Tonicity drives collecting duct maturation in the mammalian kidney.

Authors

Daisuke Inoue, Koichiro Miike, Shunsuke Tanigawa, Kei-Ichiro Yasunaga, Rae Maeda, Tomoko Ohmori, Sayoko Fujimura, Masashi Mukoyama, Tomomi Kamba, Jose Aramburu, Cristina Lopez-Rodriguez, Yuki Sugiura, Yuichiro Izumi, Ryuichi Nishinakamura

Published in

Nature communications. Volume 17. Issue 1. Oct 02, 2026. Epub Oct 02, 2026.

Abstract

Organ maturation is a fundamental biological process and a major challenge for organoid-based regenerative medicine. During kidney maturation, osmolality increases in the renal medulla for urine concentration, yet whether this extreme environment conversely contributes to kidney maturation remains unclear. Here we show that high tonicity, i.e., salt, drives morphological, transcriptional, and functional maturation of medullary collecting ducts (CDs) primarily via nuclear factor of activated T cells 5 (NFAT5). This occurs both in vitro and in vivo. Combining high tonicity with maturation-promoting hormones, we establish a robust maturation protocol for human medullary CD organoids and a functional assay to measure water permeability in CD organoids, enabling modeling of three disease states: NFAT5 deletion, and lithium-induced and congenital nephrogenic diabetes insipidus. Collectively, high tonicity drives mammalian kidney maturation, offering a promising platform to maximize the potential of organoids for future therapies.

PMID:
42827133
Bibliographic data and abstract were imported from PubMed on 03 Oct 2026.

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