Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models adjusting for atherosclerotic risk factors (per relevant risk scores), and predictive utility was determined by the C-statistic and categorical Net Reclassification Index. We show that eGFRcys is most strongly associated with CVD and mortality, and along with albuminuria adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Stem cell therapy holds great promise in medicine, but clinical development should be based on a sound understanding of potential weaknesses in supporting experimental data. The aim of this article was to provide a systematic overview of evidence relating to the efficacy of stem cell-based therapies in animal models of stroke to foster the clinical application of stem cell-based therapies and to inform the design of large-scale clinical trials. We conducted a systematic search for reports of experiments using stem cells in animal models of cerebral ischaemia, and performed DerSimmonian and Laird random effects meta-analysis. We assessed the impact of study characteristics, of publication bias and of measures to reduce bias. We identified 6059 publications, 117 met our prespecified inclusion criteria. One hundred eighty-seven experiments using 2332 animals described changes in structural outcome and 192 experiments using 2704 animals described changes in functional outcome. Median study quality score was 4 (interquartile range 3 to 6) and less than half of studies reported randomization or blinded outcome assessment; only three studies reported a sample size calculation. Nonrandomized studies gave significantly higher estimates of improvement in structural outcome, and there was evidence of a significant publication bias. For structural outcome autologous (i.e. self-derived) stem cells were more effective than allogeneic (donor-derived) cells, but for functional outcome, the reverse was true. A significant dose-response relationship was observed only for structural outcome. For structural outcome, there was an absolute reduction in efficacy of 1·5% (-2·4 to -0·6) for each days delay to treatment; functional outcome was independent of the time of administration. While stem cells appear to be of some benefit in animal models of stroke the internal and external validity of this literature is potentially confounded by poor study quality and by publication bias. The clinical development of stem cell-based therapies, in stroke and elsewhere, should acknowledge these potential weaknesses in the supporting animal data.

A systematic analysis of the literature shows that stem cell implantation can improve function in animal models of spinal cord injury, depending on the methods used.

Background Acute kidney injury (AKI) is common in COVID-19. This study investigated adults hospitalised with COVID-19 and hypothesised that risk factors for AKI would include co-morbidities and non-white race. Methods A prospective multicentre cohort study was performed using patients admitted to 254 UK hospitals with COVID-19 between January 17th 2020 and December 5th 2020. Results Of 85,687 patients, 2,198 (2.6%) received acute kidney replacement therapy (KRT). Of 41,294 patients with biochemistry data, 13,000 (31.5%) had biochemical AKI: 8,562 stage 1 (65.9%), 2,609 stage 2 (20.1%) and 1,829 stage 3 (14.1%). The main risk factors for KRT were chronic kidney disease (CKD: Adjusted odds ratio (aOR) 3.41: 95% confidence interval 3.06-3.81), male sex (aOR 2.43: 2.18-2.71) and black race (aOR 2.17: 1.79-2.63). The main risk factors for biochemical AKI were admission respiratory rate >30 breaths per minute (aOR 1.68: 1.56-1.81), CKD (aOR 1.66: 1.57-1.76) and black race (aOR 1.44: 1.28-1.61). There was a gradated rise in the risk of 28-day mortality by increasing severity of AKI: stage 1 aOR 1.58 (1.49-1.67); stage 2 aOR 2.41 (2.20-2.64); stage 3 aOR 3.50 (3.14-3.91); KRT aOR 3.06 (2.75-3.39). AKI rates peaked in April 2020 and the subsequent fall in rates could not be explained by the use of dexamethasone or remdesivir. Conclusions AKI is common in adults hospitalised with COVID-19 and it is associated with a heightened risk of mortality. Although the rates of AKI have fallen from the early months of the pandemic, high-risk patients should have their kidney function and fluid status monitored closely.