Background: It is unclear when angiotensin II receptor blockers (ARBs) produce their strongest antialbuminuric effect (AAE) in patients with diabetic nephropathy. ARBs produce stronger AAEs when urinary excretion of reactive oxygen species (ROS) and/or of angiotensinogen (AGT) is higher before treatment, although the relationship between ROS, AGT, and the urinary albumin-to-creatinine ratio (ACR) is unclear. We sought to define the relationship between ROS and ACR and establish the stage at which ARBs exert maximal AAEs.
Methods: Urinary ROS and AGT and the ACR were measured in 277 hypertensive type 2 diabetic patients before ARB treatment, and changes in the ACR were analyzed over 16 weeks.
Results: Urinary AGT and ROS showed similar changes as the disease progressed, and the increase in ACR often observed in patients with lower ROS and AGT reflects the mild AAE produced by ARBs. ROS and AGT levels and the AAE were all highest in albuminuric patients (ACR = 30-1,000 mg/g creatinine), whereas normoalbuminuric patients (ACR < 30mg/g creatinine) displayed variable ROS values and AAEs. Glycemic control exerted a stronger AAE than ARBs in normoalbuminuric patients, whereas it had a weak AAE in most nephrotic (ACR ≥ 1,000 mg/g creatinine) patients, who had low basal ROS and AGT values. Lowering blood pressure was effective at all stages and appeared to promote an AAE, even in nephrotic patients.
Conclusions: ARBs produce a maximal AAE in albuminuric patients, and lowering blood pressure enhances the AAE in patients at all stages, including the nephrotic stage.
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http://dx.doi.org/10.1093/ajh/hpt085 | DOI Listing |
Int J Mol Sci
January 2024
Department of Physiology and Hypertension Core, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Increased body weight (BW) induces inappropriate renin-angiotensin system (RAS) activation. The activation of the intrarenal RAS is associated with increased urinary angiotensinogen (uAGT), blood pressure (BP), and kidney damage. Here, we examined uAGT excretion levels in young non-diabetic human subjects with overweight (OW) and non-diabetic mice with high-fat diet (HFD)-induced OW.
View Article and Find Full Text PDFStroke
March 2023
Stroke Unit, Department of Neurology, Hospital Vall d'Hebron, Departament de Medicina, Universitat Autònoma de Barcelona, Spain (A.G.-T., M.D., M. Rubiera., J.P., D.R.L., J.J., N.R.V., C.A.M., M. Ribó).
Background: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020.
Methods: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am-8:59 pm) and nighttime (9:00 pm-7:59 am). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke.
Front Cardiovasc Med
November 2022
Key Laboratory of Metabolism and Molecular Medicine of the Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai, China.
Background: Perivascular adipose tissue (PVAT), an active endocrine organ, exerts direct effect on vascular tone through paracrine. Activation of PVAT metabolism plays an inhibitory role in atherosclerosis secreting relaxing factors. The present studies were designed to investigate the role of PVAT metabolism in regulation of hypertension.
View Article and Find Full Text PDFStroke
December 2022
Department of Neurology, Stroke Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain (M.M., A.B., L.D., M.G., D.A., N.P.d.l.O.).
Background: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion).
Methods: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke.
Pregnancy Hypertens
December 2022
Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, VIC, Australia; Gynaecology Research Centre, Royal Women's Hospital, Parkville, VIC, Australia; Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia; Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia. Electronic address:
Objectives: Preeclampsia is a life-threatening disorder of pregnancy unique to humans. Poor placentation in the first trimester of pregnancy is widely accepted to be an underlying cause of preeclampsia. Galectin-7 is abnormally elevated in chorionic villous samples and serum from women that subsequently develop pre-term preeclampsia.
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