Browsing by Subject "nephrotoxicity"

Now showing 1 - 3 of 3
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    Evidence-based development of a nephrotoxic medication list to screen for acute kidney injury risk in hospitalized children
    (Oxford, 2019-10-30) Goswami, Elizabeth; Ogden, Richard K.; Bennett, William E, Jr.; Goldstein, Stuart L; Hackbarth, Richard; Somers, Michael J G; Yonekawa, Karyn; Misurac, Jason; Pediatrics, School of Medicine
    Purpose Medications are commonly associated with acute kidney injury (AKI). However, in both clinical practice and research, consideration of specific medications as nephrotoxic varies widely. The Nephrotoxic Injury Negated by Just-in-time Action quality improvement collaborative was formed to focus on prevention or reduction of nephrotoxic medication-associated AKI in noncritically ill hospitalized children. However, there were discrepancies among institutions as to which medications should be considered nephrotoxic. The collaborative convened a Nephrotoxic Medication (NTMx) Subcommittee to develop a consensus for the classification of nephrotoxic medications. Summary The NTMx Subcommittee initially included pediatric nephrologists, a pharmacist, and a pediatric intensivist. The committee reviewed NTMx lists from the collaborative and identified changes from the initial NTMx list. The NTMx Subcommittee conducted a literature review of the disputed medications and assigned an evidence grade based on the reported association with nephrotoxicity and the quality of the data. The association between medication exposure and AKI was also determined using administrative data from the Pediatric Health Information Systems database. The NTMx Subcommittee then came to a majority consensus regarding which medications should be included on the list. The subcommittee’s recommendations were presented to the larger collaborative for approval, and consensus was achieved. The list continues to be reviewed and updated annually. Conclusion Formation of a multicenter quality-improvement initiative exposed current limitations as to which medications are considered nephrotoxic in clinical and research settings and presented an opportunity to approach this problem using an evidence-based process. A consensus definition of nephrotoxic-medication exposure was achieved.
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    Genetic Variants Contributing to Colistin Cytotoxicity: Identification of TGIF1 and HOXD10 Using a Population Genomics Approach
    (MDPI, 2017-03-18) Eadon, Michael T.; Hause, Ronald J.; Stark, Amy L.; Cheng, Ying-Hua; Wheeler, Heather E.; Burgess, Kimberly S.; Benson, Eric A.; Cunningham, Patrick N.; Bacallao, Robert L.; Dagher, Pierre C.; Skaar, Todd C.; Dolan, M. Eileen; Medicine, School of Medicine
    Colistin sulfate (polymixin E) is an antibiotic prescribed with increasing frequency for severe Gram-negative bacterial infections. As nephrotoxicity is a common side effect, the discovery of pharmacogenomic markers associated with toxicity would benefit the utility of this drug. Our objective was to identify genetic markers of colistin cytotoxicity that were also associated with expression of key proteins using an unbiased, whole genome approach and further evaluate the functional significance in renal cell lines. To this end, we employed International HapMap lymphoblastoid cell lines (LCLs) of Yoruban ancestry with known genetic information to perform a genome-wide association study (GWAS) with cellular sensitivity to colistin. Further association studies revealed that single nucleotide polymorphisms (SNPs) associated with gene expression and protein expression were significantly enriched in SNPs associated with cytotoxicity (p ≤ 0.001 for gene and p = 0.015 for protein expression). The most highly associated SNP, chr18:3417240 (p = 6.49 × 10−8), was nominally a cis-expression quantitative trait locus (eQTL) of the gene TGIF1 (transforming growth factor β (TGFβ)-induced factor-1; p = 0.021) and was associated with expression of the protein HOXD10 (homeobox protein D10; p = 7.17 × 10−5). To demonstrate functional relevance in a murine colistin nephrotoxicity model, HOXD10 immunohistochemistry revealed upregulated protein expression independent of mRNA expression in response to colistin administration. Knockdown of TGIF1 resulted in decreased protein expression of HOXD10 and increased resistance to colistin cytotoxicity. Furthermore, knockdown of HOXD10 in renal cells also resulted in increased resistance to colistin cytotoxicity, supporting the physiological relevance of the initial genomic associations.
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    Vancomycin-Associated Acute Kidney Injury in Critically Ill Adolescent and Young Adult Patients
    (Sage, 2019) Hays, William Blake; Tillman, Emma; Medicine, School of Medicine
    Background: Risk factors for the development of vancomycin-associated acute kidney injury (AKI) have been evaluated in both pediatric and adult populations; however, no previous studies exist evaluating this in the critically ill adolescent and young adult patients. Objective: Identify the incidence of AKI and examine risk factors for the development of AKI in critically ill adolescents and young adults on vancomycin. Methods: This retrospective review evaluated the incidence of AKI in patients 15 to 25 years of age who received vancomycin, while admitted to an intensive care unit. Acute kidney injury in this population was defined as an increase in serum creatinine by 0.5 mg/dL or 50% from baseline. Patients who developed AKI were evaluated for specific risk factors compared to those who did not develop AKI. Results: A total of 50 patients (20 developed AKI) were included in the study. There was no difference in vancomycin daily dose or duration of vancomycin therapy. Maximum vancomycin trough (31.15 mg/dL vs 12.5 mg/dL, P = .006), percentage of patients with concurrent nephrotoxic medication (95% vs 60%, P = .012) and concurrent vasopressor (55% vs 23%, P = .029) were higher in those who developed AKI. Percentage of patients who underwent a procedure while on vancomycin (35% vs 6.7%, P = .021) was also higher within the AKI group. Conclusions: Vancomycin-associated AKI occurred in 40% of critically ill adolescent and young adult patients. These patients may be more likely to develop vancomycin-associated AKI if they had undergone a procedure, as well as in the presence of high vancomycin trough levels, concurrent nephrotoxic agents, and concurrent vasopressor therapy.