Serum myostatin at dialysis initiation may predict 1-year mortality and hospitalization.

OBJECTIVE: Myostatin, which is known as a negative skeleton muscle regulator, is associated with mortality in maintenance hemodialysis patients. However, the significance of serum myostatin concentrations at dialysis initiation has not been established. We investigated the relation between serum myostatin concentrations and mortality or hospitalization within one year in incident dialysis patients. METHODS: After a patient initiating hemodialysis or peritoneal dialysis during 2016-2018 was enrolled, the patient's serum myostatin at dialysis initiation was measured. Composite outcomes comprising mortality and hospitalization within 1 year after dialysis initiation were compared between two groups divided according to myostatin levels. The Cox proportional hazards model was used to assess significant relations between myostatin and outcomes. RESULTS: This study examined 104 incident dialysis patients with mean age of 65.5±14.0 (68% male). Kaplan-Meier analyses indicated the 1-year hospitalization-free and survival rate as significantly lower in the lower myostatin group than in the higher myostatin group (p = .0020). Cox proportional hazards regression analyses revealed that the value of myostatin logarithm at dialysis initiation was inversely associated with the occurrence of a composite outcome, independently of age (hazard ratio 0.16, 95% confidence interval 0.05-0.57). Receiver operating characteristic (ROC) analysis showed the area under the curve of serum myostatin for predicting death or hospitalization within 1 year as higher than those of clinical indices of nutritional disturbance and frailty. CONCLUSION: Serum myostatin concentration at dialysis initiation is inversely associated with adverse outcomes in these dialysis-initiated patients.

Ferumoxytol: an emerging therapeutic for iron deficiency anemia.

INTRODUCTION: Iron deficiency anemia (IDA) is common worldwide, and various iron replacement therapies are available. Ferumoxytol is an injectable, high-dose iron formulation (510 mg) that can be administered over a short period (15 min) without test administration. The drug was approved by the Food and Drug Administration in 2009 for the treatment of IDA in patients with chronic kidney disease (CKD), and in 2018, the indication was expanded to include patients without CKD. AREAS COVERED: This paper reviews studies testing the efficacy and safety of ferumoxytol in treating IDA compared with other iron formulations. EXPERT OPINION: There is substantial evidence that ferumoxytol is effective for the treatment of IDA. The efficacy of ferumoxytol in improving anemia is comparable to that of iron sucrose and ferric carboxymaltose (FCM) and superior to that of oral iron or a placebo in replenishing iron stores. Treatment with ferumoxytol, although more expensive, is cost-effective for outpatients requiring parenteral administration because it requires fewer doses and shorter dosing times per dose. Ferumoxytol also causes less frequent hypophosphatemia than FCM. Currently, its use in children and pregnant women is under consideration, which may provide important information for the future applications of ferumoxytol in larger numbers of patients.

Metabolic Changes and Oxidative Stress in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a major cause of end-stage kidney disease, and it is crucial to understand the pathophysiology of DKD. The control of blood glucose levels by various glucose-lowering drugs, the common use of inhibitors of the renin-angiotensin system, and the aging of patients with diabetes can alter the disease course of DKD. Moreover, metabolic changes and associated atherosclerosis play a major role in the etiology of DKD. The pathophysiology of DKD is largely attributed to the disruption of various cellular stress responses due to metabolic changes, especially an increase in oxidative stress. Therefore, many antioxidants have been studied as therapeutic agents. Recently, it has been found that NRF2, a master regulator of oxidative stress, plays a major role in the pathogenesis of DKD and bardoxolone methyl, an activator of NRF2, has attracted attention as a drug that increases the estimated glomerular filtration rate in patients with DKD. This review outlines the altered stress responses of cellular organelles in DKD, their involvement in the pathogenesis of DKD, and discusses strategies for developing therapeutic agents, especially bardoxolone methyl.

Hypoxia-Inducible Factor-Prolyl Hydroxylase Domain Inhibitors to Treat Anemia in Chronic Kidney Disease.

BACKGROUND: Hypoxia-inducible factor (HIF) stabilizers, also known as inhibitors of HIF prolyl hydroxylase domain (PHD) inhibitors enzymes, are novel small-molecule agents to treat renal anemia. They increase endogenous erythropoietin (EPO) production by stabilizing HIF. This review focuses on the mechanisms by which PHD inhibitors ameliorate anemia in chronic kidney disease (CKD) and summarizes the current clinical experience with and prospects for these drugs. SUMMARY: Anemia is a serious complication of CKD and is an independent risk factor for congestive heart failure. Appropriate treatment of anemia is important in the management of advanced stage CKD, as it might help to extend life expectancy and improve the physical function of patients with CKD. However, at present, adverse effects of treatment, such as thromboembolic events, as well as high therapeutic cost have a negative impact on society. PHD inhibitors stabilize the transcription factor HIF, increasing the expression of downstream target genes, including EPO and enzymes involved in iron metabolism, resulting in increased EPO production and improved iron utilization. Key Messages: The potential advantages of PHD inhibitors over conventional EPO-based therapies include a more physiologic response to renal anemia, noninvasive oral administration, and lower cost. Phase III trials of more than 5 PHD inhibitors are ongoing, with overall demonstration of success in increasing hemoglobin levels. In this review, we focus on the mechanisms of PHD inhibitors in improving renal anemia in CKD and summarize the current clinical findings regarding these drugs.