Risk factors for vancomycin nephrotoxicity and time course of renal function during vancomycin treatment

Hirai, Toshinori; Hanada, Kazuhiko; Kanno, Ayako; Akashi, Megumi; Itoh, Toshimasa

doi:10.1007/s00228-019-02648-7

Cited by 28 publications

(29 citation statements)

References 20 publications

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“…A meta-analysis of 15 studies compared patients with VTCs less or greater than 15 µg/mL, and found that nephrotoxicity occurred 4 to 17 days after the start of vancomycin application. 2 , 9 , 14 , 20 , 33 Another study by Hirai et al 34 showed that the mean onset of vancomycin-associated nephrotoxicity was 6.9 ± 4.9 days, and 40.0% of patients recovered from it. Because of large interindividual variability of pharmacokinetic parameters of vancomycin in very old patients, vancomycin levels and AUC/MIC index have been documented significantly higher in this particular population in some studies.…”

Section: Discussionmentioning

confidence: 99%

“…Other studies also showed a positive association between concomitant aminoglycosides and vancomycin and nephrotoxicity in elderly patients. 29 , 41 , 42 Besides aminoglycosides, other studies also indicated that concomitant use of renal hypoperfusion medications such as loop/thiazide diuretics, 34 ACEI/ARBs, 43 NSAIDs 44 and potential toxins include amphotericin B, trimethoprim-sulfamethoxazole, acyclovir and calcineurin inhibitors may increase the risk of nephrotoxicity, but these results were controversial. 1 , 11 However, due to limited data in our study, not all the above agents were included in our analysis, and no statistical significance was found between some renal hypoperfusion medications or potential toxins and nephrotoxicity, except for aminoglycosides.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Outcomes and Nephrotoxicity Associated with Vancomycin Treatment in Patients 80 Years and Older

Wang¹,

Dai²,

Wei³

et al. 2021

CIA

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Purpose This retrospective observational study investigated the efficacy and safety of vancomycin to treat patients aged 80 years and older. In particular, the associations between vancomycin trough concentration (VTC) and treatment outcomes or nephrotoxicity were explored. Patients and Methods Patients aged ≥80 years had received ≥3 vancomycin treatments and ≥1 detection of VTC. Treatment outcomes were defined as success or failure. Nephrotoxicity was considered an increase in serum creatinine ≥ 44.2 mmol/L, or 50% above baseline, for ≥2 consecutive days. Univariate and multivariate analyses were performed to identify risk factors for treatment failure and nephrotoxicity. Results Of 349 patients, 120 (34.4%) experienced treatment failure. For patients with VTCs at <10, 10–15, 15–20, and ≥20 µg/mL, the clinical response rates were, respectively, 77.8, 77.0, 80.5, and 61.0%; the 30-day mortality rates were 2.8, 15.0, 15.3, and 37.8%; and the rates of persistent bacteremia were 16.7, 12.4, 11.9, and 11.0%. The multivariate analysis indicated that blood urea nitrogen ≥11 g/dL and heart failure were independently associated with treatment failure; but not VTC ( P = 0.004, 0.016, 0.828, respectively). During vancomycin treatment, 42 (12.0%) patients experienced nephrotoxicity with recovery time 7.5 ± 4.5 days. Fewer than half of patients with nephrotoxicity recovered after suspending vancomycin application. The variables found independently associated with increased nephrotoxicity were: VTC ≥15 µg/mL; treatment duration ≥15 d; and concomitant aminoglycosides administration ( P = 0.024, 0.035, 0.029). Conclusion In patients aged 80 years and older, elevated VTC level was not associated with favorable treatment outcomes. Patients with VTC ≥20 µg/mL appear to suggest a worsened prognosis compared with lower VTCs. The risk of nephrotoxicity increases with elevated VTC, longer treatment time, and concomitant aminoglycoside administration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Outcomes and Nephrotoxicity Associated with Vancomycin Treatment in Patients 80 Years and Older

Wang¹,

Dai²,

Wei³

et al. 2021

CIA

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“…The detailed study design has already been reported previously. 10 The study population included all adult patients (>15 years) who started intravenous VCM treatment between June 2015 and August 2017 at the Tokyo Women's Medical University Medical Center East (450-bed university hospital, Tokyo, Japan). Then, we excluded patients who had any renal replacement therapy or for whom no data on VCM trough concentrations were available.…”

Section: Study Design and Patient Eligibilitymentioning

confidence: 99%

“…9 We have reported that medications for renal hypoperfusion such as angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers, loop/thiazide diuretics, or non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of VCM nephrotoxicity. 10 Especially, diuretics administration pharmacologically causes volume depletion, resulting in renal hypoperfusion. In contrast, whether loop diuretics such as furosemide cause renal hypoperfusion in experimental studies has been controversial.…”

