title: Glomerular Hyperfiltration in Diabetes: Mechanisms, Clinical Significance, and Treatment.
abstract: An absolute, supraphysiologic elevation in GFR is observed early in the natural history in 10%-67% and 6%-73% of patients with type 1 and type 2 diabetes, respectively. Moreover, at the single-nephron level, diabetes-related renal hemodynamic alterations-as an adaptation to reduction in functional nephron mass and/or in response to prevailing metabolic and (neuro)hormonal stimuli-increase glomerular hydraulic pressure and transcapillary convective flux of ultrafiltrate and macromolecules. This phenomenon, known as glomerular hyperfiltration, classically has been hypothesized to predispose to irreversible nephron damage, thereby contributing to initiation and progression of kidney disease in diabetes. However, dedicated studies with appropriate diagnostic measures and clinically relevant end points are warranted to confirm this assumption. In this review, we summarize the hitherto proposed mechanisms involved in diabetic hyperfiltration, focusing on ultrastructural, vascular, and tubular factors. Furthermore, we review available evidence on the clinical significance of hyperfiltration in diabetes and discuss currently available and emerging interventions that may attenuate this renal hemodynamic abnormality. The revived interest in glomerular hyperfiltration as a prognostic and pathophysiologic factor in diabetes may lead to improved and timely detection of (progressive) kidney disease, and could provide new therapeutic opportunities in alleviating the renal burden in this population.
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands; l.tonneijck@vumc.nl.
authors.forename: Lennart
authors.initials: L
authors.lastname: Tonneijck
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Marcel H A
authors.initials: MH
authors.lastname: Muskiet
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Smits
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: van Bommel
authors.affiliation: Department of Clinical Pharmacology, University Medical Center Groningen, Groningen, The Netherlands; and.
authors.forename: Hiddo J L
authors.initials: HJ
authors.lastname: Heerspink
authors.affiliation: Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Daniël H
authors.initials: DH
authors.lastname: van Raalte
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center, Utrecht, The Netherlands.
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Joles
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology* / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000628:therapy; D005919:Glomerular Filtration Rate; D006801:Humans; D007678:Kidney Glomerulus / Q000503:physiopathology*
keywords: albuminuria; diabetes; diabetic nephropathy; glomerular filtration rate; glomerular hyperfiltration