Urine Proteomics Reveals Sex-Specific Response to Total Pancreatectomy With Islet Autotransplantation

Tue Bjerg Bennike, Kate Templeton, Kimino Fujimura, Melena D. Bellin, Saima Ahmed, Christoph N. Schlaffner, Rohit Arora, Zobeida Cruz-Monserrate, Ramy Arnaout, Gregory J. Beilman, Amit S. Grover, Darwin L. Conwell, Hanno Steen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Objectives Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical option for refractory chronic pancreatitis-related pain. Despite the known clinical implications of TPIAT, the molecular effects remain poorly investigated. We performed the first hypothesis-generating study of the urinary proteome before and after TPIAT. Methods Twenty-two patients eligible for TPIAT were prospectively enrolled. Urine samples were collected the week before and 12 to 18 months after TPIAT. The urine samples were prepared for bottom-up label-free quantitative proteomics using the "MStern"protocol. Results Using 17 paired samples, we identified 2477 urinary proteins, of which 301 were significantly changed post-TPIAT versus pre-TPIAT. Our quantitative analysis revealed that the molecular response to TPIAT was highly sex-specific, with pronounced sex differences pre-TPIAT but minimal differences afterward. Comparing post-TPIAT versus pre-TPIAT, we found changes in cell-cell adhesion, intracellular vacuoles, and immune response proteins. After surgery, immunoglobulins, complement proteins, and cathepsins were increased, findings that may reflect glomerular damage. Finally, we identified both known and novel markers for immunoglobulin A nephropathy after 1 patient developed the disease 2 years after TPIAT. Conclusions We found distinct changes in the urinary proteomic profile after TPIAT and the response to TPIAT is highly sex-specific.

Original languageEnglish
Pages (from-to)435-444
Number of pages10
Issue number5
StatePublished - May 1 2022

Bibliographical note

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© Wolters Kluwer Health, Inc. All rights reserved.


  • autoislet
  • diabetes
  • nephropathy
  • pancreatectomy
  • pancreatitis

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology


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