Lidberg et al.1 demonstrate that human serum, but not albumin, elicits changes in human proximal tubular cells in culture and propose that proteins other than albumin are responsible for tubular damage in some types of nephrotic syndrome. However, serum is derived from the clotting of blood and, therefore, contains a host of compounds released from platelets, including cytokines, other inflammatory mediators, and growth factors (not all of which are proteins), that are not normally present or are present at much lower levels in circulating blood. In addition, the serum was allogeneic and could contain antibodies reactive against the cultured cells. Therefore, it is not surprising that allogeneic serum has untoward effects on cultured proximal tubular cells. Although nonselective proteinuria may well contribute to tubular injury in certain causes of nephrotic syndrome, this cannot be concluded from Lidberg et al.’s study.
Disclosures
W.C. O’Neill reports serving in an advisory or leadership role for Elastrin Therapeutics and Inozyme Pharma; receiving research funding from Fresenius Medical Care Renal Therapies Group and the National Institutes of Health; having consultancy agreements with, and having ownership interest in, Inozyme Pharma; having patents or royalties with UpToDate; and receiving income from educational material related to ultrasonography.
Funding
None.
Footnotes
Published online ahead of print. Publication date available at www.jasn.org.
Author Contributions
W.C. O’Neill conceptualized the study, wrote the original draft, and reviewed and edited the manuscript.
Reference
- 1.Lidberg KA, Muthusamy S, Adil M, Mahadeo A, Yang J, Patel RS, et al. : Serum protein exposure activates a core regulatory program driving human proximal tubule injury. J Am Soc Nephrol 33: 949–965, 2022 [DOI] [PMC free article] [PubMed] [Google Scholar]