Dynamics of urine proteomics biomarker and disease progression in patients with IgA nephropathy
Björn Peters, Joachim Beige, Justyna Siwy, Michael Rudnicki, Ralph Wendt, Alberto Ortíz, Ana B. Sanz, Harald Mischak, Heather N. Reich, Salmir Nasic, Dana Mahmood, Anders Persson, Anders Fernström, Maria Weiner, Bernd Stegmayr, the PersTIgAN Working Group, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Justyna Siwy, Petra Zürbig, Harald Mischak, Annika Durban, Julia Raad, Igor Golovko, Heather N. Reich, Ping Lam, Stuart Yang, Ana B. Sanz, Beatriz Fernández‐Fernández, Jorge Rojas-Rivera, María Vanessa Pérez-Gómez, Alberto Ortiz, María Dolores Sánchez-Niño, Jinny Sánchez-Rodríguez, Michael Rudnicki, Julia Kerschbaum, Johannes Leierer, Gert Mayer, Bernd Stegmayr, Björn Peters
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.