Value of combined detection of urinary kidney injury markers in the diagnosis of early-stage diabetic kidney disease
	    		
		   		
		   			
		   		
	    	
    	 
    	10.3760/cma.j.cn441217-20231223-01227
   		
        
        	
        		- VernacularTitle:联合检测尿肾损伤标志物诊断早期糖尿病肾脏疾病的价值
 
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Xiaoying YUN
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Feifei WANG
			        		
			        		;
		        		
		        		
		        		
			        		Chunmiao CHEN
			        		
			        		;
		        		
		        		
		        		
			        		Bing LI
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. 海南医学院第二附属医院肾病内科,海口 571199
			        		
		        		
	        		
        		 
        	
        	
        	
        	
        		- Keywords:
        			
	        			
	        				
	        				
			        		
				        		Diabetes mellitus, type 2;
			        		
			        		
			        		
				        		Diabetic nephropathies;
			        		
			        		
			        		
				        		Urine;
			        		
			        		
			        		
				        		Kidney injury markers;
			        		
			        		
			        		
				        		Kidney glomerulus;
			        		
			        		
			        		
				        		Kidney tubules
			        		
			        		
	        			
        			
        		
 
        	
            
            
            	- From:
	            		
	            			Chinese Journal of Nephrology
	            		
	            		 2024;40(8):619-627
	            	
            	
 
            
            
            	- CountryChina
 
            
            
            	- Language:Chinese
 
            
            
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		        	Abstract:
			       	
			       		
				        
				        	Objective:To explore the value of combined detection of urinary kidney injury markers in the diagnosis of early-stage diabetic kidney disease (DKD), and to provide evidence for early-stage DKD screening.Methods:It was a retrospective study. The clinical data of patients with type 2 diabetes mellitus (T2DM) from the Second Affiliated Hospital of Hainan Medicine University from January 2022 to August 2023 were collected. According to urinary microalbumin/creatinine ratio (UACR), the patients were divided into three groups: isolated diabetes group (UACR < 30 mg/g), early-stage DKD group (30 mg/g ≤ UACR < 300 mg/g) and clinical DKD group (UACR ≥ 300 mg/g), and the differences of clinical data among three groups were compared. Glomerular injury markers urinary microalbumin, transferrin, immunoglobulin (Ig) and α2 macroglobulin, and renal tubule injury markers α1 microglobulin (α1-MG), β2 microglobulin (β2-MG), retinol-binding protein (RBP), N-acetyl-β- D-glucosidase (NAG), neutrophil gelatinase-associated lipid carrier protein (NGAL) were measured. Spearman correlation method was used to analyze the correlation between urinary kidney injury markers and clinical indicators. Multivariate logistic regression analysis method was used to analyze the risk factors of DKD occurrence (UACR > 300 mg/g). Receiver-operating characteristic curve was used to analyze the value of individual and combined detection of urinary renal injury markers in the diagnosis of early-stage DKD (30 mg/g ≤ UACR < 300 mg/g). Results:A total of 116 T2DM patients were enrolled in this study, aged (61.99±12.56) years old (30 to 91 years old), with 79 males (68.1%). There were 44 (37.9%) isolated diabetes patients, 27 (23.3%) early-stage DKD patients, and 45 (38.8%) clinical DKD patients. Serum creatinine (Scr, H=34.183, P<0.001) and blood urea nitrogen (BUN, H=34.082, P<0.001) in clinical DKD group were higher than those in isolated diabetes group and early-stage DKD group. Spearman correlation analysis showed that glomerular injury markers urinary microalbumin, transferrin, Ig and α2 macroglobulin were positively correlated with Scr, BUN and UACR, and negatively correlated with estimated glomerular filtration rate and serum albumin (all P<0.05). Renal tubule injury markers urinary α1-MG, β2-MG, NAG, RBP, and NGAL were positively correlated with Scr, BUN and UACR, and negatively correlated with estimated glomerular filtration rate and serum albumin (all P<0.05). Multivariate logistic regression analysis indicated that systolic blood pressure ≥ 140 mmHg ( OR=1.033, 95% CI 1.008-1.060, P=0.010), high urinary microalbumin ( OR=1.018, 95% CI 1.007-1.030, P=0.001), high urinary RBP ( OR=1.309, 95% CI 1.086-1.577, P=0.005), high urinary NGAL ( OR=1.004, 95% CI 1.000-1.008, P=0.037), low serum albumin ( OR=0.833, 95% CI 0.749-0.926, P=0.001) and low urinary Ig ( OR=0.994, 95% CI 0.990-0.999, P=0.018) were independent influencing factors of DKD occurrence. Receiver-operating characteristic curve revealed that the area under the curve ( AUC) was the largest for diagnosing early-stage DKD when urinary microalbumin was detected alone ( AUC=0.976, 95% CI 0.955-0.997, P<0.001), with sensitivity and specificity of 95.6% and 90.1%, respectively. The combined detection of urinary microalbumin + Ig + transferrin + α2 macroglobulin + α1-MG + β2-MG + NAG + RBP + NGAL had an AUC of 0.986 (95% CI 0.971-1.000, P<0.001), with sensitivity and specificity of 93.3% and 98.5%, respectively, which was better than each single index. Further optimized detection combination was urinary microalbumin combined with β2-MG and NGAL, which had the best diagnostic efficacy ( AUC=0.978, 95% CI 0.958-0.999, P<0.001), with sensitivity and specificity of 95.6% and 93.0%, respectively. Conclusions:Compared with the single detection of each index, the combined detection of urinary glomerular injury and renal tubule injury markers has higher value in diagnosing early-stage DKD. The combined detection of urinary microalbumin combined with β2-MG and NGAL has the highest value in diagnosing early-stage DKD.