Single gene variant in donors may affect survival of transplanted kidneys

ScienceDaily (Oct. 11, 2012) — A single genetic variant in kidney donors' cells may help determine whether their transplanted organs will survive long term, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings provide new information that might be used to improve transplant longevity by revealing that the genetic make-up of kidney transplant donors affects the survival of transplanted organs.
A transplant recipient must take lifelong immunosuppressive drugs to prevent rejection of the new organ, but these drugs can have serious side effects, including kidney damage. So, ironically, the very drugs needed to prevent kidney rejection can also be toxic to the kidneys. Research suggests that how well certain proteins pump these drugs out of kidney cells may influence the drugs' kidney toxicity.
Richard Borrows, MB (Queen Elizabeth Hospital Birmingham, in the UK) and his colleagues looked to see if variants in the genes that encode such pumps might influence the health of transplanted kidneys. They investigated the links between donor and recipient gene variants with kidney outcome among 811 immunosuppressant-treated kidney transplant recipients.
Among the major findings:
One particular variant within the multidrug resistance 1 (MDR-1) gene in donors was linked to a 69% increased risk for long-term failure of transplanted organs.The researchers validated the link in another 3,660 donors, making this the largest study of its kind.This variant affects the expression of the protein that the MDR-1 gene encodes, the drug transporter P-glycoprotein.No other genetic variants in donors or recipients were linked with organ survival or failure.
"The study of donor, as opposed to recipient, gene variation is relatively uncommon in the field of transplantation, and it certainly warrants more attention," said Dr. Borrows. He added that a single genetic variant probably has limited effect on its own, but when combined, multiple genetic variants may play an important role in transplant longevity.
Study co-authors include Jason Moore, MBBS, Amy Jayne McKnight, PhD, Bernd Döhler, PhD, Matthew Simmonds, PhD, Aisling Courtney, PhD, Oliver Brand, PhD, David Briggs, PhD, Simon Ball, PhD, Paul Cockwell, PhD, Christopher Patterson, PhD, Alexander Maxwell, PhD, Stephen Gough, PhD, and Gerhard Opelz, PhD.
Share this story on Facebook, Twitter, and Google:
Other social bookmarking and sharing tools:
Story Source:

The above story is reprinted from materials provided by American Society of Nephrology (ASN), via Newswise.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:
Richard Borrows et al. Donor ABCB1 Variant Associates with Increased Risk for Kidney Allograft Failure. Journal of the American Society of Nephrology, 2012; DOI: 10.1681/ASN.2012030260
Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Read more »

Tissue-engineered kidneys: Researchers make important strides

ScienceDaily (Oct. 18, 2012) — With a worldwide shortage of kidneys for patients who need kidney transplants, researchers are diligently working to find ways to engineer new kidney tissue from a patient's own cells or another source. They've come a step closer to realizing that goal with a breakthrough described in an upcoming Journal of the American Society of Nephrology (JASN) study. The advance could lead to more options for individuals with kidney failure, as well as better tools for understanding kidney diseases and how to treat them.

Investigators can produce tissues similar to immature kidneys from simple suspensions of embryonic kidney cells, but they have been unsuccessful at growing more mature kidney tissues in the lab because the kidneys' complicated filtering units do not form without the support of blood vessels.

Now, from suspensions of single kidney cells, Christodoulos Xinaris PhD (Mario Negri Institute for Pharmacological Research) and his colleagues have for the first time constructed "organoids" that can be integrated into a living animal and carry out kidney functions including blood filtering and molecule reabsorption. Key to their success was soaking the organoids in a solution containing molecules that promote blood vessel formation, then injecting these molecules into the recipient animals after the organoids were implanted below the kidneys. The organoids continued to mature and were viable for three to four weeks after implantation.

"The ability to build functional renal tissue starting from suspensions of single cells represents a considerable step toward the practical goal of engineering renal tissues suitable for transplantation and offers the methodological basis for a number of investigative and therapeutic applications," said Dr. Xinaris. For example, disease-related genes could be introduced into an organoid to help researchers study the mechanisms of complex kidney diseases and to perform a preliminary screening of new drugs to treat them.

Study co-authors include Valentina Benedetti, BiolSciD, Paola Rizzo, BiolSciD, Mauro Abbate, MD, Daniela Corna, Nadia Azzolini, Sara Conti, BSc, Mathieu Unbekand, PhD, Jamie A. Davies, PhD, Marina Morigi PhD, Ariela Benigni, PhD, and Giuseppe Remuzzi, MD.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by American Society of Nephrology (ASN), via Newswise.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Christodoulos Xinaris, Valentina Benedetti, Paola Rizzo, Mauro Abbate, Daniela Corna, Nadia Azzollini, Sara Conti, Mathieu Unbekandt, Jamie A. Davies, Marina Morigi, Ariela Benigni, and Giuseppe Remuzzi. In Vivo Maturation of Functional Renal Organoids Formed from Embryonic Cell Suspensions. Journal of the American Society of Nephrology, 2012; DOI: 10.1681/ASN.2012050505

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Read more »