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Direct oral anticoagulants in chronic kidney disease: an update
Purpose of review Direct oral anticoagulants (DOACs) are variably eliminated by the kidneys rendering their use potentially problematic in patients with chronic kidney disease (CKD) or necessitating appropriate dose adjustment. Recent findings Both observational and limited randomized trial data for DOACs compared with no treatment or with warfarin for patients with atrial fibrillation on maintenance dialysis were recently published. In a randomized trial in patients on hemodialysis, there was no significant difference in vascular calcification between patients who received rivaroxaban with or without vitamin K2 or vi...
Source: Current Opinion in Nephrology and Hypertension - August 1, 2020 Category: Urology & Nephrology Tags: PHARMACOLOGY AND THERAPEUTICS: Edited by Sankar D. Navaneethan Source Type: research

LDL-cholesterol reduction in chronic kidney disease: options beyond statins
Purpose of review Individuals with chronic kidney disease (CKD) are at increased risk of atherosclerotic cardiovascular disease (ASCVD) events. LDL cholesterol (LDL-C) is a key modifiable cause of ASCVD and lowering LDL-C with statins reduces the risk of ASCVD events in a wide range of populations, including those with CKD. This review considers the utility of recently developed nonstatin LDL-C-lowering therapies in CKD. Recent findings The cholesterol absorption inhibitor, ezetimibe, reduces LDL-C by 15–20% and is well tolerated in CKD. Monoclonal antibodies (mAbs) targeting proprotein convertase subtilisin kexin t...
Source: Current Opinion in Nephrology and Hypertension - August 1, 2020 Category: Urology & Nephrology Tags: PHARMACOLOGY AND THERAPEUTICS: Edited by Sankar D. Navaneethan Source Type: research

Advances in exercise therapy in predialysis chronic kidney disease, hemodialysis, peritoneal dialysis, and kidney transplantation
Purpose of review Chronic kidney disease (CKD) is characterized by poor levels of physical activity which contribute to increased morbidity across the disease trajectory. The short nature, small samples, and poor methodology across most studies have failed to translate the role of exercise in CKD into its adoption as a frontline adjunct therapeutic option. This review focuses on recent advances surrounding the benefits of exercise interventions across the CKD spectrum. Recent findings Key recent advances in exercise studies have focused on the efficacy of novel intervention strategies across the CKD spectrum. These in...
Source: Current Opinion in Nephrology and Hypertension - August 1, 2020 Category: Urology & Nephrology Tags: PHARMACOLOGY AND THERAPEUTICS: Edited by Sankar D. Navaneethan Source Type: research

Recent advances in the treatment of uremic pruritus
This article provides a focused update on uremic pruritus, highlighting the latest evidence concerning the epidemiology, pathophysiology, and treatment options for this common and bothersome condition. Recent findings Half of dialysis patients and a quarter of those with nondialysis chronic kidney disease experience bothersome itch that reduces quality of life and is increasingly recognized to be associated with poor outcomes including mortality. The KALM-1 trial, which reported effective symptomatic relief with difelikefalin, has bolstered support for the role of an imbalance of μ and κ-opioid receptor activity in pr...
Source: Current Opinion in Nephrology and Hypertension - August 1, 2020 Category: Urology & Nephrology Tags: PHARMACOLOGY AND THERAPEUTICS: Edited by Sankar D. Navaneethan Source Type: research

Pharmacologic and psychological interventions for depression treatment in patients with kidney disease
Purpose of review It remains controversial whether existing therapies, including pharmacologic and psychological interventions, are effective for treatment of depression in patients with chronic kidney disease (CKD) and end-stage kidney disease. Recent findings Most studies of depression treatment were underpowered or uncontrolled. The CKD Antidepressant Sertraline Trial showed no benefit of a serotonin-selective reuptake inhibitor (SSRI), sertraline, over double-blind matched placebo for the treatment of depressive symptoms in patients with nondialysis CKD. A Trial of Sertraline vs. Cognitive Behavioral Therapy (CBT)...
Source: Current Opinion in Nephrology and Hypertension - August 1, 2020 Category: Urology & Nephrology Tags: PHARMACOLOGY AND THERAPEUTICS: Edited by Sankar D. Navaneethan Source Type: research

Editorial: Management of cardiovascular risk factors and other comorbidities in chronic kidney disease
No abstract available (Source: Current Opinion in Nephrology and Hypertension)
Source: Current Opinion in Nephrology and Hypertension - August 1, 2020 Category: Urology & Nephrology Tags: PHARMACOLOGY AND THERAPEUTICS: Edited by Sankar D. Navaneethan Source Type: research

Editorial introduction
No abstract available (Source: Current Opinion in Nephrology and Hypertension)
Source: Current Opinion in Nephrology and Hypertension - August 1, 2020 Category: Urology & Nephrology Tags: EDITORIAL INTRODUCTION Source Type: research

Fibroblast growth factor receptor as a potential candidate for phosphate sensing
Purpose of review Phosphate plays essential roles in many biological processes. Serum phosphate level needs to be regulated because hypophosphatemia and hyperphosphatemia cause rickets/osteomalacia and ectopic calcification, respectively. Fibroblast growth factor (FGF) 23 is the principal hormone to regulate serum phosphate level. FGF23 is produced by the bone and works to reduce serum phosphate level by binding to FGF receptor (FGFR) 1c and α-Klotho complex in the kidney. It has been unclear how the bone senses the changes of serum phosphate level and how the bone regulates the production of FGF23. Recent findings O...
Source: Current Opinion in Nephrology and Hypertension - May 29, 2020 Category: Urology & Nephrology Tags: RENAL PATHOPHYSIOLOGY: Edited by Orson W. Moe and Susan E. Quaggin Source Type: research

Molecular regulation and function of FoxO3 in chronic kidney disease
Purpose of review FOXOs are transcription factors that regulate downstream target genes to counteract to cell stress. Here we review the function and regulation of FOXO transcription factors, the mechanism of FOXO3 activation in the kidney, and the role of FOXO3 in delaying the development of chronic kidney disease (CKD). Recent findings Progressive renal hypoxia from vascular dropout and metabolic perturbation is a pathogenic factor for the initiation and development of CKD. Hypoxia and low levels of α-ketoglutarate generated from the TCA cycle inhibit prolyl hydroxylase domain (PHD)-mediated prolyl hydroxylation of...
Source: Current Opinion in Nephrology and Hypertension - May 29, 2020 Category: Urology & Nephrology Tags: RENAL PATHOPHYSIOLOGY: Edited by Orson W. Moe and Susan E. Quaggin Source Type: research

The role of PPARα in autosomal dominant polycystic kidney disease
Purpose of review Metabolic reprogramming is a prominent feature of cyst epithelial cells in autosomal dominant polycystic kidney disease (ADPKD). Peroxisome proliferator activated receptor alpha (PPARα) is a transcription factor that regulates many aspects of cellular metabolism. The purpose of this review is to understand the role of PPARα in ADPKD. Recent findings PPARα expression is reduced in ADPKD kidneys of mice and humans. This downregulation is in part secondary to microRNA mediated translational repression and leads to impairment of fatty acid metabolism. Genetic studies demonstrate that deletion of PparÎ...
Source: Current Opinion in Nephrology and Hypertension - May 29, 2020 Category: Urology & Nephrology Tags: RENAL PATHOPHYSIOLOGY: Edited by Orson W. Moe and Susan E. Quaggin Source Type: research

