Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 13;20(8):1119-1131.
doi: 10.2215/CJN.0000000751.

Clinical and Histologic Predictors of Kidney Outcomes in C3 Glomerulopathy and Idiopathic Membranoproliferative GN

Malak Ghaddar  1   2 , Fernando Caravaca-Fontán  3   4 , Manuel Praga  3 , Gema Fernández-Juárez  5 , Hannah J Lomax-Browne  6 , H Terence Cook  6 , Erica Daina  7 , Marina Noris  7 , Giuseppe Remuzzi  7 , Dilshani Induruwage  2 , Bingyue Zhu  2 , Matthew C Pickering  6 , Sean J Barbour  1   2
Affiliations

Clinical and Histologic Predictors of Kidney Outcomes in C3 Glomerulopathy and Idiopathic Membranoproliferative GN

Malak Ghaddar et al. Clin J Am Soc Nephrol. .

Abstract

Key Points:

  1. Lower eGFR, paraprotein presence, and interstitial fibrosis were associated with a higher risk of kidney outcome.

  2. Native disease (versus recurrence post-transplantation), White ethnicity, and lower C4 levels were associated with a lower risk of kidney outcome.

  3. A 50% reduction in proteinuria from baseline to a value <1 g/d was associated with a lower risk of kidney outcome.

Background: C3 glomerulopathy (C3G) is a rare disease caused by abnormalities in the alternative complement pathway with significant overlap with idiopathic immune complex membranoproliferative GN (IC-MPGN). The risk factors of kidney outcomes in these conditions remain controversial, limited by small studies. We aimed to identify and assess risk factors associated with kidney outcomes.

Methods: Using a cohort of 225 patients with C3G or idiopathic IC-MPGN from three international centers, we evaluated the association between clinical and histologic variables and a composite outcome of a 30% decline in eGFR or ESKD, using Cox proportional hazards models. A prediction model was derived and internally validated through bootstrap resampling.

Results: In a multivariable model, lower eGFR, paraprotein presence, and interstitial fibrosis were associated with a higher outcome risk, whereas native disease (versus recurrence post-transplantation), White ethnicity, and lower C4 levels were associated with lower risk. The prediction model including these variables performed well (R2D: 53%, C-statistic: 0.84 [95% confidence interval, 0.82 to 0.86], integrated calibration index: 0.31) and maintained robustness after internal validation. A 50% reduction in proteinuria from baseline to a value <1 g/d was associated with a lower risk of outcome independent of other risk factors (hazard ratio, 0.35; 95% confidence interval, 0.12 to 0.97).

Conclusions: Our study evaluated the baseline clinical and histologic parameters associated with kidney outcomes using the largest C3G/idiopathic IC-MPGN cohort to date. These factors were included in a prediction model to assess individual patient risk. Our results provide an evidence-based definition of proteinuria remission that can be used for patient care and in clinical trials.

Keywords: glomerulus; primary GN.

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/C312.

References

    1. Pickering MC D'Agati VD Nester CM, et al. C3 glomerulopathy: consensus report. Kidney Int. 2013;84(6):1079–1089. doi: 10.1038/ki.2013.377 - DOI - PMC - PubMed
    1. Cook HT, Pickering MC. Histopathology of MPGN and C3 glomerulopathies. Nat Rev Nephrol. 2015;11(1):14–22. doi: 10.1038/nrneph.2014.217 - DOI - PubMed
    1. Smith RJH Appel GB Blom AM, et al. C3 glomerulopathy – understanding a rare complement-driven renal disease. Nat Rev Nephrol. 2019;15(3):129–143. doi: 10.1038/s41581-018-0107-2 - DOI - PMC - PubMed
    1. Corvillo F, Okrój M, Nozal P, Melgosa M, Sánchez-Corral P, López-Trascasa M. Nephritic factors: An Overview of Classification, Diagnostic Tools and Clinical Associations. Front Immunol. 2019;10:886. doi: 10.3389/fimmu.2019.00886 - DOI - PMC - PubMed
    1. Servais A Noël LH Roumenina LT, et al. Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int. 2012;82(4):454–464. doi: 10.1038/ki.2012.63 - DOI - PubMed

LinkOut - more resources