A non-invasive diagnostic model of immunoglobulin A nephropathy and serological markers for evaluating disease severity

Background: Immunoglobulin A nephropathy (IgAN) is the most common pathological type of glomerular disease. Kidney biopsy, the gold standard for IgAN diagnosis, has not been routinely applied in hospitals worldwide due to its invasion nature. Thus, we aim to establish a non-invasive diagnostic model and determine markers to evaluate disease severity by analyzing the serological parameters and pathological stages of patients with IgAN. Methods: A total of 272 biopsy-diagnosed IgAN inpatients and 518 non-IgA nephropathy inpatients from the Department of Nephrology of Chinese People's Liberation Army General Hospital were recruited for this study. Routine blood examination, blood coagulation testing, immunoglobulin-complement testing, and clinical biochemistry testing were conducted and pathological stages were analyzed according to Lee grading system. The serological parameters and pathological stages were analyzed. The receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic value of the clinical factors. Logistic regression was as used to establish the diagnostic model. Results: There were 15 significantly different serological parameters between the IgAN and non-IgAN groups (all P< 0.05). The ROC analysis was performed to measure the diagnostic value for IgAN of these parameters and the results showed that the area under the ROC curve (AUC) of total protein (TP), total cholesterol (TC), fibrinogen (FIB), D-dimer (D2), immunoglobulin A (IgA), and immunoglobulin G (IgG) were more than 0.70. The AUC of the "TC+ FIB + D2 + IgA + age" combination was 0.86, with a sensitivity of 85.98% and a specificity of 73.85%. Pathological grades of l,ll,lll, lV, and V accounted for 2.21%, 17.65%, 62.50%, 11.76%, and 5.88%, respectively, with grade III being the most prevalent. The levels of urea nitrogen (UN) (13.57 +/- 5.95 vs. 6.06 +/- 3.63, 5.92 +/- 2.97, 5.41 +/- 1.73, and 8.41 +/- 3.72 mmol/L, respectively) and creatinine (Cr) (292.19 +/- 162.21 vs. 80.42 +/- 24.75, 103.79 +/- 72.72, 96.41 +/- 33.79, and 163.04 +/- 47.51 mu mol/L, respectively) were significantly higher in grade V than in the other grades, and the levels of TP (64.45 +/- 7.56, 67.16 +/- 6.94, 6122 +/- 8.56, and 61.41 +/- 10.86 vs. 37.47 +/- 5.6 mgjd, respectively), direct bilirubin (DB) (2.34 +/- 1.23, 2.58 +/- 1.40, 1.91 +/- 0.97, and 1.81 +/- 1.44 vs. 0.74 +/- 0.57 mu mol/L, respectively), and IgA (310.35 +/- 103.78, 318.48+107.54, 292.58 +/- 81.85, and 323.29 +/- 181.67 vs. 227.17 +/- 68.12 g/L, respectively) were significantly increased in grades II-V compared with grade I (all P < 0.05). Conclusion: The established diagnostic model that combined multiple factors (TC, FIB, D2, IgA, and age) might be used for IgAN non-invasive diagnosis. TP, DB, IgA, Cr, and UN have the potential to be used to evaluate IgAN disease severity.