Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Year in Review
  • Published:

Glomerular disease in 2023

Reaping the rewards of mechanistic discovery in glomerular disease

Nature Reviews Nephrology volume 20, pages 77–78 (2024)Cite this article

Subjects

Several successfully completed clinical trials of novel therapies in glomerular disease were reported in 2023. Building on important mechanistic discoveries about disease onset and progression over the past several years, these therapies raise hope that multiple options will be available to reduce the risk of kidney failure in glomerular disease.

Key advances

  • A large cohort study of UK patients with IgA nephropathy (IgAN) demonstrated that lifetime risk of kidney failure is high, even among patients with low levels of proteinuria.

  • The 2-year results of the placebo-controlled phase III trial of targeted-release formulation of budesonide (NefIgArd trial) demonstrated a reduction in estimated glomerular filtration rate (eGFR) decline in patients with IgAN, building on earlier results that showed a reduction in proteinuria after 9 months of treatment.

  • The 2-year results of the active-controlled phase III trial of sparsentan, a dual endothelin and angiotensin II subtype 1 receptor antagonist, led to improvement in proteinuria and chronic eGFR decline compared with irbesartan.

  • In a phase IIa trial, inaxaplin (a small molecule inhibitor of apolipoprotein 1 channel function) provided initial evidence of reduced proteinuria over 13 weeks in patients with focal segmental glomerulosclerosis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Paths to therapeutic innovation in glomerular disease.

References

  1. Gleeson, P. J., O’Shaughnessy, M. M. & Barratt, J. IgA nephropathy in adults – treatment standard. Nephrol. Dial. Transplant. 38, 2464–2473 (2023).

    Article  PubMed  Google Scholar 

  2. Wheeler, D. C. et al. A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney Int. 100, 215–224 (2021).

    Article  CAS  PubMed  Google Scholar 

  3. Pitcher, D. et al. Long-term outcomes in IGA nephropathy. Clin. J. Am. Soc. Nephrol. 18, 727–738 (2023).

    Article  PubMed  Google Scholar 

  4. Lv, J. et al. Effect of oral methylprednisolone on decline in kidney function or kidney failure in patients with IGA nephropathy. J. Am. Med. Assoc. 327, 1888–1898 (2022).

    Article  CAS  Google Scholar 

  5. Barratt, J. et al. Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy. Kidney Int. 103, 391–402 (2023).

    Article  CAS  PubMed  Google Scholar 

  6. Lafayette, R. et al. Efficacy and safety of a targeted-release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2-year results from a randomised phase 3 trial. Lancet 402, 859–870 (2023).

    Article  CAS  PubMed  Google Scholar 

  7. Rovin, B. H. et al. Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial. Lancet 402, 2077–2090 (2023).

    Article  CAS  PubMed  Google Scholar 

  8. Thompson, A. et al. Proteinuria reduction as a surrogate end point in trials of IGA nephropathy. Clin. J. Am. Soc. Nephrol. 14, 469–481 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Egbuna, O. et al. Inaxaplin for proteinuric kidney disease in persons with two APOL1 variants. N. Engl. J. Med. 388, 969–979 (2023).

    Article  CAS  PubMed  Google Scholar 

  10. Barratt, J. et al. IgA nephropathy: the lectin pathway and implications for targeted therapy. Kidney Int. 104, 254–264 (2023).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology, University of Michigan, Ann Arbor, MI, USA

    Arpita Joshi & Laura H. Mariani

Authors
  1. Arpita Joshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laura H. Mariani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Laura H. Mariani.

Ethics declarations

Competing interests

L.H.M. has consulting agreements with several pharmaceutical companies, including Travere therapeutics and Calliditas Therapeutics and Chinook Therapeutics, and has received grant funding from Boehringer-Ingelheim and Reliant Glycoscienes; their employer, the University of Michigan, is an enrolling site for the Vertex clinical trial. A.J. declares no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Joshi, A., Mariani, L.H. Reaping the rewards of mechanistic discovery in glomerular disease. Nat Rev Nephrol 20, 77–78 (2024). https://doi.org/10.1038/s41581-023-00804-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41581-023-00804-y

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing