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Clinical Journal of the American... Aug 2023Sodium-glucose cotransporter 2 (SGLT2) inhibitors attenuate incident cardiovascular outcomes, irrespective of baseline GFR, in conservatively managed CKD. As this...
BACKGROUND
Sodium-glucose cotransporter 2 (SGLT2) inhibitors attenuate incident cardiovascular outcomes, irrespective of baseline GFR, in conservatively managed CKD. As this condition inexorably progresses to demanding KRT, drug withdrawal is supported by the current lack of evidence of safety of SGLT2 inhibitors in dialysis.
METHODS
This study was a prospective, single-center, open-label trial ( ClinicalTrials.gov identifier: NCT05343078 ) aimed at assessing the pharmacokinetic properties and safety of dapagliflozin in patients with kidney failure on regular dialysis regimens compared with those with type 2 diabetes and age- and sex-matched controls with normal kidney function. Peripheral blood samples were collected from both groups every 30 minutes for 4 hours and again after 48 hours after ingestion of dapagliflozin 10 mg, which occurred immediately before dialysis session initiation in the kidney failure group. This protocol occurred in drug-naïve patients and again after six daily doses of dapagliflozin to assess whether the drug had accumulated. The plasma and dialysate levels of dapagliflozin at each time point were determined by liquid chromatography and used to calculate pharmacokinetics parameters (peak concentration [C max ] and area under the plasma concentration-versus-time curve) for each participant.
RESULTS
Dapagliflozin C max was 117 and 97.6 ng/ml in the kidney failure and control groups, respectively, whereas the corresponding accumulation ratios were 26.7% and 9.5%. No serious adverse events were reported for either group. Dapagliflozin recovered from dialysate corresponded to 0.10% of the administered dose.
CONCLUSIONS
In patients with kidney failure on dialysis, dapagliflozin was well tolerated, was slightly dialyzable, and had nonaccumulating pharmacokinetic properties.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
Pharmacokinetics and Dialyzability of Dapagliflozin in Dialysis Patients (DARE-ESKD 1), NCT05343078.
Topics: Humans; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Prospective Studies; Peritoneal Dialysis; Renal Dialysis; Renal Insufficiency; Dialysis Solutions
PubMed: 37227937
DOI: 10.2215/CJN.0000000000000196 -
Nature Reviews. Nephrology Aug 2023Haemodialysis is life sustaining but expensive, provides limited removal of uraemic solutes, is associated with poor patient quality of life and has a large carbon... (Review)
Review
Haemodialysis is life sustaining but expensive, provides limited removal of uraemic solutes, is associated with poor patient quality of life and has a large carbon footprint. Innovative dialysis technologies such as portable, wearable and implantable artificial kidney systems are being developed with the aim of addressing these issues and improving patient care. An important challenge for these technologies is the need for continuous regeneration of a small volume of dialysate. Dialysate recycling systems based on sorbents have great potential for such regeneration. Novel dialysis membranes composed of polymeric or inorganic materials are being developed to improve the removal of a broad range of uraemic toxins, with low levels of membrane fouling compared with currently available synthetic membranes. To achieve more complete therapy and provide important biological functions, these novel membranes could be combined with bioartificial kidneys, which consist of artificial membranes combined with kidney cells. Implementation of these systems will require robust cell sourcing; cell culture facilities annexed to dialysis centres; large-scale, low-cost production; and quality control measures. These challenges are not trivial, and global initiatives involving all relevant stakeholders, including academics, industrialists, medical professionals and patients with kidney disease, are required to achieve important technological breakthroughs.
Topics: Humans; Kidneys, Artificial; Quality of Life; Renal Dialysis; Dialysis Solutions; Wearable Electronic Devices
PubMed: 37277461
DOI: 10.1038/s41581-023-00726-9 -
American Journal of Kidney Diseases :... Oct 2023Fatigue surrounding hemodialysis treatments is a common and often debilitating symptom that impacts patients' quality of life. Intradialytic fatigue develops or worsens... (Review)
Review
Fatigue surrounding hemodialysis treatments is a common and often debilitating symptom that impacts patients' quality of life. Intradialytic fatigue develops or worsens immediately before hemodialysis and persists through the dialysis treatment. Little is known about associated risk factors or pathophysiology, although it may relate to a classic conditioning response. Postdialysis fatigue (PDF) develops or worsens after hemodialysis and may persist for hours. There is no consensus on how to measure PDF. Estimates for the prevalence of PDF range from 20%-86%, likely due to variation in methods of ascertainment and participant characteristics. Several hypotheses seek to explain the pathophysiology of PDF, including inflammation, hypothalamic-pituitary-adrenal axis dysregulation, and osmotic and fluid shifts, but none is currently supported by compelling or consistent data. PDF is associated with several clinical factors, including cardiovascular and hemodynamic effects of the dialysis procedure, laboratory abnormalities, depression, and physical inactivity. Clinical trials have reported hypothesis-generating data about the utility of cold dialysate, frequent dialysis, clearance of large middle molecules, treatment of depression, and exercise as potential treatments. Existing studies are often limited by sample size, lack of a control group, observational design, or short intervention duration. Robust studies are needed to establish the pathophysiology and management of this important symptom.
