Genetic Variant Highly Associated with Kidney Injury After Cardiac Surgery Interview with:
David E. Leaf, MD, MMSc, FASN
Instructor in Medicine, Harvard Medical School
Associate Physician, Renal Division, Brigham and Women’s Hospital What is the background for this study? What are the main findings?

Dr. Leaf: Heme oxygenase-1 (HO-1), the rate-limiting enzyme in the degradation of heme, has a central role in the pathophysiology of acute kidney injury (AKI) in animal models, but data on HO-1 in human AKI are sparse. Genetic polymorphisms in the number of guanosine thymidine dinucleotide [(GT)n] repeats in the promoter of the HO-1 gene are inversely associated with HO-1 expression, and longer (GT)n repeats are associated with increased cardiovascular events and mortality in a variety of clinical settings. However, no study has evaluated the association between number of (GT)n repeats and risk of AKI in a large cohort of patients. We analyzed the allelic frequencies of (GT)n repeats in the HO-1 gene promoter in 2377 Caucasian patients who underwent cardiopulmonary bypass surgery to evaluate their association with AKI. We categorized patients as having the short (S) or long (L) allele if they had. What should readers take away from your report?

Dr. Leaf: Heme oxygenase-1 (HO-1) is an important enzyme in iron homeostasis. Deficiency of HO-1 has been implicated in acute kidney injury (AKI) in numerous animal models, but data on HO-1 in human AKI are limited. We found that a common genetic variant in the HO-1 gene, which is present in approximately 40% of Caucasian individuals, is highly associated with development of AKI following cardiac surgery. What recommendations do you have for future research as a result of this study?

Dr. Leaf: Future studies are needed to confirm these findings in other AKI settings. Additionally, future studies should test whether interventions aimed at upregulating HO-1 might be an effective strategy for preventing AKI.


Length Polymorphisms in Heme Oxygenase-1 and AKI after Cardiac Surgery
Dr. David E. Leaf, et al
JASN June 2, 2016ASN.2016010038

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