Height Constitutes an Important Predictor of Mortality in End-Stage Renal Disease

Aim. Height is an important determinant of augmentation index (AI) that anticipates cardiovascular prognosis. There is a scanty of the data whether short height predicts survival in patients with end-stage renal diseases, a high risk population. Methods. Fifty two hypertensive patients with type 2 diabetic nephropathy receiving hemodialysis and 52 patients with nondiabetic nephropathy were enrolled. In addition to AI estimated with radial artery tonometry, classical cardiovascular risk factors were considered. Patients were followed for 2 years to assess cardiovascular prognosis. Results. Cox hazards regression revealed that both smoking and shortness in height independently contributed to total mortality and indicated that smoking as well as the presence of left ventricular hypertrophy predicted cardiovascular mortality. Our findings implicated that high AI, the presence of diabetes, and low high-density lipoprotein cholesterol were significant contributors to cardiovascular events. Conclusions. Our findings provide new evidence that shortness in height independently contributes to total mortality in hemodialysis patients

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Predictors of long-term prognosis in acute kidney injury survivors who require continuous renal replacement therapy after cardiovascular surgery.

The long-term prognosis of patients with postoperative acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) after cardiovascular surgery is unclear. We aimed to investigate long-term renal outcomes and survival in these patients to determine the risk factors for negative outcomes. Long-term prognosis was examined in 144 hospital survivors. All patients were independent and on renal replacement therapy at hospital discharge. The median age at operation was 72.0 years, and the median pre-operative estimated glomerular filtration rate (eGFR) was 39.5 mL/min/1.73 m2. The median follow-up duration was 1075 days. The endpoints were death, chronic maintenance dialysis dependence, and a composite of death and chronic dialysis. Predictors for death and dialysis were evaluated using Fine and Gray's competing risk analysis. The cumulative incidence of death was 34.9%, and the chronic dialysis rate was 13.3% during the observation period. In the multivariate proportional hazards analysis, eGFR <30 mL/min/1.73 m2 at discharge was associated with the composite endpoint of death and dialysis [hazard ratio (HR), 2.1; 95% confidence interval (CI), 1.1-3.8; P = 0.02]. Hypertension (HR 8.7, 95% CI, 2.2-35.4; P = 0.002) and eGFR <30 mL/min/1.73 m2 at discharge (HR 26.4, 95% CI, 2.6-267.1; P = 0.006) were associated with dialysis. Advanced age (≥75 years) was predictive of death. Patients with severe CRRT-requiring AKI after cardiovascular surgery have increased risks of chronic dialysis and death. Patients with eGFR <30 mL/min/1.73 m2 at discharge should be monitored especially carefully by nephrologists due to the risk of chronic dialysis and death

The Relative Effects of Biotic and Abiotic Factors on the Recruitment of Freshwater Mussels (Margaritifera laevis)

Freshwater mussels, Unionoida, are endangered across the globe due to recruitment failure. In the present study, with general linear mixed models, we investigated the relative effects of biotic (host fish density) and abiotic (water depth, fine sediment, water temperature, and water quality) factors on the recruitment of Margaritifera laevis in 10 streams of Hokkaido, northern Japan. We additionally examined the factors regulating the density of the host fish Oncorhynchus masou masou with general linear models. The proportion of juvenile mussels had a unimodal relationship with the host density, which was the most influential factor among the others examined. The positive relationship between mussel recruitment and host density can be attributed to an increased host fish infection rate. The negative correlation between mussel recruitment and host density at high fish densities may be due to reduced larval growth on host fish that are in poor physical condition. We also found that host fish density was negatively affected by nutrient enrichment. Our results suggest that mitigating water quality degradation to recover host fish density should be prioritized to improve mussel recruitment. Although stock enhancement is effective for increasing the salmon population density, excess stocking can further disturb mussel recruitment