#2561 urine proteomics for prediction of disease progression in patients with iga nephropathy

Abstract Background and Aims IgA nephropathy (IgAN) may lead to kidney failure. The urinary proteomics biomarker-based classifier (IgAN237) may predict progression at the time of kidney biopsy [1]. We now studied whether IgAN237 predicts disease progression not only at the time of biopsy but also later in the course of IgAN. Method Urine samples from 103 patients with biopsy-proven IgAN were analyzed using capillary electrophoresis-mass spectrometry at baseline (IgAN237 score-1) and 89 also at follow-up (IgAN237 score-2). Patients were grouped into ‘non-progressors’ (IgAN237 score ≤0.38 Units) and ‘progressors’ (IgAN237 score >0.38 Units). Historical and follow-up data included, e.g., estimated glomerular filtration rate (eGFR)-slopes, urinary albumin/creatinine ratio (UACR)-slopes and medication. Multiple logistic regression analysis, using a stepwise model, was done with progressors and non-progressors as dependent factors including explanatory variables age, sex, eGFR- and UACR-slopes. Results Median age at biopsy was 44 years (range 11-92); 63% were male. Median interval between biopsy and IgAN237 score-1 was 65 months (0-606), and between IgAN237 score-1 and score-2 was 258 days (71-531). IgAN237 score-1 and score-2 values did not differ significantly and were correlated (rho = 0.44, p<0.001). Twenty-eight and 26% of patients were classified as progressors based on IgAN237 score-1 and score-2, respectively. The IgAN237 score inversely correlated with the chronic eGFR slopes (rho = -0.278, p = 0.02 for score-1; rho = -0.409, p = 0.002 for score-2) and with ±180days eGFR slopes (rho = -0.31, p = 0.009 and rho = -0.439, p = 0.001, respectively) (Figure 1). The ±180days eGFR-slopes were more reduced for progressors than non-progressors (median -5.98 versus -1.22 mL/min/1.73m2 per year for score-1, p<0.001; -3.02 vs 1.08 mL/min/1.73m2 per year for score-2, p = 0.047) (Figure 2). The only significant variable maintained in a multiple logistic regression analysis for IgAN237 score-1 (progressor vs non-progressor) was ±180days eGFR slope (p<0.001) and for IgAN237 score-2 the UACR (p = 0.002) and age at baseline (p = 0.016). Conclusion The urinary IgAN237 classifier represents a risk stratification tool in IgAN not only at the time of biopsy but also later in the course of the disease. It may guide physicians in management and follow-up strategies in an individualized manner.