TY - JOUR
T1 - Methylglyoxal stress, the glyoxalase system, and diabetic chronic kidney disease
AU - Hanssen, Nordin M. J.
AU - Stehouwer, Coen D. A.
AU - Schalkwijk, Casper G.
N1 - Funding Information:
N.M.J.H. is supported by a Dr E. Dekker grant by the Dutch Heart Foundation (2017T039) and a junior postdoc grant from the Dutch Diabetes Foundation (2017.81.005).
Publisher Copyright:
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2019/1
Y1 - 2019/1
N2 - Purpose of reviewChronic 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 findingsHigher 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.SummaryThe 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.
AB - Purpose of reviewChronic 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 findingsHigher 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.SummaryThe 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.
KW - chronic kidney disease
KW - diabetes
KW - end-stage renal disease
KW - glyoxalase
KW - methylglyoxal
KW - GLYCATION END-PRODUCTS
KW - OXIDATIVE STRESS
KW - ENDOTHELIAL DYSFUNCTION
KW - CARDIOVASCULAR-DISEASE
KW - LIPID-PEROXIDATION
KW - INSULIN-RESISTANCE
KW - DICARBONYL STRESS
KW - I OVEREXPRESSION
KW - RENAL-FUNCTION
KW - RAT MODEL
U2 - 10.1097/MNH.0000000000000465
DO - 10.1097/MNH.0000000000000465
M3 - (Systematic) Review article
C2 - 30320620
SN - 1062-4821
VL - 28
SP - 26
EP - 33
JO - Current Opinion in Nephrology and Hypertension
JF - Current Opinion in Nephrology and Hypertension
IS - 1
ER -