The time for ambitious action is now: Science-based recommendations for plastic chemicals to inform an effective global plastic treaty.

The ubiquitous and global ecological footprint arising from the rapidly increasing rates of plastic production, use, and release into the environment is an important modern environmental issue. Of increasing concern are the risks associated with at least 16,000 chemicals present in plastics, some of which are known to be toxic, and which may leach out both during use and once exposed to environmental conditions, leading to environmental and human exposure. In response, the United Nations member states agreed to establish an international legally binding instrument on plastic pollution, the global plastics treaty.

A Randomized Trial of Cinacalcet versus Vitamin D Analogs as Monotherapy in Secondary Hyperparathyroidism (PARADIGM).

Background And Objectives: Direct comparison of cinacalcet and vitamin D analogs as monotherapies to lower parathyroid hormone (PTH) levels has not been undertaken.

Design, Setting, Participants, & Measurements: This was a prospective, multicenter, phase 4, randomized, open-label study that enrolled participants from 2010 to 2012. Adult participants (n=312) on hemodialysis with PTH >450 pg/ml were randomized 1:1 to 12 months of treatment with either cinacalcet (n=155) or vitamin D analogs (n=157) to evaluate the mean percentage change in plasma PTH level (primary end point) and the proportion of participants achieving plasma PTH <300 pg/ml or a ≥30% decrease in PTH (secondary end points).

Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism.

Background And Objectives: Cinacalcet and vitamin D are often combined to treat secondary hyperparathyroidism (SHPT) in patients on dialysis. Independent effects on fibroblast growth factor-23 (FGF-23) concentrations in patients on hemodialysis administered cinacalcet or vitamin D analogs as monotherapies during treatment of SHPT are evaluated.

Design, Setting, Participants, & Measurements: A multicenter, randomized, open-label study to compare the efficacy of cinacalcet versus traditional vitamin D therapy for management of secondary hyperparathyroidism among subjects undergoing hemodialysis (PARADIGM) was a prospective, phase 4, multicenter, randomized, open-label study conducted globally.

Efficacy profile of a bivalent Staphylococcus aureus glycoconjugated vaccine in adults on hemodialysis: Phase III randomized study.

In a previous study in end-stage renal disease (ESRD) hemodialysis patients, a single dose of Staphylococcus aureus type 5 and 8 capsular polysaccharides (T5/T8) conjugated to nontoxic recombinant Pseudomonas aeruginosa exotoxin A investigational vaccine showed no efficacy against S. aureus bacteremia 1 year post-vaccination, but a trend for efficacy was observed over the first 40 weeks post-vaccination. Vaccine efficacy (VE) of 2 vaccine doses was therefore evaluated.

Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial.

Background: Iron-deficiency anemia in non-dialysis-dependent chronic kidney disease (NDD-CKD) frequently requires parenteral iron replacement, but existing therapies often require multiple administrations. We evaluated the efficacy and cardiovascular safety of ferric carboxymaltose (FCM), a non-dextran parenteral iron permitting large single-dose infusions, versus iron sucrose in patients with iron-deficiency anemia and NDD-CKD.

Methods: A total of 2584 participants were randomized to two doses of FCM 750 mg in one week, or iron sucrose 200 mg administered in up to five infusions in 14 days.

Sodium handling by deep nephrons and the terminal collecting duct in glomerulonephritis.

The present study was designed to characterize the effects of anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN) on sodium handling by surface nephrons, deep nephrons and the terminal collecting duct segment. Studies were performed in rats during hydropenia and volume expansion. In hydropenia, the glomerular filtration rate (GFR) and sodium excretion tended to be lower in rats with GN than in controls.

Three peptides from the ANF prohormone NH(2)-terminus are natriuretic and/or kaliuretic.

The present investigation was designed to determine whether peptides derived from the NH(2)-terminal portion of the 126-amino acid prohormone (pro) of atrial natriuretic factor (ANF) have natriuretic and diuretic properties similar to ANF. Three peptides consisting of amino acids 1-30 [(proANF-(1-30)], 31-67 [proANF-(31-67)], and 79-98 (proANF-(79-98)] of the ANF prohormone were tested and compared with the COOH-terminus peptide (ANF) with respect to their ability to increase urine volume, urine sodium and potassium excretion, and glomerular filtration rate (GFR) in anesthetized Munich-Wistar rats. Each of these peptides except proANF-(79-98) caused a significant diuresis (P less than 0.

Contribution of superficial nephron segments to sodium excretion in experimental glomerulonephritis.

The present study examined the contribution of individual superficial nephron segments to sodium excretion in antiglomerular basement membrane nephritis in the rat by sampling the same nephron successively from the end and beginning of the distal tubule and end of the proximal tubule. Whole kidney GFR in glomerulonephritic rats was reduced by approximately 40% from controls; absolute sodium excretion was about 25% of normal. Metabolic balance studies in the awake state had suggested that the animals were in sodium balance.

Contribution of the distal tubule to potassium excretion in experimental glomerulonephritis.

The renal adaptations that maintain potassium homeostasis in diffuse forms of glomerular disease are not well defined. Thus, handling of potassium by superficial nephron segments was examined in a rat model of antiglomerular basement membrane nephritis. Sampling the same nephron successively from the end and beginning of the distal tubule and the end of the proximal tubule allowed a segmental analysis.

Long-term effects of 24-hr unilateral ureteral obstruction on renal function in the rat.

To characterize the pattern of recovery following release of unilateral ureteral obstruction of 24-hr duration, rats were studied with whole kidney clearance techniques, 3 hrs, 8, 14, and 60 days after release. The single nephron glomerular filtration rate (SNGFR) of superficial and juxtamedullary nephrons was estimated with a modification of Hanssen's technique in rats studied 8 and 60 days after ureteral release. The whole kidney glomerular filtration rates (GFR) were decreased markedly 3 hrs after relief of obstruction, but gradually increased and by 14 days, the GFR of the postobstructed kidney (POK) and the contralateral kidney (CK) were comparable.

