Breaking News
September 23, 2018 - HIV and a tale of a few cities
September 23, 2018 - NIH launches clinical trial to test infusions of combination antibodies in people with HIV
September 23, 2018 - Researchers develop new system to detect consumption of synthetic cannabinoids
September 23, 2018 - Vax-Hub to influenze radical change in development and manufacturing of vaccines
September 23, 2018 - People who have slept lesser than seven hours have higher risks of car crashes
September 23, 2018 - an ancient art may work best to prevent falls in old age
September 23, 2018 - Consumption of foods with lower nutritional quality related to increased cancer risk
September 23, 2018 - Patient Health Information Often Shared Electronically
September 23, 2018 - Can machine learning bring more humanity to health care?
September 23, 2018 - Body organs undergo structural changes in response to diet
September 23, 2018 - Genetic polymorphisms linked with muscle injury and stiffness
September 23, 2018 - As states try to rein in drug spending, feds slap down one bold Medicaid move
September 22, 2018 - Why Eczema Is Tougher to Treat for Black Patients
September 22, 2018 - Team reveals that human genome could contain up to 20 percent fewer genes
September 22, 2018 - USC research uncovers previously unknown genetic risk factor for Alzheimer’s disease
September 22, 2018 - Novel method achieves accurate and precise temperature estimation in fat-containing tissues
September 22, 2018 - BSI accredits Oxehealth’s vital signs measurement software as Class IIa medical device
September 22, 2018 - Evolution of psychiatric disorders and human personality traits
September 22, 2018 - Obesity in early puberty doubles asthma risk for boy’s future offspring
September 22, 2018 - World’s most advanced real-time patient monitoring platform receives key US patent
September 22, 2018 - Study explores connection between sexuality and cognitive status in older adults
September 22, 2018 - LSTM partners with TB Alliance to develop novel TB drug regimens
September 22, 2018 - Annual wellness visits improve delivery of preventive services in elderly population
September 22, 2018 - CHMP provides positive opinion to Cabometyx for previously-treated patients with hepatocellular carcinoma
September 22, 2018 - Hispanic communities with high proportions of Hispanics face more cardiovascular-related death
September 22, 2018 - Vici syndrome – Genetics Home Reference
September 22, 2018 - Single-dose drug can shorten flu symptoms by about a day, studies suggest
September 22, 2018 - AMSBIO launches circulating tumor DNA Reference Standards
September 22, 2018 - Sandalwood mimicking odorant could stimulate hair growth in humans
September 22, 2018 - Overlooked immune cells could play a key role in cancer immunotherapy, claims new study
September 22, 2018 - Study reveals prevalence of diagnosed type 1 and type 2 diabetes among American adults
September 22, 2018 - Researchers develop fast detection strategy to know type of virus acquired by patients
September 22, 2018 - Global Prevalence of Insufficient Activity 27.5 Percent
September 22, 2018 - Strategies to protect bone health in hematologic stem cell transplant recipients
September 22, 2018 - Brigham Genomic Medicine program unravels 30 medical mysteries
September 22, 2018 - New system harnesses power of bubbles to destroy dangerous biofilms
September 22, 2018 - Inflammation plays crucial role in preventing heart attacks and strokes, study reveals
September 22, 2018 - Calorie dense, nutrient deficient meals common across the world
September 22, 2018 - Researchers develop technology to study behavior of implants without animal testing
September 22, 2018 - First gut bacteria in newborns may have lasting effect on ability to ward off chronic diseases
September 22, 2018 - Detection of BFD virus in parrots in 8 new countries raises concerns for threatened species
September 22, 2018 - Insulin treatment shows great potential against chronic bowel inflammation
September 22, 2018 - ‘Liking Gap’ Might Stand in Way of New Friendships
September 22, 2018 - Simple factors that can avoid harmful side effects in type 2 diabetes
September 22, 2018 - ALSAM Foundation invests additional $2 million for drug discovery and development projects
September 22, 2018 - Study findings may advance discussion of how to effectively curb human-wildlife conflict
September 22, 2018 - Dopamine neurons may involve in conditions ranging from Parkinson’s disease to schizophrenia
September 22, 2018 - Protein C and Protein S Tests: MedlinePlus Lab Test Information
September 22, 2018 - Obesity and diabetes—two reasons why we should be worried about the plastics that surround us
September 22, 2018 - Concern over fussy eating prompts parents to use non-responsive feeding practices
September 22, 2018 - Novel mathematical approach uncovers existence of unsuspected biological cycles
September 22, 2018 - Cancer Research UK invests £14 million to transform London into cancer biotherapeutics hub
September 22, 2018 - Scientists predict how well the body will fight lung cancer by analyzing immune cell shapes
September 22, 2018 - New outbreak of rare eye disease identified in contact lens wearers
September 22, 2018 - Iterum Initiates SURE 2 and SURE 3 Phase 3 Clinical Trials of IV and Oral Sulopenem in Complicated Urinary Tract and Complicated Intra-abdominal Infections
September 22, 2018 - Research finds divide in dental health accessibility between city and regional areas
September 22, 2018 - Premature babies show better brain development when fed breast milk, finds study
September 22, 2018 - Novel system uses AI to detect abnormalities in fetal hearts
September 22, 2018 - UNC scientists reveal new approach to prevent obesity and diabetes
September 22, 2018 - CWRU receives NIH grant to learn how non-coding genes contribute to spread of colorectal cancer
September 22, 2018 - Scientists better understand influenza virus and how it spreads
September 22, 2018 - Scientists to focus on length of time when a person is alive and healthy
September 22, 2018 - Study shows positive financial impacts of Medicaid expansion for low-income Michigan residents
September 22, 2018 - Innovative approach for developing vaccine against most prevalent human malaria parasite
September 22, 2018 - Study finds excess emissions from diesel cars produced by major auto manufacturers in Europe
September 22, 2018 - Decision aids for parents of children with minor head injuries help communicate with physicians
September 22, 2018 - Research scientist at Kessler Foundation receives $10,000 grant to study aphasia after stroke
September 22, 2018 - New findings on characteristics of Burning Mouth Syndrome
September 22, 2018 - Study sheds light on molecular mechanisms underlying progression of prion diseases
September 22, 2018 - Innovation Fund Denmark supports research project that aims to fight Clostridium difficile diarrhea
September 22, 2018 - Survey estimates caregiving costs for family members
September 22, 2018 - Inhibiting NF-kB improves heart function in a mouse model of Duchenne muscular dystrophy
September 22, 2018 - Introducing new EMR system may affect several aspects of clinic workflow
September 22, 2018 - Study finds why some human genes are more popular with biomedical researchers
September 22, 2018 - Finding epigenetic signature appears to predict inflammation risk in serious type of IBD
September 22, 2018 - Researchers develop light-based technique to measure very weak magnetic fields
September 22, 2018 - UAB researchers study dysfunction of the immune system associated with NSAID carprofen
September 22, 2018 - QIAGEN and DiaSorin launch automated, CE-marked workflow for high-throughput TB screening
September 22, 2018 - EFS checklist provides user-friendly tool for evaluating feeding skills in preterm infants
September 22, 2018 - Family history in blacks, Latinos associated with higher risk of AFib
Researchers explore treatment target for acute kidney injury

