Precise low-dose drug monitoring essential for long-term kidney
6 August 2008
The ability of blood tests to precisely measure very low doses of
anti-rejection drugs in kidney transplant patients may make a
significant difference in assuring long-term viability and survival,
according to research presented at the American Association for Clinical
Chemistry (AACC) annual meeting last week.
The current thinking in transplant medicine favours reducing doses of
tacrolimus and other immune-suppressive drugs as much as possible after
kidney-transplant procedures. "Even though we are succeeding in
preventing organ rejection, we haven’t made much progress to improve
long-term survival," said Sudarshan Hebbar, MD, senior medical director,
"Unfortunately, most kidney transplant patients will go back on
dialysis in eight to ten years, in part because the anti-rejection drugs
can be toxic to the kidneys."
Dr Hebbar added that kidney-transplant patients have high incidence
of heart attacks and other cardiovascular disorders from long-term
effects of renal disease. Therefore, minimizing drug toxicity over time
is considered one way to help improve long-term graft survival and
preserve quality of life for transplant patients.
To minimize long-term toxicity of transplant medications, physicians
frequently aim to taper down doses of immunosuppressive drugs to as low
a level as possible without risking rejection. "Successful low-dose
regimens of tacrolimus and other anti-rejection medications require
highly precise, ultra-sensitive drug-monitoring assays," said Daniel
Levine, PhD, director of the clinical laboratory, Iris and B Gerald
Cantor Clinical Research Laboratory at The Rogosin Institute in New York
Dr Levine emphasized the importance of using an accurate and precise
test to monitor patients on low-dose treatment regimens. "At low doses,
even the slightest variation in blood-level readings could be
devastating to transplant patients. The consequence for the laboratory
is twofold: it must have accurate, precise testing for immunosuppressive
drugs, and tacrolimus tests that are accurate to 4 ng/mL are no longer
adequate," he explained.
Dr Levine reported results of his studies evaluating the performance
of the Abbott Architect assay for tacrolimus, the most widely used
immunosuppressant drug. He said the usual dosing range for the
medication is between 2 and 15 ng/mL, with lower doses preferred. "The
challenge for the laboratory, therefore, is to assure with the utmost
confidence to the physician that a tacrolimus blood level of 3 ng/mL is
exactly right and not 5," Levine said.
In the trials, the Abbott Architect tacrolimus assay was accurate and
precise at low levels and showed consistent results. "The functional
sensitivity in our hands was 0.9 ng/mL, exceeding the package insert
claim of 2 ng/mL. We are fully confident the Architect tacrolimus assay
meets our requirement for low-level tacrolimus monitoring," Levine said.
"The Architect tacrolimus assay is the only automated transplant
monitoring test that meets international standards for low-level
monitoring," according to Dr Hebbar.
The Architect tacrolimus assay is used for the quantitative
determination of tacrolimus in human whole blood, as an aid in managing
liver and kidney transplant patients receiving tacrolimus therapy.