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Non-invasive molecular imaging of kidney diseases

Nature Reviews Nephrology volume 17, pages 688–703 (2021)Cite this article

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A Publisher Correction to this article was published on 05 July 2021

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Abstract

In nephrology, differential diagnosis or assessment of disease activity largely relies on the analysis of glomerular filtration rate, urinary sediment, proteinuria and tissue obtained through invasive kidney biopsies. However, currently available non-invasive functional parameters, and most serum and urine biomarkers, cannot capture intrarenal molecular disease processes specifically. Moreover, although histopathological analyses of kidney biopsy samples enable the visualization of pathological morphological and molecular alterations, they only provide information about a small part of the kidney and do not allow longitudinal monitoring. These limitations not only hinder understanding of the dynamics of specific disease processes in the kidney, but also limit the targeting of treatments to active phases of disease and the development of novel targeted therapies. Molecular imaging enables non-invasive and quantitative assessment of physiological or pathological processes by combining imaging technologies with specific molecular probes. Here, we discuss current preclinical and clinical molecular imaging approaches in nephrology. Non-invasive visualization of the kidneys through molecular imaging can be used to detect and longitudinally monitor disease activity and can therefore provide companion diagnostics to guide clinical trials, as well as the safe and effective use of drugs.

Key points

  • Today, nephrology relies on the analysis of glomerular filtration rate, urinary sediment, proteinuria and invasive kidney biopsies to assess disease activity; molecular imaging is a more specific non-invasive approach that visualizes pathological processes within the kidneys with high accuracy.

  • 18F-fluorodeoxyglucose–PET is currently the most commonly used approach of molecular kidney imaging, although it does not reflect a specific disease or pathway.

  • Most clinical trials of molecular kidney imaging are performed in patients with renal cell carcinomas and promising targets include carbonic anhydrase 9 and prostate-specific membrane antigen.

  • Molecular imaging of the kidneys is challenging because it is a major elimination organ and non-specific probe uptake can be high; however, preclinical experiments and early clinical studies have identified targets and established imaging protocols for molecular imaging of acute and chronic kidney diseases, with a focus on acute epithelial or endothelial cell injury, inflammation or fibrosis.

  • Similar to oncology, molecular kidney imaging might improve disease staging, prognostication, monitoring of treatment responses and patient management.

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Fig. 1: Categories of use and their opportunities in molecular kidney imaging.
Fig. 2: Targets for molecular imaging in kidney diseases.
Fig. 3: Examples of in vivo kidney fibrosis imaging in mice.

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Acknowledgements

This work was funded by the German Research Foundation (DFG; SFB/TRR57 P25&P33, SFB/TRR219 Project-ID 322900939, BO3755/13-1 Project-ID 454024652, Research Training Group 331065168), the German Federal Ministry of Education and Research (BMBF: STOP-FSGS-01GM1901A), the German Federal Ministry of Economic Affairs and Energy (BMWi: EMPAIA project), the Medical Faculty of the RWTH Aachen (START 109/20), the European Research Council (ERC: CoG-864121 Meta-Targeting and 101001791 AIM.imaging.CKD), the ITN INTRICARE of European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska Curie (grant 722609).

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Authors and Affiliations

  1. Institute of Pathology, RWTH Aachen University Hospital, Aachen, Germany

    Barbara M. Klinkhammer & Peter Boor

  2. Institute for Experimental Molecular Imaging, RWTH Aachen University Hospital, Aachen, Germany

    Twan Lammers & Fabian Kiessling

  3. Department of Pharmaceutics, Utrecht University, Utrecht, Netherlands

    Twan Lammers

  4. Department of Targeted Therapeutics, University of Twente, Enschede, Netherlands

    Twan Lammers

  5. Department of Nuclear Medicine, University Hospital RWTH, Aachen, Germany

    Felix M. Mottaghy

  6. Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands

    Felix M. Mottaghy

  7. Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany

    Fabian Kiessling

  8. Department of Nephrology and Immunology, RWTH Aachen University Hospital, Aachen, Germany

    Jürgen Floege & Peter Boor

  9. Electron Microscopy Facility, RWTH Aachen University Hospital, Aachen, Germany

    Peter Boor

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Contributions

All authors made substantial contributions to discussions of the manuscript content. B.M.K. researched the data for the article and wrote the first draft of the manuscript. T.L., F.M.M., F.K., J.F. and P.B. reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Peter Boor.

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Competing interests

F.M.M. is an advisory board member for Advanced Accelerator Applications/Novartis and Bayer, holds speaker positions at Siemens, GE Healthcare and Bayer, and receives institutional grants from GE Healthcare and Nanomab. F.K. consults for Merck Darmstadt, holds patents and has running patent applications with Bayer, Roche and Visualsonics, has stock options for Molecular Targeting Inc. and co-owns InVivoContrast GmbH. The remaining authors declare no competing interests.

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Nature Reviews Nephrology thanks A. Smith, L.J. Zhang, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Nanobodies

Antibody fragments in the form of a single monomeric variable antibody domain; also known as single-domain antibodies.

Aptamers

Molecules (DNA or RNA oligonucleotides) that bind with high affinity to a target molecule.

Antibody- or peptide-functionalized microbubbles

Gas-filled microbubbles with a surface that is functionalized with antibodies or peptides as targeting ligands for molecular ultrasound imaging.

Extraction efficiency

A metric used to assess the elimination of an agent from the blood by comparing its arterial and venous concentrations.

Banff score

An international consensus classification for the reporting of biopsy findings from solid organ transplants.

Standardized uptake value

A semi-quantitative measure commonly used in PET imaging for nuclide enrichment that takes into account nuclide decay, administered dose and patient weight.

Mean transit time

The average time required for a tracer to travel through a tissue.

Time–activity curve

A graph in which radioactivity is plotted against time to display the kinetics of a tracer.

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Klinkhammer, B.M., Lammers, T., Mottaghy, F.M. et al. Non-invasive molecular imaging of kidney diseases. Nat Rev Nephrol 17, 688–703 (2021). https://doi.org/10.1038/s41581-021-00440-4

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