Section: Introductionmentioning

confidence: 99%

Involvement of the effect of renal hypoperfusion medications on vancomycin trough concentration: A secondary analysis using a retrospective observational data

Hirai

Hanada

Iwamoto

et al. 2021

Basic Clin Pharma Tox

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This study examined the association between vancomycin (VCM) trough concentration and confounding factors including renal hypoperfusion medications which include angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, loop/thiazide diuretics, or non-steroidal anti-inflammatory drugs. This secondary analysis included patients aged >15 years who were administered VCM intravenously between June 2015 and August 2017 at the Tokyo Women's Medical University Medical Center East. We investigated predictors for three (initial, mean, and final) dose-normalized VCM trough concentration (dose-normalized VCM trough ) as outcome using a multiple linear regression analysis. In total, 208 patients were analysed (use of loop/thiazide diuretics: 48 [23%]). Multiple linear regression analysis revealed that the initial dose-normalized VCM trough was negatively correlated with estimated glomerular filtration rate (eGFR) (p = 0.028) and positively correlated with the use of loop/thiazide diuretics (p = 0.003). Meanwhile, there was a positive correlation between the mean dose-normalized VCM trough and age (p = 0.023). The mean dose-normalized VCM trough was negatively correlated with eGFR (p < 0.001) and serum albumin (p < 0.001).The final dose-normalized VCM trough was positively associated with age (p = 0.034) and negatively associated with eGFR (p = 0.032) and serum albumin (p = 0.007). Clinicians should closely monitor VCM trough concentration while receiving VCM and loop/thiazide diuretics.

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“…Hirai and colleagues observed that patients in their study showed poor recovery from vancomycin nephrotoxicity although vancomycin trough concentrations improved. In cases where vancomycin was continued, nephrotoxicity recovered in 40% of the patients [14]. Although VA-AKI is usually considered a reversible phenomenon, the consequences of AKI can be severe, ranging from increased length of hospitalization, long term dialysis, and transplantation.…”

Section: Introductionmentioning

confidence: 99%

Incidence and risk factors of vancomycin-associated acute kidney injury in a single center: Retrospective study

Yalamarti¹,

Zonoozi²,

Ntoso³

et al. 2021

J Clini Nephrol

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Background: There is enough evidence to suggest that vancomycin increases the risk of acute kidney injury (AKI) but the exact mechanism is not well understood. This study aims to understand the incidence of vancomycin-associated acute kidney injury (VA-AKI) among hospitalized patients and to identify the risk factors for VA-AKI. Methods: Patients aged 18 and above who received a minimum of 24 hours of intravenous vancomycin and who had serial creatinine measurements over a 13-month period were identified through electronic records. Patients with pre-existing AKI, or eGFR of less than 30ml/min, and patients with end stage kidney disease were excluded. Results were analyzed using t-test and Fisher’s test. A logistic regression model was used to identify the predictors for VA-AKI. Results: From the 598 patients who met the inclusion criteria, 70 developed AKI. Compared to those without AKI, patients with VA-AKI had higher mean serum vancomycin trough levels (22.6 mg/L vs. 14.6 mg/L), and a statistically significant longer duration of vancomycin use (6.7 vs. 5.2 days). Multivariate analysis revealed that serum vancomycin level of > 20 mg/L was associated with a six-fold increase in odds of VA-AKI when compared to those with vancomycin levels < 15 mg/L. The presence of hypotension, iodinated contrast use, and concomitant use of piperacillin-tazobactam were all associated with increased odds of VA-AKI. Conclusion: The incidence of VA-AKI in hospitalized patients with eGFR > 30 ml/min was 11.7%. Serum vancomycin levels of > 20 mg/L, hypotension and administration of iodinated contrast significantly increased the risk of VA-AKI. Piperacillin-tazobactam, when used with vancomycin, was noted to be an independent predictor of AKI, regardless of serum vancomycin trough levels, prompting a reevaluation of the safety of this widespread practice as empiric therapy. Close monitoring of kidney function, avoiding high serum vancomycin levels, maintaining hemodynamic stability, and avoiding unnecessary use of iodinated contrast seem to be essential for the prevention of VA-AKI.

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Risk factors for vancomycin nephrotoxicity and time course of renal function during vancomycin treatment

Cited by 28 publications

References 20 publications

Outcomes and Nephrotoxicity Associated with Vancomycin Treatment in Patients 80 Years and Older

Outcomes and Nephrotoxicity Associated with Vancomycin Treatment in Patients 80 Years and Older

Involvement of the effect of renal hypoperfusion medications on vancomycin trough concentration: A secondary analysis using a retrospective observational data

Incidence and risk factors of vancomycin-associated acute kidney injury in a single center: Retrospective study

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