The role of urinary biomarkers of kidney injury in the prediction of adverse clinical outcomes in acute renal failure (ARF) has not been well described. The relationship between urinary N-acetyl-␤-(D)-glucosaminidase activity (NAG) and kidney injury molecule-1 (KIM-1) level and adverse clinical outcomes was evaluated prospectively in a cohort of 201 hospitalized patients with ARF. NAG was measured by spectrophotometry, and KIM-1 was measured by a microsphere-based Luminex technology. Mean Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score was 16, 43% had sepsis, 39% required dialysis, and hospital mortality was 24%. Urinary NAG and KIM-1 increased in tandem with APACHE II and Multiple Organ Failure scores. Compared with patients in the lowest quartile of NAG, the second, third, and fourth quartile groups had 3.0-fold (95% confidence interval [CI] 1.3 to 7.2), 3.7-fold (95% CI 1.6 to 8.8), and 9.1-fold (95% CI 3.7 to 22.7) higher odds, respectively, for dialysis requirement or hospital death (P < 0.001). This association persisted after adjustment for APACHE II, Multiple Organ Failure score, or the combined covariates cirrhosis, sepsis, oliguria, and mechanical ventilation. Compared with patients in the lowest quartile of KIM-1, the second, third, and fourth quartile groups had 1.4-fold (95% CI 0.6 to 3.0), 1.4-fold (95% CI 0.6 to 3.0), and 3.2-fold (95% CI 1.4 to 7.4) higher odds, respectively, for dialysis requirement or hospital death (P ‫؍‬ 0.034). NAG or KIM-1 in combination with the covariates cirrhosis, sepsis, oliguria, and mechanical ventilation yielded an area under the receiver operator characteristic curve of 0.78 (95% CI 0.71 to 0.84) in predicting the composite outcome. Urinary markers of kidney injury such as NAG and KIM-1 can predict adverse clinical outcomes in patients with ARF.

The purpose of this study was to compare the performance of six candidate urinary biomarkers, kidney injury molecule 1 (KIM-1), N-acetyl-β-(D)-glucosaminidase (NAG), neutrophil gelatinaseassociated lipocalin (NGAL), interleukin 18 (IL-18), cystatin C, and α-1 microglobulin, measured 2 hours following cardiopulmonary bypass (CPB) for the early detection of acute kidney injury (AKI) in a prospective cohort of patients undergoing cardiac surgery. 103 subjects were enrolled, AKI developed in 13%. Urinary KIM-1 achieved the highest area under-the-receiver-operatorcharacteristic curve (AUC = 0.78, 95% CI 0.64-0.91), followed by IL-18 and NAG. Only urinary KIM-1 remained independently associated with AKI after adjustment for a preoperative AKI prediction score (Cleveland Clinic Foundation score; P= 0.02), or CPB perfusion time (P = 0.006). In this small pilot-cohort, KIM-1 performed best as an early biomarker for AKI. Larger studies are needed to further explore the role of biomarkers for early detection of AKI following cardiac surgery.

This study demonstrates that C5a inhibits neutrophil apoptosis via a PI 3-K signaling pathway. This effect may be an important mechanism that improves cell survival and function in the inflammatory milieu.

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This study demonstrates that in addition to the PI 3-K pathway, C5a also inhibits neutrophil apoptosis via an ERK-signalling pathway, resulting in phosphorylation of Bad and blockade of proteolytic cleavage of caspases. The activation of this additional survival-signalling pathway may be another important cellular mechanism that enhances neutrophil survival in inflammatory states.

Reactive oxygen species are important mediators of injury in acute renal failure (ARF). Although polymorphisms that affect key pro-and antioxidant enzymes might alter the susceptibility to oxidative stress-mediated injury, the use of genetic epidemiology for the study of oxidative stress-related genes has received little attention in ARF. The relationship of single-nucleotide polymorphisms in the coding region (C to T substitution at position ؉242) of the pro-oxidant enzyme NADPH oxidase p22phox subunit gene and in the promoter region (C to T substitution at position ؊262) of the antioxidant enzyme catalase gene to adverse clinical outcomes was evaluated prospectively in a cohort of 200 hospitalized patients with established ARF of mixed cause and severity. Genomic DNA was extracted from peripheral blood leukocytes and analyzed with a restriction fragment length polymorphism PCR method. Genotype-phenotype associations were characterized by measuring circulating nitrotyrosine and catalase activity. Observed and expected genotype frequencies were not significantly different, and overall baseline characteristics were not significantly different according to the various genotype groups. A genotype-phenotype association was demonstrable between the NADPH oxidase p22phox genotypes and plasma nitrotyrosine level (P ‫؍‬ 0.06), as well as between the catalase genotypes and whole-blood catalase activity (P < 0.001). Compared with the NADPH oxidase p22phox CC genotype group, the T-allele group had a higher cumulative probability of remaining hospitalized (P ‫؍‬ 0.03). Compared with the NADPH oxidase p22phox CC genotype, the T-allele carrier state was associated with 2.1-fold higher odds for dialysis requirement or hospital death (P ‫؍‬ 0.01). This association persisted with 2.0-to 2.2-fold higher odds for this composite outcome after adjustment for race; gender; age; and the Acute Physiology and Chronic Health Evaluation II score (P ‫؍‬ 0.03), the Multiple Organ Failure score (P ‫؍‬ 0.01), or presence of sepsis (P ‫؍‬ 0.02). The polymorphism in the gene that encodes the NADPH oxidase p22phox subunit at position ؉242 is associated with dialysis requirement or hospital death among patients with ARF. Larger studies are needed to confirm these relationships.

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