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    The KPMP is designed to support a wide variety of stakeholders interested in advancing kidney medicine

  • 1.

    de Boer IH, et al. Rationale and design of the Kidney Precision Medicine Project. Kidney Int 2021; 99:498510. doi: 10.1016/j.kint.2020.08.039

  • 2.

    Genovese G, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 2010; 329:841845. doi: 10.1126/science.1193032

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    • Search Google Scholar
    • Export Citation
  • 3.

    El-Achkar TM, et al. A multimodal and integrated approach to interrogate human kidney biopsies with rigor and reproducibility: Guidelines from the Kidney Precision Medicine Project. Physiol Genomics 2021; 53:111. doi: 10.1152/physiolgenomics.00104.2020

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Butler CR, et al. A participant-centered approach to understanding risks and benefits of participation in research informed by the Kidney Precision Medicine Project. Am J Kidney Dis [published onlilne ahead of print December 4, 2021]. doi: 10.1053/j.ajkd.2021.10.006; https://www.ajkd.org/article/S0272-6386(21)01008-8/fulltext

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  • 5.

    Patel J, et al. Molecular signatures of diabetic kidney disease hiding in a patient with hypertension-related kidney disease: A clinical pathologic molecular correlation. Clin J Am Soc Nephrol [published online ahead of print Decemer 15, 2021]. doi: 10.2215/cjn.10350721; https://cjasn.asnjournals.org/content/early/2022/02/12/CJN.10350721

    • Search Google Scholar
    • Export Citation
  • 6.

    Schmidt IM, et al. Cadherin-11, Sparc-related modular calcium binding protein-2, and pigment epithelium-derived factor are promising non-invasive biomarkers of kidney fibrosis. Kidney Int 2021; 100:672683. doi: 10.1016/j.kint.2021.04.037

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Menez S, et al. Urinary EGF and MCP-1 and risk of CKD after cardiac surgery. JCI Insight 2021; 6:e147464. doi: 10.1172/jci.insight.147464

  • 8.

    Lake BB, et al. An atlas of healthy and injured cell states and niches in the human kidney. bioRxiv July 29, 2021. https://www.biorxiv.org/content/10.1101/2021.07.28.454201v1

    • Search Google Scholar
    • Export Citation
  • 9.

    Hansen J, et al. A reference tissue atlas for the human kidney. bioRxiv September 15, 2021. https://www.biorxiv.org/content/10.1101/2020.07.23.216507v2#:~:text=A%20bstract%20Kidney%20Precision%20Medicine%20Project%20%28KPMP%29%20is,details%20of%20the%20kidney%20in%20health%20and%20disease.

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The Kidney Precision Medicine Project (KPMP). An Update and Vision for the Future

  • 1 Steven Menez, MD, MHS, is with the Division of Nephrology, Department of Medicine, Johns Hopkins Medicine, Baltimore, MD. Ashveena L. Dighe, MS, MPH, and Ian H. de Boer, MD, are with the Kidney Research Institute and the Division of Nephrology, Department of Medicine, University of Washington, Seattle.
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The Kidney Precision Medicine Project (KPMP) is a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-funded, multi-year collaboration of leading research institutions across the United States that aims to better understand the mechanisms of acute kidney injury (AKI) and chronic kidney disease (CKD) (1).

Our understanding of the pathophysiology of certain kidney diseases has improved dramatically in recent years, with discovery of the genetic mechanisms behind phenotypes, such as non-diabetic focal segmental glomerular sclerosis in patients with high-risk APOL1 genotypes (2). However, CKD and, in particular, AKI are defined broadly using serum creatinine and

The Kidney Precision Medicine Project (KPMP) is a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)-funded, multi-year collaboration of leading research institutions across the United States that aims to better understand the mechanisms of acute kidney injury (AKI) and chronic kidney disease (CKD) (1).

Our understanding of the pathophysiology of certain kidney diseases has improved dramatically in recent years, with discovery of the genetic mechanisms behind phenotypes, such as non-diabetic focal segmental glomerular sclerosis in patients with high-risk APOL1 genotypes (2). However, CKD and, in particular, AKI are defined broadly using serum creatinine and urine output, which in the acute setting, can be highly inaccurate and imprecise. Therefore, the major goals of KPMP have been to collect research kidney biopsies in an ethical manner from consented individuals with AKI and CKD to achieve the following: 1) create a kidney tissue atlas, 2) define new disease subgroups, and 3) identify new therapeutic targets and pathways of kidney diseases.

The KPMP consortium consists of 1) a central hub that manages study organization, data collection, and data visualization center; 2) clinical sites that prospectively recruit eligible participants with CKD or AKI; and 3) tissue interrogation sites that apply various omics technologies to kidney tissue to construct a comprehensive kidney tissue atlas. Patients with kidney diseases inform and contribute to all aspects of KPMP, including study design, leadership, and dissemination.

