Levels and clinical significance of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 in patients with diabetic nephropathy

Objective To explore the levels and clinical significance of urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) in patients with diabetic nephropathy (DN).

Methods A total of 254 DN patients were selected as study group, 230 patients with simple type 2 diabetes in the same period were selected as control group, and the clinical materials were compared between the two groups. According to the estimate glomerular filtration rate (eGFR), DN patients were divided into stage I group (n=32), stage Ⅱ group (n=84), stage Ⅲ group (n=90) and stage Ⅳ group (n=48); according to serum creatinine level and urinary volume, the DN patients were divided into AKI group (n=19) and non-AKI group (n=235); the differences in levels of serum creatinine, urinary TIMP-2 and IGFBP7 in different groups were compared. The levels of urinary TIMP-2, IGFBP7 and urinary creatinine were detected by enzyme-linked immunosorbent assay; Pearson test was used to analyze the relationships of urinary TIMP-2 and IGFBP7 with related indicators; receiver operating characteristic (ROC) curve was used to evaluate the efficiency of urinary TIMP-2, IGFBP7 and serum creatinine in diagnosing AKI in DN patients.

Results The levels of serum creatinine, glycosylated hemoglobin (HbA1c), blood uric acid, urea nitrogen, urinary microalbumin, 24-hour urinary protein quantitation and urinary β₂-microglobulin in the study group were significantly higher than those in the control group, while the levels of serum albumin and eGFR were significantly lower than those in the control group (P < 0.05). The levels of serum creatinine, urinary TIMP-2 to urinary creatinine ratio (TIMP-2/urinary creatinine) and urinary IGFBP7 to urinary creatinine ratio (IGFBP7/urinary creatinine) in DN patients in stage Ⅲ and Ⅳ were significantly higher than those in patients in stage Ⅰand Ⅱ(P < 0.05); compared with the non-AKI group, the levels of serum creatinine, urinary TIMP-2/urinary creatinine and urinary IGFBP7/urinary creatinine were significantly higher in the AKI group (P < 0.05). Urinary TIMP-2 and IGFBP7 were positively correlated with serum creatinine, HbA1c, blood uric acid, urea nitrogen, urinary microalbumin, 24-h urinary protein quantitation and urinary β₂-microglobulin (P < 0.05), but were negatively correlated with serum albumin and eGFR (P < 0.05). ROC curve showed that the areas under the curve (AUC) of urinary TIMP-2, IGFBP7 and serum creatinine in predicting incidence of AKI in DN patients were 0.676 (95%CI, 0.587 to 0.756), 0.864 (95%CI, 0.792 to 0.918), 0.618 (95%CI, 0.528 to 0.703) respectively, and the AUC of urinary TIMP-2 combined with IGFBP7 in predicting incidence of AKI in DN patients was 0.926 (95%CI, 0.866 to 0.965).

Conclusion The levels of urinary TIMP-2 and IGFBP7 in DN patients increase with the aggravation of the disease, which have a certain predictive value for AKI in DN patients.