Researchers explore treatment target for acute kidney injury

image_pdfDownload PDFimage_print

When you have diabetes then get an acute kidney injury there is a multiplier effect that can worsen your prognosis and destroy your kidneys.

Now scientists have evidence that at least part of the problem is that diabetes impairs the ability of kidney cells to consume the garbage they generate in the process of filtering more than 100 quarts of your blood daily.

It’s called autophagy, and it helps kidney cells operate at a premium and that’s where the problems occur, says Dr. Zheng Dong, cellular biologist, Regents’ Professor and Leon Henri Charbonnier Endowed Chair in the Department of Cellular Biology and Anatomy at the Medical College of Georgia.

In diabetes, hardworking kidney cells must work even harder to handle high levels of glucose, which produces even more garbage, while autophagy activity is down. An acute kidney injury on top of that further heightens the trash and the damage.

Dong is principal investigator on a new $2.2 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases that is helping parse just how autophagy is hampered in diabetes and finding targets to bolster autophagy and help patients and their kidneys better survive diabetes and recover from an acute kidney injury.

An acute kidney injury is mostly what it sounds like: when kidney function deteriorates in a few hours or days. It can result from a literal blow to the kidney, in a fall or car accident, or from dehydration in an overzealous student athlete. In the face of general good health, most patients recover fully and quickly, Dong says.

