| BackgroundUrokinase-type plasminogen activator receptor(uPAR)and its soluble form(suPAR),as new injury biomarkers,are widely used in research of infectious diseases,cancers,cardiovascular diseases,autoimmune diseases,etc.Recently,the uPAR and criculating suPAR has been suggested to play an important role in various renal diseases.Relative researches between uPAR/suPAR and type 2 diabetic kidney disease are rare.ObjectiveImmunohistochemistry staining for uPAR was performed in renal tissues of type 2 diabetics with biopsy-proven diabetic nephropathy and serum suPAR of 70 diabetic patients with or without diabetic kidney disease and 15 healthy controls were measured.The objective of this research was to investigate the correlation between uPAR/suPAR and the severity of kidney impairment and to evaluate its application value in type 2 diabetic kidney disease.MethodTwo major parts of subjects were recuirted.For the first part,thirty-two renal tissues were collected from 32 subjects.Twenty-two tissues came from biopsy-proven diabetic glomerulopathy of type 2 diabetics and the other 10 tissues came from renal cancer subjects.The non-cancerous renal tissues after nephrectomy were used as control.Image ProPlus 6.0 software was used for quantitative analysis.The second part contained 70 subjects in different stages of diabetic kidney diasease,which were divided into groups according to the standarded stages of Mogensen and difined as DM group(T2DM without proteinuria,n= 18),MicroA group(T2DM with microalbuminuria,n= 17),MacroP group(T2DM with macroproteinuria and low eGFR,n=17)and ESRD group(T2DM with eGFR<15 mL/min/1.73m2 or dialysis,n=18).Another 15 subjects from healthy physical examination were recuited over the same period in the same hospital as the health controls(HC group,n=15).Serum suPAR and interleukin-18 of 70 diabetic patients and 15 healthy controls were measured.SPSS 24.0 software was used for statistical analyses.Result1.Immunohistochemical staining for uPARThe uPAR expression significantly increased in renal tissues with biopsy-proven diabetic nephropathy.It mainly expressed on the cell membrane surface of both glomerular cells and tubular cells.2.Clinical characteristics of subjects in different stages of diabetic kidney disease and healthy controlsFor all diabitic patients,there was a downward tendency of albumin,triglyceride and total cholesterol and upward tendency of urinary protein creatinine ratio in the wake of the staging of diabetic kidney disease.the estimated glomerular filtration rate significantly decreased and uric acid significantly rised along with the staging of diabetic kidney disease(P<0.05).ESRD group had a lower albumin and glycosylated hemoglobin and higher urinary protein creatinine ratio and creatinine compared with other diabetic groups(P<0.05).The incidence of diabetic retinopathy,peripheral neuropathy and carotid ultrasound increased with the progression of diabetic kidney disease.3.Serum level of suPAR,interleukin-18The levels of serum suPAR and interleukin-18 increased gradually with the advanced staging of diabetic kidney disease.4.Correlation analysis of suPAR,interleukin-18 with eGFR and proteinuriaSerum suPAR was negatively correlated with estimated glomerular filtration rate(p?-0.735,P<0.01)and positively correlated with urinary protein creatinine ratio(p=0.730,P<0.01).Serum interleukin-18 concentration increased gradually with the advanced staging of diabetic kidney disease and negatively correlated with estimated glomerular filtration rate(p=-0.504,P<0.01)and positively correlated with urinary protein creatinine ratio(p= 0.440,P<0.01).5.Receiver operating characteristic curvesIn predicting the appearance of albuminuria in diabetic kidney diasease,the area under curve of suPAR was 0.845(P=0.000,95%CI:0.754?0.935)with the sencitivity 65.4%and specificity 94.4%.The area under curve of interleukin-18 was 0.753(P=0.001,95%CI:0.615?0.891)with the sencitivity 78.8%and specificity 66.1%.In predicting the decline of renal function,the area under curve of suPAR was 0.895(P=0.000,95%CI:0.821?0.968)with the sencitivity82.9%and specificity 92.9%.The area under curve of interleukin-18 was 0.796(P=0.000,95%CI:0.692?0.899)with the sencitivity 80.0%and specificity 68.6%.ConclusionsThe uPAR and circulating suPAR may involve in renal impairment in patients with type 2 diabetes and serum suPAR is a useful biomarker for assessing stages and severity of diabetic kidney disease and has higher predictive value than interleukin-18. |
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