An increased risk of cardiovascular disease, independent of conventional risk factors, is present even at minor levels of renal impairment and is highest in patients with end-stage renal disease (ESRD Show more
An increased risk of cardiovascular disease, independent of conventional risk factors, is present even at minor levels of renal impairment and is highest in patients with end-stage renal disease (ESRD) requiring dialysis. Renal dysfunction changes the level, composition and quality of blood lipids in favour of a more atherogenic profile. Patients with advanced chronic kidney disease (CKD) or ESRD have a characteristic lipid pattern of hypertriglyceridaemia and low HDL cholesterol levels but normal LDL cholesterol levels. In the general population, a clear relationship exists between LDL cholesterol and major atherosclerotic events. However, in patients with ESRD, LDL cholesterol shows a negative association with these outcomes at below average LDL cholesterol levels and a flat or weakly positive association with mortality at higher LDL cholesterol levels. Overall, the available data suggest that lowering of LDL cholesterol is beneficial for prevention of major atherosclerotic events in patients with CKD and in kidney transplant recipients but is not beneficial in patients requiring dialysis. The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Lipid Management in CKD provides simple recommendations for the management of dyslipidaemia in patients with CKD and ESRD. However, emerging data and novel lipid-lowering therapies warrant some reappraisal of these recommendations. Show less
Understanding the extent of genomic transcription and its functional relevance is a central goal in genomics research. However, detailed genome-wide investigations of transcriptome complexity in major Show more
Understanding the extent of genomic transcription and its functional relevance is a central goal in genomics research. However, detailed genome-wide investigations of transcriptome complexity in major mammalian organs have been scarce. Here, using extensive RNA-seq data, we show that transcription of the genome is substantially more widespread in the testis than in other organs across representative mammals. Furthermore, we reveal that meiotic spermatocytes and especially postmeiotic round spermatids have remarkably diverse transcriptomes, which explains the high transcriptome complexity of the testis as a whole. The widespread transcriptional activity in spermatocytes and spermatids encompasses protein-coding and long noncoding RNA genes but also poorly conserves intergenic sequences, suggesting that it may not be of immediate functional relevance. Rather, our analyses of genome-wide epigenetic data suggest that this prevalent transcription, which most likely promoted the birth of new genes during evolution, is facilitated by an overall permissive chromatin in these germ cells that results from extensive chromatin remodeling. Show less