From Science Daily
Advanced computer simulations show that failures of cell adhesion and inhibition cause two types of kidney cyst formation
Credit: Indiana University
Using virtual tissue technology, researchers at Indiana University have identified a potential new drug target in the fight against polycystic kidney disease, an illness with no effective FDA-approved treatment that affects 200,000 people per year in the United States.
The study appears in the journal Molecular Biology of the Cell. It reveals that errors in how cells stick together give rise to two forms of kidney cysts.
These cysts can cause an adult kidney -- normally about the size of a fist and weighing less than a pound -- to grow to the size of a football that weights 20 to 30 pounds. Currently, only dialysis or a kidney transplant can delay death from the disease.
"This is the first study to show the actual cell behaviors caused by mutations in genes causally linked to polycystic kidney disease, an important new step in the path towards treatment," said Dr. Robert L. Bacallao, associate professor of medicine at the IU School of Medicine in Indianapolis.
The technology used in the study was developed by the Biocomplexity Institute at the IU School of Informatics and Computing, directed by James A. Glazier, professor in the IU Bloomington Department of Intelligent Systems Engineering. Julio Belmonte and Sherry G. Clendenon of the Biocomplexity Institute are the primary authors on the paper.
"Not many medical researchers are employing virtual tissue technology," Glazier said. "The majority of researchers who use these simulations are pursuing basic science. So it's extremely exciting to apply the technology to research directed at identifying drug targets to help people suffering from a specific disease."
To conduct the study, Glazier's team took data from Bacallao's medical research to develop a virtual nephron -- the core, tube-shaped functional unit of the kidney -- using an open-source software program. Called CompuCell3D, the program was developed by Maciej Swat of the Biocomplexity Institute, who is also a co-author on the paper. The computer model simulated cell activity triggered by mutations in PKD1 and PKD2, the genes implicated in polycystic kidney disease. [Read more]
From News Wise, University of Maryland
Baltimore, Md. – June 27, 2016 – In a first-of-its-kind procedure in the United States, a patient was able to avoid dialysis when surgeons simultaneously removed two diseased kidneys and also transplanted a kidney from a living donor – all as part of a 28-person paired kidney exchange (PKE). The procedure, performed in May on a patient with polycystic kidney disease (PKD), eliminated the need for the patient to ever undergo dialysis.
“We worked closely with the National Kidney Registry, which coordinated the 28-person swap that led to a compatible living donor for our patient,” says David B. Leeser, MD, associate professor of surgery at the University of Maryland School of Medicine (UM SOM) and chief of kidney and pancreas transplant at the University of Maryland Medical Center (UMMC), who developed the plan. “On the day of the transplant, we removed our patient’s two large kidneys, weighing 10 pounds each, precisely timing our procedure with the hospital that was providing the donor kidney, so our patient was able to avoid dialysis.”
The recipient’s wife was unable to donate a kidney to her husband, due to incompatible blood types. Because kidneys from living donors have better outcomes than those from deceased donors, a kidney swap was the only option for him to get a living donor kidney. As part of the PKE, the patient’s wife donated a kidney to another patient, continuing the chain.
“The success of the procedure was even more dramatic because the UMMC pair was the key to fast-track repair for this swap that involved 28 surgeries over a three-week window,” says Garet Hil, CEO of the National Kidney Registry (NKR). “These kinds of bold and complex breakthroughs are what we have come to expect from NKR member centers that are always looking to find new ways to improve the lives of patients suffering from kidney failure.”
Leeser explained that University of Maryland surgeons routinely remove both polycystic kidneys during a transplant, with one team working in one operating room, and another team in an adjacent OR to procure the donor organ. While another center had combined PKD removal with a PKE swap for a patient who was already on dialysis, this procedure was especially complex due to the need for precise timing in the absence of dialysis. [Read more]
The bioengineered blood of Humacyte, called Humacyl, has the potential to eliminate surgeries to resectioning the existing blood vessels of a patient for procedures such as coronary artery bypass. Humacyte
Halfway through 2016, several medical breakthroughs have been made by startups and established research establishments expected to have a major impact on medicine in the coming years. Leading the list is Humacyte’s engineered blood vessels.
The North Carolina-based startup grows human tissues in labs which could be implanted safely in the body. Designed for kidney dialysis patients, Humacyte uses donor cells to grow human tissue needed to make the blood vessels, reports The Wall Street Journal.
The patients’ immune system does not reject the blood vessels since Humacyte cleanses the donor cells prior to implantation. When the bioengineered blood vessels are merged with natural cells, the patient is less prone to infection and more durable compared to metal tubes usually used to facilitate blood flow during dialysis, according to two mid-stage studies by Humacyte, published in the Lancet journal in May.
Making blood vessels is a step forward in bioengineering functioning human tissues which regenerates similar to natural tissue, says Laura Niklason, co-founder of Humacyte and anaesthesiologist and scientist at Yale University. She adds engineered blood vessels are still a far cry from engineered whole organs which could be about 20 years away.
Humacyte is just one of the institutions involved in tissue engineering. At Harvard University, Jennifer Lewis uses a 3-D bioprinter to layer a mix of cells in the form of blood vessels. Mesoblast in Australia is developing tissues grown in the lab made from stem cells for use to repair organs or form new blood vessels. Another startup, Organovo in San Diego, uses also 3-D printing to make kidneys and livers for transplant, reports Statnews.
The bioengineered blood vessel of Humacyte, called Humacyl, is waiting for approval by the US Food and Drug Administration. The product has the potential to eliminate surgeries to resectioning the existing blood vessels of a patient for procedures such as coronary artery bypass by the use of Humacyl instead, reports CNBC. [Read more]
Nephrocalcinosis can be associated with renal stones, however, it is more likely to be due to an underlying metabolic disorder. It may be divided into three categories although there is a substantial degree of overlap between them.
These categories are chemical, microscopic, and macroscopic nephrocalcinosis. It can also be differentiated into medullar and cortical nephrocalcinosis.
In chemical nephrocalcinosis, there is predominantly an increase of calcium in renal cells. This increase is seen particularly in the tubular epithelium and results in significant compromise to renal function and structure, leading to increased water, potassium, sodium, magnesium, and calcium excretion.
Microscopic nephrocalcinosis is only seen with a magnifying instrument and presents with calcium precipitates in crystalline form as phosphate and/or oxalate. Macroscopic nephrocalcinosis presents with large areas of calcifications that do not require magnifying in order to be seen.
The most frequent form of nephrocalcinosis is medullary nephrocalcinosis. It is characterized by the involvement of the renal medullary pyramids. Moreover, it usually is associated with dysregulation of calcium homeostasis (balance or equilibrium).
Cortical nephrocalcinosis is a much rarer form of nephrocalcinosis and it typically involves the entire renal parenchyma. Serious metabolic derangements like end-stage kidney disease, hyperoxaluria (excess oxalate excretion in the urine), hemolytic uremic syndrome, and polycystic kidney disease are frequently implicated in cortical nephrocalcinosis. [Read more]
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