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Experimental concerns regarding suPAR-related proteinuria

Nature Reviews Nephrology volume 13, page 593 (2017)Cite this article

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We are writing in response to the News & Views commentary by L. Gallon and S. Quaggin (Glomerular disease: a suPAR kidney connection found in the bone marrow. Nat Rev Nephrol. 13, 263–264; 2017)1, which discusses a recent study by Hahm et al. (Bone marrow-derived immature myeloid cells are a main source of circulating suPAR contributing to proteinuric kidney disease. Nat. Med. 23, 100–106; 2017)2. We wish to highlight a number of points in response to their commentary.

First, Gallon and Quaggin write that “bone-marrow-derived cells transferred from proteinuric mice are sufficient to produce proteinuria in wild-type mice”. However, the study of Hahm and colleagues demonstrates the occurrence of proteinuria after bone marrow transplantation in Plaur−/− mice only1,2. Previous studies by ourselves and others suggest that soluble urokinase plasminogen activator receptor (suPAR) might induce proteinuria in Plaur−/− mice but not in wild-type animals3,4,5. The reason for this discrepancy is unclear, but the possibility exists that lack of uPAR might induce constitutive and secondary changes, such as overexpression of β3 integrins on podocyte membranes, that lead to an explosive response to exogenous suPAR.

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References

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Authors and Affiliations

  1. UMR_S 1155 Institut National de la Santé et de la Recherch Médicale (Inserm), Rare and Common Kidney Diseases, Matrix Remodeling and Tissue Repair, 4 Rue de la chine, Paris, France; and at Assistance Publique — Hôpitaux de Paris, Urgences Néphrologiques et Transplantation Rénale, Hôpital Tenon, Paris, France.,

    Laurent Mesnard, Yosu Luque & Eric Rondeau

  2. at Sorbonne Universités, UPMC Université, Paris, France,

    Laurent Mesnard, Yosu Luque & Eric Rondeau

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  1. Laurent Mesnard
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  2. Yosu Luque
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Correspondence to Laurent Mesnard.

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Mesnard, L., Luque, Y. & Rondeau, E. Experimental concerns regarding suPAR-related proteinuria. Nat Rev Nephrol 13, 593 (2017). https://doi.org/10.1038/nrneph.2017.108

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