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Hyperphosphatemia has been associated with higher mortality risk in CKD 5 patients receiving dialysis. Here, we determined the association between the use of single and combined phosphate-binding agents and survival in 6797 patients of the COSMOS study: a 3-year follow-up, multicenter, open-cohort, observational prospective study carried out in 227 dialysis centers from 20 European countries. Patient phosphate-binding agent prescriptions (time-varying) and the case-mix-adjusted facility percentage of phosphate-binding agent prescriptions (instrumental variable) were used as predictors of the relative all-cause and cardiovascular mortality using Cox proportional hazard regression models. Three different multivariate models that included up to 24 variables were used for adjustments. After multivariate analysis, patients prescribed phosphate-binding agents showed a 29 and 22% lower all-cause and cardiovascular mortality risk, respectively. The survival advantage of phosphate-binding agent prescription remained statistically significant after propensity score matching analysis. A decrease of 8% in the relative risk of mortality was found for every 10% increase in the case-mix-adjusted facility prescription of phosphate-binding agents. All single and combined therapies with phosphate-binding agents, except aluminum salts, showed a beneficial association with survival. The findings made in the present association study need to be confirmed by randomized controlled trials to prove the observed beneficial effect of phosphate-binding agents on mortality.

The COSMOS baseline results show important differences across Europe in the management of CKD-MBD.

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Objective The present study was performed to examine in two-kidney, one clip (2K1C) Goldblatt hypertensive mice, first, the relative contribution of angiotensin II (ANG II) receptor subtypes 1A (AT1A) and 1B (AT1B); second, the role of ANG II type 2 (AT2) receptors in the development of hypertension in wild-type (AT1A+/+) and AT1A receptor knockout (AT1A−/−) mice and third, the role of increased nitric oxide synthase (NOS) activity in counteracting the hypertensinogenic action of ANG II in this model. Methods AT1A+/+ and AT1A−/− mice underwent clipping of one renal artery and were infused with either saline vehicle or with the selective AT2 receptor agonist CGP-42112A (CGP). Blood pressure (BP) was monitored by radiotelemetry. BP responses to the NOS inhibitor nitro-L-arginine-methyl-ester (L-NAME) were evaluated. Results AT1A+/+ mice responded to clipping by a rise in BP which was not modified by CGP infusion. Clip placement caused a slight increase in BP in AT1A−/− mice which remained significantly lower than in AT1A+/+ mice. Acute NOS inhibition caused greater increases in BP in 2K1C/AT1A+/+ than in AT1A+/+ mice. Conclusions The present data support the critical role AT1A receptors in the development of 2K1C hypertension, whereas AT1B receptors play only a minor role in BP regulation in this model of ANG II-dependent hypertension. Activation of AT2 receptors does not play an antagonistic role in the AT1 receptor-mediated hypertensinogenic actions of ANG II in this model. Finally, enhanced NOS activity plays a protective role by counteracting the vasoconstrictor influences of ANG II in 2K1C hypertensive mice.