Effects of Patiromer and Sodium Zirconium Cyclosilicate on Blood Pressure in Rats with Chronic Kidney Disease.

Background: Potassium-binders patiromer and sodium zirconium cyclosilicate (SZC) are approved to treat hyperkalaemia, which is frequently observed in chronic kidney disease (CKD). Elevated blood pressure (BP) is common in CKD, due in part to impaired sodium excretion. The effect of patiromer, which exchanges calcium for potassium and SZC, which exchanges sodium or hydrogen for potassium, on BP was assessed in a CKD rat model.

Unbiased kidney-centric molecular categorization of chronic kidney disease as a step towards precision medicine.

Current classification of chronic kidney disease (CKD) into stages using indirect systemic measures (estimated glomerular filtration rate (eGFR) and albuminuria) is agnostic to the heterogeneity of underlying molecular processes in the kidney thereby limiting precision medicine approaches. To generate a novel CKD categorization that directly reflects within kidney disease drivers we analyzed publicly available transcriptomic data from kidney biopsy tissue. A Self-Organizing Maps unsupervised artificial neural network machine-learning algorithm was used to stratify a total of 369 patients with CKD and 46 living kidney donors as healthy controls.

Maintaining Renin-Angiotensin-Aldosterone System Inhibitor Treatment with Patiromer in Hyperkalaemic Chronic Kidney Disease Patients: Comparison of a Propensity-Matched Real-World Population with AMETHYST-DN.

Introduction: Guideline-directed renin-angiotensin-aldosterone system inhibitor (RAASi) therapy is rarely achieved in clinical settings, often due to hyperkalaemia. We assessed the potassium binder, patiromer, on continuation of RAASi therapy in hyperkalaemic patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) in the AMETHYST-DN trial, propensity score-matched to a real-world cohort not receiving patiromer (Salford Kidney Study).

Methods: The phase 2, open-label AMETHYST-DN trial (NCT01371747) randomized 304 adults with CKD on RAASi, T2DM, hyperkalaemia (serum potassium [sK+] >5.

Patiromer utility as an adjunct treatment in patients needing urgent hyperkalaemia management (PLATINUM): design of a multicentre, randomised, double-blind, placebo-controlled, parallel-group study.

Introduction: Hyperkalaemia is common, life-threatening and often requires emergency department (ED) management; however, no standardised ED treatment protocol exists. Common treatments transiently reducing serum potassium (K) (including albuterol, glucose and insulin) may cause hypoglycaemia. We outline the design and rationale of the Patiromer Utility as an Adjunct Treatment in Patients Needing Urgent Hyperkalaemia Management (PLATINUM) study, which will be the largest ED randomised controlled hyperkalaemia trial ever performed, enabling assessment of a standardised approach to hyperkalaemia management, as well as establishing a new evaluation parameter (net clinical benefit) for acute hyperkalaemia treatment investigations.

Patiromer Treatment in Patients With CKD, Hyperkalemia, and Hyperphosphatemia: A Post Hoc Analysis of 3 Clinical Trials.

Rationale & Objective: Patients with chronic kidney disease (CKD), hyperkalemia (serum potassium [sK]>5.0 mEq/L), and hyperphosphatemia experience poor clinical outcomes. Patiromer, a potassium binder that uses calcium as the exchange ion, may also reduce serum phosphorus (sP).

Patiromer utilization in patients with advanced chronic kidney disease under nephrology care in Germany.

Background: Hyperkalemia (HK) is a frequent condition in patients with chronic kidney disease (CKD) that is associated with high morbidity and mortality. Patiromer has recently been introduced as a potassium binder. Data on patiromer use in patients with CKD in the real-world setting in Europe are lacking.

Safety and Efficacy of Patiromer in Hyperkalemic Patients with CKD: A Pooled Analysis of Three Randomized Trials.

Background: Hyperkalemia is a common electrolyte abnormality in patients with CKD, which is associated with worse outcomes and limits use of renin-angiotensin-aldosterone system inhibitors (RAASi). This subgroup analysis of three clinical trials evaluated the efficacy and safety of the sodium-free, potassium-binding polymer, patiromer, for the treatment of hyperkalemia in adults with nondialysis CKD.

