Recent advances in renal epithelial transport

Abstract

Besides the excretion of metabolic wastes, the kidneys regulate the balance of sodium, potassium, and acid-base (15). Impairment of certain transport functions is known to play an important role in the pathogenesis of diseases such as proteinuria and hypertension. But despite decades of research, aspects of renal epithelial transport mechanisms have yet to be fully elucidated. This editorial focus will highlight recent advances in our understanding of renal epithelial transport, obtained from experimental and theoretical studies. Some of these studies were published in response to a recent Call for Papers of this journal: Molecular Mechanism of Renal Tubule Transport.

Differentiated kidney tubular cell-derived extracellular vesicles enhance maturation of tubuloids

“…Due to their self-renewal and self-organizational capabilities, organoids are state of the art cell culture models to study kidney development and disease [9]. Interestingly, progenitor cells derived from adult kidneys; upon culturing, allow for long-term expansion and generation of tubule-like structure, the tubuloids, with primary functional renal epithelium reflecting several aspects of all tubular regions of the mature nephron [10][11][12]. Despite being more mature than (induced) pluripotent stem cell-derived organoids, tubuloids do not yet present a fully developed phenotype, especially for proximal tubules and their capacity to promote transepithelial transport, limiting their application in biomedical, pharmacological and toxicological studies [13,14].…”

“…The ability of the kidney to actively excrete metabolic waste, drugs and their metabolites is given by the presence of transporters in the membranes of proximal tubule cells [12]. Among these, organic anion transporter 1 (OAT1) is highly expressed that together with apical efflux pumps like multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP) contributes to the transfer of a large range of organic compounds from the blood circulation to the urine, in a highly controlled manner [15,16].…”

Differentiated kidney tubular cell-derived extracellular vesicles enhance maturation of tubuloids

“…An interesting alternative cell source to pluripotent stem cells are kidney progenitor cells derived from adult kidneys; upon culturing, these tissue models, defined as tubuloids, do not form nephron structures but instead allow for long-term expansion and generation of primary functional renal epithelium reflecting several aspects of all tubular regions of the mature nephron [10,11]. Tubuloids are a promising tool for kidney disease modeling and personalized drug screening, but also for regenerative medicine purposes, as adult progenitors can be patient-derived and do not require any genetic modification [10–12]. However, despite being more mature than (induced) pluripotent stem cell-derived organoids, tubuloids do not yet present a fully developed phenotype, especially for proximal tubules [10].…”

“…The ability of the kidney to actively excrete metabolic waste, drugs and their metabolites is given by the presence of transporters in the membranes of proximal tubule cells [12]. Among these, organic anion transporter 1 (OAT1) is highly expressed that together with apical efflux pumps like multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP) contributes to the transfer of a large range of organic compounds from the blood circulation to the urine, including drugs and endogenous metabolites, in a highly controlled manner [15,16].…”