Molecular Signatures of Glomerular Neovascularization in a Patient with Diabetic Kidney Disease

Kidney Precision Medicine Project, Michael J. Ferkowicz, Ashish Verma, Daria Barwinska, Ricardo Melo Ferreira, Joel M. Henderson, Mary Kirkpatrick, Paolo S. Silva, Devin W. Steenkamp, Carrie L. Phillips, Sushrut S. Waikar, Timothy A. Sutton, Blue Lake, Kun Zhang, Stewart Lecker, Alexander Morales, Isaac Stillman, Steve Bogen, Afolarin A. Amodu, Laurence BeckJoel Henderson, Titlayo Ilori, Shana Maikhor, Ingrid Onul, Insa Schmidt, Ashish Verma, Sushrut Waikar, Pranav Yadati, Guanghao Yu, Mia R. Colona, Gearoid McMahon, Astrid Weins, Nir Hacohen, Anna Greka, Paul J. Hoover, Jamie L. Marshall, Mark Aulisio, William Bush, Yijiang Chen, Dana Crawford, Anant Madabhushi, Vidya S. Viswanathan, Lakeshia Bush, Leslie Cooperman, Crystal Gadegbeku, Leal Herlitz, Stacey Jolly, Jane Nguyen, Charles O'Malley, John O'Toole, Ellen Palmer, Emilio Poggio, Kassandra Spates-Harden, John Sedor, Dianna Sendrey, Jonathan Taliercio, Paul Appelbaum, Olivia Balderes, Jonathan Barasch, Cecilia Berroue, Andrew Bomback, Pietro A. Canetta, Vivette D'Agati, Krzysztof Kiryluk, Satoru Kudose, Karla Mehl, Maya Sabatello, Ning Shang, German Varela, Joana De Pinho Gonçalves, Roy Lardenoije, Lukasz Migas, Raf Van De Plas, Laura Barisoni, Helmut Rennke, Evren Azeloglu, Kirk Campbell, Steven Coca, Cijang He, John He, Srinivas Ravi Iyengar, Seanee Lefferts, Girish Nadkarni, Marissa Patel, Joji Tokita, Stephen Ward, Yuguang Xiong, Abraham Verdoes, Angela Sabo, Daria Barwinska, Debora Lidia Gisch, James Williams, Katherine Kelly, Kenneth Dunn, Mahla Asghari, Michael Eadon, Michael Ferkowicz, Pierre Dagher, Ricardo Melo Ferreira, Seth Winfree, Sharon Bledsoe, Stephanie Wofford, Tarek El-Achkar, Timothy Sutton, William Bowen, Ying Hua Cheng, Austen Slade, Elizabeth Record, Yinghua Cheng, Katy Borner, Bruce Herr, Yashvardhan Jain, Ellen Quardokus, Mohamed Atta, Lauren Bernard, Steven Menez, Chirag Parikh, Celia Pamela Corona Villalobos, Ashley Wang, Yumeng Wen, Alan Xu, Sarah Chen, Isabel Donohoe, Camille Johansen, Sylvia Rosas, Jennifer Sun, Joseph Ardayfio, Jack Bebiak, Keith Brown, Taneisha Campbell, Monica Fox, Lynda Hayashi, Nichole Jefferson, Jennifer Jones Richard Knight, Robert Koewler, Roy Pinkeney, John Saul, Anna Shpigel, Christy Stutzke, Pottumarthi Prasad, Sethu M. Madhavan, Samir Parikh, Brad Rovin, John P. Shapiro, Christopher Anderton, Jessica Lukowski, Ljiljana Pasa-Tolic, Dusan Velickovic, George Oliver, Weiguang Mao, Rachel Sealfon, Olga Troyanskaya, Aaron Wong, Ari Pollack, Yury Goltsev, Brandon Ginley, Brendon Lutnick, Kavya Anjani, Zoltan G. Laszik, Tariq Mukatash, Garry Nolan, David Beyda, Erika Bracamonte, Frank Brosius, Baltazar Campos, Nicole Marquez, Katherine Mendoza, Raymond Scott, Bijin Thajudeen, Rebecca Tsosie, Gregory Woodhead, Milda Saunders, Rita R. Alloway, Paul J. Lee, Adele Rike, Tiffany Shi, E. Steve Woodle, Petter Bjornstad, Elena Hsieh, Jessica Kendrick, Laura Pyle, Joshua Thurman, Carissa Vinovskis, Julia Wrobel, Nicholas Lucarelli, Pinaki Sarder, James Bui, Eunice Carmona-Powell, Ron Gaba, Tanika Kelly, James Lash, Natalie Meza, Devona Redmond, Amada Renteria, Ana Ricardo, Suman Setty, Matthew Rosengart, Jeannine Basta, Joseph Gaut, Sanjay Jain, Anitha Vijayan

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The Kidney Precision Medicine Project (KPMP) aims to create a kidney tissue atlas, define disease subgroups, and identify critical cells, pathways, and targets for novel therapies through molecular investigation of human kidney biopsies obtained from participants with AKI or CKD. We present the case of a 66-year-old woman with diabetic kidney disease who underwent a protocol KPMP kidney biopsy. Her clinical history included diabetes mellitus complicated by neuropathy and eye disease, increased insulin resistance, hypertension, albuminuria, and relatively preserved glomerular filtration rate (early CKD stage 3a). The patient's histopathology was consistent with diabetic nephropathy and arterial and arteriolar sclerosis. Three-dimensional, immunofluorescence imaging of the kidney biopsy specimen revealed extensive periglomerular neovascularization that was underestimated by standard histopathologic approaches. Spatial transcriptomics was performed to obtain gene expression signatures at discrete areas of the kidney biopsy. Gene expression in the areas of glomerular neovascularization revealed increased expression of genes involved in angiogenic signaling, proliferation, and survival of endothelial cells, as well as new vessel maturation and stability. This molecular correlation provides additional insights into the development of kidney disease in patients with diabetes and spotlights how novel molecular techniques used by the KPMP can supplement and enrich the histopathologic diagnosis obtained from a kidney biopsy.

Original languageEnglish
Pages (from-to)266-275
Number of pages10
JournalClinical Journal of the American Society of Nephrology
Volume19
Issue number2
DOIs
StatePublished - Feb 2024

Keywords

  • diabetic kidney disease

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