Methods: Data from the 4-week treatment periods of AMETHYST-DN, OPAL-HK, and TOURMALINE studies were combined.

Patiromer for the management of hyperkalaemia in patients receiving renin-angiotensin-aldosterone system inhibitors for heart failure: design and rationale of the DIAMOND trial.

Aims: In patients with current or a history of hyperkalaemia, treatment with renin-angiotensin-aldosterone system inhibitors (RAASi) is often compromised. Patiromer, a novel potassium (K ) binder, may improve serum K levels and adherence to RAASi.

Methods: The DIAMOND trial will enroll ∼820 patients with heart failure with reduced ejection fraction (HFrEF; ejection fraction ≤40%).

Hyperkalemia excursions are associated with an increased risk of mortality and hospitalizations in hemodialysis patients.

Background: Hyperkalemia is common among hemodialysis (HD) patients and has been associated with adverse clinical outcomes. Previous studies considered a single serum potassium (K) measurement or time-averaged values, but serum K excursions out of the target range may be more reflective of true hyperkalemia events. We assessed whether hyperkalemia excursions lead to an elevated risk of adverse clinical outcomes.

Characteristics, Symptom Severity, and Experiences of Patients Reporting Chronic Kidney Disease in the PatientsLikeMe Online Health Community: Retrospective and Qualitative Study.

Background: Chronic kidney disease (CKD) is a major global health burden, and is associated with increased adverse outcomes, poor quality of life, and substantial health care costs. While there is an increasing need to build patient-centered pathways for improving CKD management in clinical care, data in this field are scarce.

Objective: The aim of this study was to understand patient-reported experiences, symptoms, outcomes, and treatment journeys among patients with CKD through a retrospective and qualitative approach based on data available through PatientsLikeMe (PLM), an online community where patients can connect and share experiences.

Sodium zirconium cyclosilicate increases serum bicarbonate concentrations among patients with hyperkalaemia: exploratory analyses from three randomized, multi-dose, placebo-controlled trials.

Background: Sodium zirconium cyclosilicate (SZC) binds potassium and ammonium in the gastrointestinal tract. In addition to serum potassium reduction, Phase 2 trial data have shown increased serum bicarbonate with SZC, which may be clinically beneficial because maintaining serum bicarbonate ≥22 mmol/L preserves kidney function. This exploratory analysis examined serum bicarbonate and urea, and urine pH data from three SZC randomized, placebo-controlled Phase 3 studies among patients with hyperkalaemia [ZS-003 (n = 753), HARMONIZE (n = 258) and HARMONIZE-Global (n = 267)].

Optimization of RNA extraction from laser captured microdissected glomeruli from formalin-fixed paraffin-embedded mouse kidney samples for Nanostring analysis.

Optimized protocols for the microdissection of specific areas from archival tissues and the subsequent RNA analysis are needed but challenging due to RNA degradation and chemical modifications. The aim of this study was to present the most appropriate protocol for utilizing mouse FFPE kidney for laser capture microdissection and Nanostring gene expression analysis. We evaluated different section thicknesses (3, 5, 10 μm), 2 RNA extraction kits (Qiagen and Roche) and different H&E staining methods to optimize microdissection and RNA extraction from glomeruli and cortical tubules samples from FFPE mouse kidney.

Renal Pre-Competitive Consortium (RPC): discovering therapeutic targets together.

Despite significant effort, patients with kidney disease have not seen their outcomes improved significantly over the past two decades. This has motivated clinicians and researchers to consider alternative methods to identifying risk factors, disease progression markers, and effective therapies. Genome-scale data sets from patients with renal disease can be used to establish a platform to improve understanding of the molecular basis of disease; however, such studies require expertise and resources.

Inhibition of T-cell activation by the CTLA4-Fc Abatacept is sufficient to ameliorate proteinuric kidney disease.

Diabetic nephropathy (DN) remains an unmet medical challenge as its prevalence is projected to continue to increase and specific medicines for treatment remain undeveloped. Activation of the immune system, in particular T-cells, is emerging as a possible mechanism underlying DN disease progression in humans and animal models. We hypothesized that inhibition of T-cell activation will ameliorate DN.