Topics: Humans; Quality of Life; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Renal Dialysis; Fatigue
PubMed: 37187283
DOI: 10.1053/j.ajkd.2023.02.008 -
Journal of the American Society of... Apr 2024Apparent treatment-resistant hypertension is defined as an elevated BP despite the use of ≥3 antihypertensive medications from different classes or the use of ≥4... (Review)
Review
Apparent treatment-resistant hypertension is defined as an elevated BP despite the use of ≥3 antihypertensive medications from different classes or the use of ≥4 antihypertensives regardless of BP levels. Among patients receiving maintenance hemodialysis or peritoneal dialysis, using this definition, the prevalence of apparent treatment-resistant hypertension is estimated to be between 18% and 42%. Owing to the lack of a rigorous assessment of some common causes of pseudoresistance, the burden of true resistant hypertension in the dialysis population remains unknown. What distinguishes apparent treatment-resistance from true resistance is white-coat hypertension and adherence to medications. Accordingly, the diagnostic workup of a dialysis patient with apparent treatment-resistant hypertension on dialysis includes the accurate determination of BP control status with the use of home or ambulatory BP monitoring and exclusion of nonadherence to the prescribed antihypertensive regimen. In a patient on dialysis with inadequately controlled BP, despite adherence to therapy with maximally tolerated doses of a β -blocker, a long-acting dihydropyridine calcium channel blocker, and a renin-angiotensin system inhibitor, volume-mediated hypertension is the most important treatable cause of resistance. In daily clinical practice, such patients are often managed with intensification of antihypertensive therapy. However, this therapeutic strategy is likely to fail if volume overload is not adequately recognized or treated. Instead of increasing the number of prescribed BP-lowering medications, we recommend diet and dialysate restricted in sodium to facilitate achievement of dry weight. The achievement of dry weight is facilitated by an adequate time on dialysis of at least 4 hours for delivering an adequate dialysis dose. In this article, we review the epidemiology, diagnosis, and management of resistant hypertension among patients on dialysis.
Topics: Humans; Antihypertensive Agents; Renal Dialysis; Hypertension; Calcium Channel Blockers; White Coat Hypertension; Blood Pressure
PubMed: 38227447
DOI: 10.1681/ASN.0000000000000315 -
JPMA. the Journal of the Pakistan... May 2024This communication conceptualizes and characterizes the phenomenon of dialysis distress, commonly encountered in persons living with end stage kidney disease on...
This communication conceptualizes and characterizes the phenomenon of dialysis distress, commonly encountered in persons living with end stage kidney disease on dialysis. Dialysis distress can be defined as an emotional state, marked by extreme apprehension, anxiety, despair and/or dejection, due to a perceived inability to cope with the challenges and demands of living with dialysis. This concept can be extrapolated to persons who undergo renal replacement therapy such as renal transplant. Dialysis distress should be identified in a timely manner, and managed using appropriate support, counselling and education, delivered in an empathic manner.
Topics: Humans; Renal Dialysis; Kidney Failure, Chronic; Stress, Psychological; Psychological Distress; Adaptation, Psychological; Anxiety
PubMed: 38783457
DOI: 10.47391/JPMA.24-37 -
Kidney International Sep 2023Individuals with kidney failure undergoing maintenance dialysis frequently report a high symptom burden that can interfere with functioning and diminish life...
