title: Non-proteinuric pathways in loss of renal function in patients with type 2 diabetes.
abstract: Largely on the basis of data from patients with type 1 diabetes, the natural history of diabetic renal disease has been classified as a sequence of three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. Progressive decline of glomerular filtration rate (GFR) was thought to parallel the onset of macroalbuminuria (overt nephropathy), whereas glomerular hyperfiltration was deemed a hallmark of early disease. However, researchers have since shown that albuminuria is a continuum and that GFR can start to decline before progression to overt nephropathy. In addition to proteinuria, other risk factors might contribute to GFR deterioration including female sex, obesity, dyslipidaemia (in particular hypertriglyceridaemia), hypertension, and glomerular hyperfiltration, at least in a subgroup of patients. This phenomenon could explain why patients with type 2 diabetes can have renal insufficiency even before the onset of overt nephropathy, and might also suggest why the heterogeneous phenotype of type 2 diabetic renal disease does not necessarily associate with typical histological lesions of diabetic renal disease, unlike in type 1 diabetic renal disease. Patients with renal insufficiency but without albuminuria are usually excluded from randomised clinical trials in overt nephropathy, thus optimum treatment for this group of patients is unknown. The wide inter-patient variability of the disease probably needs individually tailored intervention.
authors.affiliation: Center for Biomedical Research of the Canary Islands (CIBICAN), University of La Laguna, Tenerife, Spain. Electronic address: estebanporrini72@hotmail.com.
authors.forename: Esteban
authors.initials: E
authors.lastname: Porrini
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
authors.affiliation: Department of Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Carl Erik
authors.initials: CE
authors.lastname: Mogensen
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Ljubljana University Medical Center, Ljubljana, Slovenia.
authors.forename: Drazenka Pongrac
authors.initials: DP
authors.lastname: Barlovic
authors.affiliation: Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Praga
authors.affiliation: Department of Nephrology, Hospital Universitario de Bellvitge, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Cruzado
authors.affiliation: Department of Nephrology, Clinic for Internal Medicine, University Clinical Centre and Faculty of Medicine, University of Maribor, Maribor, Slovenia.
authors.forename: Radovan
authors.initials: R
authors.lastname: Hojs
authors.affiliation: Department of Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Manuela
authors.initials: M
authors.lastname: Abbate
authors.affiliation: Division of Nephrology, Department of Medicine, Leiden University Medical Center and Leiden University, Leiden, Netherlands.
authors.forename: Aiko P J
authors.initials: AP
authors.lastname: de Vries
mesh_terms: D000419:Albuminuria / Q000150:complications / Q000652:urine; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000150:complications / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D010641:Phenotype; D012307:Risk Factors