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

Abstract

Background:

Immunoglobulin A 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 also predicts progression later in the course of IgAN. Methods:

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 slopes were calculated. Results:

Median age at biopsy was 44 years, interval between biopsy and IgAN237-1 was 65 months and interval between IgAN237-1 and IgAN237-2 was 258 days (interquartile range 71–531). IgAN237-1 and IgAN237-2 values did not differ significantly and were correlated (rho = 0.44, P < .001). Twenty-eight percent 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 = .02 for score-1; rho = –0.409, P = .002 for score-2) and with ±180 days eGFR slopes (rho = –0.31, P = .009 and rho = –0.439, P = .001, respectively). The ±180 days eGFR slopes were worse for progressors than for non-progressors (median –5.98 versus –1.22 mL/min/1.73 m2 per year for IgAN237-1, P < .001; –3.02 vs 1.08 mL/min/1.73 m2 per year for IgAN237-2, P = .0047). In multiple regression analysis baseline progressor/non-progressor according to IgAN237 was an independent predictor of eGFR180days-slope (P = .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.