Tailoring the sampling time of single-sample GFR measurement according to expected renal function: a multisite audit.

BACKGROUND: The 2018 BNMS Glomerular Filtration Rate (GFR) guidelines recommend a single-sample technique with the sampling time dictated by the expected renal function, but this is not known with any accuracy before the test. We aimed to assess whether the sampling regime suggested in the guidelines is optimal and determine the error in GFR result if the sample time is chosen incorrectly. We can then infer the degree of flexibility in the sampling regime. METHODS: Data from 6328 patients referred for GFR assessment at 6 different hospitals for a variety of indications were reviewed. The difference between the single-sample (Fleming) GFR result at each sample time and the slope-intercept GFR result at each hospital was calculated. A second dataset of 777 studies from one hospital with nine samples collected from 5 min to 8 h post-injection was analysed to provide a reference GFR to which the single-sample results were compared. RESULTS: Recommended single-sample times have been revised: for an expected GFR above 90 ml/min/1.73m2 a 2-h sample is recommended; between 50 and 90 ml/min/1.73m2 a 3-h sample is recommended; and between 30 and 50 ml/min/1.73m2 a 4-h sample is recommended. Root mean square error in single-sample GFR result compared with slope-intercept can be kept less than or equal to 3.30 ml/min/1.73m2 by following these recommendations. CONCLUSION: The results of this multisite study demonstrate a reassuringly wide range of sample times for an acceptably accurate single-sample GFR result. Modified recommended single-sample times have been proposed in line with the results, and a lookup table has been produced of rms errors across the full range of GFR results for the three sample times which can be used for error reporting of a mistimed sample.

Specific volume-hole volume correlations in amorphous carbohydrates: effect of temperature, molecular weight, and water content.

The specific volume and the nanostructure of the free volume of amorphous blends of maltose with a narrow molecular weight distribution maltopolymer were systematically studied as a function of temperature, water content, pressure, and blend composition. Correlations between the hole free volume and the specific volume were investigated in the glassy and rubbery phases and in solution using positron annihilation lifetime spectroscopy (PALS) and pressure-volume-temperature (PVT) measurements, with the aim to provide a consolidated mechanistic understanding of the relation between changes in molecular packing and at the molecular level and the behavior of the specific volume at the macrolevel. Both specific volume and hole volume show a linear dependence on the temperature, but with a slope which is higher in the rubbery state than in the glassy state. As a function of temperature, the hole volume and the specific volume are linearly related, with no discontinuity at the glass transition temperature (T(g)). In the glassy state, both the specific volume and the hole volume decrease nonlinearly with the addition of maltose to the maltopolymer matrix, due to a more efficient molecular packing. For variations in carbohydrate composition, a linear dependence between the hole volume and the specific volume was again observed. The role of water was found to be significantly more complex, with increasing water content causing an increase in density in both the glassy and rubbery phases indicating that water exists in a highly dispersed state with a significantly lower specific molar volume than in bulk water. At very low water contents, the hole volume and the specific volume both decrease with increasing water content, which suggests that water acts as both a hole filler and a plasticizer. In the glassy state at slightly higher water contents, the specific volume continues to slowly decrease, but the hole size passes through a minimum before it starts to increase. This gives rise to a negative correlation between the hole volume and the specific volume which has not previously been observed and which can be interpreted in terms of water molecules which are dispersed within the glassy carbohydrate matrix and which thereby influence the hydrogen bonding between the carbohydrate molecules.

Molecular packing in amorphous carbohydrate matrixes.

The molecular packing of bidisperse matrixes of amorphous carbohydrates consisting of a fractionated maltopolymer supplemented with various amounts of the disaccharide maltose is investigated by combining Positron Annihilation Lifetime Spectroscopy (PALS) with specific volume measurements. The maltopolymer-maltose blends are equilibrated at a range of water activities between 0 and 0.75 at 25 degrees C in order to investigate the effect of water content and carbohydrate molecular weight distribution on the size of the molecular free volume holes in both the glassy and rubbery states. In the rubbery state, the size of the intermolecular holes is only very weakly dependent on the carbohydrate molecular weight, provided that the carbohydrate blends are analyzed at the same water content. In contrast, in the glassy state, significant differences in the size of the free volume holes are observed between the various blends at constant water content. Both the specific volume and the hole volume decrease with increasing maltose content, initially rapidly up to a maltose content of about 40 wt % on total carbohydrate. In addition, we find that the role of water as a plasticizer and matrix constituent is a complex one. At very low water contents, water acts by filling the free volume holes between the carbohydrate molecules. This hole-filling mechanism could well be related to the phenomenon of anti-plasticization observed before. At higher water contents, corresponding generally to water activities above 0.11 at 25 degrees C, water conversely increases the average hole volume in the carbohydrate matrixes, most likely caused by water interfering with the hydrogen bonding between the carbohydrate molecules, leading to a local expansion of the molecular packing.

Organization and mobility of water in amorphous and crystalline trehalose.

The disaccharide trehalose is accumulated by microorganisms, such as yeasts, and multicellular organisms, such as tardigrades, when conditions of extreme drought occur. In this way these organisms can withstand dehydration through the formation of an intracellular carbohydrate glass, which, with its high viscosity and hydrogen-bonding interactions, stabilizes and protects the integrity of complex biological structures and molecules. This property of trehalose can also be harnessed in the stabilization of liposomes, proteins and in the preservation of red blood cells, but the underlying mechanism of bioprotection is not yet fully understood. Here we use positron annihilation lifetime spectroscopy to probe the free volume of trehalose matrices; specifically, we develop a molecular picture of the organization and mobility of water in both amorphous and crystalline states. Whereas in amorphous matrices, water increases the average intermolecular hole size, in the crystalline dihydrate it is organized as a confined one-dimensional fluid in channels of fixed diameter that allow activated diffusion of water in and out of the crystallites. We present direct real-time evidence of water molecules unloading reversibly from these channels, thereby acting as both a sink and a source of water in low-moisture systems. We postulate that this behaviour may provide the overall stability required to keep organisms viable through dehydration conditions.