Preventing CKD in Developed Countries

Chronic kidney disease (CKD) is an important public health concern in developed countries because of both the number of people affected and the high cost of care when prevention strategies are not effectively implemented. Prevention should start at the governance level with the institution of multisectoral polices supporting sustainable development goals and ensuring safe and healthy environments. Primordial prevention of CKD can be achieved through implementation of measures to ensure healthy fetal (kidney) development. Public health strategies to prevent diabetes, hypertension, and obesity as risk factors for CKD are important. These approaches are cost-effective and reduce the overall noncommunicable disease burden. Strategies to prevent nontraditional CKD risk factors, including nephrotoxin exposure, kidney stones, infections, environmental exposures, and acute kidney injury (AKI), need to be tailored to local needs and epidemiology. Early diagnosis and treatment of CKD risk factors such as diabetes, obesity, and hypertension are key for primary prevention of CKD. CKD tends to occur more frequently and to progress more rapidly among indigenous, minority, and socioeconomically disadvantaged populations. Special attention is required to meet the CKD prevention needs of these populations. Effective secondary prevention of CKD relies on screening of individuals at risk to detect and treat CKD early, using established and emerging strategies. Within high-income countries, barriers to accessing effective CKD therapies must be recognized, and public health strategies must be developed to overcome these obstacles, including training and support at the primary care level to identify individuals at risk of CKD, and appropriately implement clinical practice guidelines

Calcium channel blockade blunts the renal effects of acute nitric oxide synthase inhibition in healthy humans

Montanari A, Lazzeroni D, Pelà G, Crocamo A, Lytvyn Y, Musiari L, Cabassi A, Cherney DZ. Calcium channel blockade blunts the renal effects of acute nitric oxide synthase inhibition in healthy humans. Am J Physiol Renal Physiol 312: F870–F878, 2017. First published February 8, 2017; doi:10.1152/ajprenal.00568. 2016.—Our aim was to investigate whether blockade of calcium channels (CCs) or angiotensin II type 1 receptors (AT1R) modulates renal responses to nitric oxide synthesis inhibition (NOSI) in humans. Fourteen sodium-replete, healthy volunteers underwent 90-min infusions of 3.0 g·kg1·min1 NG-nitro-L-arginine methyl ester (L-NAME) on 3 occasions, preceded by 3 days of either placebo (PL), 10 mg of manidipine (MANI), or 50 mg of losartan (LOS). At each phase, mean arterial pressure (MAP), glomerular filtration rate (GFR; inulin), renal blood flow (RBF; p-aminohippurate), urinary sodium (UNaV), and 8-isoprostane (U8-iso-PGF2V; an oxidative stress marker) were measured. With PL L -NAME, the following changes were observed: 6% MAP (P 0.005 vs. baseline), 10% GFR, 20% RBF, 49% UNaV (P 0.001), and 120% U8-iso-PGF2V (P 0.01). In contrast, MAP did not increase during LOS L-NAME or MANI L-NAME (P 0.05 vs. baseline), whereas renal changes were the same during LOS L-NAME vs. PL L-NAME (ANOVA, P 0.05). However, during MANI L-NAME, changes vs. baseline in GFR (6%), RBF (12%), and UNaV (34%) were blunted vs. PL L-NAME and LOS L-NAME (P 0.005), and the rise in U8-iso-PGF2V was almost abolished (37%, P 0.05 vs. baseline; P 0.01 vs. PL L-NAME or LOS L-NAME). We conclude that, since MANI blunted L-NAME-induced renal hemodynamic changes, CCs participate in the renal responses to NOSI in healthy, sodium-replete humans independent of changes in MAP and without the apparent contribution of the AT1R. Because the rise in U8-iso-PGF2V was essentially prevented during MANI L-NAME, CC blockade may oppose the renal effects of NOSI in part by counteracting oxidative stress responses to acutely impaired renal NO bioavailability

Pooled analysis of Phase III trials indicate contrasting influences of renal function on blood pressure, body weight, and HbA1c reductions with empagliflozin

