Breaking News
December 17, 2018 - In-school nutrition programs among students limit increases in BMI, finds study
December 17, 2018 - Risk for Hospitalization for Heart Failure Greater With Diabetes
December 17, 2018 - Food assistance may help older adults adhere to diabetes meds
December 17, 2018 - Supporting a family’s goals during a difficult pregnancy
December 17, 2018 - Neurons with Good Housekeeping Are Protected from Alzheimer’s
December 17, 2018 - CTF along with NTAP and Sage announce first-ever open data portal for neurofibromatosis
December 17, 2018 - Intimacy: The Elusive Fountain of Youth?
December 17, 2018 - Will saliva translate to a real diagnostic tool?
December 17, 2018 - DFG establishes nine new Research Units and one new Clinical Research Unit
December 17, 2018 - Assisted living’s breakneck growth leaves patient safety behind
December 17, 2018 - America’s teens report dramatic increase in their use of vaping devices in just one year
December 17, 2018 - Enlarged heart linked to a higher risk of dementia
December 17, 2018 - Prostate cancer detection using MRI now first-line investigation tool
December 17, 2018 - Loughborough academics part of new project investigating effectiveness of personalized breast cancer screening
December 17, 2018 - Adolescents who use cognitive reappraisal had better metabolic measures, shows study
December 17, 2018 - Probiotics may offer therapeutic benefits for biopolar patients
December 17, 2018 - Stealth BioTherapeutics Granted Fast Track Designation for Elamipretide for the Treatment of Dry Age-Related Macular Degeneration with Geographic Atrophy
December 17, 2018 - Studies reveal role of red meat in gut bacteria, heart disease development
December 17, 2018 - Eisai enters into agreement with Eurofarma for its anti-obesity agent lorcaserin
December 17, 2018 - Researchers use brain connectome to reassess neuroimaging findings of Alzheimer’s disease
December 17, 2018 - “Miracle” baby survives Ebola in Congo and rapid a new Ebola detection device
December 17, 2018 - Mechanisms behind neonatal diabetes uncovered
December 17, 2018 - AHF urges the WHO to expedite approval process for vaccine effective against Ebola
December 17, 2018 - Study finds misuse of benzodiazepines to be highest among young adults
December 17, 2018 - TGen receives PayPal grant to underwrite costs of genetic tests for children with rare disorders
December 17, 2018 - New research highlights why HIV-infected patients suffer higher rates of cancer
December 17, 2018 - Antibiotic-resistant bacteria could soon be targeted with Alzheimer’s drug
December 17, 2018 - Rutgers scientists take an important step in making diseased hearts heal themselves
December 17, 2018 - Tailored Feedback at CRC Screen Improves Lifestyle Behaviors
December 17, 2018 - Loss of two genes drives a deadly form of colorectal cancer, reveals a potential treatment
December 17, 2018 - How the Mediterranean Diet Can Help Women’s Hearts
December 17, 2018 - Sustained connections associated with symptoms of autism
December 17, 2018 - Concussion rates among young football players were higher than previously reported
December 17, 2018 - Cresco Labs granted approval to operate marijuana dispensary in Ohio
December 17, 2018 - Study provides insight into health risks facing new mothers
December 17, 2018 - AMSBIO expands Wnt signaling pathway product range to aid research
December 16, 2018 - Surgical treatment unnecessary for many prostate cancer patients
December 16, 2018 - Excess weight responsible for cancers globally finds report
December 16, 2018 - Regular sex associated with greater enjoyment of life in seniors
December 16, 2018 - Social stigma contributes to poor mental health in the autistic community
December 16, 2018 - Multidisciplinary team successfully performs complex surgery on patient suffering from enlarged skull
December 16, 2018 - Experts analyze data that can guide antidepressant discontinuation
December 16, 2018 - Menlo Therapeutics’ Successful Phase 2 Clinical Trial of Serlopitant Demonstrates Reduction of Pruritus Associated with Psoriasis
December 16, 2018 - Siblings of children with autism or ADHD are at elevated risk for both disorders
December 16, 2018 - New project aims to understand why and how metabolic disorders develop in patients
December 16, 2018 - Diets containing GM maize have no harmful effects on health or metabolism of rats
December 16, 2018 - Are doctors and teachers confusing immaturity and attention deficit?
December 16, 2018 - Hearing loss linked with increased risk for premature death
December 16, 2018 - Chromatrap buffer reagents for lysing cells offer many benefits
December 16, 2018 - Young Breast Cancer Patients Face Higher Risk for Osteoporosis
December 16, 2018 - 3-D printing offers helping hand to people with arthritis
December 16, 2018 - Community Health Choice helps manage complex and chronic care conditions
December 16, 2018 - Regular trips out could dramatically reduce depression in older age
December 16, 2018 - CWRU to use VivaLNK’s Vital Scout device for stress study in student athletes
December 16, 2018 - ‘Easy Way Out’? Stigma May Keep Many From Weight Loss Surgery
December 16, 2018 - Gout drug may protect against chronic kidney disease
December 16, 2018 - Talking about memories enhances the wellbeing of older and younger people
December 16, 2018 - Occupational exposure to pesticides increases risk for cardiovascular disease among Latinos
December 16, 2018 - A biomarker in the brain’s circulation system may be Alzheimer’s earliest warning
December 16, 2018 - Magnesium may play important role in optimizing vitamin D levels, study shows
December 16, 2018 - The effect of probiotics on intestinal flora of premature babies
December 16, 2018 - Parents spend more time talking with kids about mechanics of using mobile devices
December 16, 2018 - Biohaven Announces Positive Results from Ongoing Rimegepant Long-Term Safety Study
December 16, 2018 - Arterial stiffness may predict dementia risk
December 16, 2018 - Study explores link between work stress and increased cancer risk
December 16, 2018 - Sex work criminalization linked to incidences of violence finds study
December 16, 2018 - Johns Hopkins researchers discover swarming behavior in fish-dwelling parasite
December 16, 2018 - Schistosomiasis prevention and treatment could help control HIV
December 16, 2018 - Early postpartum opioids linked with persistent usage
December 16, 2018 - Johns Hopkins researchers identify molecular causes of necrotizing enterocolitis in preemies
December 16, 2018 - Advanced illumination expands capabilities of light-sheet microscopy
December 16, 2018 - Alzheimer’s could possibly be spread via contaminated neurosurgery
December 16, 2018 - Unraveling the complexity of cancer biology can prompt new avenues for drug development
December 16, 2018 - Inflammatory Bowel Disease, Prostate Cancer Linked
December 16, 2018 - Cannabis youth prevention strategy should target mental wellbeing
December 15, 2018 - Recent developments and challenges in hMAT inhibitors
December 15, 2018 - Sewage bacteria found lurking in Hudson River sediments
December 15, 2018 - CDC selects UMass Amherst biostatistician model that helps predict influenza outbreaks
December 15, 2018 - Researchers reveal brain mechanism that drives itch-evoked scratching behavior
December 15, 2018 - New computer model helps predict course of the disease in prostate cancer patients
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