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

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.