Urinary acute kidney injury biomarkers in very low-birth-weight infants on indomethacin for patent ductus arteriosus.

BACKGROUND: Serum creatinine (SCr)- or urine output-based definitions of acute kidney injury (AKI) have important limitations in neonates. This study evaluates the diagnostic value of urinary biomarkers in very low-birth-weight (VLBW) infants receiving indomethacin for closure of a patent ductus arteriosus (PDA). METHODS: Prospective cohort study in 14 indomethacin-treated VLBW infants and 18 VLBW infants without indomethacin as controls. Urinary biomarkers were measured before, during, and after indomethacin administration. RESULTS: Indomethacin therapy was associated with significantly higher SCr concentrations at 36, 84, and 120 h compared to controls. At 36 h, three indomethacin-treated patients met the criteria for neonatal modified Kidney Disease: Improving Global Outcomes (KDIGO) AKI. The product of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]•[IGFBP7]) was significantly elevated in the AKI subgroup at 12 h (P < 0.05), hence 24 h earlier than the increase in SCr. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin were significantly increased in the indomethacin group at 12 h (P < 0.05), irrespective of fulfillment of the AKI criteria. Urinary kidney injury molecule-1 (KIM-1) was not significantly altered. CONCLUSION: While urinary [TIMP-2]•[IGFBP7] proves valuable for the early diagnosis of neonatal modified KDIGO-defined AKI, elevated urinary NGAL and calprotectin concentrations in indomethacin-treated VLBW infants not fulfilling the AKI criteria may indicate subclinical kidney injury.

Urinary calprotectin, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin for the prediction of adverse outcome in pediatric acute kidney injury.

Early identification of patients with acute kidney injury (AKI) being at high risk for adverse outcome can influence medical treatment. This study compares urinary calprotectin, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) for their performance in predicting mortality and need for renal replacement therapy (RRT) in pediatric AKI patients. Urinary biomarker concentrations were assessed prospectively in 141 subjects aged 0-18 years including 55 patients with established AKI according to pediatric Risk, Injury, Failure, Loss, and End-stage kidney disease (pRIFLE) criteria, 27 patients without AKI, and 59 healthy children. Within the AKI group, receiver operating characteristic (ROC) curve analysis revealed moderate to poor performance of calprotectin and KIM-1 in the prediction of 30-day mortality (calprotectin area under the curve (AUC) 0.55; KIM-1 AUC 0.55) and 3-month mortality (calprotectin AUC 0.61; KIM-1 AUC 0.60) and fair performance in the prediction of RRT requirement (calprotectin AUC 0.72; KIM-1 AUC 0.71). Urinary NGAL showed good performance in predicting 30-day (AUC 0.79) and 3-month (AUC 0.81) mortality and moderate performance in predicting RRT (AUC 0.61). CONCLUSIONS: Whereas urinary calprotectin and KIM-1 can be useful for the prediction of RRT, urinary NGAL has a good diagnostic performance in predicting mortality in pediatric patients with AKI of heterogeneous etiology. What is known: • There is increasing evidence that urinary biomarkers like neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are valuable for the prediction of adverse outcome in adult acute kidney injury (AKI), whereas data on pediatric AKI is scarce. What is new: • Urinary calprotectin and KIM-1 do not predict mortality in our heterogeneous pediatric AKI cohort, but they show moderate performance in the prediction of dialysis. • Urinary NGAL is a good predictor of mortality performing better than pRIFLE stage, eGFR, or creatinine, but it shows moderate performance in the prediction of dialysis.

Urinary biomarkers for the differentiation of prerenal and intrinsic pediatric acute kidney injury.

BACKGROUND: Urinary calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) have recently been identified as promising biomarkers for the differentiation of prerenal and intrinsic acute kidney injury (AKI) in adults. In the study reported here we examined the diagnostic accuracy of calprotectin, NGAL, and kidney injury molecule 1 (KIM-1) in pediatric patients. METHODS: Urinary calprotectin, NGAL, and KIM-1 concentrations were assessed in a study population of 139 pediatric subjects including 39 patients with intrinsic AKI, 14 with prerenal AKI, and 86 non-AKI subjects. RESULTS: Median urinary calprotectin and NGAL concentrations were higher in patients with intrinsic AKI than in those with prerenal AKI (calprotectin by 22-fold, NGAL by 9-fold). Receiver operating characteristic (ROC) curve analyses for the differentiation of intrinsic and prerenal AKI resulted in an area under the curve (AUC) of 0.90 [95 % confidence interval (CI) 0.81-0.98] for calprotectin and 0.73 (95 % CI 0.58-0.87) for NGAL. Median urinary KIM-1 concentrations were not significantly different between patients with prerenal AKI and those with intrinsic disease (P = 0.98; AUC 0.50, 95 % CI, 0.35-0.65). The AUC for the fractional excretion of sodium (FENa) and proteinuria was 0.78 (95 % CI 0.63-0.92) and 0.77 (CI 0.65-0.90), respectively. CONCLUSIONS: Urinary calprotectin outperforms NGAL, KIM-1, FENa, and proteinuria as a biomarker for the differentiation of prerenal and intrinsic AKI in pediatric patients with a high diagnostic accuracy.

