Genetic study predicts optimal use of “Tacrolimus” for kidney transplant patients

They studied the effect of genes and their variants involved in determining drug concentrations in the blood of patients.

Thiruvananthapuram: In a groundbreaking genetic study that could dramatically reduce the risk of organ rejection and other medical complications, scientists at the Rajiv Gandhi Center for Biotechnology (RGCB) have formulated here a method to predict the optimal dose of an immunosuppressive drug administered to a kidney transplant. the patients.

The dose prediction study focused on the immunosuppressive drug tacrolimus, which is given to a kidney, heart, or liver transplant patient to lower the body’s immunity and thereby significantly reduce the chance of rejection. organ.

For maximum effectiveness, the level of the drug should be maintained at an optimal concentration in the blood, especially during the initial period after transplantation.

Radhakrishnan Nair and ALekshmy Srinivas of the Division of Laboratory Medicine and Molecular Diagnostics, RGCB, conducted the pharmacogenetic study involving patients who underwent kidney transplantation at Government Medical College, Thiruvananthapuram, and those who received tacrolimus as an immunosuppressant .

They studied the effect of genes and their variants involved in determining drug concentrations in the blood of patients.

“We have developed an equation / technique that can be used by nephrologists to predict the initial dose of tacrolimus, which must be given to patients to achieve an optimal level of drug in the initial period after surgery, based on their profiles. genetic, ”said Nair.

This variation, along with their body weight, can be used to calculate the optimal starting drug dose for the patient. It will help patients achieve optimal Tacrolimus levels after transplantation and thus prevent unwanted effects due to overdose and rejection.

Currently, the dose is calculated based on the patient’s body weight. This approach can cause many variations in drug levels.

“This equation is specific to Kerala patients who are undergoing kidney transplantation. The molecular method uses the testing of patients’ DNA for specific variation, before transplant surgery,” said Lekshmy Srinivas.

To achieve this, blood levels must be closely monitored and drug doses adjusted, as lower levels can lead to rejection of the transplanted kidney, while higher levels can lead to unwanted medical complications. Not only is this trial and error method of dose adjustment time consuming and expensive, it also leads to many complications in patients.

“Although there have been similar studies in other populations before, the predictive value of the pharmacogenetic factors identified was insufficient and little used clinically. The new development would help prevent the adverse effects of overdose and thus help to many patients, ”said Chandrabhas Narayana, director, RGCB.

The pioneering study was conducted in collaboration with Noble Gracious from the Department of Nephrology, Government Medical College, Thiruvananthapuram.

The group also discovered genetic variants that increase the chances of rejection and side effects associated with the drug.

The research, which has the potential to significantly save the lives of kidney transplant patients, was jointly funded by the Scientific and Technical Research Council (SERB) and the RGCB.

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