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. 2024 Mar 27;39(4):569-580.
doi: 10.1093/ndt/gfae025.

Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group

Safak Mirioglu  1   2 , Lisa Daniel-Fischer  3 , Ilay Berke  4 , Syed Hasan Ahmad  5 , Ingeborg M Bajema  6 , Annette Bruchfeld  7   8 , Gema M Fernandez-Juarez  9 , Jürgen Floege  10 , Eleni Frangou  11 , Dimitrios Goumenos  12 , Megan Griffith  13 , Sarah M Moran  14 , Cees van Kooten  15 , Stefanie Steiger  16 , Kate I Stevens  17 , Kultigin Turkmen  18 , Lisa C Willcocks  5 , Andreas Kronbichler  19
Affiliations

Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group

Safak Mirioglu et al. Nephrol Dial Transplant. .

Erratum in

Abstract

The histopathological lesions, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are entities without immune complex deposits which can cause podocyte injury, thus are frequently grouped under the umbrella of podocytopathies. Whether MCD and FSGS may represent a spectrum of the same disease remains a matter of conjecture. Both frequently require repeated high-dose glucocorticoid therapy with alternative immunosuppressive treatments reserved for relapsing or resistant cases and response rates are variable. There is an unmet need to identify patients who should receive immunosuppressive therapies as opposed to those who would benefit from supportive strategies. Therapeutic trials focusing on MCD are scarce, and the evidence used for the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guideline for the management of glomerular diseases largely stems from observational and pediatric trials. In FSGS, the differentiation between primary forms and those with underlying genetic variants or secondary forms further complicates trial design. This article provides a perspective of the Immunonephrology Working Group (IWG) of the European Renal Association (ERA) and discusses the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases focusing on the management of MCD and primary forms of FSGS in the context of recently published evidence, with a special emphasis on the role of rituximab, cyclophosphamide, supportive treatment options and ongoing clinical trials in the field.

Keywords: FSGS; KDIGO; MCD; guideline; podocytopathy.

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Conflict of interest statement

S.M. received honoraria from Baxter, and support for meeting registration and travel from Abdi Ibrahim Otsuka, Amgen, Roche, and Sanofi Genzyme. L.D.-F. received research grants from Delta 4. I.M.B. consulted for Boehringer-Ingelheim, GSK, Novartis, Catalyst Biosciences, Toleranzia, Vera, and Hansa Biopharma and received educational grants from CSL Vifor. She is the owner of BiPath and on the BOD of the Renal Pathology Society. A.B. received consultancy fees and honoraria from Amgen, AstraZeneca, Bayer, Fresenius, and CSL Vifor. M.G. received an advisory board fee from Retrophin. K.I.S. received consultancy fees from Bayer and Boehringer Ingelheim. A.K. received consultancy fees from CSL Vifor, Otsuka, GSK, Walden Biosciences, Catalyst Biosciences, and Delta4; and received unrestricted research grants from CSL Vifor and Otsuka. S.M., E.F., S.S., and A.K. are editorial board members of the journal NDT. The remaining authors disclosed no conflicts of interest.

Figures

Figure 1:
Figure 1:
The KDIGO 2021 Clinical Practice Guidelines (left) highlight that a correct classification is pivotal to choose the correct management strategy. Immunosuppression might only be started in patients with a primary FSGS form, which is likely due to circulating factor(s). Emerging new variants contribute to the large group of genetic forms, and of course different stimuli can induce a secondary form of FSGS. The Columbia Classification (right) proposed the use of five different histological patterns. These patterns do not correlate with treatment response in ‘presumed’ primary cases, nor do they allow to distinguish between primary and secondary forms of FSGS. FSGS: focal segmental glomerulosclerosis; MCD: minimal change disease; NOS: not otherwise specified. Parts of the figure were created with BioRender.com.
Figure 2:
Figure 2:
Summary of the recommendations on the management of minimal change disease in 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases compared to the 2012 guideline [6, 70]. CI: contraindication; CNI: calcineurin inhibitor; CYC: cyclophosphamide; FR: frequently relapsing; GC: glucocorticoid; MCD: minimal change disease; MMF: mycophenolate mofetil; MPS: mycophenolate sodium; KDIGO: Kidney Disease: Improving Global Outcomes; RTX: rituximab; SD: steroid-dependent.
Figure 3:
Figure 3:
Summary of the recommendations on the management of focal segmental glomerulosclerosis in 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases compared to the 2012 guideline [6, 70]. CI: contraindication; CNI: calcineurin inhibitor; CsA: cyclosporine; CYC: cyclophosphamide; FSGS: focal segmental glomerulosclerosis; GC: glucocorticoid; KDIGO: Kidney Disease: Improving Global Outcomes; MCD: minimal change disease; MMF: mycophenolate mofetil; MPS: mycophenolate sodium; RTX: rituximab.
Figure 4:
Figure 4:
A schematic overview of potential drug targets, and emerging therapies tested or used in the management of podocytopathies. These potential candidates include immune system suppressing, immunomodulatory, podocyte skeleton stabilizing, and therapies aiming to lower systemic and intraglomerular hypertension. Modified from de Cos et al. [66] and created with BioRender.com.
See this image and copyright information in PMC

References

    1. Maas RJ, Deegens JK, Smeets Bet al. . Minimal change disease and idiopathic FSGS: manifestations of the same disease. Nat Rev Nephrol 2016;12:768–76. 10.1038/nrneph.2016.147 - DOI - PubMed
    1. May CJ, Chesor M, Hunter SEet al. . Podocyte protease activated receptor 1 stimulation in mice produces focal segmental glomerulosclerosis mirroring human disease signaling events. Kidney Int 2023;104:265–78. 10.1016/j.kint.2023.02.031 - DOI - PMC - PubMed
    1. Watts AJB, Keller KH, Lerner Get al. . Discovery of autoantibodies targeting nephrin in minimal change disease supports a novel autoimmune etiology. J Am Soc Nephrol 2022;33:238–52. 10.1681/ASN.2021060794 - DOI - PMC - PubMed
    1. Shirai Y, Miura K, Ishizuka Ket al. . A multi-institutional study found a possible role of anti-nephrin antibodies in post-transplant focal segmental glomerulosclerosis recurrence. Kidney Int 2023. 10.1016/j.kint.2023.11.022. - DOI - PubMed
    1. Mariani LH, Eddy S, AlAkwaa FMet al. . Precision nephrology identified tumor necrosis factor activation variability in minimal change disease and focal segmental glomerulosclerosis. Kidney Int 2023;103:565–79. 10.1016/j.kint.2022.10.023 - DOI - PMC - PubMed