Genetic differences can explain why some patients undergoing heart surgery later experience shock and kidney complications, according to a study by researchers at the Charité – Universitätsmedizin Berlin, the Max-Delbrück-Center for Molecular Medicine (MDC) Berlin-Buch in Germany and the Austin Hospital in Melbourne, Australia. The results indicate that performing a genetic test on patients before they have surgery can help guide treatment after they leave the operating room (Journal of the American Society of Nephrology, JASN, doi 10.1681/ASN.2008080915)*.
The researchers studied the gene that encodes the enzyme catechol-O-methyltransferase (COMT). Certain variants of the COMT gene have long been suspected to play a role in shock and kidney failure in patients following heart surgery. The COMT enzyme is involved in metabolizing norepinephrine (noradrenalin), a drug that is given to patients post-surgery to stimulate their blood flow and to normalize their blood pressure.
Professor Duska Dragun, MD, Charité, Professor Friedrich Luft, MD (Experimental and Clinical Research Center , MDC) and Dr. Wolf-Hagen Schunck (MDC) studied the COMT gene in 260 patients who underwent heart bypass surgery. They were able to show that the genetic variant they call "LL" can lower the activity of the COMT enzyme. As a result, LL patients are more likely to develop shock and kidney failure.
In addition, LL patients who experience shock do not respond very well to treatment with norepinephrine. Since the activity of the COMT enzyme is lowered in LL patients, norepinephrine cannot fully be metabolized. As a result, too much norepinephrine remains in the body and the drug is no longer effective.
Therefore, the researchers suggest that "perhaps, more suitable hemodynamics could be achieved in LL patients were they given vasopressin rather than noradrenaline (norepinephrine) and acute kidney injury might be attenuated by avoidance of cardiopulmonary bypass and nephrotoxic medication." Larger clinical trials are necessary to show whether patients need to undergo genetic testing prior to heart surgery to determine their risk for shock and kidney failure.
Decreased Catecholamine Degradation Associates with Shock and Kidney Injury after Cardiac Surgery
Anja Haase-Fielitz,*† Michael Haase,*† Rinaldo Bellomo,* Gavin Lambert,‡ George Matalanis,§ David Story,§ Laurie Doolan,§ Brian Buxton,§ Geoff Gutteridge,* Friedrich C. Luft,II Wolf-Hagen Schunck,¶ and Duska Dragun†**
*Department of Intensive Care, Austin Health, Melbourne, Australia; †Department of Nephrology and Intensive Care Medicine, Campus Virchow Clinic, Medical Faculty of the Charité, Berlin, Germany; ‡Baker Heart Research Institute, Melbourne, Australia; §Departments of Anaesthesiology and Cardiac Surgery, Austin Health, Melbourne, Australia; _Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and HELIOS Klinikum, Berlin, Germany; ¶Max Delbrück Center for Molecular Medicine, Berlin, Germany; **Center for Cardiovascular Research, Charité, Berlin, Germany
Barbara Bachtler
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Journal
Journal of the American Society of Nephrology