RESUMO
BACKGROUND: Cisplatin (Cis), carboplatin (Carb), and ifosfamide (Ifos) are common nephrotoxic chemotherapies. Biomarkers of tubular injury may allow for early acute kidney injury (AKI) diagnosis. PROCEDURE: We performed a two-center (Canada, United States) pilot study to prospectively measure serum creatinine (SCr), urine neutrophil gelatinase-associated lipocalin (NGAL), and interleukin-18 (IL-18) in children receiving Cis/Carb (27 episodes), Ifos (30 episodes), and in 15 hospitalized, nonchemotherapy patients. We defined AKI using the Kidney Disease Improving Global Outcomes (KDIGO) definition. We compared postchemotherapy infusion NGAL and IL-18 concentrations (immediate postdose to 3 days later) to pre-infusion concentrations. We calculated area under the receiver operating characteristic curve (AUC) for postinfusion biomarkers to discriminate for AKI. RESULTS: Prechemotherapy infusion NGAL and IL-18 concentrations were not higher than nonchemotherapy control concentrations. Increasing chemotherapy dose was associated with increasing postinfusion (0-4 hr after infusion) NGAL (P < 0.05). Post-Ifos, immediate postdose, and daily postdose NGAL and IL-18 were significantly higher than pre-infusion biomarker concentrations (P < 0.05), during AKI episodes. NGAL and IL-18 did not rise significantly after Cis-Carb infusion, relative to predose concentrations (P > 0.05). NGAL and IL-18 measured immediately after Ifos infusion discriminated for AKI with AUCs is 0.80 (standard error = 0.13) and 0.73 (standard error = 0.16), respectively. NGAL and IL-18 were not diagnostic of Cis-Carb-associated AKI. When AUCs were adjusted for age, all biomarker AUCs (Cis-Carb and Ifos) improved. CONCLUSION: Urine NGAL and IL-18 show promise as early AKI diagnostic tests in children treated with ifosfamide and may have a potential role in drug toxicity monitoring.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/urina , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Injúria Renal Aguda/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores/urina , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Interleucina-18/sangue , Lipocalina-2/sangue , Masculino , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Neoplasias/urina , Projetos Piloto , Estudos ProspectivosRESUMO
BACKGROUND: Serum cystatin C (CysC) is a more accurate glomerular filtration rate marker than serum creatinine (SCr) and may rise more quickly with acute kidney injury (AKI). METHODS: We performed a prospective cohort study of 81 non-critically ill children during 110 aminoglycoside (AG) treatments. We calculated area under the curve (AUC) for CysC to diagnose SCr-defined AKI and predict persistent AKI. SCr-AKI definition was based on the Kidney Disease: Improving Global Outcomes (≥stage 1: ≥50 % or 26.5 µmol/l SCr rise from baseline; stage 2: SCr doubling); CysC-AKI was based on a modified version using CysC rise. RESULTS: SCr-AKI and CysC-AKI developed in 45 and 48 % treatments, respectively. CysC rise predicted stage 1 (AUC = 0.75, 95 % CI 0.60-0.90) and 2 (AUC = 0.85, 95 % CI 0.75-0.95) SCr-AKI 2 days before SCr-AKI attainment. The best combined sensitivity/specificity for percent CysC rise to predict stage 1 SCr-AKI was with a 44 % CysC rise (sensitivity = 65 %, specificity = 83 %). CysC rise on day of SCr-AKI development was associated with SCr-AKI ≥48 h (AUC = 0.73, 95 % CI 0.56-0.90) and ≥50 % persistent SCr rise at treatment end (AUC = 0.76, 95 % CI 0.61-0.90). CONCLUSIONS: CysC is as an early AKI biomarker and predictive of persistent AKI on aminoglycoside treatment.
Assuntos
Injúria Renal Aguda/sangue , Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Cistatina C/sangue , Injúria Renal Aguda/complicações , Injúria Renal Aguda/epidemiologia , Adolescente , Área Sob a Curva , Infecções Bacterianas/complicações , Infecções Bacterianas/tratamento farmacológico , Biomarcadores/sangue , Criança , Pré-Escolar , Estudos de Coortes , Creatinina/sangue , Feminino , Humanos , Incidência , Masculino , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Resultado do TratamentoRESUMO
Acute kidney injury (AKI) in children is associated with increased mortality and prolonged length of hospital stay and may also be associated with long-term chronic kidney disease development. Despite encouraging results on AKI treatment in animal studies, no specific treatment has yet been successful in humans. One of the important factors contributing to this problem is the lack of an early AKI diagnostic test. Serum creatinine, the current main diagnostic test for AKI, rises late in AKI pathophysiology and is an inaccurate marker of acute changes in glomerular filtration rate. Therefore, new biomarkers of AKI are needed. With great advancements in genomics, proteomics, and metabolomics, new AKI biomarkers, mainly consisting of urinary proteins that appear in response to renal tubular cell injury, have been, and continue to be, discovered. These new biomarkers offer promise for early AKI diagnosis and for the depiction of severity of renal injury occurring with AKI. This review provides a summary of what a biomarker is, why we need new biomarkers of AKI, and how biomarkers are discovered and should be evaluated. The review also provides a summary of selected AKI biomarkers that have been studied in children.
Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/metabolismo , Biomarcadores/urina , Animais , Biomarcadores/sangue , Criança , Genômica , Humanos , Metabolômica , ProteômicaRESUMO
Aim: NGAL, IL-18, KIM-1 as well as urinary TIMP2 and IGFBP7 and their mathematical product (TIMP2*IGFBP7) were evaluated for detecting pediatric aminoglycoside acute kidney injury (AG-AKI). Methods: In a prospective study, noncritically ill children received aminoglycosides (AG) ≥3 days. The area under the curve (AUC) for biomarkers to detect AKI was calculated by a) days before AKI onset; b) treatment days. Results: There were 113 AG episodes (68% febrile neutropenia). The AKI group had a higher proportion with febrile neutropenia. The AKI group had significantly lower NGAL 3 days before AKI, as patients with febrile neutropenia had a lower NGAL during AG treatment (p < 0.05). NGAL, IL-18 and TIMP2*IGFBP7 had AUC ≥0.73 at 3, 2 and 2 days before AKI onset. Conclusion: NGAL, IL-18 and TIMP2*IGFBP7 were modest early biomarkers of AG-AKI. Febrile neutropenia was associated with lower NGAL.