipients, which monitors national transplant data for the U.S. Department of Health and Human Services. The statistics examine one-month, one-year and three-year survival rates.

“This is truly a great achievement for our faculty and the entire kidney transplant team,” said Dr. Jean deKernion, chair of the department of urology.

“These long-term results reflect the excellent care provided by referring physicians, as well as the benefits of a dedicated kidney transplant program with integrated nursing, medical and surgical care,” said Dr. H. Albin Gritsch, surgical director of the kidney transplant program.

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UC Davis study is a clarion call for clinicians to pay close attention to transplant evaluation process.

A large study of children awaiting transplantation conducted by researchers at the UC Davis School of Medicine has found that girls are significantly less likely than boys to be placed on the waiting list to receive a new kidney.The study, published online in the journal Pediatric Transplantation, found that among children and young adults under 21 years of age starting dialysis, girls were 22 percent less likely than boys to be placed on the waiting list for a new organ.

Earlier research by UC Davis found that the sooner a child with advanced chronic kidney disease receives a new kidney, the better their long-term health and the longer the life of the organ.

“If the goal is to get them transplanted as soon as possible, then they need to be wait-listed as soon as possible,” said Stephanie Nguyen, assistant professor of pediatric nephrology at the UC Davis School of Medicine and the study’s lead author. “The longer they’re waiting for a transplant, the worse their outcomes will be,” she said.

Nguyen said the study is a clarion call for clinicians to pay close attention to the transplant evaluation process and to ensure that girls are given opportunities to receive transplants as quickly as possible.

For the study, UC Davis researchers reviewed data from approximately 4,473 patients whose health information was included in the North American Pediatric Renal Trials and Collaborative Studies database, a large, voluntary collaborative effort of 150 renal treatment centers in the United States, Canada, Mexico and Costa Rica.

The study found that girls were less likely to have been placed on the wait list to receive a new kidney at dialysis initiation, six months after starting dialysis and even 12 months after starting dialysis.

The study found that there were no other readily apparent factors that would account for girls not being wait-listed as frequently as boys, such as medical reasons or family preference. The study also notes that girls were less likely to have a living-related donor and also were less likely to have pre-emptive transplants than boys.

Girls are less likely than boys to be on the transplant wait list, even after adjusting for multiple confounding factors, such as age, race or ethnicity, underlying diagnosis and time of follow up. The reason most often given for why girls were not placed on the wait list at every point in time was that their “work-up was in progress.”

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California corrections officer donates kidney to fellow officer.

A pair of sisters attracted – national attention in January when Mississippi governor Haley Barbour released them from prison-on condition that one donate a kidney to the other.

In early March a variant – of a sort, anyway – played out at Ronald Reagan UCLA Medical Center when one Southern California corrections officer gave a kidney to another from a different facility. They were complete strangers to each other and only met for the first time about a week before their March 8 surgery, when both came to UCLA for their final blood cross match and clinic appointments.

It all started in October, when California Department of Corrections and Rehabilitation (CDCR) Officer Gaston Benjamin of Lancaster, who works in the Antelope Valley facility, found out that his kidneys were failing due to a genetic condition that also struck one of his sisters, putting her on dialysis. A single father of four young children, he was worried about his future … and that of his family.

His diagnosis was all the more surprising in that he did not exhibit any symptoms and had learned of it only during a routine medical examination.

But by chance Officer Benjamin ran into Ken Lewis, a community resource manager for the California prison system, at a local Walmart. Officer Benjamin told Lewis about his deteriorating health – the fatigue and other attendant problems associated with declining kidney function – and of his fears for the future. More than 100,000 people were on the waiting list for a kidney, he said, and the odds were not in his favor.

Lewis quickly stepped into action and generated a flier he sent out by email to about 40,000 CDCR fellow employees. Nearly 20 responded that they would be willing to donate a kidney to Officer Benjamin.

Two were a match and Officer Luis Hernandez, a guard at the facility in Calipatria, was the perfect match. Strangers until the call for help, Officer Hernandez and Officer Benjamin have become fast friends.

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Study indicates that there are potentially millions of Americans with undiagnosed — and misdiagnosed — kidney disease.

A new strategy for diagnosing kidney disease proved significantly more accurate than the current standard approach, indicating that there are potentially millions of Americans with undiagnosed – and misdiagnosed – kidney disease, according to a large, multicenter study led by researchers at the San Francisco VA Medical Center and the University of California, San Francisco.

The authors said that the results of the study, which will appear in the April 20 issue of the Journal of the American Medical Association, have important national implications for the detection and classification of kidney disease. The study is being published early online to coincide with its presentation at the World Congress of Nephrology.

In the study of more than 26,000 adults, the scientists determined that a panel of three tests for kidney disease – creatinine, cystatin C, and urine albumin-to-creatinine ratio (ACR) – was much more accurate in identifying kidney disease and predicting risk of kidney failure and death than the test for creatinine alone, which is the current standard diagnostic test.

Sixteen percent of study participants who were not shown to have chronic kidney disease according to creatinine levels were correctly identified by tests for cystatin C and ACR as having CKD, along with elevated risk of eventual kidney failure and death.

“These were persons with kidney disease who were at high risk of complications and who were simply missed by creatinine,” said lead author Carmen A. Peralta, MD, MAS, an SFVAMC researcher and an assistant professor of medicine in residence in the division of nephrology at UCSF.

Conversely, among subjects identified as having CKD through elevated creatinine, 24 percent were revealed to not have CKD as shown by measurements of cystatin C and ACR. These participants had the same risk of kidney failure and death as participants with normal creatinine.

Overall, the 3 percent of study participants identified as having CKD according to all three tests had an eight-fold risk of death and a hundred-fold risk of kidney failure compared with participants identified as having CKD according to creatinine alone. More than 70 percent of kidney failures observed during the course of the study occurred among this group.

“Based on creatinine levels, about 14 million people in the United States are currently classified as having CKD,” said Peralta. “We estimate that testing for cystatin C and albumin in the urine would reclassify about 5 million of these people as being without increased risk for kidney disease, and would more accurately predict the risks of kidney failure and death for the other 9 million.”

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Next step is to scale up the devices for further testing in large animals and humans.

Shuvo Roy, UC San Francisco

Researchers are using microelectromechanical systems, or MEMS, to develop what could be the world’s first implantable artificial kidney. Bioengineer Shuvo Roy of the University of California, San Francisco, explains that one of the attractions of MEMS technology is that it’s very manufacturable.

“So, it’s not like we’re making these special membranes using tools that we’ll have to worry about to scale-up,” Roy said. “We’re actually using production level tools that we can translate into manufacturing later on.”

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