PURPOSE OF REVIEW: Chronic kidney disease (CKD) remains a serious diabetic complication despite the use of widely employed interventions such as angiotensin-converting enzyme inhibitors and glucose-lowering treatments. Accumulation of methylglyoxal, a highly reactive glucose metabolite and a major precursor in the formation of advanced glycation end products, may link the hemodynamic, inflammatory, metabolic, and structural changes that drive diabetic CKD. Therefore, methylglyoxal may serve as a potential therapeutic target to prevent diabetic CKD. RECENT FINDINGS: Higher plasma methylglyoxal levels were shown to be associated with a decline in the estimated glomerular filtration rate. Furthermore, interventions that lower methylglyoxal levels reduced albuminuria in rodent models of diabetes. In addition, the glyoxalase system, which detoxifies methylglyoxal into D-lactate, has been identified as a key protective enzymatic system against diabetic CKD in both human and rodent studies. Recently, several promising treatments to lower methylglyoxal directly or to boost the glyoxalase system have been identified. SUMMARY: The review highlights the mechanisms through which methylglyoxal is formed in diabetes, and how methylglyoxal contributes to the mechanisms that drive CKD in diabetes. Furthermore, we discuss the role of glyoxalase-1 in diabetic CKD. Finally, we discuss recent data about treatments that lower methylglyoxal stress.
PURPOSE OF REVIEW: Chronic kidney disease (CKD) remains a serious diabetic complication despite the use of widely employed interventions such as angiotensin-converting enzyme inhibitors and glucose-lowering treatments. Accumulation of methylglyoxal, a highly reactive glucose metabolite and a major precursor in the formation of advanced glycation end products, may link the hemodynamic, inflammatory, metabolic, and structural changes that drive diabetic CKD. Therefore, methylglyoxal may serve as a potential therapeutic target to prevent diabetic CKD. RECENT FINDINGS: Higher plasma methylglyoxal levels were shown to be associated with a decline in the estimated glomerular filtration rate. Furthermore, interventions that lower methylglyoxal levels reduced albuminuria in rodent models of diabetes. In addition, the glyoxalase system, which detoxifies methylglyoxal into D-lactate, has been identified as a key protective enzymatic system against diabetic CKD in both human and rodent studies. Recently, several promising treatments to lower methylglyoxal directly or to boost the glyoxalase system have been identified. SUMMARY: The review highlights the mechanisms through which methylglyoxal is formed in diabetes, and how methylglyoxal contributes to the mechanisms that drive CKD in diabetes. Furthermore, we discuss the role of glyoxalase-1 in diabetic CKD. Finally, we discuss recent data about treatments that lower methylglyoxal stress.
Authors: David Philipp Wohlfart; Bowen Lou; Chiara Simone Middel; Jakob Morgenstern; Thomas Fleming; Carsten Sticht; Ingrid Hausser; Rüdiger Hell; Hans-Peter Hammes; Julia Szendrödi; Peter Paul Nawroth; Jens Kroll Journal: Redox Biol Date: 2022-01-26 Impact factor: 11.799
Authors: Remy J H Martens; Natascha J H Broers; Bernard Canaud; Maarten H L Christiaans; Tom Cornelis; Adelheid Gauly; Marc M H Hermans; Constantijn J A M Konings; Frank M van der Sande; Jean L J M Scheijen; Frank Stifft; Joris J J M Wirtz; Jeroen P Kooman; Casper G Schalkwijk Journal: PLoS One Date: 2019-08-13 Impact factor: 3.240
Authors: Mariana G de Oliveira; Matheus L de Medeiros; Edith B G Tavares; Fabiola Z Mónica; Edson Antunes Journal: Front Physiol Date: 2020-04-03 Impact factor: 4.566