Contribution of individual superficial nephron segments to ammonium handling in chronic metabolic acidosis in the rat. Evidence for ammonia disequilibrium in the renal cortex.

Ammonia entry along surface nephron segments of rats was studied with micropuncture techniques under control and chronic metabolic acidosis conditions. Tubule fluid was collected successively from sites at the end and beginning of the distal tubule and at the end of the proximal tubule of the same nephron. During chronic metabolic acidosis, ammonium excretion doubled.

Transport of ammonia in the rabbit cortical collecting tubule.

Nonionic diffusion and diffusion equilibrium of ammonia have been generally accepted as the mechanism of urinary ammonium excretion. However, these characteristics have not been examined directly in vitro. In the present studies, nonionic diffusion and diffusion equilibrium of ammonia were examined in rabbit cortical collecting tubules perfused in vitro.

Handling of ammonium by the renal proximal tubule during acute metabolic acidosis.

The present studies were designed to assess the handling of ammonium (NH+4) by the proximal tubule during acute metabolic acidosis (AMA). After tubule fluid collections were obtained with micropuncture techniques and in situ pH was determined near the end of the proximal tubule, 0.2 N HCl was infused intravenously at 17 microliter X min-1 X 100 g body wt-1.

Relation of nephron recruitment to detectable filtration and recovery of function after release of ureteral obstruction.

In this study, the role of nephron recruitment to measurable filtration in the recovery of whole kidney GFR following release of ureteral obstruction of 18 hr duration was characterized in the young rat with a modification of Hanssen's technique. Following release of bilateral (BUO) or unilateral (UUO) ureteral obstruction, the expected increases in fractional sodium and water excretion were observed and remained constant throughout the interval of the study (approximately 3 hr). However, the GFR of the postrelease kidney of rats subjected to BUO and UUO increased significantly within this time frame.

Effect of reduced renal mass on ammonium handling and net acid formation by the superficial and juxtamedullary nephron of the rat. Evidence for impaired reentrapment rather than decreased production of ammonium in the acidosis of uremia.

Papillary and surface micropuncture were used to study the handling of ammonium and the formation of net acid by surface nephrons, deep nephrons, and the terminal segment of collecting duct (CD) after renal mass was reduced by two-thirds. Net acid excretion by the remnant kidney (RK) was significantly reduced, averaging 794+/-81 neq/min (SE) compared with 1,220+/-105 neq/min after sham operation (P < 0.001), due to a decrease in ammonium excretion (494+/-54 vs.

Segmental analysis of the renal tubule in buffer production and net acid formation.

Papillary and surface micropuncture in Munich-Wistar rats was used to assess the role of proximal segments of superficial and juxtamedullary (JM) nephrons, the distal tubule of superficial nephrons, and the terminal collecting duct in acid excretion. The relative role of these segments in ammonium production, bicarbonate reclamation, and net acid formation was assessed under hydropenic conditions and after a chronic acid load. In these two settings the proximal segment of both kinds of nephrons is the major site of ammonium production and bicarbonate reclamation.

Deep nephron and collecting duct function after unilateral reduction in renal mass.

Papillary micropuncture was used to study juxtamedullary nephron and terminal collecting duct function in the remnant kidney when the contralateral kidney was present. Urine osmolality from the remnant kidney was significantly lower than that measured for the control kidney. Surface nephron function appeared unaffected by remnant formation.

Ammonium handling by superficial and juxtamedullary nephrons in the rat. Evidence for an ammonia shunt between the loop of Henle and the collecting duct.

Papillary and surface micropuncture was used to assess the effects of a chronic metabolic acidosis on the renal tubular handling of ammonium by surface nephrons, juxtamedullary nephrons, and the terminal segment of collecting duct. Rats chronically fed ammonium chloride had an expected decline in arterial pH and bicarbonate concentration associated with a doubling in the amount of ammonium excreted and a decline in urine pH. The glomerular filtration rate and absolute delivery of water and sodium to micropuncture sites of surface and deep nephrons was not measurably altered.

Role of deep nephrons and the terminal collecting duct in a mannitol-induced diuresis.

Recollection micropuncture in Munich-Wistar rats was used to study the effects of intravenous hypertonic mannitol infusions on fluid reabsorption by surface nephrons, prior to the bend of Henle's loop of deep nephrons, and along the papillary collecting duct. During mannitol diuresis, single nephron glomerular filtration rate rose significantly in surface nephrons but fell in deep nephrons. Although mannitol increased the delivery of sodium and water to the end of the proximal tubule and to the first portion of the distal tubule of surface nephrons, water and sodium were reabsorbed between these two sites.

Effects of urinary tract obstruction on renal function.

This paper reviews the effects of urinary tract obstruction of renal function. The mechanisms by which obstruction decreases glomerular filtration rate and renal plasma flow are considered. The effects of obstructive uropathy on renal concentrating ability, renal acid excretion, and renal metabolism are also discussed.

Response of deep nephrons and the terminal collecting duct to a reduction in renal mass.

Juxtamedullary (JM) nephron and collecting duct function was studied after a two-thirds reduction in renal mass in the young rat. The glomerular filtration rate of JM nephrons was twofold greater in the remnant kidney (RK) group than in controls, but this increase was proportional to the increase measured in surface nephrons. Despite an increase in absolute reabsorption, delivery of sodium and water to the end of the proximal tubule of superficial nephrons and to the bend of Henle's loop of JM nephrons was increased.