title: Capillary Rarefaction Associates with Albuminuria: The Maastricht Study.
abstract: Albuminuria may be a biomarker of generalized (i.e., microvascular and macrovascular) endothelial dysfunction. According to this concept, endothelial dysfunction of the renal microcirculation causes albuminuria by increasing glomerular capillary wall permeability and intraglomerular pressure, the latter eventually leading to glomerular capillary dropout (rarefaction) and further increases in intraglomerular pressure. However, direct evidence for an association between capillary rarefaction and albuminuria is lacking. Therefore, we examined the cross-sectional association between the recruitment of capillaries after arterial occlusion (capillary density during postocclusive peak reactive hyperemia) and during venous occlusion (venous congestion), as assessed with skin capillaroscopy, and albuminuria in 741 participants of the Maastricht Study, including 211 participants with type 2 diabetes. Overall, 57 participants had albuminuria, which was defined as a urinary albumin excretion ≥30 mg/24 h. After adjustment for potential confounders, participants in the lowest tertile of skin capillary recruitment during postocclusive peak reactive hyperemia had an odds ratio for albuminuria of 2.27 (95% confidence interval, 1.07 to 4.80) compared with those in the highest tertile. Similarly, a comparison between the lowest and the highest tertiles of capillary recruitment during venous congestion yielded an odds ratio of 2.89 (95% confidence interval, 1.27 to 6.61) for participants in the lowest tertile. In conclusion, lower capillary density of the skin microcirculation independently associated with albuminuria, providing direct support for a role of capillary rarefaction in the pathogenesis of albuminuria.
authors.affiliation: Department of Internal Medicine, Division of Nephrology and.|School of Nutrition and Translational Research in Metabolism.
authors.forename: Remy J H
authors.initials: RJ
authors.lastname: Martens
authors.affiliation: Departments of Internal Medicine and.|Cardiovascular Research Institute Maastricht.
authors.forename: Ronald M A
authors.initials: RM
authors.lastname: Henry
authors.affiliation: Departments of Internal Medicine and.|Cardiovascular Research Institute Maastricht.
authors.forename: Alfons J H M
authors.initials: AJ
authors.lastname: Houben
authors.affiliation: Departments of Internal Medicine and.|Cardiovascular Research Institute Maastricht.
authors.forename: Carla J H
authors.initials: CJ
authors.lastname: van der Kallen
authors.affiliation: Departments of Internal Medicine and.|Cardiovascular Research Institute Maastricht.
authors.forename: Abraham A
authors.initials: AA
authors.lastname: Kroon
authors.affiliation: Departments of Internal Medicine and.|Cardiovascular Research Institute Maastricht.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.affiliation: Departments of Internal Medicine and.|Cardiovascular Research Institute Maastricht.
authors.forename: Miranda T
authors.initials: MT
authors.lastname: Schram
authors.affiliation: Departments of Internal Medicine and.|Cardiovascular Research Institute Maastricht.
authors.forename: Simone J S
authors.initials: SJ
authors.lastname: Sep
authors.affiliation: Departments of Internal Medicine and.|Cardiovascular Research Institute Maastricht.|School for Public Health and Primary Care.
authors.forename: Nicolaas C
authors.initials: NC
authors.lastname: Schaper
authors.affiliation: Cardiovascular Research Institute Maastricht.|School for Public Health and Primary Care.|Department of Epidemiology, and.
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dagnelie
authors.affiliation: Departments of Internal Medicine and.|Cardiovascular Research Institute Maastricht.
authors.forename: Dennis M J
authors.initials: DM
authors.lastname: Muris
authors.affiliation: Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands; and.|School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Ed H B M
authors.initials: EH
authors.lastname: Gronenschild
authors.affiliation: Department of Internal Medicine, Division of Nephrology and.
authors.forename: Frank M
authors.initials: FM
authors.lastname: van der Sande
authors.affiliation: Department of Internal Medicine, Division of Nephrology and.|School of Nutrition and Translational Research in Metabolism.
authors.forename: Karel M L
authors.initials: KM
authors.lastname: Leunissen
authors.affiliation: Department of Internal Medicine, Division of Nephrology and.|School of Nutrition and Translational Research in Metabolism.
authors.forename: Jeroen P
authors.initials: JP
authors.lastname: Kooman
authors.affiliation: Departments of Internal Medicine and cda.stehouwer@mumc.nl.|Cardiovascular Research Institute Maastricht.
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000419:Albuminuria / Q000209:etiology*; D002196:Capillaries / Q000473:pathology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000150:complications*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D011446:Prospective Studies; D012867:Skin / Q000098:blood supply*
keywords: chronic kidney disease; diabetic nephropathy; endothelium; microalbuminuria