Urinary Neutrophil Gelatinase–Associated Lipocalin (NGAL) Distinguishes Sustained From Transient Acute Kidney Injury After General Surgery

This prospective study tests the hypothesis that after general surgery urinary neutrophil gelatinase–associated lipocalin (NGAL) can distinguish between sustained acute kidney injury (AKI), typical of nephron damage, and transient AKI, commonly seen with hemodynamic variation and prerenal azotemia. Methods: Urine was collected in 510 patients within 2 to 3 hours after general surgery, and urinary NGAL was determined using enzyme-linked immunosorbent assay. Patients who met AKIN stage 1 criteria of AKI were subclassified into those with sustained AKI (serum creatinine elevation for at least 3 days) and those with transient AKI (serum creatinine elevation for less than 3 days). Results: Seventeen of 510 patients (3.3%) met the stage 1 AKIN criteria within 48 hours of surgery. Elevations in serum creatinine were sustained in 9 and transient in 8 patients. Urinary NGAL was significantly elevated only in patients with sustained AKI (204.8 ± 411.9 ng/dl); patients with transient AKI had urinary NGAL that was indistinguishable from that of patients who did not meet AKIN criteria at all (30.8 ± 36.5 ng/dl vs. 31.9 ± 113 ng/dl). The area under the curve of the receiver operating characteristic curve of urinary NGAL to predict sustained AKI was 0.85 (95% confidence interval: 0.773–0.929, P < 0.001). Discussion: Urinary NGAL levels measured 2 to 3 hours after surgery were able to distinguish the kinetics of creatinine (sustained AKI vs. transient AKI) over the subsequent week. Transient AKI is an easily reversible state that is likely not associated with substantial tubular injury and therefore NGAL release. Using AKIN criteria, both transient and sustained AKI are classified as AKI even though our data demonstrate that they are possibly different entities

Defining the Relationship of Oxygen Delivery and Consumption: Use of Biologic System Models

To determine the most appropriate mathematical description of the relationship between oxygen consumption and oxygen delivery, we compared the statistical validity of a piecewise linear model to two different biologic system models—-Michaelis-Menten (MM) kinetics (used for enzyme systems) and the exponential dose-response relationship (used to describe drug administration and induced response). Nine rabbits underwent five incremental steps of normovolemic hemodilution to progressively decrease D o 2 . V o 2 was measured concurrently by a metabolic gas monitor. All three models (piecewise linear, Michaelis-Menten, and exponential) provided a very close population curve fit to the data points ( r 2 = 0.88, 0.91, and 0.92). However, there were significant differences in maximum predicted V o 2 ( V o 2max )—6.8, 9.9, 7.2 ml O 2·kg -1·min-1( P < 0.0002)—and a wide range in the model-specific parameters for individual rabbits (critical D o 2 6.5-11.8 ml O 2·kg -1·min -1, K m 4.2-11.4 ml O 2·kg -1·min -1, and k 0.12-0.23 ml O -1 2·kg*middot;min). In the curvilinear models, average and population parameters were not significantly different. However, in the piecewise linear model, population critical D o 2 (10.9 ml O 2·kg -1·min -1) was 30% more than the average critical D o 2 (8.4 ml O 2·kg -1·min -1) for the nine rabbits ( P < 0.005). V o 2max values predicted by the piecewise linear and exponential dose-response model were more consistent with those in previous publications than was the higher V o 2max predicted by the MM model. The difference in the average versus population critical D o 2 in the piecewise linear model meant that population modeling was inaccurate because it yielded a critical D o 2 higher than that demonstrated by eight of nine individual rabbits. Despite the high r 2 values for all three models and the historical use of the piecewise linear model, we consider the exponential dose-response model the most appropriate description of the D o 2 / V o 2 relationship given its advantages with regard to V o 2max prediction and population modeling

Treatment limitations in the era of ECMO

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