title: The impact of hyperfiltration on the diabetic kidney.
abstract: More than two decades ago, hyperfiltration (HF) in diabetes was postulated to be a maladaptive response observed early in the course of diabetic kidney disease (DKD), which may eventually predispose to irreversible damage to nephrons and development of progressive renal disease. Despite this, the potential mechanisms leading to renal HF in diabetes are not fully understood, although several hypotheses have been proposed, including alterations in glomerular haemodynamic function and tubulo-glomerular feedback. Furthermore, the role of HF as a causative factor in renal disease progression is still unclear and warrants further prospective longer-term studies. Although HF has been entrenched as the first stage in the classic albuminuric pathway to end-stage renal disease in DKD, and HF has been shown to predict the progression of albuminuria in many, but not all studies, the concept that HF predisposes to the development of chronic kidney disease (CKD) stage 3, that is, glomerular filtration rate (GFR) decline to<60mL/min/1.73m(2), remains to be proved. Further long-term studies of GFR gradients therefore are required to establish whether HF ultimately leads to decreased kidney function, after adjustment for glycaemic control and other confounders. Whether reversal of HF with therapeutic agents is protective against reducing the risk of development of albuminuria and renal impairment is also worth investigating in prospective randomized trials.
authors.affiliation: Endocrine Centre & Department of Medicine, Austin Health & University of Melbourne, Victoria, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Premaratne
authors.affiliation: Endocrine Centre & Department of Medicine, Austin Health & University of Melbourne, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Verma
authors.affiliation: Endocrine Centre & Department of Medicine, Austin Health & University of Melbourne, Victoria, Australia; Menzies Institute of Health Research, Darwin, Northern Territory, Australia.
authors.forename: E I
authors.initials: EI
authors.lastname: Ekinci
authors.affiliation: Departments of Endocrinology & Diabetes and Medicine, St Vincent's Hospital Melbourne & University of Melbourne, Victoria, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Theverkalam
authors.affiliation: Endocrine Centre & Department of Medicine, Austin Health & University of Melbourne, Victoria, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Jerums
authors.affiliation: Departments of Endocrinology & Diabetes and Medicine, St Vincent's Hospital Melbourne & University of Melbourne, Victoria, Australia. Electronic address: r.macisaac@unimelb.edu.au.
authors.forename: R J
authors.initials: RJ
authors.lastname: MacIsaac
mesh_terms: D003928:Diabetic Nephropathies / Q000503:physiopathology*; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D024821:Metabolic Syndrome; D009765:Obesity
keywords: Diabetic kidney disease; Diabetic nephropathy; Hyperfiltration; Metabolic syndrome; Obesity; Vascular disease