Abstract
The prevalence of diabetes reaches epidemic proportions. Diabetes is the leading cause of end-stage kidney disease (ESKD) since 30–40% of diabetic patients develop diabetic nephropathy. Albuminuria and glomerular filtration rate used to assess kidney function are considered surrogate outcomes of chronic kidney disease. The search for a biomarker that predicts progression to diabetic kidney disease is intense. We analyzed the association of serum advanced glycation end-products (AGEs) index (AGI) with impaired kidney function in poorly controlled type II diabetic patients. We observed an association between AGI and impaired kidney function in microalbuminuria patients with hyperglycemia. A significant association between AGEs, particularly carboxymethyl lysine (CML), and impaired kidney function were observed. Administration of AGEs to mice showed heavy proteinuria and glomerular abnormalities. Reduced podocyte number in mice administered with AGEs could be attributed to the epithelial-mesenchymal transition of podocytes. Our study suggests CML could be independently related to the podocyte injury and the risk of DN progression to ESKD in patients with microalbuminuria. AGEs in general or CML could be considered a prognostic marker to assess diabetic kidney disease.
Highlights
Diabetes has long been a growing epidemic, and Asia accounts for 60% of the world’s diabetic population [1, 2]
Together the data suggest that excess advanced glycation end-products (AGEs), CML associated with decreased podocin expression, foot-process effacement of podocytes from type II patients with nephropathy
We found the HbA1c, GA, AGI index significantly associated with decreased kidney function
Summary
Diabetes has long been a growing epidemic, and Asia accounts for 60% of the world’s diabetic population [1, 2]. AGEs Induce Podocyte Injury and Proteinuria (ESKD) cases, with 6% attributed to type I and 38% attributed to type II diabetes [3]. During the early DN stage, a patient shows hyperfiltration, represented by a rise in GFR and occasional microalbuminuria (ratio of urine albumin to creatinine ≥ 30 mg/g) [4]. The DN’s progressive stage is represented by a gradual decline of the GFR, persistence of microalbuminuria, and subsequent macroalbuminuria (ratio of urine albumin to creatinine ≥ 300 mg/g). The advanced DN stage is characterized by severe proteinuria and chronic kidney insufficiency that manifest in ESKD. Both albuminuria and impaired GFR are the strongest predictors of progression to ESKD in patients with diabetes
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