A retrospective study of renal dysfunction in acute stroke: incidence, impact and outcomes

Stroke is a leading cause of death and neurological disability worldwide. Chronic kidney disease (CKD) is associated with an increased risk of stroke. Conversely, CKD confers worse outcomes following a stroke, with the highest mortality seen in end-stage renal disease. In comparison, the relationship between AKI and stroke is not well described, with a lack of UK data. In this single-centre, retrospective observational study of hospitalisations with acute stroke, I sought to determine the incidence of renal dysfunction and its impact on outcomes. AKI incidence was determined using preadmission serum creatinine (SCr) as ‘baseline’ renal function, compared with 4 surrogate methods. AKI was common, with an overall incidence of 20%, and was associated with increased 30-day and 1-year mortality using all AKI methods. Admission SCr most closely agreed with preadmission SCr but all surrogate methods exhibited bi-directional misclassification of AKI. CKD prevalence was high (over 30%) and was associated with increased mortality in univariable analyses. CKD patients underwent fewer imaging modalities and thrombectomy, possibly suggesting the presence of ‘renalism’. Contrast exposure was not found to be a risk factor for AKI. Vascular calcification and carotid artery disease were univariably associated with CKD. Multi-centre studies are needed to confirm the findings

Stratified analyses refine association between TLR7 rare variants and severe COVID-19

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (<60 years) cases with no reported clinical risk factors (n = 378), compared to 0.24% of controls (odds ratio [OR] = 12.3, p = 1.27 × 10−10). Incorporation of the results of either functional assays or protein modeling led to a pronounced increase in effect size (ORmax = 46.5, p = 1.74 × 10−15). Association signals for the X-chromosomal gene TLR7 were also detected in the female-only subgroup, suggesting the existence of additional mechanisms beyond X-linked recessive inheritance in males. Additionally, supporting evidence was generated for a contribution to severe COVID-19 of the previously implicated genes IFNAR2, IFIH1, and TBK1. Our results refine the genetic contribution of rare TLR7 variants to severe COVID-19 and strengthen evidence for the etiological relevance of genes in the interferon signaling pathway