No abstract

Background The effects of the sodium-glucose co-transporter-2 inhibitor empagliflozin on renal and cardiovascular disease have not been tested in a dedicated population of people with chronic kidney disease (CKD). Methods The EMPA-KIDNEY trial is an international randomized, double-blind, placebo-controlled trial assessing whether empagliflozin 10 mg daily reduces risk of kidney disease progression or cardiovascular death in people with CKD. People with or without diabetes mellitus (DM) were eligible provided they had: (i) an estimated glomerular filtration rate (eGFR) ≥20, <45 mL/min/1.73m2;  or (ii) an eGFR ≥ 45, <90 mL/min/1.73m2 with a urinary albumin: creatinine ratio (uACR) ≥200 mg/g. The trial design is streamlined: extra work for collaborating sites is kept to a minimum, and only essential information is collected. Results Between 15 May 2019 and 16 April 2021, 6609 people from eight countries in Europe, North America and East Asia were randomized. Mean age at randomization was 63.8 (SD 13.9) years, 2192 (33%) were female, and 3570 (54%) had no prior history of DM. Mean eGFR was 37.5 (14.8) mL/min/1.73m2, including 5185 (78%) with an eGFR < 45 mL/min/1.73m2. Median (Q1-Q3) uACR was 412 (94–1190) mg/g, with a uACR < 300 mg/g in 3194 (48%). The causes of kidney disease included diabetic kidney disease (n = 2057 [31%]), glomerular disease (n = 1669 [25%]), hypertensive/renovascular disease (n = 1445 [22%]), other (n = 808 [12%]), and unknown causes (n = 630 [10%]). Conclusions EMPA-KIDNEY will evaluate the efficacy and safety of empagliflozin in a widely generalizable population of people with CKD at risk of kidney disease progression. Results are anticipated in 2022.

The pathophysiology and trajectory of post-Coronavirus Disease 2019 (COVID-19) syndrome is uncertain. To clarify multisystem involvement, we undertook a prospective cohort study including patients who had been hospitalized with COVID-19 (ClinicalTrials.gov ID NCT04403607). Serial blood biomarkers, digital electrocardiography and patient-reported outcome measures were obtained in-hospital and at 28–60 days post-discharge when multisystem imaging using chest computed tomography with pulmonary and coronary angiography and cardio-renal magnetic resonance imaging was also obtained. Longer-term clinical outcomes were assessed using electronic health records. Compared to controls (n = 29), at 28–60 days post-discharge, people with COVID-19 (n = 159; mean age, 55 years; 43% female) had persisting evidence of cardio-renal involvement and hemostasis pathway activation. The adjudicated likelihood of myocarditis was ‘very likely’ in 21 (13%) patients, ‘probable’ in 65 (41%) patients, ‘unlikely’ in 56 (35%) patients and ‘not present’ in 17 (11%) patients. At 28–60 days post-discharge, COVID-19 was associated with worse health-related quality of life (EQ-5D-5L score 0.77 (0.23) versus 0.87 (0.20)), anxiety and depression (PHQ-4 total score 3.59 (3.71) versus 1.28 (2.67)) and aerobic exercise capacity reflected by predicted maximal oxygen utilization (20.0 (7.6) versus 29.5 (8.0) ml/kg/min) (all P < 0.01). During follow-up (mean, 450 days), 24 (15%) patients and two (7%) controls died or were rehospitalized, and 108 (68%) patients and seven (26%) controls received outpatient secondary care (P = 0.017). The illness trajectory of patients after hospitalization with COVID-19 includes persisting multisystem abnormalities and health impairments that could lead to substantial demand on healthcare services in the future.

No abstract

No abstract

Background Lymphocyte ratios reflect inflammation and have been associated with adverse outcomes in a range of diseases. We sought to determine any association between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and mortality in a haemodialysis cohort, including a COVID-19 infection subpopulation. Methods A retrospective analysis was performed of adults commencing hospital haemodialysis in the West of Scotland 2010–2021. NLR and PLR were calculated from routine samples around haemodialysis initiation. Kaplan-Meier and Cox proportional hazards analyses assessed mortality associations. Results In 1720 haemodialysis patients over a median of 21.9 (IQR 9.1–42.9) months, there were 840 all-cause deaths. NLR but not PLR was associated with all-cause mortality after multivariable adjustment [adjusted hazard ratio (aHR) for in participants with baseline NLR in quartile 4 (NLR ≥ 8.23) versus quartile 1 (NLR &lt; 3.12) 1.63, 95% confidence interval (CI) 1.32–2.00]. The association was stronger for cardiovascular death (NLR quartile 4 versus 1 aHR 3.06, 95% CI 1.53–6.09) than for non-cardiovascular death (NLR quartile 4 versus 1 aHR 1.85, 95% CI 1.34–2.56). In the COVID-19 subpopulation, both NLR and PLR at haemodialysis initiation were associated with risk of COVID-19-related death after adjustment for age and sex (NLR: aHR 4.69, 95% CI 1.48–14.92 and PLR: aHR 3.40, 95% CI 1.02–11.36; for highest vs lowest quartiles). Conclusions NLR is strongly associated with mortality and specifically COVID-19-related death in haemodialysis patients while the association between PLR and adverse outcomes is weaker. NLR is an inexpensive, readily available biomarker with potential utility in risk stratification of haemodialysis patients.

Characterizing structural and tissue abnormalities of the kidney is fundamental to understanding kidney disease. Functional multi‐parametric renal magnetic resonance imaging (MRI) is a noninvasive imaging strategy whereby several sequences are employed within a single session to quantify renal perfusion, tissue oxygenation, fibrosis, inflammation, and oedema without using ionizing radiation. In this review, we discuss evidence surrounding its use in several clinical settings including acute kidney injury, chronic kidney disease, hypertension, polycystic kidney disease and around renal transplantation. Kidney size on MRI is already a validated measure for making therapeutic decisions in the setting of polycystic kidney disease. Functional MRI sequences, T1 mapping and apparent diffusion coefficient, can non‐invasively quantify interstitial fibrosis and so may have a near‐future role in the nephrology clinic to stratify the risk of progressive chronic kidney disease or transplant dysfunction. Beyond this, multi‐parametric MRI may be used diagnostically, for example differentiating inflammatory versus ischaemic causes of renal dysfunction, but this remains to be proven. Changes in MRI properties of kidney parenchyma may be useful surrogate markers to use as end points in clinical trials to assess if drugs prevent renal fibrosis or alter kidney perfusion. Large, multi‐centre studies of functional renal MRI are ongoing which aim to provide definitive answers as to its role in the management of patients with renal dysfunction.

Bioimpedance devices estimate body water and fat by measuring opposition to an electrical current applied via the skin. The most commonly reported device from existing dialysis literature is the Fresenius Body Composition Monitor (BCM), which uses bioimpedance spectroscopy (BIS). Although sometimes used interchangeably, BIS is not synonymous with bioimpedance analysis (BIA). BIA traditionally used only a single frequency before multifrequency BIA devices were developed, which measure impedance at 50-200 discrete frequencies from 3 to 1000 kHz. BIS extends this range by extrapolation to zero and infinity kHz. Greater frequency range improves discrimination of extracellular (ECW) from intracellular water. All BIS/BIA devices also estimate lean and fat tissue, but the BCM uniquely specifically quantifies fluid overload independent of body composition using the threecompartment model [1].