Frequency of and Risk Factors for Acute Kidney Injury Associated With Vancomycin Use in the Pediatric Intensive Care Unit

Abstract

BACKGROUND:Published information evaluating frequency of and risk factors for vancomycin-induced acute kidney injury (AKI) in the pediatric intensive care unit (PICU) population is conflicting. OBJECTIVES: The primary objective was to describe the proportion of our PICU patients who developed AKI with intravenous (IV) vancomycin. The secondary objective was to describe the associated potential risk factors. METHODS: Pediatric patients (0-18 years) who received their first IV vancomycin dose in the PICU were evaluated in this retrospective chart review. AKI was defined based on Pediatric-Modified RIFLE (pRIFLE) criteria. Patient demographics, vancomycin trough concentrations, concomitant nephrotoxins, and estimated creatinine clearance changes were analyzed. RESULTS: Of 265 patients included, the primary outcome of AKI (defined by meeting any pRIFLE criteria) occurred in 62 (23.4%) patients (48 category R, 11 category I, 3 category F). Patients who received vancomycin treatment for ≥ 5 days were more likely to develop AKI (unadjusted odds ratio [uOR]: 2.52; 95% confidence interval [CI]: 1.11-5.73), as were patients with a maximum vancomycin trough level ≥ 20 mg/L (OR: 2.99; 95% CI: 1.54-5.78) and patients on 1 (uOR: 2.29; 95% CI: 1.12-4.66) or more concurrent nephrotoxin (uOR: 3.11; 95% CI: 1.43-6.77). Among nephrotoxins, patients receiving furosemide concomitantly with vancomycin were more likely to develop AKI (uOR: 3.47; 95% CI: 1.92-6.27). After adjustment, only furosemide was a significant predictor of risk of AKI/AKI (adjusted OR: 3.52; 95% CI: 1.88-6.62). The study was limited by its retrospective and observational design, and confounding variables. CONCLUSIONS: Patients who were receiving vancomycin with concurrent furosemide were at highest risk of developing AKI.INDEX TERMS: acute kidney injury, critical illness, drug monitoring, pediatrics, vancomycin J Pediatr Pharmacol Ther 2016;21(6): [486][487][488][489][490][491][492][493]

Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

“…A total of 17 studies reporting PK-parameters of vancomycin in critically ill children were identified by the search, with more than 1000 PICU patients included in total over the whole pediatric age range [41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57]. Most studies included a mixed population, but also specific populations (such as patients with hematologic/oncologic [43,45], cardiac [51,53,56,57], traumatic [50] and infectious diseases [44,48]) being studied separately.…”

“…Most studies used intermittent dosing with daily doses of vancomycin ranging from 30 to 60 mg/kg/day, with only 1 study reporting higher mean doses (81 mg/kg/day) [45] and 1 study not mentioning the dose at all [41]. Two studies reported data on continuous dosing schedules, using a loading dose of 15 mg/kg and a maintenance dose of 40-45 mg/ kg over 24 h [42,55].…”

Piperacillin-tazobactam versus cefepime incidence of acute kidney injury in combination with vancomycin and tobramycin in pediatric cystic fibrosis patients

“…pRIFLE defines loss of kidney function as renal failure for at least 4 weeks and end stage renal disease as failure for at least 3 months. 6 Patients were evaluated for any level of kidney dysfunction (risk, injury, or failure) within the first 14 days of therapy or the end of their therapy, whichever occurred first. The primary outcome was defined as the incidence of acute kidney injury.…”

“…Cies and colleagues evaluated beta lactam monotherapy compared to combination therapy with vancomycin and did not find a statistically significant difference in the incidence of renal injury (8.8% vs 8.9%, P = 1) in a critically ill pediatric population, despite a mean vancomycin trough of 17.8 ±3.1 mcg/mL. 6 In a subsequent study completed by the same group, they did not observe a statistically significant difference in the rate of nephrotoxicity (8.8% vs 5.4%, P = 0.72), despite different target vancomycin trough concentrations (17.5 vs 8.4 mcg/mL, P < 0.001). Nephrotoxicity was defined as an increase in SCr > 0.3 mg/dL or 1.5-2 times baseline.…”

“…The length of admission was longer in the piperacillintazobactam group (13 [9][10][11][12][13][14][15] days vs cefepime 10 [6][7][8][9][10][11][12][13][14] days, P = 0.042), the duration of vancomycin and study antibiotics was similar in both groups (piperacillin-tazobactam 9 [6][7][8][9][10][11][12][13] days vs cefepime 10 [6-13] days, P = 0.454). Three patients in the cefepime group had pre-existing CF-related diabetes, but there were not any LECLEIR AND PETTIT | 1001 differences between the medications identified with potential for nephrotoxicity ( Table 1).…”