Aminoglycosides (AG) cause acute kidney injury (AKI), but the incidence and severity distribution are unclear, particularly in non-critically ill children. We determined the incidence, severity and risk factors of AG-associated AKI and assessed for associations with longer hospitalization and higher costs.
At Texas Children's Hospital, we conducted a retrospective cohort study of children treated with AG for ≥ 5 days in 2005, excluding children with admission primary renal diagnoses. AKI was defined by the paediatric Risk, Injury, Failure, Loss, End Stage Kidney Disease (pRIFLE) and Acute Kidney Injury Network (AKIN) definitions. Multiple logistic and linear regression analyses were used to assess independence of associations with outcomes.
Five hundred and fifty-seven children [mean ± SD age = 8.0 ± 5.9 years, 286 (51%) male, 489 (88%) gentamicin] were studied. The AKI rate was 33% and 20% by pRIFLE and AKIN definitions, respectively. Longer treatment, higher baseline estimated glomerular filtration rate, being on a medicine (versus surgical) treatment service and prior AG treatment were independent risk factors for AKI development. AKI by pRIFLE or AKIN was independently associated with longer hospital stay and higher total hospital costs. The pRIFLE definition was more sensitive for AKI detection, but the AKIN definition was more strongly related to outcomes.
AKI is common and associated with poorer outcomes in non-critically ill children treated with AG. Future research should attempt to understand how to best define AKI in the non-critical illness paediatric setting.
"However, nephrotoxicity is the principal limitation of GM therapeutic efficacy [13, 14]. Several recent intrahospital observational studies evidence an incidence of GM-induced acute kidney injury (defined by different criteria) ranging from 20% to 35.6% [15–17]. The molecular and pathophysiological mechanisms of GM-induced nephrotoxicity are well characterized. "
[Show abstract][Hide abstract] ABSTRACT: Sulforaphane (SFN), an isothiocyanate naturally occurring in Cruciferae, induces cytoprotection in several tissues. Its protective effect has been associated with its ability to induce cytoprotective enzymes through an Nrf2-dependent pathway. Gentamicin (GM) is a widely used antibiotic; nephrotoxicity is the main side effect of this compound. In this study, it was investigated if SFN is able to induce protection against GM-induced nephropathy both in renal epithelial LLC-PK1 cells in culture and in rats. SFN prevented GM-induced death and loss of mitochondrial membrane potential in LLC-PK1 cells. In addition, it attenuated GM-induced renal injury (proteinuria, increases in serum creatinine, in blood urea nitrogen, and in urinary excretion on N-acetyl- β -D-glucosaminidase, and decrease in creatinine clearance and in plasma glutathione peroxidase activity) and necrosis and apoptosis in rats. The apoptotic death was associated with enhanced active caspase-9. Caspase-8 was unchanged in all the studied groups. In addition, SFN was able to prevent GM-induced protein nitration and decrease in the activity of antioxidant enzymes catalase and glutathione peroxidase in renal cortex. In conclusion, the protective effect of SFN against GM-induced acute kidney injury could be associated with the preservation in mitochondrial function that would prevent the intrinsic apoptosis and nitrosative stress.
Evidence-based Complementary and Alternative Medicine 04/2013; 2013(9):135314. DOI:10.1155/2013/135314 · 1.88 Impact Factor
"27. Li S, Krawczeski CD, Zappitelli M et al (2011) Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery: a prospective multicenter study. Crit Care Med 39:1493–1499. "
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Cardiopulmonary bypass (CPB)-related inflammatory response might be one mechanism by which cardiac surgery associated acute kidney injury (CS-AKI) occurs. Interventions that may attenuate inflammation, including glucocorticoids or phosphodiesterase inhibitors, could therefore have a role in its prevention. We aimed to determine the role of inflammatory mediators in CS-AKI in children and the efficacy of commonly used peri-operative interventions to reduce CS-AKI risk.
We prospectively studied 109 children undergoing heart surgery. Using regression modeling (adjusting for covariates), we (1) evaluated the association between inflammatory mediators [interleukin (IL)-6, IL-8, C-reactive protein, and tumor necrosis factor-α levels] and CS-AKI, and (2) evaluated risk/prevention factors for CS-AKI including glucocorticoid and milrinone administration. CS-AKI was defined based on pRIFLE methods.
CS-AKI occurred in 68% of children. No inflammatory mediator measured had an independent association with CS-AKI. Higher pre-operative glomerular filtration rate (GFR), sustained decrease in mean arterial pressure during CPB, post-operative single ventricle physiology, deep hypothermic circulatory arrest, and milrinone use at 24 h post-operatively were significant independent predictors of CS-AKI. Intra-operative steroid administration had no effect on the rate of CS-AKI.
Although inflammatory mediators are up-regulated following CPB, we found no association between levels of inflammatory cytokines and CS-AKI. CS-AKI has complex pathophysiology and the observation that milrinone was associated with increased AKI risk (and that higher GFR predicts more injury) suggests that mechanisms beyond inflammation play a significant role. Intra-operative administration of glucocorticoid does not appear to be an effective intervention for reducing the risk of CS-AKI.
Intensive Care Medicine 02/2013; 39(5). DOI:10.1007/s00134-013-2849-4 · 7.21 Impact Factor
"With the exception of a few studies in hospitalised children and stem-cell transplant recipients [40, 41], the RIFLE/AKIN classifications are seldom applied in the noncritical care setting (i.e., hospital or community), and variable definitions of AKI continue to confound prevalence and incidence rates. The prevalence of hospital-acquired AKI is thought to be approximately 5–10 times greater than community-acquired AKI, with reported rates of AKI in 5–7% of hospitalised patients [35, 42]. "
[Show abstract][Hide abstract] ABSTRACT: This paper addresses the epidemiology of AKI specifically in relation to recent changes in AKI classification and revisits the controversies regarding the timing of initiation of dialysis and the use of peritoneal dialysis as a renal replacement therapy for AKI. In summary, the new RIFLE/AKIN classifications of AKI have facilitated more uniform diagnosis of AKI and clinically significant risk stratification. Regardless, the issue of timing of dialysis initiation still remains unanswered and warrants further examination. Furthermore, peritoneal dialysis as a treatment modality for AKI remains underutilised in spite of potential beneficial effects. Future research should be directed at identifying early reliable biomarkers of AKI, which in conjunction with RIFLE/AKIN classifications of AKI could facilitate well-designed large randomised controlled trials of early versus late initiation of dialysis in AKI. In addition, further studies of peritoneal dialysis in AKI addressing dialysis dose and associated complications are required for this therapy to be accepted more widely by clinicians.
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