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McMahon, Gearoid

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McMahon

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Gearoid

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McMahon, Gearoid
Author's Publications: search.filters.isAuthorOfPublication.587cfbb5-e12d-4e9c-86f1-8e7f0af95d37

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    Length Polymorphisms in Heme Oxygenase-1 and AKI after Cardiac Surgery
    (American Society of Nephrology (ASN), 2016) Leaf, David; Body, Simon; Muehlschlegel, Jochen; McMahon, Gearoid; Lichtner, P.; Collard, C. D.; Shernan, S. K.; Fox, A. A.; Waikar, Sushrut
    Heme oxygenase-1 (HO-1) catalyzes the degradation of heme, which may be involved in the pathogenesis of AKI. Length polymorphisms in the number of GT dinucleotide repeats in the HO-1 gene (HMOX1) promoter inversely associate with HMOX1 mRNA expression. We analyzed the association between allelic frequencies of GT repeats in the HMOX1 gene promoter and postoperative AKI in 2377 white patients who underwent cardiac surgery with cardiopulmonary bypass. We catego- rized patients as having the short allele (S; ,27 GT repeats) or long allele (L; $27 GT repeats), and defined AKI as an increase in serum creatinine $0.3 mg/dl within 48 hours or $50% within 5 days, or the need for RRT. Compared with patients with the SS genotype, patients with the LL genotype had 1.58-fold (95% confidence interval, 1.06 to 2.34; P=0.02) higher odds of AKI. After adjusting for baseline and operative characteristics, the odds ratio for AKI per L allele was 1.26 (95% confidence interval, 1.05 to 1.50; P=0.01). In conclusion, longer GT repeats in the HMOX1 gene pro- moter associate with increased risk of AKI after cardiac surgery, consistent with heme toxicity as a pathogenic feature of cardiac surgery-associated AKI, and with HO-1 as a potential therapeutic target.
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    Excessive diagnostic testing in acute kidney injury
    (BioMed Central, 2016) Leaf, David; Srivastava, Anand; Zeng, Xiaoxi; McMahon, Gearoid; Croy, Heather E.; Mendu, Mallika; Kachalia, Allen; Waikar, Sushrut
    Background: The patterns, performance characteristics, and yield of diagnostic tests ordered for the evaluation of acute kidney injury (AKI) have not been rigorously evaluated. Methods: We characterized the frequency of AKI diagnostic testing for urine, blood, radiology, and pathology tests in all adult inpatients who were admitted with or developed AKI (N = 4903 patients with 5731 AKI episodes) during a single calendar year. We assessed the frequency of abnormal test results overall and by AKI stage. We manually reviewed electronic medical records to evaluate the diagnostic yield of selected urine, blood, and radiology tests. Diagnostic yield of urine and blood tests was determined based on whether an abnormal test affected AKI diagnosis or management, whereas diagnostic yield of radiology tests was based on whether an abnormal test resulted in a procedural intervention. In sensitivity analyses we also evaluated appropriateness of testing using prespecified criteria. Results: Frequency of testing increased with higher AKI stage for nearly all diagnostic tests, whereas frequency of detecting an abnormal result increased for some, but not all, tests. Frequency of detecting an abnormal result was highly variable across tests, ranging from 0 % for anti-glomerular basement membrane testing to 71 % for urine protein testing. Many of the tests evaluated had low diagnostic yield. In particular, selected urine and blood tests were unlikely to impact AKI diagnosis or management, whereas radiology tests had greater clinical utility. Conclusions: In patients with AKI, many of the diagnostic tests performed, even when positive or abnormal, may have limited clinical utility.
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    The association between vitamin B12, albuminuria and reduced kidney function: an observational cohort study
    (BioMed Central, 2015) McMahon, Gearoid; Hwang, Shih-Jen; Tanner, Rikki M; Jacques, Paul F; Selhub, Jacob; Muntner, Paul; Fox, Caroline
    Background: Variants in CUBN, the gene encoding cubilin, a proximal tubular transport protein, have been associated with albuminuria and vitamin B12 (B12) deficiency. We hypothesized that low levels of B12 would be associated with albuminuria in a population-based cohort. Methods: We analyzed participants from the Framingham Heart Study (n = 2965, mean age 58 years, 53% female) who provided samples for plasma B12. Logistic regression models adjusted for covariates including homocysteine were constructed to test the association between B12 and prevalent albuminuria (UACR ≥17 mg/g [men] and ≥25 mg/g [women]) and reduced kidney function (defined as an eGFR < 60 ml/min/1.73 m2, RKF). Because of a significant interaction between B12 and homocysteine in the prevalent RKF model (p = 0.005), the model was stratified by the median homocysteine levels. Logistic regression models were constructed to test the association between B12 and incident albuminuria and RKF. The results were replicated in 4445 participants from NHANES 2003–2004. Results: Baseline B12 levels ranged from 50-1690 pg/ml. Elevated B12 was associated with prevalent albuminuria (OR 1.44 per 1 SD increase, 95% CI 1.10-1.87) and RKF (OR 1.83, 95% CI 1.30-2.60). However after stratifying by median homocysteine levels, this relationship remained only in the higher homocysteine stratum. There was no association between B12 and incident albuminuria (OR 1.17, 95% CI 0.79 – 1.73) or RKF (OR 1.45, 95% CI 0.97 – 1.88). In the NHANES cohort, elevated B12 was associated with RKF after full covariate adjustment (OR 3.06, 95% CI 2.30-4.08). There was no association with albuminuria. Conclusion: In participants with high baseline homocysteine levels, increased plasma B12 was associated with RKF.
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    Needle Size and the Risk of Kidney Biopsy Bleeding Complications
    (Elsevier, 2016) Cui, Salena; Heller, Howard T.; Waikar, Sushrut; McMahon, Gearoid