Dynamics of urine proteomics biomarker and disease progression in patients with IgA nephropathy

Abstract

Background and Aims IgA-nephropathy (IgAN) frequently leads to kidney failure. The urinary proteomics-based classifier IgAN237 may predict disease progression at the time of kidney biopsy. We studied whether IgAN237 predicts progression also later in the course of IgAN. Method Urine from patients with biopsy-proven IgAN was analyzed using capillary electrophoresis-mass spectrometry at baseline (IgAN237-1, n = 103) and at follow-up (IgAN237-2, n = 89). Patients were categorized as ‘non-progressors’ (IgAN237 ≤0.38) and ‘progressors’ (IgAN237 >0.38). Estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio (UACR) slopes were calculated. Results Median age at biopsy was 44 years, interval between biopsy and IgAN237-1 65 months and interval between IgAN237-1 and IgAN237-2 258 days (IQR 71-531). IgAN237-1 and IgAN237-2 values did not differ significantly and were correlated (rho = 0.44, p<0.001). Twenty-eight and 26% of patients were progressors based on IgAN237-1 and IgAN237-2, respectively. IgAN237 inversely correlated with 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). The ±180days eGFR-slopes were worser for progressors than for non-progressors (median -5.98 versus -1.22 mL/min/1.73m2 per year for IgAN237-1, p<0.001; -3.02 vs 1.08 mL/min/1.73m2 per year for IgAN237-2, p = 0.0047). In multiple regression analysis baseline progressor/non-progressor according to IgAN237 was an independent predictor of eGFR180days-slope (p = 0.001). Conclusion The urinary IgAN237 classifier represents a risk stratification tool in IgAN also later in the course of the dynamic disease. It may guide patient management in an individualized manner.

Non-Invasive Biomarkers for Diagnosis, Risk Prediction, and Therapy Guidance of Glomerular Kidney Diseases: A Comprehensive Review

“…An algorithm based on these protein fragments (IgAN237) and clinical data showed significant added value for the prediction of IgAN progression, as compared with clinical parameters alone (area under the curve (AUC) 0.89 versus 0.72). IgAN237 was recently validated in an independent set of prospective collected urine samples of 103 patients with biopsy-proven IgAN [ 18 ]. Patients were grouped into non-progressors and progressors according to their urinary peptidomic profile.…”