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The kidney stroma in development and disease

Nature Reviews Nephrology (2025)Cite this article

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Abstract

The kidney is one of the most complex organs in the body. It is made up of thousands of patterned epithelial and endothelial tubules that work together to maintain body chemistry. Precise spatial integration of these different cell types is essential for the organ to function optimally. A complex and heterogeneous network of cells collectively referred to as ‘stroma’ lies between the epithelial and endothelial tubules. A growing body of evidence suggests that the stroma mediates communication between the epithelia and endothelia, and functions to support a variety of processes during kidney development and in the adult kidney, with implications for disease. However, stromal cells remain far less well defined than the epithelia and endothelia, and we understand only a fraction of their functions, leading some to refer to the stroma as the ‘dark matter’ of the kidney. In this Review, we discuss the developmental origins of the stroma and describe current understanding of its roles in the growth and patterning of the renal epithelia and endothelia, and in the maintenance and repair of the adult organ. Finally, we highlight critical questions that remain unanswered and the resources that will be required to answer them so that we can fully understand the function of these enigmatic cells.

Key points

  • The kidney stroma is a heterogeneous population of vascular mural cells, fibroblasts, smooth muscle and leukocytes that arise from at least three unique cellular lineages.

  • The different stromal cell types produce a wide array a signalling proteins, small molecules and metabolites, extracellular matrix and hormones that create regional microenvironments in the kidney.

  • Studies using genetic mouse models and kidney organoids have revealed essential roles for the stroma in the development of nephrons and the vasculature.

  • Growing evidence indicates that the stroma of the adult organ is as diverse as that of the embryo, suggesting that it might have essential roles in tissue maintenance, repair and disease progression.

  • The development of new tools is expected to uncover additional roles for the stroma in both the embryonic and adult organ.

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Fig. 1: Stromal cells along the cortical–medullary axis of the kidney.
Fig. 2: Lineage tracing of stromal progenitors.
Fig. 3: Signalling from the stroma during ureteric bud induction and branching morphogenesis.
Fig. 4: Signals from the stroma induce mesenchymal-to-epithelial transition in a subset of nephron progenitor cells.
Fig. 5: Vascular patterning is regulated by stromal PBX1 and NTN1 signalling.
Fig. 6: Regulation of nephrogenesis by FGF and WNT.
Fig. 7: Stromal populations during embryonic development.

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Authors and Affiliations

  1. Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA

    Alexandria N. Fusco & Thomas J. Carroll

  2. Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA

    Alexandria N. Fusco & Thomas J. Carroll

  3. The Rogosin Institute, New York, NY, USA

    Leif Oxburgh

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Fusco, A.N., Oxburgh, L. & Carroll, T.J. The kidney stroma in development and disease. Nat Rev Nephrol (2025). https://doi.org/10.1038/s41581-025-00985-8

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