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Advances in proteomic profiling of pediatric kidney diseases

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Abstract

Chronic kidney disease (CKD) can progress to kidney failure and require dialysis or transplantation, while early diagnosis can alter the course of disease and lead to better outcomes in both pediatric and adult patients. Significant CKD comorbidities include the manifestation of cardiovascular disease, heart failure, coronary disease, and hypertension. The pathogenesis of chronic kidney diseases can present as subtle and especially difficult to distinguish between different glomerular pathologies. Early detection of adult and pediatric CKD and detailed mechanistic understanding of the kidney damage can be helpful in delaying or curtailing disease progression via precise intervention toward diagnosis and prognosis. Clinically, serum creatinine and albumin levels can be indicative of CKD, but often are a lagging indicator only significantly affected once kidney function has severely diminished. The evolution of proteomics and mass spectrometry technologies has begun to provide a powerful research tool in defining these mechanisms and identifying novel biomarkers of CKD. Many of the same challenges and advances in proteomics apply to adult and pediatric patient populations. Additionally, proteomic analysis of adult CKD patients can be transferred directly toward advancing our knowledge of pediatric CKD as well. In this review, we highlight applications of proteomics that have yielded such biomarkers as PLA2R, SEMA3B, and other markers of membranous nephropathy as well as KIM-1, MCP-1, and NGAL in lupus nephritis among other potential diagnostic and prognostic markers. The potential for improving the clinical toolkit toward better treatment of pediatric kidney diseases is significantly aided by current and future development of proteomic applications.

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Funding

This work was supported by NIDDK-NIH (DK110077 to JBK, WES), and clinical research funding from the University of Louisville Kidney Disease Program.

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Authors and Affiliations

  1. Division of Nephrology and Hypertension, Clinical Proteomics Center, University of Louisville School of Medicine, 570 S. Preston St, Louisville, KY, 40202, USA

    Timothy D. Cummins, Michael L. Merchant, Michelle T. Barati & Jon B. Klein

  2. Bluewater Diagnostics, Mount Washington, KY, USA

    Erik A. Korte

  3. Nationwide Children’s Hospital, The Ohio State University, Columbus, OH, USA

    Sagar Bhayana & William E. Smoyer

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  1. Timothy D. Cummins
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  3. Sagar Bhayana
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Cummins, T.D., Korte, E.A., Bhayana, S. et al. Advances in proteomic profiling of pediatric kidney diseases. Pediatr Nephrol 37, 2255–2265 (2022). https://doi.org/10.1007/s00467-022-05497-2

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