While there is general agreement on the necessity to measure glomerular filtration rate (GFR) in many clinical situations, there is less agreement on the best method to achieve this purpose. As the gold standard method for GFR determination, urinary (or renal) clearance of inulin, fades into the background due to inconvenience and high cost, a diversity of filtration markers and protocols compete to replace it. In this review, we suggest that iohexol, a non-ionic contrast agent, is most suited to replace inulin as the marker of choice for GFR determination. Iohexol comes very close to fulfilling all requirements for an ideal GFR marker in terms of low extra-renal excretion, low protein binding and in being neither secreted nor reabsorbed by the kidney. In addition, iohexol is virtually non-toxic and carries a low cost. As iohexol is stable in plasma, administration and sample analysis can be separated in both space and time, allowing access to GFR determination across different settings. An external proficiency programme operated by Equalis AB, Sweden, exists for iohexol, facilitating interlaboratory comparison of results. Plasma clearance measurement is the protocol of choice as it combines a reliable GFR determination with convenience for the patient. Single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations. In low GFRs one or more late samples should be included to improve accuracy. In patients with large oedema or ascites, urinary clearance protocols should be employed. In conclusion, plasma clearance of iohexol may well be the best candidate for a common GFR determination method.
Objective: Recent in vivo results have shown prominent tissue sparing effect of radiotherapy with ultra-high dose rates (FLASH) compared to conventional dose rates (CONV). Oxygen depletion has been proposed as the underlying mechanism, but in vitro data to support this have been lacking. The aim of the current study was to compare FLASH to CONV irradiation under different oxygen concentrations in vitro. Methods: Prostate cancer cells were irradiated at different oxygen concentrations (relative partial pressure ranging between 1.6 and 20%) with a 10 MeV electron beam at a dose rate of either 600 Gy/s (FLASH) or 14 Gy/min (CONV), using a modified clinical linear accelerator. We evaluated the surviving fraction of cells using clonogenic assays after irradiation with doses ranging from 0 to 25 Gy. Results: Under normoxic conditions, no differences between FLASH and CONV irradiation were found. For hypoxic cells (1.6%), the radiation response was similar up to a dose of about 5–10 Gy, above which increased survival was shown for FLASH compared to CONV irradiation. The increased survival was shown to be significant at 18 Gy, and the effect was shown to depend on oxygen concentration. Conclusion: The in vitro FLASH effect depends on oxygen concentration. Further studies to characterize and optimize the use of FLASH in order to widen the therapeutic window are indicated. Advances in knowledge: This paper shows in vitro evidence for the role of oxygen concentration underlying the difference between FLASH and CONV irradiation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.