The role of uric acid in inflammasome-mediated kidney injury
Purpose of review Uric acid is produced after purine nucleotide degradation, upon xanthine oxidase catalytic action. In the evolutionary process, humans lost uricase, an enzyme that converts uric acid into allantoin, resulting in increased serum uric acid levels that may vary according to dietary ingestion, pathological conditions, and other factors. Despite the controversy over the inflammatory role of uric acid in its soluble form, crystals of uric acid are able to activate the NLRP3 inflammasome in different tissues. Uric acid, therefore, triggers hyperuricemic-related disease such as gout, metabolic syndrome, and kid...
Source: Current Opinion in Nephrology and Hypertension - May 29, 2020 Category: Urology & Nephrology Tags: RENAL PATHOPHYSIOLOGY: Edited by Orson W. Moe and Susan E. Quaggin Source Type: research

Hypoxia-inducible factor prolyl hydroxylase inhibitor in the treatment of anemia in chronic kidney disease
Purpose of review Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are orally active small molecules and are launched as novel therapeutic agents for anemia in chronic kidney disease (CKD). In contrast to conventional exogenous erythropoietin (EPO) administration, HIF-PHIs stimulate endogenous EPO production and improve iron metabolism via stabilization of hypoxia-inducible factor (HIF). This review summarizes the mechanism of action, the results of clinical trials, and future perspectives of HIF-PHIs. Recent findings Six HIF-PHIs are currently under phase III studies, some of which have been already ...
Source: Current Opinion in Nephrology and Hypertension - May 29, 2020 Category: Urology & Nephrology Tags: RENAL PATHOPHYSIOLOGY: Edited by Orson W. Moe and Susan E. Quaggin Source Type: research

Uric acid stone disease: lessons from recent human physiologic studies
Purpose of review An overly acidic urine resulting in supersaturation of urine with respect to uric acid is the major mechanism responsible for uric acid nephrolithiasis. The present review summarizes findings from recent human physiologic studies examining the pathophysiology and reversibility of low urine pH in uric acid stone formers. Recent findings Epidemiologic and metabolic studies have confirmed an increase in the prevalence of uric acid nephrolithiasis and reported its association with several features of the metabolic syndrome including dyslipidemia, hyperglycemia, hepatic steatosis, and greater visceral adi...
Source: Current Opinion in Nephrology and Hypertension - May 29, 2020 Category: Urology & Nephrology Tags: MINERAL METABOLISM: Edited by Aline Martin and Tamara Isakova Source Type: research

Lessons from rodent gastric bypass model of enteric hyperoxaluria
Purpose of review The aim of the article is to review studies on bone health and oxalate metabolism/therapeutics in the obese rodent model of Roux-en-Y gastric bypass (RYGB) and examine pathways to decrease procedural morbidity. Recent findings Compared with controls, RYGB rodents have up to 40-fold more fat in their stool (steatorrhea) which positively correlates to increased urinary oxalate. These unabsorbed intestinal fatty acids bind calcium and prevent gut calcium oxalate formation, increasing soluble luminal oxalate availability and absorption (enteric hyperoxaluria). When intraluminal fecal fat exceeded about 1...
Source: Current Opinion in Nephrology and Hypertension - May 29, 2020 Category: Urology & Nephrology Tags: MINERAL METABOLISM: Edited by Aline Martin and Tamara Isakova Source Type: research

Stiripentol identifies a therapeutic target to reduce oxaluria
Purpose of review Oxalate is a metabolic end-product promoting the formation of calcium oxalate crystals in urine. Massive urine oxalate excretion occurs in genetic diseases, mainly primary hyperoxaluria type I and II, threatening renal function. Ethylene glycol poisoning may induce the precipitation of calcium oxalate crystals in renal tubules, leading to acute renal failure. In both cases, oxalate results from glyoxylate transformation to oxalate in the liver, by lactate dehydrogenase (LDH) enzymes, especially the LDH-5 isoenzyme. The purpose of the review is to highlight LDH as a potential therapeutic target according...
Source: Current Opinion in Nephrology and Hypertension - May 29, 2020 Category: Urology & Nephrology Tags: MINERAL METABOLISM: Edited by Aline Martin and Tamara Isakova Source Type: research