Genetic predisposition and high exposure to colistin in the early treatment period as independent risk factors for colistin-induced nephrotoxicity
© 2024 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics..
Colistin is known to cause nephrotoxicity due to its extensive reabsorption and accumulation in renal tubules. In vitro studies have identified the functional role of colistin transporters such as OCTN2, PEPT2, megalin, and P-glycoprotein. However, the role of these transporter gene variants in colistin-induced nephrotoxicity has not been studied. Utilizing targeted next-generation sequencing, we screened for genetic polymorphisms covering the colistin transporters (SLC15A1, SLC15A2, SLC22A5, LRP2, and ABCB1) in 42 critically ill patients who received colistimethate sodium. The genetic variants rs2257212 ((NM_021082.4):c.1048C>G) and rs13397109 ((NM_004525.3):C.7626C > T) were identified as being associated with an increased incidence of acute kidney injury (AKI) on Day 7. Colistin area under the curve (AUC) was predicted using a previously published pharmacokinetic model of colistin. Using logistic regression analysis, the predicted 24-h AUC of colistin was identified as an important contributor for increased odds of AKI on Day 7. Among 42 patients, 4 (9.5%) were identified as having high predisposition to colistin-induced AKI based on the presence of predisposing genetic variants. Determination of the presence of the abovementioned genetic variants and early therapeutic drug monitoring may reduce or prevent colistin-induced nephrotoxicity and facilitate dose optimization of colistimethate sodium.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Clinical and translational science - 17(2024), 3 vom: 12. März, Seite e13764 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mathew, Sumith K [VerfasserIn] |
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| Links: |
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| Themen: |
Anti-Bacterial Agents |
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| Anmerkungen: |
Date Completed 14.03.2024 Date Revised 17.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1111/cts.13764 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM369658108 |
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| 245 | 1 | 0 | |a Genetic predisposition and high exposure to colistin in the early treatment period as independent risk factors for colistin-induced nephrotoxicity |
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| 520 | |a Colistin is known to cause nephrotoxicity due to its extensive reabsorption and accumulation in renal tubules. In vitro studies have identified the functional role of colistin transporters such as OCTN2, PEPT2, megalin, and P-glycoprotein. However, the role of these transporter gene variants in colistin-induced nephrotoxicity has not been studied. Utilizing targeted next-generation sequencing, we screened for genetic polymorphisms covering the colistin transporters (SLC15A1, SLC15A2, SLC22A5, LRP2, and ABCB1) in 42 critically ill patients who received colistimethate sodium. The genetic variants rs2257212 ((NM_021082.4):c.1048C>G) and rs13397109 ((NM_004525.3):C.7626C > T) were identified as being associated with an increased incidence of acute kidney injury (AKI) on Day 7. Colistin area under the curve (AUC) was predicted using a previously published pharmacokinetic model of colistin. Using logistic regression analysis, the predicted 24-h AUC of colistin was identified as an important contributor for increased odds of AKI on Day 7. Among 42 patients, 4 (9.5%) were identified as having high predisposition to colistin-induced AKI based on the presence of predisposing genetic variants. Determination of the presence of the abovementioned genetic variants and early therapeutic drug monitoring may reduce or prevent colistin-induced nephrotoxicity and facilitate dose optimization of colistimethate sodium | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Chapla, Aaron |e verfasserin |4 aut | |
| 700 | 1 | |a Venkatesan, Padmanaban |e verfasserin |4 aut | |
| 700 | 1 | |a Eriyat, Vishnu |e verfasserin |4 aut | |
| 700 | 1 | |a Aruldhas, Blessed Winston |e verfasserin |4 aut | |
| 700 | 1 | |a Prabha, Ratna |e verfasserin |4 aut | |
| 700 | 1 | |a Neely, Michael N |e verfasserin |4 aut | |
| 700 | 1 | |a Rao, Shoma V |e verfasserin |4 aut | |
| 700 | 1 | |a Kandasamy, Subramani |e verfasserin |4 aut | |
| 700 | 1 | |a Mathew, Binu Susan |e verfasserin |4 aut | |
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