Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Organ transplant recipients face serious kidney-failure risk, study finds

04.09.2003


Anti-rejection drugs and pre-transplant health problems both play a role



As if the ordeal of waiting for, receiving and living with an organ transplant weren’t enough, a new study finds that people who get a second chance at life from new hearts, lungs, livers or intestines are very likely to have their lives cut short by failing kidneys.

In fact, 16.5 percent of all non-kidney transplant recipients develop chronic kidney failure, and almost a third of those patients go on to develop full-blown end-stage renal disease, according to new data published in the New England Journal of Medicine by researchers from the University of Michigan Health System.


And those whose kidneys begin to fail after their transplant face a much larger risk of dying than those whose kidneys stay healthy, the study finds. Only a second transplant -- to put in a new kidney -- mitigates the fatal consequences of ESRD.

The researchers weren’t able to pinpoint the exact causes of the kidney failure seen in the study of 69,321 people who received transplants of any solid organ except kidney or pancreas between 1990 and 2000. But in the largest-ever study of its kind, they identified several factors that put patients at a higher risk of kidney failure and death: older age; being a woman; pre-transplant hepatitis C infection, high blood pressure or diabetes; and kidney problems before or immediately after transplant.

They also know that some kidney damage is caused by the very drugs that all transplant recipients take to prevent their bodies from rejecting their new organs.

"Every doctor involved in transplant sees these patients come through clinic, but there has never been a detailed attempt to quantify the issue," says Akinlolu Ojo, M.D., Ph.D., the associate professor of nephrology at the U-M Medical School who led the study. "We can see now how large the problem is, what the risk factors are, and what the implications and costs might be for the dialysis and transplant systems. We can also see that damage caused by anti-rejection drugs is one of the reasons for this effect, but not the only reason."

In the lead editorial that accompanies the paper, two Harvard University transplant experts call the findings "cause for concern." The U-M team and editorialists both say the results have implications for counseling given to patients awaiting a transplant, the design of less-damaging anti-rejection treatment regimens, and the decision of when to place transplant recipients with failing kidneys on the kidney transplant list.

The results that Ojo and his colleagues report in the new paper come from a cross-analysis of data contained in three national databases.

The researchers relied heavily on the detailed medical information about all American solid-organ transplant recipients contained in the Scientific Registry of Transplant Recipients. The SRTR is administered on behalf of the U.S. government by the University Renal Research and Education Association, a not-for-profit health research foundation, in collaboration with the U-M. The SRTR is run with oversight and funding from the Health Resources and Services Administration, a division of the U.S. Department of Health and Human Services.

"We compiled SRTR data on all the patients who had never received a kidney or pancreas transplant before they received their heart, lung, liver, intestine or combination heart-lung transplant," says senior author Robert Merion, M.D., a transplant surgeon and professor of surgery at the U-M. "These data allowed us to calculate a measure of kidney function, called glomerular filtration rate, that indicates kidney failure of varying degrees in a standard way." A small number of patients who had combination heart-liver, liver-kidney or heart-kidney transplants were excluded.

The team then cross-referenced those patients with the federal Centers for Medicare and Medicaid Services list of all those who received treatment for end-stage renal disease during the same time period. Treatment could include dialysis or kidney transplant. They also searched the Social Security Administration’s list of deaths, so that they had complete information on which transplant recipients had died for any reason during the study period, which ended in 2001.

Besides the overall incidence of kidney failure, which increased steadily as time went on and led to an escalating rate of ESRD and a 4.5-times-greater overall death risk, the researchers found many other trends that may be significant for pre-and post-transplant treatment.

For example, the risk of developing chronic kidney failure varied greatly depending on the type of organ received. Only 6.8 percent of heart transplant patients had developed kidney failure by the third anniversary of their transplant, as compared with 10 percent of lung recipients, 13.9 percent of liver recipients and 14.2 percent of intestine recipients. By the fifth year, nearly 11 percent of heart recipients had failing kidneys, as opposed to nearly 15 percent of lung recipients, 18 percent of liver recipients and 21.3 percent of intestine recipients.

The researchers were able to obtain data on use of anti-rejection drugs in the immediate post-transplant period for nearly all the patients in the study. Because almost all transplant recipients in the 1990s took one of three such drugs -- cyclosporine, tacrolimus or sirolimus -- it was impossible to tell exactly how much they may have contributed to an individual’s kidney failure.

The only statistically significant finding related to anti-rejection drugs was that the excess risk of developing chronic kidney failure was greater among liver transplant recipients who took cyclosporine than among those who took tacrolimus. Sirolimus was introduced toward the end of the study period; only 1 percent of patients in the study took it, so comparisons with other drugs did not produce statistically significant findings.

Both the researchers and the editorialists call for further studies of the outcomes for patients taking these three drugs, and newer regimens with less-toxic medications.

The findings regarding kidney transplant for patients whose kidneys entered end-stage failure were interesting, says Ojo, who treats many kidney transplant candidates and recipients.

"For years, we had been finding that non-kidney transplant patients had been coming back to clinic in need of dialysis or a kidney transplant," he notes. "These data show that each year, one percent of all the transplant patients who had chronic kidney failure progressed to end-stage renal disease, and that those patients who received a kidney transplant soon after this progression had a lower overall death risk than those who received dialysis."

However, Ojo and his colleagues say, the ongoing shortage of kidneys from living and deceased donors already means that many kidney transplant candidates do not get an organ in time. The same is bound to be true for many non-kidney transplant recipients who find themselves needing a new kidney.

And, the cost of dialysis and transplants for these second-time-around transplant candidates could add millions to the already costly Medicare system that insures kidney failure patients. Already, the nation’s 300,000 ESRD patients make up only 0.8 percent of Medicare recipients, but account for 6 percent of all Medicare costs -- more than $13 billion annually.

In all, the researchers call for better counseling of non-kidney transplant candidates, to make sure they understand the risk that among other complications, their kidneys may fail as a result of their life-saving transplant. They also call for better understanding of the co-existing risk factors -- especially diabetes, hypertension and hepatitis C infection -- that might influence an individual’s risk of developing kidney failure after a transplant. And, they say that transplant teams should do more to prevent kidney-harming complications during and immediately after surgery to give a patient a new heart, liver, lung or intestine.

In addition to Ojo and Merion, the study’s authors include U-M nephrologists Alan Leichtman, M.D. and Eric Young, M.D., M.S.; emeritus U-M nephrology professor and current URREA president Friedrich K. Port, M.D., M.S.; URREA founder and former U-M professor Philip J. Held; U-M School of Public Health professor Robert A. Wolfe, Ph.D.; and research associates Julie Arndorfer, M.P.H. and Laura Christensen, M.S.



Chronic Renal Failure after Transplantation of a Nonrenal Organ
Ojo, A. et al
New England Journal of Medicine, Vol 349, No. 10, pp 931-940.

The Growing Problem of Chronic Renal Failure after Transplantation of a Nonrenal Organ
Colm Magee, M.D., M.P.H, and Manuel Pascual, M.D.
New England Journal of Medicine, Vol 349, No. 10, pp 994-996.

Kara Gavin | EurekAlert!
Further information:
http://www.med.umich.edu/1toolbar/whatsnew.htm

More articles from Health and Medicine:

nachricht Inselspital: Fewer CT scans needed after cerebral bleeding
20.03.2019 | Universitätsspital Bern

nachricht Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Solving the efficiency of Gram-negative bacteria

22.03.2019 | Life Sciences

Bacteria bide their time when antibiotics attack

22.03.2019 | Life Sciences

Open source software helps researchers extract key insights from huge sensor datasets

22.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>