MR-derived renal morphology and renal function in patients with atherosclerotic renovascular disease

Appropriate selection of patients with atherosclerotic renovascular disease (ARVD) for revascularization might be improved if accurate non-invasive investigations were used to assess severity of pre-existing parenchymal damage. The purpose of this study was to evaluate the associations between magnetic resonance imaging (MRI)-measured renal morphological parameters and single-kidney glomerular filtration rate (GFR) in ARVD. Three-dimensional (3D)-MRI was performed on 35 ARVD patients. Renal bipolar length (BL), parenchymal volume, parenchymal (PT), and cortical thicknesses (CT) were measured in 65 kidneys. Thirteen kidneys were supplied by normal vessels, 13 had insignificant (<50%) renal artery stenosis (RAS), 33 significant (≥50%) RAS, and six complete vessel occlusion. All patients underwent radioisotopic measurement of single-kidney GFR (isoSK-GFR). Overall, 3D parameters such as parenchymal volume were better correlates of isoSK-GFR (r=0.86, P<0.001) than BL (r=0.78, P<0.001), PT (r=0.63, P<0.001) or CT (r=0.60, P<0.001). Kidneys with ≥50% RAS did show significant reduction in mean CT compared to those supplied by normal vessel (5.67±1.63 vs 7.28±1.80 mm, P=0.002; 22.1% reduction) and an even greater loss of parenchymal volume (120.65±47.15 vs 179.24±86.90 ml, P<0.001; 32.7% reduction) with no significant reduction in BL. In a proportion of ≥50% RAS kidneys, a disproportionately high parenchymal volume to isoSK-GFR was observed supporting a concept of ‘hibernating parenchyma’. 3D parameters of parenchymal volume are stronger correlates of isoSK-GFR than two-dimensional measures of BL, PT or CT. 3D morphological evaluation together with isoSK-GFR might be useful in aiding patient selection for renal revascularization. Kidneys with increased parenchymal volume to SK-GFR might represent a subgroup with the potential to respond beneficially to angioplasty

Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III—rationale, trial design and baseline data

BACKGROUND: Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. METHODS: UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor-neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but &lt;60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) &gt;20 mg/mmol or eGFR ≥20 but &lt;45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin-angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. RESULTS: Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. CONCLUSIONS: UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD

Motion correction of free-breathing magnetic resonance renography using model-driven registration

Introduction Model-driven registration (MDR) is a general approach to remove patient motion in quantitative imaging. In this study, we investigate whether MDR can effectively correct the motion in free-breathing MR renography (MRR). Materials and methods MDR was generalised to linear tracer-kinetic models and implemented using 2D or 3D free-form deformations (FFD) with multi-resolution and gradient descent optimization. MDR was evaluated using a kidney-mimicking digital reference object (DRO) and free-breathing patient data acquired at high temporal resolution in multi-slice 2D (5 patients) and 3D acquisitions (8 patients). Registration accuracy was assessed using comparison to ground truth DRO, calculating the Hausdorff distance (HD) between ground truth masks with segmentations and visual evaluation of dynamic images, signal-time courses and parametric maps (all data). Results DRO data showed that the bias and precision of parameter maps after MDR are indistinguishable from motion-free data. MDR led to reduction in HD (HDunregistered = 9.98 ± 9.76, HDregistered = 1.63 ± 0.49). Visual inspection showed that MDR effectively removed motion effects in the dynamic data, leading to a clear improvement in anatomical delineation on parametric maps and a reduction in motion-induced oscillations on signal-time courses. Discussion MDR provides effective motion correction of MRR in synthetic and patient data. Future work is needed to compare the performance against other more established methods

Is metabolic syndrome predictive of prevalence, extent, and risk of coronary artery disease beyond its components? results from the multinational coronary ct angiography evaluation for clinical outcome: An international multicenter registry (confirm)

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent ≥64-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n=690) were matched 1:1:1 to those with 1 component (n=690) and 2 components (n=690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p=0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p=0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome

Magnetic resonance imaging biomarkers for chronic kidney disease: a position paper from the European Cooperation in Science and Technology Action PARENCHIMA