Urinary Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) • Insulin-Like Growth Factor-Binding Protein 7 (IGFBP7) Predicts Adverse Outcome in Pediatric Acute Kidney Injury.

BACKGROUND: The G1 cell cycle inhibitors tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as promising biomarkers for the prediction of adverse outcomes including renal replacement therapy (RRT) and mortality in critically ill adult patients who develop acute kidney injury (AKI). However, the prognostic value of urinary TIMP-2 and IGFBP7 in neonatal and pediatric AKI for adverse outcome has not been investigated yet. METHODS: The product of the urinary concentration of TIMP-2 and IGFBP7 ([TIMP-2]•[IGFBP7]) was assessed by a commercially available immunoassay (NephroCheck™) in a prospective cohort study in 133 subjects aged 0-18 years including 46 patients with established AKI according to pRIFLE criteria, 27 patients without AKI (non-AKI group I) and 60 apparently healthy neonates and children (non-AKI group II). AKI etiologies were: dehydration/hypovolemia (n = 7), hemodynamic instability (n = 7), perinatal asphyxia (n = 9), septic shock (n = 7), typical hemolytic-uremic syndrome (HUS; n = 5), interstitial nephritis (n = 5), vasculitis (n = 4), nephrotoxic injury (n = 1) and renal vein thrombosis (n = 1). RESULTS: When AKI patients were classified into pRIFLE criteria, 6/46 (13%) patients fulfilled the criteria for the category "Risk", 13/46 (28%) for "Injury", 26/46 (57%) for "Failure" and 1/46 (2%) for "Loss". Patients in the "Failure" stage had a median 3.7-fold higher urinary [TIMP-2]•[IGFBP7] compared to non-AKI subjects (P<0.001). When analyzed for AKI etiology, highest [TIMP-2]•[IGFBP7] values were found in patients with septic shock (P<0.001 vs. non-AKI I+II). Receiver operating characteristic (ROC) curve analyses in the AKI group revealed good performance of [TIMP-2]•[IGFBP7] in predicting 30-day (area under the curve (AUC) 0.79; 95% CI, 0.61-0.97) and 3-month mortality (AUC 0.84; 95% CI, 0.67-0.99) and moderate performance in predicting RRT (AUC 0.67; 95% CI, 0.50-0.84). CONCLUSIONS: This study shows that urinary [TIMP-2]•[IGFBP7] has a good diagnostic performance in predicting adverse outcomes in neonatal and pediatric AKI of heterogeneous etiology.

Memory performance related to organic and psychosocial illness attributions in somatoform pain disorder patients.

OBJECTIVE: Somatoform disorders are characterized by patterns of persistent bodily complaints. Organic illness attributions are assumed to represent a central supporting factor in the development and maintenance of somatoform disorders. Using group control design, we aimed to investigate the processing of illness-belief-related word stimuli in somatoform pain disorder patients. METHODS: Organic-related, psychosocial-related, and neutral word stimuli were presented to 14 somatoform pain patients with a predominantly organic illness attribution, 14 somatoform pain patients with a predominantly psychosocial illness attribution, and 14 control participants. Behavioral measures were taken during free recall and recognition tasks. RESULTS: Our study revealed cognitive impairment in somatoform pain patients with an organic attribution of pain symptoms as compared to somatoform pain patients with a psychosocial attribution and healthy controls in both free recall test and recognition test. However, selective processing of word stimuli was not observed for patient groups. CONCLUSION: We conclude that the observed impairment of memory performance in somatoform pain patients with an organic illness attribution may play an important role in the illness behavior of this patient group and ultimately result in the maintenance of symptoms and a more critical clinical outcome.