Oana Milas1, Florica Gadalean2, Adrian Vlad3, Victor Dumitrascu4, Silvia Velciov1, Cristina Gluhovschi5, Flaviu Bob1, Roxana Popescu6, Sorin Ursoniu7, Dragos Catalin Jianu8, Petru Matusz9, Agneta-Maria Pusztai10, Alina Secara1, Anca Simulescu1, Maria Stefan1, Mihaela Patruica1, Flaviu Petrica11, Daliborca Vlad4, Ligia Petrica12. 1. Dept. of Nephrology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania; "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. 2. Dept. of Nephrology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania; "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. Electronic address: fnnicorici@yahoo.com. 3. Dept. of Diabetes and Metabolic Diseases, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania; "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. Electronic address: vlad.adrian@umft.ro. 4. Dept. of Pharmacology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania; "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. 5. Dept. of Nephrology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania; "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. Electronic address: gluh@umft.ro. 6. Dept. of Cellular and Molecular Biology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania; "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. 7. Dept. of Public Health Medicine, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania; Centre of Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania; "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. 8. Dept. of Neurology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania; "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. 9. Dept. of Anatomy and Embryology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania; "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. Electronic address: matusz@umft.ro. 10. Dept. of Anatomy and Embryology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania; "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. 11. Nefrotim Medical Center, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania. 12. Dept. of Nephrology, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania; Centre of Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania; "Victor Babes" University of Medicine and Pharmacy Timisoara, Romania.
Abstract
AIMS: To evaluate if there is a link between inflammation (expressed by inflammatory cytokines) and the early stage of diabetic kidney disease (DKD), as shown by markers of podocyte damage and proximal tubular (PT) dysfunction. METHODS: In this study were enrolled 117 type 2 DM patients (36-normoalbuminuria, 42-microalbuminuria, 39- macroalbuminuria), and 11 healthy subjects. Serum and urinary IL-1 alpha, IL-8, IL-18, urinary albumin:creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (podocalyxin, synaptopodin, nephrin) and of PT dysfunction (KIM-1, NAG) were assessed. RESULTS: In multivariable regression urinary Il-1 alpha correlated positively with podocalyxin and NAG (p < 0.0001, R2= 0.57); urinary IL-8 correlated directly with synaptopodin, NAG, nephrin, and KIM-1 (p < 0.0001, R2 = 0.67); urinary IL-18 correlated directly with synaptopodin, NAG, and nephrin (p < 0.0001, R2 = 0.59). Serum IL-1 alpha correlated positively with nephrin, synaptopodin, NAG (P < 0.0001, R2 = 0.68); serum IL-8 correlated directly with synaptopodin and NAG (p < 0.0001, R2 = 0.66); serum IL-18 correlated directly with NAG, KIM-1, and podocalyxin (p < 0.0001, R2=0.647). CONCLUSIONS: Pro-inflammatory interleukins are associated with podocyte injury and PT dysfunction in early DKD. These could exert a key role in the pathogenesis of early DKD, before the development of albuminuria.
AIMS: To evaluate if there is a link between inflammation (expressed by inflammatory cytokines) and the early stage of diabetic kidney disease (DKD), as shown by markers of podocyte damage and proximal tubular (PT) dysfunction. METHODS: In this study were enrolled 117 type 2 DM patients (36-normoalbuminuria, 42-microalbuminuria, 39- macroalbuminuria), and 11 healthy subjects. Serum and urinary IL-1 alpha, IL-8, IL-18, urinary albumin:creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (podocalyxin, synaptopodin, nephrin) and of PT dysfunction (KIM-1, NAG) were assessed. RESULTS: In multivariable regression urinary Il-1 alpha correlated positively with podocalyxin and NAG (p < 0.0001, R2= 0.57); urinary IL-8 correlated directly with synaptopodin, NAG, nephrin, and KIM-1 (p < 0.0001, R2 = 0.67); urinary IL-18 correlated directly with synaptopodin, NAG, and nephrin (p < 0.0001, R2 = 0.59). Serum IL-1 alpha correlated positively with nephrin, synaptopodin, NAG (P < 0.0001, R2 = 0.68); serum IL-8 correlated directly with synaptopodin and NAG (p < 0.0001, R2 = 0.66); serum IL-18 correlated directly with NAG, KIM-1, and podocalyxin (p < 0.0001, R2=0.647). CONCLUSIONS: Pro-inflammatory interleukins are associated with podocyte injury and PT dysfunction in early DKD. These could exert a key role in the pathogenesis of early DKD, before the development of albuminuria.
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