But acute kidney injury mostly occurs in people who already have another medical problem like diabetes. In fact, most are in the hospital when it happens, with problems like bleeding or shock, failure of other organs like the heart, even an overdose of over-the-counter nonsteroidal anti-inflammatories for problems like the cold or flu, according to the National Kidney Foundation.

Despite these typically heightened scenarios, there aren’t any targeted therapies for acute kidney injury, says Dong, rather supportive therapies like hydration, possible short-term dialysis and addressing the injury cause.

Even without an acute kidney injury, the heavy burden of glucose and inflammation that comes with diabetes causes related kidney damage in about a third of patients in about 15 years of living with the disease. The ceaseless filtering and reabsorption work of the kidney gets overwhelmed with the extra glucose, which can increase oxidative stress, prompt sugars to start binding to proteins, which can reduce their function, and inflammation becomes chronic and destructive.

In fact, diabetes and high blood pressure are the leading causes of kidney failure in the United States, according to the National Kidney Foundation.

Dong’s team has evidence that diabetes makes people more susceptible to an acute kidney injury from which they don’t recover well, which ties back full circle because an acute injury also increases the chronic kidney disease risk.

The bottom line is that in this so-called “comorbid” state, patients are at heightened risk for significant kidney damage, even kidney failure.

His team focuses on the acute injury piece of this interrelated health dilemma and the reality that treatment for acute kidney injury hasn’t really improved after a half-century search for good therapies, Dong says. That’s why he is looking for targets and therapeutic agents.

Blood enters the kidneys through clusters of small blood vessels called glomeruli. We have more than a million of these filtering units that each connect to a collecting tube called a tubule, which passes waste along to the bladder for elimination. Tubular cells also daily resorb nearly 50 gallons of usable items, including salt and glucose the kidneys filter from the blood. They typically resorb 80-90 percent of the glucose.

In their effort to maximize autophagy in the face of higher glucose, Dong and his team are delineating how diabetes reduces autophagy with the idea of restoring this innate ability when a patient is also bombarded with an acute kidney injury. They have their sites on some of our smallest RNA.

They have evidence that activity of ULK1, an enzyme and key initiator of autophagy, is reduced in the kidney both in diabetes and also by putting a lot of glucose directly on kidney cells.

MicroRNA, or miRNA, generally suppress expression of their target genes, and Dong’s team also has evidence that in diabetes, expression of at least one miRNA is increased, which, in turn, decreases ULK1 expression and autophagy. Right now they don’t know a lot about its functions, but high levels are associated with overgrowth of tubules and thickening and scarring of the kidney.

Also up in diabetes is p53, a known tumor suppressor that can help assess damage to a cell, help drive its repair if possible and its suicide if it’s not. In a healthy cell, p53 levels are low.

Higher levels of p53 are associated with lower levels of autophagy and Dong has shown p53 is even more highly activated with an acute kidney injury, likely to help kill off freshly injured cells.

“Autophagy is generally a protective mechanism, so as this protective mechanism goes down, an injury mechanism goes up,” Dong says of this inverse relationship.

He thinks his miRNA is essentially the middleman with p53 signaling for it to reduce autophagy and it responding by turning down expression of the ULK1 gene. That pivotal role makes the miRNA a likely and probably amenable drug target, he says.

“We need to find a way to make it go down,” Dong says. “Maybe if we can normalize autophagy a little better we can help kidneys survive this period.”

The new grant is enabling them to sort the details of how p53 induces the miRNA in diabetic kidneys, how it, in turn, suppresses ULK1 and autophagy and, finally, how reduced autophagy makes the kidneys more vulnerable to injury.

This shift is likely what makes a patient with diabetes more vulnerable to acute kidney injury. Another thing they are exploring further is what happens to cell death rates, but Dong has already watched tubule cells become less efficient and die. He’s also now exploring the relationship between reduced autophagy and increased inflammation.

Diabetes is a common, chronic stressor of the kidney, Dong says. And he expects other common stressors, like the all too common hypertension, make some of the same unhealthy adjustments to tubule cells. In fact, he is collaborating with China’s Central South University with the idea of delineating the autophagy pathway in a hypertension model as well.

Source:

The search is on for a treatment target for acute kidney injury

Tagged with:

About author

Related Articles