Functional renal magnetic resonance imaging (MRI) has seen a number of recent advances, and techniques are now available that can generate quantitative imaging biomarkers with the potential to improve the management of kidney disease. Such biomarkers are sensitive to changes in renal blood flow, tissue perfusion, oxygenation and microstructure (including inflammation and fibrosis), processes that are important in a range of renal diseases including chronic kidney disease. However, several challenges remain to move these techniques towards clinical adoption, from technical validation through biological and clinical validation, to demonstration of cost-effectiveness and regulatory qualification. To address these challenges, the European Cooperation in Science and Technology Action PARENCHIMA was initiated in early 2017. PARENCHIMA is a multidisciplinary pan-European network with an overarching aim of eliminating the main barriers to the broader evaluation, commercial exploitation and clinical use of renal MRI biomarkers. This position paper lays out PARENCHIMA’s vision on key clinical questions that MRI must address to become more widely used in patients with kidney disease, first within research settings and ultimately in clinical practice. We then present a series of practical recommendations to accelerate the study and translation of these techniques

Is metabolic syndrome predictive of prevalence, extent, and risk of coronary artery disease beyond its components? results from the multinational coronary CT angiography evaluation for clinical outcome : an international multicenter registry (CONFIRM)

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent 6564-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n=690) were matched 1:1:1 to those with 1 component (n=690) and 2 components (n=690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p=0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p=0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome

Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Multiple sclerosis is a complex neurological disease, with 3c20% of risk heritability attributable to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that much of the remaining heritability is also due to additive effects of common variants rather than epistasis between these variants or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that up to 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common-variant signals, highlighting key pathogenic roles for regulatory T cell homeostasis and regulation, IFN\u3b3 biology, and NF\u3baB signaling. As low-frequency variants do not show substantial linkage disequilibrium with other variants, and as coding variants are more interpretable and experimentally tractable than non-coding variation, our discoveries constitute a rich resource for dissecting the pathobiology of MS. In a large multi-cohort study, unexplained heritability for multiple sclerosis is detected in low-frequency coding variants that are missed by GWAS analyses, further underscoring the role of immune genes in MS pathology

Supplementary Material for: Meta-Analysis of Lipid-Lowering Therapy in Maintenance Dialysis Patients

<p><b><i>Background/Aims:</i></b> The use of lipid-lowering therapy (LLT) in patients on chronic dialysis is contentious. Here we present an aggregate data meta-analysis of randomised controlled trials (RCTs) comparing long-term LLT versus placebo in dialysis patients. <b><i>Method:</i></b> A search of Medline, Google Scholar, COCHRANE database, EMBASE, and cardiovascular and nephrology society proceedings was performed. Criteria for inclusion were RCTs of LLT versus placebo, in which LLT was demonstrated to significantly reduce low-density lipoprotein cholesterol, >12 months of follow-up, and at least one cardiovascular or mortality endpoint in an independently reported dialysis population. Meta-analysis was performed for atherosclerotic cardiovascular events, stroke and mortality using a random-effects method for odds ratio (OR) of risk. <b><i>Results:</i></b> Three studies were included with 7,051 patients (3,541 treatment and 3,510 placebo). Twenty-five percent of the LLT patients suffered an atherosclerotic cardiovascular event versus 27% for placebo. The OR was 0.89 (95% CI: 0.80-0.99, p = 0.04). For stroke (haemorrhagic and non-haemorrhagic combined), the figures were 6.2% (LLT) versus 5.7% (placebo) [OR = 1.11 (95% CI: 0.85-1.46, p = 0.45)]. For all-cause mortality, the figures were 40 versus 42% [OR = 0.97 (95% CI: 0.88-1.06, p = 0.49)]. <b><i>Conclusion:</i></b> There was an overall significant reduction in risk for atherosclerotic cardiovascular events in dialysis patients treated with LLT compared to placebo. There was a numerical but not a statistical reduction in mortality. There was no statistically significant increase in risk of stroke as has been previously reported.</p