Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets.

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation.

Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney.

The kidney is an organ of key relevance to blood pressure (BP) regulation, hypertension and antihypertensive treatment. However, genetically mediated renal mechanisms underlying susceptibility to hypertension remain poorly understood. We integrated genotype, gene expression, alternative splicing and DNA methylation profiles of up to 430 human kidneys to characterize the effects of BP index variants from genome-wide association studies (GWASs) on renal transcriptome and epigenome.

Hypertension and renin-angiotensin system blockers are not associated with expression of angiotensin-converting enzyme 2 (ACE2) in the kidney.

Aims: Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)-the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported.

Methods And Results: We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing.

Uncovering genetic mechanisms of kidney aging through transcriptomics, genomics, and epigenomics.

Nephrons scar and involute during aging, increasing the risk of chronic kidney disease. Little is known, however, about genetic mechanisms of kidney aging. We sought to define the signatures of age on the renal transcriptome using 563 human kidneys.

Correlation between serum low-density lipoprotein cholesterol concentration and arterial wall stiffness.

Background: Elevated serum low-density lipoprotein cholesterol (LDL-C) concentration is a risk factor for atherosclerosis, which involves remodelling of the arterial walls with their subsequent stiffening.

Aim: We sought to evaluate the relationship between serum lipid levels and the elastic properties of the arterial wall.

Methods: The study group comprised 315 men and women aged 55.

Signatures of miR-181a on the Renal Transcriptome and Blood Pressure.

MicroRNA-181a binds to the 3' untranslated region of messenger RNA (mRNA) for renin, a rate-limiting enzyme of the renin-angiotensin system. Our objective was to determine whether this molecular interaction translates into a clinically meaningful effect on blood pressure and whether circulating miR-181a is a measurable proxy of blood pressure. In 200 human kidneys from the TRANScriptome of renaL humAn TissuE (TRANSLATE) study, renal miR-181a was the sole negative predictor of renin mRNA and a strong correlate of circulating miR-181a.

Nephroprotective effect of pentoxifylline in renal ischemia-reperfusion in rat depends on the timing of its administration.

Background: Renal ischemia-reperfusion injury (IRI) induces inflammatory reaction damaging kidney. Pentoxifylline (PTX) given before IRI attenuates inflammation and prevents ischemic acute kidney injury (iAKI). Given that in clinical settings IRI is not always predictable, we aimed to assess whether PTX administration during or shortly after IRI affects the course of iAKI in the rat.

Coronary artery disease predisposing haplogroup I of the Y chromosome, aggression and sex steroids--genetic association analysis.

Objective: Amongst middle-aged men, haplogroup I is associated with ≈ 50% higher risk of coronary artery disease than other paternal lineages of Y chromosome. We hypothesised that carriers of haplogroup I had higher levels of aggression and estrogens and/or lower levels of androgens early in life and thus might be more prone to cardiovascular disease than men with other lineages of Y chromosome.

Methods: We reconstructed phylogenetic tree of the Y chromosome in >1000 young apparently healthy white men from the general population.

Peritoneal dialysis as a mode of treatment for acute kidney injury in sub-Saharan Africa.

Background: Developing sustainable treatment programs for kidney failure in most countries of sub-Saharan Africa continues to remain an imposing challenge. While long-term renal replacement therapies in end-stage renal disease appear beyond national financial capabilities, there exist opportunities for a short-term and affordable treatment of acute kidney injury (AKI). Peritoneal dialysis (PD) is an effective and simpler modality compared to hemodialysis (HD) and can be performed without the need for machinery or electricity, making it an ideal choice in a low-resource setting.

Different mortality predictor pattern in hemodialysis and peritoneal dialysis diabetic patients in 4-year prospective observation.

Introduction: The aim was to identify factors carrying an ominous prognosis in a cohort of diabetic patients (pts) on a hemodialysis (HD) and peritoneal dialysis (PD) program.

Materials And Methods: We analyzed survival rates of 61 diabetic dialysis pts (35 HD/26 PD). The participants were matched in baseline characteristics, standard indicators of dialysis care and laboratory parameters.

Longer leukocyte telomeres are associated with ultra-endurance exercise independent of cardiovascular risk factors.