Beginning in 2017, the primary aim of the first phase of KPMP was to establish an ethical and safe clinical protocol for collection of biosamples (including kidney tissue, urine, and blood), with optimization and validation of tissue processing, including rigorous quality control (3, 4). Eligible participants have been recruited from three AKI recruitment sites (Columbia University, University of Pittsburgh, and Johns Hopkins-Yale Universities) and three CKD recruitment sites (Cleveland Clinic, University of Texas Southwestern, and Brigham and Women's Hospital-Boston University-Joslin Diabetes Center-Beth Israel Deaconess Medical Center). Biosamples obtained at these various recruitment sites are transferred to the KPMP central biorepository and then sent to tissue interrogation sites for next-generation sequencing, three-dimensional (3D) tissue imaging and cytometry (fluorescence imaging), proteomics, spatial metabolomics, and other advanced technologies (see https://www.kpmp.org/help-docs/technologies). Data are then centrally integrated, standardized, and validated before being added to the ever-growing open-access kidney tissue atlas (see atlas.kpmp.org).

KPMP remains committed to new avenues for scientific discovery, with Opportunity Pool funding available for research groups interested in joining KPMP (see https://www.kpmp.org/opportunity-pool). These have included additional new technologies, enhanced clinical phenotyping (advanced retinal imaging, functional magnetic resonance imaging [MRI], and kidney functional reserve), recruitment of healthy individuals for reference tissue, and a sub-study, enrolling adults hospitalized with COVID-19.

As of March 10, 2022, 150 participants (32 with AKI, 95 with CKD, and 23 healthy volunteers who were donating a kidney or undergoing kidney stone surgery) have consented to participate and have undergone the protocol KPMP kidney biopsy. An additional 89 participants have been enrolled in the COVID-19 blood and urine collection study. KPMP pathology has been remarkably heterogenous, even within groups of patients with “common” presentations of AKI or CKD. Individual clinical-pathological-molecular case evaluations have demonstrated proof of concept that detailed omics interrogation of kidney tissue can add value to traditional pathology (5), data from the kidney atlas have been used to enhance the interpretation of novel biomarker studies (6, 7), and systems biology analyses have generated initial versions of a kidney atlas (8, 9).

KPMP will embark on its second 5 years of activity from 2022 to 2027. During this next phase, both enrollment and tissue interrogation will be scaled up. Based on our participants’ generous contributions, KPMP is poised to continue scientific discovery in both AKI and CKD, with further enrichment of the kidney tissue atlas—a publicly available resource (atlas.kpmp.org) where researchers and clinicians can explore many of the findings generated through this consortium (Figure 1).

Figure 1
Figure 1

The KPMP is designed to support a wide variety of stakeholders interested in advancing kidney medicine

Citation: Kidney News 14, 4

References

  • 1.

    de Boer IH, et al. Rationale and design of the Kidney Precision Medicine Project. Kidney Int 2021; 99:498510. doi: 10.1016/j.kint.2020.08.039

  • 2.

    Genovese G, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 2010; 329:841845. doi: 10.1126/science.1193032

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3.

    El-Achkar TM, et al. A multimodal and integrated approach to interrogate human kidney biopsies with rigor and reproducibility: Guidelines from the Kidney Precision Medicine Project. Physiol Genomics 2021; 53:111. doi: 10.1152/physiolgenomics.00104.2020

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Butler CR, et al. A participant-centered approach to understanding risks and benefits of participation in research informed by the Kidney Precision Medicine Project. Am J Kidney Dis [published onlilne ahead of print December 4, 2021]. doi: 10.1053/j.ajkd.2021.10.006; https://www.ajkd.org/article/S0272-6386(21)01008-8/fulltext

    • Search Google Scholar
    • Export Citation
  • 5.

    Patel J, et al. Molecular signatures of diabetic kidney disease hiding in a patient with hypertension-related kidney disease: A clinical pathologic molecular correlation. Clin J Am Soc Nephrol [published online ahead of print Decemer 15, 2021]. doi: 10.2215/cjn.10350721; https://cjasn.asnjournals.org/content/early/2022/02/12/CJN.10350721

    • Search Google Scholar
    • Export Citation
  • 6.

    Schmidt IM, et al. Cadherin-11, Sparc-related modular calcium binding protein-2, and pigment epithelium-derived factor are promising non-invasive biomarkers of kidney fibrosis. Kidney Int 2021; 100:672683. doi: 10.1016/j.kint.2021.04.037

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Menez S, et al. Urinary EGF and MCP-1 and risk of CKD after cardiac surgery. JCI Insight 2021; 6:e147464. doi: 10.1172/jci.insight.147464

  • 8.

    Lake BB, et al. An atlas of healthy and injured cell states and niches in the human kidney. bioRxiv July 29, 2021. https://www.biorxiv.org/content/10.1101/2021.07.28.454201v1

    • Search Google Scholar
    • Export Citation
  • 9.

    Hansen J, et al. A reference tissue atlas for the human kidney. bioRxiv September 15, 2021. https://www.biorxiv.org/content/10.1101/2020.07.23.216507v2#:~:text=A%20bstract%20Kidney%20Precision%20Medicine%20Project%20%28KPMP%29%20is,details%20of%20the%20kidney%20in%20health%20and%20disease.

    • Search Google Scholar
    • Export Citation
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