Patiromer induces rapid and sustained potassium lowering in patients with chronic kidney disease and hyperkalemia

Patients with chronic kidney disease (CKD) have a high risk of hyperkalemia, which increases mortality and can lead to renin–angiotensin–aldosterone system inhibitor (RAASi) dose reduction or discontinuation. Patiromer, a nonabsorbed potassium binder, has been shown to normalize serum potassium in patients with CKD and hyperkalemia on RAASi. Here, patiromer's onset of action was determined in patients with CKD and hyperkalemia taking at least one RAASi. After a 3-day potassium- and sodium-restricted diet in an inpatient research unit, those with sustained hyperkalemia (serum potassium 5.5 – under 6.5 mEq/l) received patiromer 8.4 g/dose with morning and evening meals for a total of four doses. Serum potassium was assessed at baseline (0 h), 4 h postdose, then every 2–4 h to 48 h, at 58 h, and during outpatient follow-up. Mean baseline serum potassium was 5.93 mEq/l and was significantly reduced by 7 h after the first dose and at all subsequent times through 48 h. Significantly, mean serum potassium under 5.5 mEq/l was achieved within 20 h. At 48 h (14 h after last dose), there was a significant mean reduction of 0.75 mEq/l. Serum potassium did not increase before the next dose or for 24 h after the last dose. Patiromer was well tolerated, without serious adverse events and no withdrawals. The most common gastrointestinal adverse event was mild constipation in two patients. No hypokalemia (serum potassium under 3.5 mEq/l) was observed. Thus, patiromer induced an early and sustained reduction in serum potassium and was well tolerated in patients with CKD and sustained hyperkalemia on RAASis

The Dynamics of Brane-World Cosmological Models

Brane-world cosmology is motivated by recent developments in string/M-theory and offers a new perspective on the hierarchy problem. In the brane-world scenario, our Universe is a four-dimensional subspace or {\em brane} embedded in a higher-dimensional {\em bulk} spacetime. Ordinary matter fields are confined to the brane while the gravitational field can also propagate in the bulk, leading to modifications of Einstein's theory of general relativity at high energies. In particular, the Randall-Sundrum-type models are self-consistent and simple and allow for an investigation of the essential non-linear gravitational dynamics. The governing field equations induced on the brane differ from the general relativistic equations in that there are nonlocal effects from the free gravitational field in the bulk, transmitted via the projection of the bulk Weyl tensor, and the local quadratic energy-momentum corrections, which are significant in the high-energy regime close to the initial singularity. In this review we discuss the asymptotic dynamical evolution of spatially homogeneous brane-world cosmological models containing both a perfect fluid and a scalar field close to the initial singularity. Using dynamical systems techniques it is found that, for models with a physically relevant equation of state, an isotropic singularity is a past-attractor in all orthogonal spatially homogeneous models (including Bianchi type IX models). In addition, we describe the dynamics in a class of inhomogeneous brane-world models, and show that these models also have an isotropic initial singularity. These results provide support for the conjecture that typically the initial cosmological singularity is isotropic in brane-world cosmology.Comment: Einstein Centennial Review Article: to appear in CJ