Globally, the number of patients undergoing maintenance dialysis is increasing, yet throughout the world there is significant variability in the practice of initiating dialysis. Factors such as availability of resources, reasons for starting dialysis, timing of dialysis initiation, patient education and preparedness, dialysis modality and access, as well as varied "country-specific" factors significantly affect patient experiences and outcomes. As the burden of end-stage kidney disease (ESKD) has increased globally, there has also been a growing recognition of the importance of patient involvement in determining the goals of care and decisions regarding treatment. In January 2018, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference focused on dialysis initiation, including modality choice, access, and prescription. Here we present a summary of the conference discussions, including identified knowledge gaps, areas of controversy, and priorities for research. A major novel theme represented during the conference was the need to move away from a "one-size-fits-all" approach to dialysis and provide more individualized care that incorporates patient goals and preferences while still maintaining best practices for quality and safety. Identifying and including patient-centered goals that can be validated as quality indicators in the context of diverse health care systems to achieve equity of outcomes will require alignment of goals and incentives between patients, providers, regulators, and payers that will vary across health care jurisdictions.

Background: Most cases of hyponatremia – serum sodium concentration ([Na⁺]) <135 mEq/l (<135 mM) – are associated with an elevated plasma arginine vasopressin level. This study investigated the efficacy and tolerability of intravenous conivaptan (YM087), a vasopressin V_1A/V₂-receptor antagonist, in treating euvolemic and hypervolemic hyponatremia. Methods: Eighty-four hospitalized patients with euvolemic or hypervolemic hyponatremia (serum [Na⁺] 115 to <130 mEq/l) were randomly assigned to receive intravenous placebo or conivaptan administered as a 30-min, 20-mg loading dose followed by a 96-hour infusion of either 40 or 80 mg/day. The primary efficacy measure was change in serum [Na⁺], measured by the baseline-adjusted area under the [Na⁺]-time curve. The secondary measures included time from first dose to a confirmed ≧4 mEq/l serum [Na⁺] increase, total time patients had serum [Na⁺] ≧4 mEq/l higher than baseline, change in serum [Na⁺] from baseline to the end of treatment, and number of patients with a confirmed ≧6 mEq/l increase in serum [Na⁺] or normal [Na⁺] (≧135 mEq/l). Results: Both conivaptan doses increased area under the [Na⁺]-time curve during the 4-day treatment (p < 0.0001 vs. placebo). From baseline to the end of treatment, the least-squares mean ± standard error serum [Na⁺] increase associated with placebo was 0.8 ± 0.8 mEq/l; with conivaptan 40 mg/day, 6.3 ± 0.7 mEq/l; and with conivaptan 80 mg/day, 9.4 ± 0.8 mEq/l. Conivaptan significantly improved all secondary efficacy measures (p < 0.001 vs. placebo, both doses). Conivaptan was generally well tolerated, although infusion-site reactions led to the withdrawal of 1 (3%) and 4 (15%) of patients given conivaptan 40 and 80 mg/day, respectively. Conclusion: Among patients with euvolemic or hypervolemic hyponatremia, 4-day intravenous infusion of conivaptan 40 mg/day significantly increased serum [Na⁺] and was well tolerated.

Abstract. Current treatment of secondary hyperparathyroidism in chronic kidney failure with calcium and active vitamin D is potentially limited by hypercalcemia and hyperphosphatemia. AMG 073 represents a new class of compounds for the treatment of hyperparathyroidism known as calcimimetics, which reduce parathyroid hormone (PTH) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor (CaR) to extracellular calcium. The current study evaluates the efficacy and safety of AMG 073 when added to conventional treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD). Seventy-one hemodialysis patients with uncontrolled secondary hyperparathyroidism, despite standard therapy with calcium, phosphate binders, and active vitamin D sterols, were treated in this 18-wk, dosetitration study with single daily oral doses of AMG 073/ placebo up to 100 mg. Changes in plasma PTH, serum calcium, serum phosphorus, and calcium ϫ phosphorus levels were compared between AMG 073 and placebo groups. Mean PTH decreased by 33% in the AMG 073 patients compared with an increase of 3% in placebo patients (P ϭ 0.001). A significantly greater proportion of AMG 073 patients (44%) had a mean PTH Յ 250 pg/ml compared with placebo patients (20%; P ϭ 0.029). Also, a significantly greater proportion of AMG 073 patients (53%) had a decrease in PTH Ն30% compared with placebo patients (23%; P ϭ 0.009). Calcium ϫ phosphorus levels decreased by 7.9% in AMG 073 patients compared with an increase of 11.3% in placebo patients (P ϭ 0.013). Adverse event rates were low and mostly mild to moderate in severity; however, the incidence of vomiting was higher in AMG 073 patients. In this study, the calcimimetic AMG 073 at doses up to 100 mg for 18 wk provided a safe and effective means to attain significant reductions in PTH and calcium ϫ phosphorus levels in ESRD patients. AMG 073 represents a novel and promising therapy to improve the management of secondary hyperparathyroidism.The current standard treatment for secondary hyperparathyroidism in ESRD uses calcium supplementation, phosphate binders, and active vitamin D sterols in various combinations to attempt correction of hypocalcemia, hyperphosphatemia, and 1,25 (OH) 2 vitamin D 3 deficiency (1,2). Each component of this combined treatment strategy addresses abnormalities responsible for the pathogenesis of hyperparathyroidism, but each has limitations due to potential undesirable side effects at doses required to effectively suppress PTH hypersecretion (3-6). In this regard, treatment with vitamin D sterols is often complicated by hypercalcemia and hyperphosphatemia (7-10), resulting in elevate calcium ϫ phosphorus levels, predisposition to soft tissue calcification, and increased mortality risk in the ESRD population (11-15). Large doses of orally administered calcium to control hyperphosphatemia also predispose patients to episodes of hypercalcemia, chronic positive calcium balance, and increased soft tissue calcification in dialysis patients (15,...

No abstract