Telomere length is recognized as a marker of biological age, and shorter mean leukocyte telomere length is associated with increased risk of cardiovascular disease. It is unclear whether repeated exposure to ultra-endurance aerobic exercise is beneficial or detrimental in the long-term and whether it attenuates biological aging. We quantified 67 ultra-marathon runners' and 56 apparently healthy males' leukocyte telomere length (T/S ratio) using real-time quantitative PCR.

Male-specific region of the Y chromosome and cardiovascular risk: phylogenetic analysis and gene expression studies.

Objective: Haplogroup I of male-specific region of the human Y chromosome is associated with 50% increased risk of coronary artery disease. It is not clear to what extent conventional cardiovascular risk factors and genes of the male-specific region may explain this association.

Approach And Results: A total of 1988 biologically unrelated men from 4 white European populations were genotyped using 11 Y chromosome single nucleotide polymorphisms and classified into 13 most common European haplogroups.

[Carbohydrate sweeteners and obesity].

The U.S. prevalence of obesity increases since the mid-70s of the 20th century.

Elderly dialysis patients: analysis of factors affecting long-term survival in 4-year prospective observation.

Purpose: To assess factors influencing the long-term survival of elderly dialysis patients.

Methods: The study group consisted of 51 prevalent dialysis patients aged over 70 years (32 F and 19 M, all caucasians), who had been on a chronic hemodialysis (27) or peritoneal dialysis program (24) for at least 2 months; median age was 77 years, median time on dialysis before inclusion was 16 months, and median residual diuresis was 600 ml. The patients were prospectively followed up to 4 years, and an analysis of factors affecting survival was performed.

Gene expression profiling reveals renin mRNA overexpression in human hypertensive kidneys and a role for microRNAs.

The kidney has long been invoked in the etiology of essential hypertension. This could involve alterations in expression of specific genes and microRNAs (miRNAs). The aim of the present study was to identify, at the transcriptome-wide level, mRNAs and miRNAs that were differentially expressed between kidneys of 15 untreated hypertensive and 7 normotensive white male subjects of white European ancestry.

Systemic vascular hemodynamics and transplanted kidney survival.

Introduction: High blood pressure and arterial stiffness contribute independently to cardiovascular mortality in uremic patients. High blood pressure is an established risk factor for chronic allograft nephropathy, recently named interstitial fibrosis/tubular atrophy (IF/TA). We sought to assess whether heart afterload determinants: arterial stiffness and vascular resistance or impedance accelerate kidney graft failure upon long-term observation.

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events.

Pathway analysis shows association between FGFBP1 and hypertension.

Variants in the gene encoding fibroblast growth factor 1 (FGF1) co-segregate with familial susceptibility to hypertension, and glomerular upregulation of FGF1 associates with hypertension. To investigate whether variants in other members of the FGF signaling pathway may also associate with hypertension, we genotyped 629 subjects from 207 Polish families with hypertension for 79 single nucleotide polymorphisms in eight genes of this network. Family-based analysis showed that parents transmitted the major allele of the rs16892645 polymorphism in the gene encoding FGF binding protein 1 (FGFBP1) to hypertensive offspring more frequently than expected by chance (P=0.

Genetic architecture of ambulatory blood pressure in the general population: insights from cardiovascular gene-centric array.

Genetic determinants of blood pressure are poorly defined. We undertook a large-scale, gene-centric analysis to identify loci and pathways associated with ambulatory systolic and diastolic blood pressure. We measured 24-hour ambulatory blood pressure in 2020 individuals from 520 white European nuclear families (the Genetic Regulation of Arterial Pressure of Humans in the Community Study) and genotyped their DNA using the Illumina HumanCVD BeadChip array, which contains ≈ 50 000 single nucleotide polymorphisms in >2000 cardiovascular candidate loci.

FGF21 signalling pathway and metabolic traits - genetic association analysis.

Fibroblast growth factor 21 (FGF21) is a novel master regulator of metabolic profile. The biological actions of FGF21 are elicited upon its klotho beta (KLB)-facilitated binding to FGF receptor 1 (FGFR1), FGFR2 and FGFR3. We hypothesised that common polymorphisms in the FGF21 signalling pathway may be associated with metabolic risk.