title: Circulating microRNAs associate with diabetic nephropathy and systemic microvascular damage and normalize after simultaneous pancreas-kidney transplantation.
abstract: Because microvascular disease is one of the most important drivers of diabetic complications, early monitoring of microvascular integrity may be of clinical value. By assessing profiles of circulating microRNAs (miRNAs), known regulators of microvascular pathophysiology, in healthy controls and diabetic nephropathy (DN) patients before and after simultaneous pancreas-kidney transplantation (SPK), we aimed to identify differentially expressed miRNAs that associate with microvascular impairment. Following a pilot study, we selected 13 candidate miRNAs and determined their circulating levels in DN (n = 21), SPK-patients (n = 37), healthy controls (n = 19), type 1 diabetes mellitus patients (n = 15) and DN patients with a kidney transplant (n = 15). For validation of selected miRNAs, 14 DN patients were studied longitudinally up to 12 months after SPK. We demonstrated a direct association of miR-25, -27a, -126, -130b, -132, -152, -181a, -223, -320, -326, -340, -574-3p and -660 with DN. Of those, miR-25, -27a, -130b, -132, -152, -320, -326, -340, -574-3p and -660 normalized after SPK. Importantly, circulating levels of some of these miRNAs tightly associate with microvascular impairment as they relate to aberrant capillary tortuosity, angiopoietin-2/angiopoietin-1 ratios, circulating levels of soluble-thrombomodulin and insulin-like growth factor. Taken together, circulating miRNA profiles associate with DN and systemic microvascular damage, and might serve to identify individuals at risk of experiencing microvascular complications, as well as give insight into underlying pathologies.
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Bijkerk
authors.forename: J M G J
authors.initials: JM
authors.lastname: Duijs
authors.forename: M
authors.initials: M
authors.lastname: Khairoun
authors.forename: C J H
authors.initials: CJ
authors.lastname: Ter Horst
authors.forename: P
authors.initials: P
authors.lastname: van der Pol
authors.forename: M J
authors.initials: MJ
authors.lastname: Mallat
authors.forename: J I
authors.initials: JI
authors.lastname: Rotmans
authors.forename: A P J
authors.initials: AP
authors.lastname: de Vries
authors.forename: E J
authors.initials: EJ
authors.lastname: de Koning
authors.forename: J W
authors.initials: JW
authors.lastname: de Fijter
authors.forename: T J
authors.initials: TJ
authors.lastname: Rabelink
authors.forename: A J
authors.initials: AJ
authors.lastname: van Zonneveld
authors.forename: M E J
authors.initials: ME
authors.lastname: Reinders
mesh_terms: D000293:Adolescent; D000328:Adult; D003928:Diabetic Nephropathies / Q000097:blood*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D016035:Pancreas Transplantation; D055815:Young Adult
chemical_list: D035683:MicroRNAs
keywords: basic (laboratory) research/science; biomarker; clinical research/practice; diabetes: secondary complications; kidney transplantation/nephrology; molecular biology: micro RNA; pancreas/simultaneous pancreas-kidney transplantation; vascular biology