Urinary [TIMP-2]•[IGFBP7] in established AKI according to pRIFLE classification.

<p>Boxplots of urinary [TIMP-2]•[IGFBP7] for the AKI cohort (n = 46) stratified for the different pRIFLE stages. Groups were composed as follows: non-AKI I+II (n = 87), “Risk” (n = 6), “Injury” (n = 13), “Failure” (n = 26), “Loss” (n = 1). For explanation of boxplots and unit for [TIMP-2]•[IGFBP7] see legend of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143628#pone.0143628.g001" target="_blank">Fig 1</a>. P<0.001 for “Failure” vs. non-AKI I+II by Kruskal-Wallis test and Dunn’s multiple comparison test.</p

Urinary [TIMP-2]•[IGFBP7] in non-AKI and AKI subjects stratified for age.

<p>Boxplots of urinary [TIMP-2]•[IGFBP7] for different age ranges for the non-AKI group I (white boxes), non-AKI group II (light grey boxes) and the AKI group (dark grey boxes). Selected age groups were composed as follows: 0–28 days (non-AKI group I, n = 4; non-AKI group II, n = 18; AKI group, n = 14), 29 days—2 years (non-AKI group I, n = 9; non-AKI group II, n = 4; AKI group, n = 10), 2–5 years (non-AKI group I, n = 7; non-AKI group II, n = 13; AKI group, n = 9), 6–11 years (non-AKI group I, n = 4; non-AKI group II, n = 17; AKI group, n = 4), 12–18 years (non-AKI group I, n = 3; non-AKI group II, n = 8; AKI group, n = 9). The lower and upper edges of the box represent the first and third quartile, respectively, while the horizontal line within the box indicates the median. The vertical length of the box represents the interquartile range (IQR). The most extreme sample values (within a distance of 1.5 x IQR) are the endpoints of the whiskers. Outliers (1.5–3.0 x IQR outside the box) are shown as dots, extremes (> 3.0 x IQR) as triangles. Unit for [TIMP-2]•[IGFBP7] is (ng/mL)²/1,000. Abbreviations: d, days; yrs, years. *P<0.05 vs. AKI of same age group, **P<0.05 vs. age group 0–28 days and 29 days– 2 years of non-AKI group II by Kruskal-Wallis test and Dunn’s multiple comparison test.</p

Urinary [TIMP-2]•[IGFBP7] in established AKI of heterogeneous etiology.

<p>Boxplots of urinary [TIMP-2]•[IGFBP7] for the different AKI etiologies. Cause of AKI is listed under the boxplot, number of patients of each group in brackets. For explanation of boxplots and unit for [TIMP-2]•[IGFBP7] see legend of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143628#pone.0143628.g001" target="_blank">Fig 1</a>. Abbreviations: HUS, hemolytic uremic syndrome. *P<0.001 by Kruskal-Wallis test and Dunn’s multiple comparison test.</p

Characteristics of the study population.

<p>Numeric data are presented as median and interquartile range due to non-normal distribution. Statistical tests used for the individual parameters are presented in the statistics section. Unit for [TIMP-2]•[IGFBP7] is (ng/mL)²/1,000. Abbreviations: AKI, acute kidney injury; SCr, serum creatinine; eCCl, estimated creatinine clearance; CrP, C-reactive protein; RRT, renal replacement therapy; ICU, intensive care unit.</p><p>Characteristics of the study population.</p

Kaplan—Meier curves for death or dialysis within 3 months after study enrollment.

<p>Composite endpoint of death or dialysis within 3 months for patients with established AKI (pRIFLE “Risk” stage or higher). A time period of only 30 days is shown as all first events of the composite endpoint occurred within this time period. Urinary [TIMP-2]<b>•</b>[IGFBP7] ranges of ≤0.3 (long dashed line, n = 15), 0.3 to ≤2.0 (short dashed line, n = 18), and >2.0 (solid line, n = 13) are shown. Log-rank P = 0.003 for [TIMP-2]<b>•</b>[IGFBP7] >2.0 vs. [TIMP-2]<b>•</b>[IGFBP7] ≤0.3.</p

Experimental parameters of the multi-capillary column ion mobility spectrometer (MCC/IMS) as used in the present study.

*<p>Multichrom, Novosibirsk, Russia.</p

Signal intensities of exemplary analytes that accumulate during hemodialysis.

<p>Signal intensities of analytes P9 and P11 in 28 healthy controls, 26 patients with chronic renal failure (CRF) stage 2–4 according to K/DOQI-criteria, 28 patients with end-stage renal disease (ESRD, CRF stage 5D) prior to and 22 after hemodialysis. Signal intensities were tested for statistical significance by two-tailed t-tests; *p<0.05, **p<0.01, ***p<0.001.</p

Representative multi-capillary column/ion mobility spectra (MCC/IMS) of breath samples.

<p>Breath sample of (A) a healthy adult, (B) an end-stage renal disease proband before and (C) after hemodialysis treatment. Areas of interest are marked and labeled by numbers. Substances corresponding to these numbers are given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046258#pone-0046258-t002" target="_blank">Table 2</a>. Signal intensity is coded by colours (yellow: very high; red high, blue: moderate, white: no signal).</p

Scheme of an ion mobility spectrometer (MCC/IMS).

<p>The multi-capillary column (MCC) provides a preseparation of the molecules in the gas phase. In the ionization chamber proton transfer from the reactant ions to the analyte molecules takes place, thus forming protonated analyte ions. The drift time of the ions in the electric field depends on size and shape of the analytes. The retention time in the MCC and mobility in the IMS characterize the identity of the analyte. The intensity of the signal is a measure of the analyte's concentration.</p

Signal intensities of exemplary analytes that accumulate with decreasing renal function and are eliminated by dialysis.

<p>Figures A–C present signal intensities of exemplary analytes P1–P3 and Figure D the sum of the signal intensities of the five analytes that accumulate with decreasing function and are eliminated by dialysis (P1–P5) in 28 healthy controls, 26 patients with chronic renal failure (CRF) stage 2–4 according to K/DOQI-criteria, 28 patients with end-stage renal disease (ESRD, CRF stage 5D) prior to and 22 after hemodialysis. Signal intensities were tested for statistical significance by two-tailed t-tests; *p<0.05, **p<0.01, ***p<0.001.</p