Urine biomarkers of acute kidney injury in noncritically ill, hospitalized children treated with chemotherapy.

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.

Serum cystatin C for acute kidney injury evaluation in children treated with aminoglycosides.

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.

Male hypogonadism associated with advanced cancer: a systematic review.

Male hypogonadism is commonly diagnosed on the basis of subphysiological concentrations of androgen hormones, and is associated with many symptoms present in advanced cancer. Androgen deficiency might be an important cause of muscle wasting in both cancer cachexia and sarcopenia. We did a systematic review of the clinical association of male hypogonadism in advanced cancer. We searched PubMed, Medline, and Embase for publications on the relation between male hypogonadism and functional status, nutritional status, body composition, symptoms, and quality of life in patients with advanced cancer. Of 381 publications identified, six original articles were included. We found no definitive association between nutritional, functional, or quality-of-life characteristics and male hypogonadism. Possible associations between male hypogonadism and weight loss, low albumin, low-body cell mass index, low-peripheral fat and muscle mass, higher inflammation, higher pain, higher opioid consumption, worse scores for anxiety, depression, and emotional and functional well-being need to be confirmed by better designed studies. There is no clear epidemiological data to indicate whether male hypogonadism is independently associated with clinical and biological sequelae of cancer cachexia, such as higher inflammation, fatigue, and body wasting. Standardised kits sensitive to low concentrations of free-testosterone or bioavailable testosterone are needed to diagnose androgen deficiency in women. A clearer epidemiology of androgen deficiencies in advanced cancer will help determine which patients should receive testosterone-replacement therapy for alleviating cancer cachexia symptoms and improving quality of life.