Sodium glucose cotransporter 2 (SGLT2) inhibitors reduce HbA1c, blood pressure, and weight in patients with type 2 diabetes. To investigate the effect of renal function on reductions in these parameters with the SGLT2 inhibitor empagliflozin, we assessed subgroups by baseline estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease) in pooled data from five 24-week trials of 2286 patients with type 2 diabetes randomized to empagliflozin or placebo. Reductions in HbA1c with empagliflozin versus placebo significantly diminished with decreasing baseline eGFR. Reductions in systolic blood pressure (SBP) with empagliflozin were maintained in patients with lower eGFR. The mean placebo-corrected changes from baseline in systolic blood pressure at week 24 with empagliflozin were -3.2 (95% confidence interval -4.9,-1.5) mmHg, -4.0 (-5.4, -2.6) mmHg, -5.5 (-7.6, -3.4) mmHg, and -6.6 (-11.4, -1.8) mmHg in patients with an eGFR of 90 or more, 60 to 89, 30 to 59, and under 30 ml/min/1.73m(2), respectively. Similar trends were observed for diastolic blood pressure. Weight loss with empagliflozin versus placebo tended to be attenuated in patients with a lower eGFR. Results were consistent in a 12-week ambulatory blood pressure monitoring trial in 823 patients with type 2 diabetes and hypertension. Thus, unlike HbA1c reductions, systolic blood pressure and weight reductions with empagliflozin are generally preserved in patients with chronic kidney disease.Peer reviewe

DC Inclined-Plane Tracking and Erosion Test of Insulating Materials

The paper reviews previous work on the DC inclined plane test and suggests equivalent DC voltage levels in parallel to AC voltage in the ASTM inclined plane tracking and erosion test. The aim of this work is to provide a basis for standardizing the inclined plane test for DC voltage. Round robin tests done in five laboratories on five specimens of a silicone rubber material were done with the purpose of establishing appropriate ratios by which the equivalent DC voltages can be determined with respect to the corresponding AC voltages. These levels were determined as 67% and 87%, for +DC and-DC respectively, of the AC initial tracking voltage, and for practical purposes, these levels are rounded to 70 and 90%.Peer reviewed: YesNRC publication: Ye

Renal hyperfiltration defined by high estimated glomerular filtration rate:A risk factor for cardiovascular disease and mortality

Renal hyperfiltration, defined as an increased glomerular filtration rate above normal values, is associated with early phases of kidney disease in the setting of various conditions such as obesity and diabetes. Although it is recognized that glomerular hyperfiltration, that is, increased filtration per nephron unit (usually studied at low glomerular filtration levels and often referred to as single nephron hyperfiltration), is a risk factor for the progression of chronic kidney disease, the implications of having renal hyperfiltration for cardiovascular disease and mortality risk are incompletely understood. Recent evidence from diverse populations, including healthy individuals and patients with diabetes or established cardiovascular disease, suggests that renal hyperfiltration is associated with a higher risk of cardiovascular disease and all-cause mortality. In this review, we critically summarize the existing studies, discuss possible mechanisms, and describe the remaining gaps in our knowledge regarding the association of renal hyperfiltration with cardiovascular disease and mortality risk

Half-integer Higher Spin Fields in (A)dS from Spinning Particle Models

We make use of O(2r+1) spinning particle models to construct linearized higher-spin curvatures in (A)dS spaces for fields of arbitrary half-integer spin propagating in a space of arbitrary (even) dimension: the field potentials, whose curvatures are computed with the present models, are spinor-tensors of mixed symmetry corresponding to Young tableaux with D/2 - 1 rows and r columns, thus reducing to totally symmetric spinor-tensors in four dimensions. The paper generalizes similar results obtained in the context of integer spins in (A)dS.Comment: 1+18 pages; minor changes in the notation, references updated. Published versio

Maxwell-like Lagrangians for higher spins

We show how implementing invariance under divergence-free gauge transformations leads to a remarkably simple Lagrangian description of massless bosons of any spin. Our construction covers both flat and (A)dS backgrounds and extends to tensors of arbitrary mixed-symmetry type. Irreducible and traceless fields produce single-particle actions, while whenever trace constraints can be dispensed with the resulting Lagrangians display the same reducible, multi-particle spectra as those emerging from the tensionless limit of free open-string field theory. For all explored options the corresponding kinetic operators take essentially the same form as in the spin-one, Maxwell case.Comment: 77 pages, revised version. Erroneous interpretation and proof of the gauge-fixing procedure for mixed-symmetry fields corrected. As a consequence, the mixed-symmetry, one-particle Lagrangians are to be complemented with conditions on the divergences of the fields; all other conclusions unchanged. Additional minor changes including references added. To appear in JHE

The STAR Time Projection Chamber: A Unique Tool for Studying High Multiplicity Events at RHIC

The STAR Time Projection Chamber (TPC) is used to record collisions at the Relativistic Heavy Ion Collider (RHIC). The TPC is the central element in a suite of detectors that surrounds the interaction vertex. The TPC provides complete coverage around the beam-line, and provides complete tracking for charged particles within +- 1.8 units of pseudo-rapidity of the center-of-mass frame. Charged particles with momenta greater than 100 MeV/c are recorded. Multiplicities in excess of 3,000 tracks per event are routinely reconstructed in the software. The TPC measures 4 m in diameter by 4.2 m long, making it the largest TPC in the world.Comment: 28 pages, 11 figure