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  • Review Article
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Cell and gene therapy for kidney disease

Nature Reviews Nephrology volume 19, pages 451–462 (2023)Cite this article

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Abstract

Kidney disease is a leading cause of morbidity and mortality across the globe. Current interventions for kidney disease include dialysis and renal transplantation, which have limited efficacy or availability and are often associated with complications such as cardiovascular disease and immunosuppression. There is therefore a pressing need for novel therapies for kidney disease. Notably, as many as 30% of kidney disease cases are caused by monogenic disease and are thus potentially amenable to genetic medicine, such as cell and gene therapy. Systemic disease that affects the kidney, such as diabetes and hypertension, might also be targetable by cell and gene therapy. However, although there are now several approved gene and cell therapies for inherited diseases that affect other organs, none targets the kidney. Promising recent advances in cell and gene therapy have been made, including in the kidney research field, suggesting that this form of therapy might represent a potential solution for kidney disease in the future. In this Review, we describe the potential for cell and gene therapy in treating kidney disease, focusing on recent genetic studies, key advances and emerging technologies, and we describe several crucial considerations for renal genetic and cell therapies.

Key points

  • Despite the use of cell and gene therapies in the clinic for other tissues, no such interventions are available that target the kidney.

  • Approximately 30% of chronic kidney diseases are inherited, and the genetic basis is well understood, meaning that they are suitable for targeting by cell or gene therapy before development of irreparable renal failure.

  • Genetic studies in mouse models have revealed the potential of gene therapy for kidney disease.

  • Delivery of therapeutic material to the kidney is the main hurdle to cell and gene therapy development.

  • Innovations in vector technology, delivery and an enhanced understanding of kidney disease pathogenesis provide hope for future kidney cell and gene therapies.

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Fig. 1: Approved cell and gene therapies worldwide.
Fig. 2: Genetic kidney disease target location within the nephron, the basic functional unit of the kidney.
Fig. 3: Vector considerations for cell and gene therapy of kidney disease.

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Acknowledgements

J.L.P. is supported by DK134046 and T32GM007347 from the NIH. M.H.W. is supported by BK004258 from the Department of Veterans Affairs and DK093660 and EB033676 from the NIH.

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Authors and Affiliations

  1. Medical Scientist Training Program, Vanderbilt University School of Medicine, Nashville, TN, USA

    Jennifer L. Peek

  2. Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA

    Jennifer L. Peek & Matthew H. Wilson

  3. Department of Pharmacology, Vanderbilt University, Nashville, TN, USA

    Matthew H. Wilson

  4. Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA

    Matthew H. Wilson

  5. Department of Veterans Affairs, Tennessee Valley Health Services, Nashville, TN, USA

    Matthew H. Wilson

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  1. Jennifer L. Peek
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  2. Matthew H. Wilson
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The authors contributed equally to all aspects of the article.

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Correspondence to Matthew H. Wilson.

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Nature Reviews Nephrology thanks Rachel Lennon and Naoya Uchida for their contribution to the peer review of this work.

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Peek, J.L., Wilson, M.H. Cell and gene therapy for kidney disease. Nat Rev Nephrol 19, 451–462 (2023). https://doi.org/10.1038/s41581-023-00702-3

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