We have demonstrated that ouabain regulates protein trafficking of the Na/K-ATPase α1 subunit and NHE3 (Na/H exchanger, isoform 3) via ouabain-activated Na/K-ATPase signaling in porcine LLC-PK1 cells. To investigate whether this mechanism is species-specific, ouabain-induced regulation of the α1 subunit and NHE3 as well as transcellular 22Na+ transport were compared in three renal proximal tubular cell lines (human HK-2, porcine LLC-PK1, and AAC-19 originated from LLC-PK1 in which the pig α1 was replaced by ouabain-resistant rat α1). Ouabain inhibited transcellular 22Na+ transport due to an ouabain-induced redistribution of the α1 subunit and NHE3. In LLC-PK1 cells, ouabain also inhibited the endocytic recycling of internalized NHE3, but has no significant effect on recycling of endocytosed α1 subunit. These data indicated that the ouabain-induced redistribution of the α1 subunit and NHE3 is not a species-specific phenomenon, and ouabain-activated Na/K-ATPase signaling influences NHE3 regulation.
We examined whether we could develop models based on data provided to the United States Renal Data System (USRDS) to accurately predict survival. Records were obtained from patients beginning dialysis in 1990 through 2007. We developed linear and neural network models and optimized the fit of these models to the actual time to death. Next, we examined whether we could accurately predict survival in a dataset containing censored and uncensored patients. The results with these models were contrasted with those obtained with a Cox proportional hazards model fit to the entire dataset. The average C statistic over a 6-month to 10-year time range achieved with these models was approximately 0.7891 (linear model), 0.7804 (transformed dataset linear model), 0.7769 (neural network model), 0.7774 (transformed dataset neural network model), 0.8019 (Cox model), and 0.7970 (transformed dataset Cox model). When we used the Cox proportional hazards model, superior C statistic results were found at time points between 2 and 10 years but at earlier time points, the Cox model was slightly inferior. These results suggest that data provided to the USRDS can allow for predictive models which have a high degree of accuracy years following the initiation of dialysis.
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