Plasma proteomics of acute tubular injury.

The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ's metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development. Using the SomaScan proteomics platform on 434 patients with biopsy-confirmed kidney disease, we here identify plasma biomarkers associated with ATI severity. We employ regional transcriptomics and proteomics, single-cell RNA sequencing, and pathway analysis to explore biomarker protein and gene expression and enriched biological pathways. Additionally, we examine ATI biomarker associations with acute kidney injury (AKI) in the Kidney Precision Medicine Project (KPMP) (n = 44), the Atherosclerosis Risk in Communities (ARIC) study (n = 4610), and the COVID-19 Host Response and Clinical Outcomes (CHROME) study (n = 268). Our findings indicate 156 plasma proteins significantly linked to ATI with osteopontin, macrophage mannose receptor 1, and tenascin C showing the strongest associations. Pathway analysis highlight immune regulation and organelle stress responses in ATI pathogenesis.

Participant Experience with Protocol Research Kidney Biopsies in the Kidney Precision Medicine Project.

BACKGROUND: Kidney biopsies are procedures commonly performed in clinical nephrology and are increasingly used in research. In this study we aimed to evaluate the experiences of participants who underwent research kidney biopsies in the Kidney Precision Medicine Project (KPMP). METHODS: KPMP research participants with acute kidney injury (AKI) or chronic kidney disease (CKD) were enrolled at nine recruitment sites in the United States between September 2019 to January 2023. At 28 days post-biopsy, participants were invited to complete a survey to share their experiences, including: motivation to participate in research; comprehension of informed consent; pain and anxiety during and after the biopsy procedure; overall satisfaction with KPMP participation; and impact of the study on their lives. The survey was developed in collaboration with the KPMP Community Engagement Committee and the Institute of Translational Health Sciences at the University of Washington. RESULTS: 111 participants completed the survey, 23 enrolled for AKI and 88 for CKD. Median age was 61 (IQR 48-67) years, 43% were women, 28% were Black, and 18% were of Hispanic ethnicity. Survey respondents most commonly joined KPMP to help future patients (59%). The consent form was understood by 99% and 97% recognized their important role in the study. Pain during the biopsy was reported by 50%, at a median level of 1 (IQR 0-3) on a 0-10 scale. Anxiety during the biopsy was described by 64% at a median level of 3 (IQR 1-5) on a 0-10 scale. More than half conveyed that KPMP participation impacted their diet, physical activity, and how they think about kidney disease. CONCLUSIONS: KPMP survey respondents were most commonly motivated to participate in research protocol kidney biopsies by altruism, with excellent understanding of the informed consent process.