Incipient diagnosis and noninvasive forecasts using urinary biomarkers are important for preventing diabetic kidney disease (DKD) progression, but they are also controversial. Previous studies have shown a potential relationship between urinary tubular biomarkers (UTBs) and traditional Chinese medicine (TCM) syndrome in patients with DKD. Thus, we further evaluated the clinical significance of combined detection of urinary biomarkers in noninvasively predicting the extent of renal damage in patients with early DKD with kidney qi deficiency syndrome, and preliminarily explored the potential biological link between UTBs and TCM syndrome in DKD. We categorized 92 patients with Type 2 diabetes mellitus into three groups as follows: 20 patients with normoalbuminuria, 50 patients with microalbuminuria, and 22 patients with macroalbuminuria. We found that, in all groups, 24 hr urinary albumin (24hUAlb) and urinary albumin-to-creatinine ratio (UACR) showed stepwise and significant increases. Urinary cystatin C (UCysC), urinary N-acetyl-β-d-glucosaminidase (UNAG), and urinary retinol-binding protein (URBP) synchronously increased gradually, consistent with the degree of albuminuria in all groups. Moreover, 24hUAlb and UACR were positively correlated with UCysC, UNAG, and URBP, respectively. In 72 patients with Type 2 DKD with albuminuria, a positive correlation was observed between UNAG and URBP, UCysC was also positively correlated with UNAG and URBP, respectively. Additionally, TCM syndrome distributional characteristics in all patients were consistent with clinical manifestations of kidney qi deficiency syndrome. Therefore, the combined detection of UCysC, UNAG, URBP, and UAlb may be used as a practical clinical technique to noninvasively forecast the extent of renal injury in patients with early Type 2 DKD with kidney qi deficiency syndrome. UTBs may be one of the biological bases of the specific TCM syndromes in DKD.
Detection of microalbuminuria is important in the management of diabetic patients since it is predictive of development of proteinuria and nephropathy. Two sensitive and specific in-house ELISAs for microalbuminuria were established and validated. One of the ELISAs was based on antigen coating while the other employed antibody coating. Recovery and linearity experiments gave acceptable results of 100 +/- 10%, while precision results were <10% for intra-assay and <12% for inter-assay coefficients of variation (CVs). The standard curve ranged from 10-625 ug/l, equivalent to 0.2-12.5 mg/l for urine samples diluted 1:20 fold. When the antibody coated ELISA was compared to antigen coated ELISA, a correlation of r=0.996 was obtained. When compared to commercial kits, the in-house ELISAs gave good correlations of r=0.961 versus the Boehringer Mannheim Micral Test strips and r=0.940 versus Ames Microalb Turbidimetry. The normal microalbumin reference ranges determined for 12h, first morning and random urine samples were 0.7-5.3 mg, 0.1-10.2 mg/l and 0.8-26.1 mg/l respectively. The normal albumin excretion rate (AER) was 1.0-7.3 ug/min while untimed urine samples gave results of 0.1-0.9 and 0.2-1.6 mg/mmol after dividing by creatinine concentrations. The ELISAs were used to detect microalbuminuria in 338 random urine samples from diabetic patients. A high percentage 47.9% was found to be positive for microalbuminuria and 18.0% had macroalbuminuria >25 mg/mmol. Thus screening for microalbuminuria together with creatinine measurements using random urine samples can be used for management of diabetic patients.
BACKGROUND AND OBJECTIVE: Microalbuminuria is early stage of diabetic nephropathy as well as a marker of cardiovascular disease. The objective of this study is to determine the prevalence of microalbuminuria and associated risk factors among type 2 diabetic outpatients, attending a diabetic clinic in University Sains Malaysia Hospital (HUSM).
PATIENTS AND METHODS: Prospective study design was used in the data collection process. The study sample consists of 1066 type 2 diabetes mellitus outpatients who fit the inclusion criteria. All the patients were recruited from the diabetic outpatient clinics from HUSM. The study period was from January till December 2008. Microalbuminuria was diagnosed if the urinary albumin excretion more than 30 mg/g of creatinine.
RESULTS: A total of 1661 patients were included in this study. Microalbuminuria was diagnosed in 273 (25.4%) patients. Multivariate logistic regression analysis indicated that microalbuminuria was positively associated with duration of hypertension (P=0.044), HbA1c (P=0.004), systolic blood pressure (<0.001), creatinine clearance (P=0.007) and the presence of neuropathy (P=0.004).
CONCLUSION: High prevalence of microalbuminuria was in type 2 diabetic outpatients. Predictive factors for microalbuminuria were duration of hypertension, HbA1c, systolic blood pressure, creatinine clearance and the presence of neuropathy. The study suggests the need to screen for microalbuminuria early and the active management of modifiable risk factors in particular, hyperglycemia, hypertension and creatinine clearance, to reduce the burden of end-stage renal disease in the future.