Individuals with kidney failure undergoing maintenance dialysis frequently report a high symptom burden that can interfere with functioning and diminish life satisfaction. Until recently, the focus of nephrology care for dialysis patients has been related primarily to numerical targets for laboratory measures, and outcomes such as cardiovascular disease and mortality. Routine symptom assessment is not universal or standardized in dialysis care. Even when symptoms are identified, treatment options are limited and are initiated infrequently, in part because of a paucity of evidence in the dialysis population and the complexities of medication interactions in kidney failure. In May of 2022, Kidney Disease: Improving Global Outcomes (KDIGO) held a Controversies Conference-Symptom-Based Complications in Dialysis-to identify the optimal means for diagnosing and managing symptom-based complications in patients undergoing maintenance dialysis. Participants included patients, physicians, behavioral therapists, nurses, pharmacists, and clinical researchers. They outlined foundational principles and consensus points related to identifying and addressing symptoms experienced by patients undergoing dialysis and described gaps in the knowledge base and priorities for research. Healthcare delivery and education systems have a responsibility to provide individualized symptom assessment and management. Nephrology teams should take the lead in symptom management, although this does not necessarily mean taking ownership of all aspects of care. Even when options for clinical response are limited, clinicians should focus on acknowledging, prioritizing, and managing symptoms that are most important to individual patients. A recognized factor in the initiation and implementation of improvements in symptom assessment and management is that they will be based on locally existing needs and resources.
Topics: Humans; Kidney; Kidney Diseases; Kidney Failure, Chronic; Nephrology; Renal Dialysis
PubMed: 37290600
DOI: 10.1016/j.kint.2023.05.019 -
Clinical Journal of the American... Mar 2024Peritoneal dialysis (PD) enables people to have a home-based therapy, permitting greater autonomy for individuals along with enhanced treatment satisfaction compared... (Review)
Review
Peritoneal dialysis (PD) enables people to have a home-based therapy, permitting greater autonomy for individuals along with enhanced treatment satisfaction compared with in-center dialysis care. The burden of treatment on PD, however, remains considerable and underpins the need for person-centered care. This reflects the need to address the patient as a person with needs and preferences beyond just the medical perspective. Shared decision making is central to the recent International Society for Peritoneal Dialysis recommendations for prescribing PD, balancing the potential benefits of PD on patient well-being with the burden associated with treatment. This review considers the role of high-quality goal-directed prescribing, incremental dialysis, and remote patient monitoring in reducing the burden of dialysis, including an approach to implementing incremental PD. Although patient-related outcomes are important in assessing the response to treatment and, particularly life participation, the corollary of dialysis burden, there are no clear routes to the clinical implementation of patient-related outcome measures. Delivering person-centered care is dependent on treating people both as individuals and as equal partners in their care.
Topics: Humans; Peritoneal Dialysis; Renal Dialysis; Outcome Assessment, Health Care; Patients
PubMed: 37611155
DOI: 10.2215/CJN.0000000000000281 -
JAMA Jan 2024
Topics: Renal Dialysis; Healthcare Disparities; Government Regulation; Federal Government; United States
PubMed: 38193972
DOI: 10.1001/jama.2023.18590 -
The Surgical Clinics of North America Aug 2023Many end-stage kidney failure patients require hemodialysis as a life-sustaining treatment. Hemodialysis access via arteriovenous fistula or graft creation is preferred... (Review)
Review
Many end-stage kidney failure patients require hemodialysis as a life-sustaining treatment. Hemodialysis access via arteriovenous fistula or graft creation is preferred over long-term dialysis catheters, but intervention to maintain patency and prevent access failure is common. Endovascular and open surgical techniques are both utilized to address the underlying etiology of failure. Endovascular options include balloon angioplasty, angioplasty with stenting, and drug-eluting stents. Open revision is commonly needed for recurrent stenosis, aneurysmal or pseudoaneurysmal change, hemodialysis access-induced distal ischemia, and infection. Treatment plans should be guided by patient's individualized goals of care and require a multidisciplinary approach to the management of this complex disease.
Topics: Humans; Graft Occlusion, Vascular; Vascular Patency; Renal Dialysis; Kidney Failure, Chronic; Angioplasty, Balloon; Stents; Treatment Outcome
PubMed: 37455032
DOI: 10.1016/j.suc.2023.05.004 -
The Surgical Clinics of North America Aug 2023End-stage kidney disease (ESKD) affects nearly 800,000 patients in the United States. The choice of peritoneal dialysis (PD) versus hemodialysis (HD) should be patient... (Review)
Review
End-stage kidney disease (ESKD) affects nearly 800,000 patients in the United States. The choice of peritoneal dialysis (PD) versus hemodialysis (HD) should be patient centric. An ESKD Life-Plan is crucial with the goal of creating the right access, for the right patient, at the right time, for the right reason. Complex access should be considered when straightforward access options have been exhausted. Evolving techniques such as percutaneous access for HD and PD should be further investigated. Shared decision-making and palliative care is an essential part of the care of patients with CKD and ESKD..
Topics: Humans; United States; Renal Dialysis; Arteriovenous Shunt, Surgical; Peritoneal Dialysis; Kidney Failure, Chronic; Catheterization, Central Venous
PubMed: 37455031
DOI: 10.1016/j.suc.2023.05.006