Kidney growth, hypertrophy and the unifying mechanism of diabetic complications

• Published in: Amino acids Vol. 33; no. 2; pp. 331 - 339
• Main Author: Satriano, J
• Format: Journal Article
• Language: English
• Published: Austria Vienna : Springer-Verlag 01.08.2007; Springer Nature B.V
• Subjects: Amino acids; Animals; Carrier Proteins - physiology; Cyclin-Dependent Kinase Inhibitor p27 - physiology; Damage; Diabetes; Diabetes Complications - etiology; Diabetes mellitus; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - physiopathology; Eflornithine - pharmacology; Eukaryotic Initiation Factor-4E - physiology; Feedback, Physiological; Fibrosis; Glomerular Filtration Rate - drug effects; Humans; Hyperfiltration; Hyperglycemia; Hypertrophy; insulin-dependent diabetes mellitus; Intercellular Signaling Peptides and Proteins - physiology; Kidney - drug effects; Kidney - growth & development; Kidney - pathology; Kidney Tubules - growth & development; Kidney Tubules - pathology; Kidney Tubules - physiology; Kidneys; Metabolic Networks and Pathways - physiology; Ornithine Decarboxylase - physiology; Oxidative Stress; Pathways; Phosphoproteins - physiology; Polyamines; Proteinuria; reactive oxygen species; Reactive Oxygen Species - metabolism; Tubuloglomerular feedback
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-007-0529-9

Michael Brownlee has proposed a 'Unifying Mechanism' of hyperglycemia-induced damage in diabetes mellitus. At the crux of this hypothesis is the generation of reactive oxygen species (ROS), and their impact on glycolytic pathways. Diabetes is the leading cause of chronic kidney failure. In the early phase of diabetes, prior to establishment of proteinuria or fibrosis, comes kidney growth and hyperfiltration. This early growth phase consists of an early period of hyperplasia followed by hypertrophy. Hypertrophy also contributes to cellular oxidative stress, and may precede the ROS perturbation of glycolytic pathways described in the Brownlee proposal. This increase in growth promotes hyperfiltration, and along with the hypertrophic phenotype appears required for hyperglycemia-induced cell damage and the progression of downstream diabetic complications. Here we will evaluate this growth phenomenon in the context of diabetes mellitus.