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Wave-like propagation of [Ca2+]i increases is a remarkable intercellular communication characteristic in astrocyte networks, intercalating neural circuits and vasculature. Mechanically-induced [Ca2+]i increases and their subsequent propagation to neighboring astrocytes in culture is a classical model of astrocyte calcium wave and is known to be mediated by gap junction and extracellular ATP, but the role of each pathway remains unclear. Pharmacologic analysis of time-dependent distribution of [Ca2+]i revealed three distinct [Ca2+]i increases, the largest being in stimulated cells independent of extracellular Ca2+ and inositol 1,4,5-trisphosphate-induced Ca2+ release. In addition, persistent [Ca2+]i increases were found to propagate rapidly via gap junctions in the proximal region, and transient [Ca2+]i increases were found to propagate slowly via extracellular ATP in the distal region. Simultaneous imaging of astrocyte [Ca2+]i and extracellular ATP, the latter of which was measured by an ATP sniffing cell, revealed that ATP was released within the proximal region by volume-regulated anion channel in a [Ca2+]i independent manner. This detailed analysis of a classical model is the first to address the different contributions of two major pathways of calcium waves, gap junctions and extracellular ATP.

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Despite improvements in medical care, the mortality of critically ill patients with acute kidney injury (AKI) who require renal replacement therapy (RRT) remains high. We describe a new approach, sustained hemodiafiltration, to treat patients who suffered from acute kidney injury and were admitted to intensive care units (ICUs). In our study, 60 critically ill patients with AKI who required RRT were treated with either continuous venovenous hemodiafiltration (CVVHDF) or sustained hemodiafiltration (S-HDF). The former was performed by administering a postfilter replacement fluid at an effluent rate of 35 mL/kg/h, and the latter was performed by administering a postfilter replacement fluid at a dialysate-flow rate of 300-500 mL/min. The S-HDF was delivered on a daily basis. The baseline characteristics of the patients in the two treatment groups were similar. The primary study outcome--survival until discharge from the ICU or survival for 30 days, whichever was earlier--did not significantly differ between the two groups: 70% after CVVHDF and 87% after S-HDF. The hospital-survival rate after CVVHDF was 63% and that after S-HDF was 83% (P < 0.05). The number of patients who showed renal recovery at the time of discharge from the ICU and the hospital and the duration of the ICU stay significantly differed between the two treatments (P < 0.05). Although there was no significant difference between the mean number of treatments performed per patient, the mean duration of daily treatment in the S-HDF group was 6.5 +/- 1.0 h, which was significantly shorter. Although the total convective volumes--the sum of the replacement-fluid and fluid-removal volumes--did not differ significantly, the dialysate-flow rate was higher in the S-HDF group. Our results suggest that in comparison with conventional continuous RRT, including high-dose CVVHDF, more intensive renal support in the form of postdilution S-HDF will decrease the mortality and accelerate renal recovery in critically ill patients with AKI.