Myeloid-related protein 8/14 complex describes microcirculatory alterations in patients with type 2 diabetes and nephropathy.
BACKGROUND
Inflammation contributes to cardiovascular complications in type 2 diabetes, which are often characterized by microvascular alterations. We investigated whether myeloid-related protein 8/14 complex (MRP8/14) secreted by transmigrating monocytes and granulocytes may represent a biomarker for microvascular alterations in patients with type 2 diabetes and nephropathy.


METHODS
MRP8/14 was measured in 43 patients with type 2 diabetes and nephropathy. Additionally, the inflammatory markers Interleukin-6 (IL-6), Tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP) were quantified. To detect microvascular alterations proteinuria and retinal vessel caliber were used as classical and novel marker, respectively. Proteinuria was quantified by protein-creatinine ratio (PCR); retinal vessel caliber was quantified after retina photography on digitalized retina pictures.


RESULTS
MRP8/14 was positively associated with inflammation (r = 0.57), proteinuria (r = 0.40) and retinal arterial caliber (r = 0.48). Type 2 diabetic patients with MRP8/14 values above the median of 5.8 microg/ml demonstrated higher proteinuria and larger retinal artery caliber than patients with MRP8/14 values below the median (logPCR: -0.51 +/- 0.52 versus -0.96 +/- 0.46, P < 0.01; retinal artery lumen (microm): 178.3 +/- 14.1 versus 162.7 +/- 14.9 P < 0.01). Both groups did not differ with regard to metabolic factors and blood pressure. MRP8/14 was an independent predictor of retinal artery caliber in multivariate stepwise regression analysis (beta = 0.607) and was positively associated with IL-6 (r = 0.57, P < 0.001) and TNF-alpha (r = 0.36, P < 0.05).


CONCLUSIONS
MRP8/14--a marker for transendothelial migration--describes not only the state of inflammation in diabetic nephropathy, but additionally the degree of microvascular alterations in the glomerular and retinal bed. Therefore, MRP8/14 may be a potentially selective novel biomarker for microcirculatory defects in diabetic nephropathy.
Burkhardt
Klaus
K
Nephrological Clinic Weissenburg, 91781 Weissenburg, Germany. praxis-dr-burkhardt@t-online.de
Schwarz
Sonja
S
Pan
Chengrui
C
Stelter
Felix
F
Kotliar
Konstantin
K
Von Eynatten
Maxilian
M
Sollinger
Daniel
D
Lanzl
Ines
I
Heemann
Uwe
U
Baumann
Marcus
M
D018528:ATP-Binding Cassette Transporters / Q000097:blood*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D040502:Calgranulin B / Q000097:blood*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012171:Retinal Vessels / Q000503:physiopathology
C435500:ABCC11 protein, human; D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D040502:Calgranulin B; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept