Serum expression levels of rho-associated coiled-coil containing protein kinase 2 and retinol-binding protein 4 in patients with IgA nephropathy and their values in evaluating disease condition and predicting prognosis

Objective  To detect the expression levels of rho-associated coiled-coil containing protein kinase 2 （ROCK2） and retinol-binding protein 4 （RBP4） and examine the value of ROCK2/RBP4 in evaluating disease condition and predicting prognosis in patients with immunoglobulin A nephropathy （IgAN）.

Methods  From June 2016 to June 2019, 98 IgAN patients were selected as IgAN group, including mild IgAN （n=36）, moderate IgAN （n=32） and severe IgAN （n=30）. And 100 healthy subjects receiving physical examination during the same period were designated as control group. Serum levels of ROCK2 and RBP4 were detected by enzyme-linked immunosorbent assay （ELISA）. Kaplan-Meier survival curve was plotted for examining the relationship between the expression level of ROCK2/RBP4 and prognosis; Pearson's method was employed for analyzing the correlation between ROCK2 and RBP4 expressions; Receiver operating characteristic curve （ROC） for examining the diagnostic value of ROCK2/RBP4 for IgAN; COX method for analyzing the prognostic factors.

Results  The serum expression levels of ROCK2 and RBP4 were significantly higher in IgAN group than those in control group （24.25 ± 5.31） μg/L, （59.70 ± 9.43） μg/L vs （15.57 ± 4.16） μg/L, （32.14 ± 7.82） μg/L）. The difference was statistically significant （t=12.818, 22.404, all P＜0.001）. The serum expression levels of ROCK2 and RBP4 were （18.69 ± 4.36） μg/L vs （23.75 ± 5.31） μg/L, （31.46 ± 5.62） μg/L vs （45.37 ± 7.86） μg/L and （62.48 ± 8.12） μg/L vs （73.94 ± 8.65） μg/L in mild/moderate/severe IgAN patients. With the worsening of disease, the expression levels of serum ROCK2 and RBP4 were up-regulated and the difference was statistically significant （F=51.854, 102.234, all P＜0.05）. The serum expression levels of ROCK2 and RBP4 were correlated with Lee's grade, IgA/C3 ratio and disease severity （P＜0.05）; The prognosis survival rates of patients with a high expression of ROCK2/RBP4 were significantly lower than those with a low expression of ROCK2/RBP4 （60.00% vs 74.19%, 89.71% vs 91.67%） and the difference was statistically significant （Log rank=4.674, P=0.031）; ROC curve results indicated that AUC of serum level of ROCK2 for diagnosing IgAN was 0.889 with a sensitivity of 80.61%, a specificity of 80.00% and a cut-off value of 18.79 μg/L; AUC of RBP4 for diagnosing IgAN was 0.986 with a sensitivity of 96.94%, a specificity of 95.00% and a cut-off value of 41.31 μg/L; AUC of the combined detection was 0.997 with a sensitivity of 98.98% and a specificity of 94.86%. Pearson’s correlation analysis revealed that the serum expression levels of ROCK2 and RBP4 were correlated positively （r=0.701, P＜0.001）; Multivariate COX regression analysis revealed that IgA/C3 （OR=2.683, 95%CI :1.060-6.794）, ROCK2 （OR=1.831, 95%CI :1.027-3.264） and RBP4 （OR=1.517, 95%CI : 1.104-2.084） were the influencing factors of prognosis and survival in IgAN patients （all P＜0.05）.

Conclusion  ROCK2 and RBP4 are highly expressed in sera of IgAN patients. Both are correlated closely with the clinicopathological characteristics, disease severity and prognosis of IgAN patients. The expression levels of ROCK2 and RBP4 have some diagnostic values.