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. 2025 Apr 10;20(7):978-992.
doi: 10.2215/CJN.0000000707.

Proteinuria Trajectory and Disease Progression in Children and Adults with IgA Nephropathy/Vasculitis

Dorey A Glenn  1 , Ashley W Carver  1 , Margaret E Helmuth  2 , Abigail R Smith  3 , Richard A Lafayette  4 , Prasanth Ravipati  5 , Andrea L Oliverio  2 , Dana V Rizk  6 , Jan Novak  6 , Francesca Lugani  7 , Sharon M Bartosh  8 , Krzysztof Mucha  9 , Krzysztof Kiryluk  10 , Manish K Saha  1 , Cynthia C Nast  11 , Jean Hou  11 , Laura E Biederman  12 , Nidia Messias  13 , Avi Z Rosenberg  14 , Heather N Reich  15 , Pietro A Canetta  10 , Patrick H Nachman  16 , Carla Nester  17 , Raed Bou-Matar  18 , Shikha Wadhwani  3 , Laura H Mariani  2 , Myda Khalid  19 ; CureGN IgA Working Group
Collaborators, Affiliations

Proteinuria Trajectory and Disease Progression in Children and Adults with IgA Nephropathy/Vasculitis

Dorey A Glenn et al. Clin J Am Soc Nephrol. .

Abstract

Key Points:

  1. Defining risk of kidney function loss in IgA nephropathy and IgA vasculitis with nephritis is important for patient counseling and risk-based enrollment of clinical trials.

  2. Proteinuria trajectory over 2 years can uniquely identify patients at risk of loss of kidney function or kidney failure.

  3. Children and adults with the highest levels of proteinuria had a higher risk of progressive kidney disease compared with those with intermediate levels.

Background: Identifying patients with IgA nephropathy at risk of disease progression is critical for clinical decision making, risk-based patient counseling, and optimal enrollment of clinical trials.

Methods: Patients with IgA nephropathy and IgA vasculitis with nephritis were enrolled in the Cure Glomerulonephropathy Network, a multicenter observational cohort study. Children and adults were analyzed separately in four cohorts: (1) full, (2) incident, (3) prevalent, and (4) histology. Groups were defined using latent class trajectory modeling using proteinuria measurements over 2 years. Linear mixed models were used to calculate predicted eGFR slope. In adults, Cox proportional hazard models were used to model time to kidney failure or 40% eGFR decline as a function of the proteinuria trajectory group.

Results: Of 919 patients with IgA nephropathy/IgA vasculitis with nephritis enrolled into the Cure Glomerulonephropathy Network, 368 adults and 234 children were included in the analysis. In the full adult cohort, group 1 had the lowest levels of proteinuria (interquartile range [IQR], 0.1–0.4 g/g), while groups 2 and 3 had intermediate and higher levels of proteinuria (IQR, 0.5–1.5 and IQR, 1.8–4.1 g/g), respectively. The average predicted time to eGFR <15 ml/min per 1.73 m2 was >90, 16, and 8 years and >90, 67, and 11 years for proteinuria trajectory groups 1, 2, and 3 in the full adult and pediatric cohorts, respectively. In adults, adjusting for age, eGFR at enrollment, immunosuppression exposure, and hypertension, group 3 membership was associated with 3.13 (95% confidence interval [CI], 1.84 to 5.33), 1.98 (95% CI, 0.97 to 4.06), and 3.36 (95% CI, 1.59 to 7.13) times higher hazard of progressing to a composite outcome compared with group 2 membership in the full, prevalent, and histology cohorts, respectively, but not associated with progression in the incident cohort.

Conclusions: Proteinuria trajectory is a major predictor of disease progression in patients with IgA nephropathy.

Keywords: CKD; Henoch-Schonlein purpura (IgA vasculitis); IgA nephropathy; clinical epidemiology; glomerular disease; pediatric nephrology; pediatrics.

PubMed Disclaimer

Conflict of interest statement

Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/CJN/C243.

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