Human primary proximal tubular epithelial cells and sepsis: a scoping review

Sepsis impairs proximal renal tubular epithelial cell (PTEC) function, and this impairment contributes to the pathophysiology of sepsis-associated acute kidney injury (SA-AKI). By closely replicating in vivo conditions, primary human PTEC offer superior biological relevance for studying SA-AKI. The purpose of this scoping review was to identify and investigate experiments, where human primary PTEC have been used to study sepsis-related factors.

A comprehensive literature search strategy was developed, and our reported items adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) checklist. Peer-reviewed articles published in English or Scandinavian languages between 1946 and 2024 were included.

The literature search provided 292 results. Twelve studies were included, out of which only two were published after 2010. Eight studies used human primary PTEC isolated from healthy tissue during tumor nephrectomy, while four studies used primary PTEC purchased from commercially available providers. Experimental methods were heterogenous. The included studies applied E. coli porine, E. coli, Staphylococcal enterotoxin B, cytokines and lipopolysaccharide with differing dosages, exposure lengths, and combinations.

Although human primary PTEC more closely resembles the in vivo environment in human kidneys, their use in sepsis and SA-AKI research remains remarkably limited, leading to substantial research gaps in the field. In addition, there is significant heterogeneity in the methodologies employed across existing studies. Standardizing and expanding the use of primary PTECs in future in vitro research could be pivotal for unraveling novel and relevant insights into the pathophysiology of SA-AKI.