Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Sodium Intake as a Modulator of Kidney Function

Individual responses to alterations in salt intake vary widely. While salt has no effect on blood pressure in some people, it may substantially increase pressure in others. The reason why this difference exists is not very clear yet but many observations point towards the kidney as an important mediator. The adaptation in urinary output of sodium after a salt challenge (increase or decrease) also is not uniform. It is thought that the renin-angiotensin system may play an important role in determining how much sodium the body expels or retains after salt intake is suddenly reduced or augmented. Recent data suggest that the peptide Ang (1-7) and the endogenous nitric oxide inhibitor asymmetric dimethylarginine could be critically involved in the regulation of the renal response to altered salt intake

Sensitivity of Blood Pressure and Renin Activation During Sodium Restriction

Abstract The objective of the present study was to explore the interrelationships among cumulative sodium loss, renin activation, and blood pressure changes during sodium restriction in essential hypertensive patients. Specifically, we wanted to know whether the degree of sodium sensitivity of blood pressure depends on renin activation during steady state or on initial renin activation during the first days of sodium restriction. Sixty-seven untreated essential hypertensive patients were admitted to a metabolic ward for 8 days and put on a sodium restricted diet of 55 mmol/d from the second to the last day. Urinary excretions of sodium, potassium, and creatinine were determined along with mean arterial pressure and weight during 7 days. Besides measurements in steady state condition (after 7 days), active plasma renin concentration, aldosterone, and catecholamines were also assessed during the first 3 days of sodium restriction. Analyzable data are available for 55 patients. Baseline sodium excretion and the activation of renin during the first 3 days both appeared to be predictors of total sodium loss after 7 days. Changes in blood pressure were not related to changes in sodium balance, but they were to baseline blood pressure, baseline norepinephrine, and renin activation during the early phase of sodium restriction. In addition, blood pressure appeared to fall more when the normal relationship between sodium loss and early (but not late) activation of renin was disturbed. We conclude that sodium sensitivity of blood pressure during sodium restriction is associated with a relative unresponsiveness of the renin system during the early phase of sodium loss rather than to absolute renin levels during steady state. </jats:p

General practitioner use of D-dimer in suspected venous thromboembolism: historical cohort study in one geographical region in the Netherlands

Objectives To investigate how many general practitioner (GP)-referred venous thromboembolic events (VTEs) are diagnosed during 1 year in one geographical region and to investigate the (urgent) referral pathway of VTE diagnoses, including the role of laboratory D-dimer testing.Design Historical cohort study.Setting GP patients of 47 general practices in a demarcated geographical region of 161 503 inhabitants in the Netherlands.Participants We analysed all 895 primary care patients in whom either the GP determined a D-dimer value or who had a diagnostic work-up for suspected VTE in a non-academic hospital during 2015.Primary and secondary outcome measures The primary outcomes of this study were the total number of VTEs per year and the diagnostic pathways—including the role of GP determined D-dimer testing—of patients urgently referred to secondary care for suspected VTE. Additionally, we explored the use of an age-adjusted D-dimer cut-off.Results The annual VTE incidence was 0.9 per 1000 inhabitants. GPs annually ordered 5.1 D-dimer tests per 1000 inhabitants. Of 470 urgently GP-referred patients, 31.3% had a VTE. Of those urgently referred based on clinical assessment only (without D-dimer testing), 73.8% (96/130) had a VTE; based on clinical assessment and laboratory D-dimer testing yielded 15.0% (51/340) VTE. Applying age-adjusted D-dimer cut-offs to all patients aged 50 years or older resulted in a reduction of positive D-dimer results from 97.9% to 79.4%, without missing any VTE.Conclusions Although D-dimer testing contributes to the diagnostic work-up of VTE, GPs have a high detection rate for VTE in patients who they urgently refer to secondary care based on clinical assessment only

Impact of phosphate binders on quality of life in dialysis patients: Results from the prospective Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes study

Background: Phosphate binders cause high pill burden for dialysis patients, complicate medication regimens, and have unpleasant taste and large size which may affect patients' quality of life. This study explores the association between phosphate binder pill burden and health-related quality of life (HRQoL) in dialysis patients. Methods: We conducted a cross-sectional multi-centre cohort study in 21 Dutch dialysis centres. Phosphate binder pill burden was extracted from electronic patient records. Primary outcome was HRQoL measured with the Short Form 12 physical and mental component summary scores (PCS and MCS). Secondary endpoints were severity of gastro-intestinal symptoms, itching, dry mouth, and mental health symptoms, measured with the Dialysis Symptom Index. Results: Of 388 included patients, aged 62 ± 16 years, 77% underwent haemodialysis. PCS scores were comparable for patients with and without phosphate binders. Patients using 1–3 pills reported lower scores for decreased appetite (β −0.5; 95%CI −0.9 to −0.2), implying better appetite, than patients without phosphate binders. Patients using 4–6 pills also reported lower scores for decreased appetite (β −0.5; 95%CI −0.8 to −0.1) and for itching (β −0.5; 95%CI −0.9 to −0.1). Patients using >6 pills reported lower MCS (β −2.9; 95%CI −6.2–0.4) and higher scores for feeling nervous (β 0.6; 95%CI 0.1–1.1) and feeling sad (β 0.4; 95%CI 0.0–0.9). Conclusion: Phosphate binder pill burden is not associated with physical quality of life. A higher pill burden is associated with better appetite and less itching. Patients using >6 pills per day report lower mental quality of life and felt nervous and sad more often