Metabolomic Analysis For Serum And Urine Of Patients At Different Stages Of Diabetic Nephropathy

Objective:This study aims to work out the metabolomic profile in serum and urine of patients with DN at different stages, and find out biomarkers for early diagnosis and prognosis of DN.Methods:Ninety male patients diagnosed as type2diabetic mellitus(T2DM) were enrolled and divided into3groups (normoalbuminuria, microalbuminuria, and proteinuria). Twenty-five healthy controls were included. Serum and urine metabolites were analyzed using gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS).Results:Distinct metabolomic differences were observed between different stages of DN. All the three groups of patients showed clear dysfunction of glycolysis and tricarboxylic acid cycle. Activation of protein kinase C pathway and hexosamine biosythesis pathway were also demonstrated. Serum branched-chain amino acids increased in the diseased group. Serum non-essential fatty acid elevated, while L-cartinine and acyl CoA decreased, which indicated the dysfunction of P-oxidation of fatty acids. Palmitic acid in the serum, as well as PC(P-19:l(12Z)/0:1) and dodecanedioic acid in the urine might be candidate biomarker for early diagnosis of DN. Decanoyl-L-carnitine, PC(9:0/0:0) and Dg(17:2(9Z,12Z)/20:3(8Z,11Z,14Z)/0:0) in the serum, as well as uridine diphosphate and lysoPC(16:0) might be candidate biomarkers for prognosis of DN.Conclusion:Our study demonstrated the changes of metabolic profile in different stages of DN, and provided candidate biomarkers for early diagnosis and prognosis.Objective:Inflammation participates in renal injury of obesity related glomerulopathy(ORG). Since mast cells are regarded as important regulators of inflammatory responses, this study aimed to investigate whether mast cells infiltration was involved in renal damage of ORG.Methods:Forty patients with ORG, eighteen patients with idiopathic focal segmental glomerular sclerosis(FSGS) and ten normal controls were included in this study. Immunohistochemistry was used to detect tryptase, monocyte chemoattractant protein-1(MCP-1) and CD68. Associations between the infiltration of mast cells with inflammation and clinicopathological parameters were assessed.Results:Mast cells infiltration increased in ORG compared with FSGS and the control group. The number of mast cells was positively correlated with body mass index (r=0.432,P=0.006), systolic blood pressure (r=0.445, P=0.005), and serum creatinine (r=0.489, P=0.002). Increased expression of MCP-1and CD68were also observed, and MCP-1colocalized with the cytoplasm of mast cells as well as other cell types, while macrophages distributed around mast cells. The positive area of tubulointerstitial MCP-1was correlated with the number of mast cells(r=-0.695, P<0.001) and interstitial fibrosis(r=0.327, P=0.042). The proportion of glomerular sclerosis (r=0.466, P=0.003) and segmental sclerosis (r=0.407,P=0.010), as well as the degree of tubular atrophy (r=0.470, P=0.003) and interstitial fibrosis (r=0.669, P<0.001) were well correlated with mast cells infiltration. Multivariate regression showed that the number of mast cells was an independent predictor for eGFR (R2=0.313, P<0.001).Conclusions:Mast cells infiltration is involved in renal damage of ORG. Inflammation and renal fibrosis might contribute to such process.