Development of a Biomarker Panel to Distinguish Risk of Progressive Chronic Kidney Disease

Owens, Evan P.; Tan, Ken‐Soon; Ellis, Robert J.; Vecchio, S. Del; Humphries, Tyrone L.R.; Lennan, Erica; Vesey, David A.; Healy, Helen; Hoy, Wendy E.; Gobé, Glenda C.

doi:10.3390/biomedicines8120606

Cited by 11 publications

(8 citation statements)

References 56 publications

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“…Urinary or serum proteomics for the study of DKD produced compelling results, [108][109][110] which could be conjugated with metabolomics for integrative analysis. For instance, Liu et al 104 concluded that the accuracy of DKD prediction could be improved by performing integrative serum proteomics and metabolomics data analysis Owens et al 111 aimed to develop a model for predicting progressive kidney damage based on a biomarker panel of serum creatinine, osteopontin, tryptase, urea and eGFR. Owens and collaborators obtained an accuracy of 84.3% in predicting future progressive chronic kidney disease at baseline, greater than eGFR (66.1%), sCr (67.7%), albuminuria (53.2%), or albumin-creatinine ratio (53.2%).…”

Section: Towards the Future: Multi-omics Analysis And Panels Of Bioma...mentioning

confidence: 99%

Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease

Pereira

Carrageta

Oliveira

et al. 2022

Medicinal Research Reviews

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Diabetic kidney disease (DKD) is one of the most prevalent comorbidities of diabetes mellitus and the leading cause of the end‐stage renal disease (ESRD). DKD results from chronic exposure to hyperglycemia, leading to progressive alterations in kidney structure and function. The early development of DKD is clinically silent and when albuminuria is detected the lesions are often at advanced stages, leading to rapid kidney function decline towards ESRD. DKD progression can be arrested or substantially delayed if detected and addressed at early stages. A major limitation of current methods is the absence of albuminuria in non‐albuminuric phenotypes of diabetic nephropathy, which becomes increasingly prevalent and lacks focused therapy. Metabolomics is an ever‐evolving omics technology that enables the study of metabolites, downstream products of every biochemical event that occurs in an organism. Metabolomics disclosures complex metabolic networks and provide knowledge of the very foundation of several physiological or pathophysiological processes, ultimately leading to the identification of diseases' unique metabolic signatures. In this sense, metabolomics is a promising tool not only for the diagnosis but also for the identification of pre‐disease states which would confer a rapid and personalized clinical practice. Herein, the use of metabolomics as a tool to identify the DKD metabolic signature of tubule interstitial lesions to diagnose or predict the time‐course of DKD will be discussed. In addition, the proficiency and limitations of the currently available high‐throughput metabolomic techniques will be discussed.

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Section: Towards the Future: Multi-omics Analysis And Panels Of Bioma...mentioning

confidence: 99%

Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease

Pereira

Carrageta

Oliveira

et al. 2022

Medicinal Research Reviews

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“…This finding has implications beyond AKI, as tissue injury due to various causes can raise OPN serum levels in humans, including but not limited to direct lung injury by COVID-19, bacterial pneumonia ( 46 ), sepsis from various causes ( 32 , 47 , 48 ), or cardiac injury ( 44 , 47 ). OPN has also been described as a marker of kidney injury and declining kidney function, as example ( 49 , 50 ), but not much is known about the mechanisms involved. All these conditions are highly associated with multiorgan failure, particularly AKI and ALI or its most severe form, ARDS.…”

Section: Discussionmentioning

confidence: 99%

Identification of kidney injury–released circulating osteopontin as causal agent of respiratory failure

et al. 2022

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Tissue injury can drive secondary organ injury; however, mechanisms and mediators are not well understood. To identify interorgan cross-talk mediators, we used acute kidney injury (AKI)–induced acute lung injury (ALI) as a clinically important example. Using kidney and lung single-cell RNA sequencing after AKI in mice followed by ligand-receptor pairing analysis across organs, kidney ligands to lung receptors, we identify kidney-released circulating osteopontin (OPN) as a novel AKI-ALI mediator. OPN release from kidney tubule cells triggered lung endothelial leakage, inflammation, and respiratory failure. Pharmacological or genetic OPN inhibition prevented AKI-ALI. Transplantation of ischemic wt kidneys caused AKI-ALI, but not of ischemic OPN–global knockout kidneys, identifying kidney-released OPN as necessary interorgan signal to cause AKI-ALI. We show that OPN serum levels are elevated in patients with AKI and correlate with kidney injury. Our results demonstrate feasibility of using ligand-receptor analysis across organs to identify interorgan cross-talk mediators and may have important therapeutic implications in human AKI-ALI and multiorgan failure.

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“…OPN has also been described as a marker of kidney injury and declining kidney function e.g. 53,54 , but not much is known about the mechanisms involved. All these conditions are highly associated with multiorgan failure, in particular AKI and ALI or its most severe form acute respiratory distress syndrome (ARDS).…”

Section: Discussionmentioning

confidence: 99%

Circulating osteopontin released by injured kidneys causes pulmonary inflammation and edema

Khamissi¹,

Ning²,

Kefaloyianni³

et al. 2021

Preprint

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Multiorgan failure is devastating, and its mechanisms and mediators are not clear. Tissue injury in one organ appears to trigger disease in remote organs. Kidney and lung are frequently affected, such as when acute kidney injury (AKI) causes acute lung injury (ALI), a frequent clinical condition with high mortality. Here we identify factors secreted from the injured kidney that cause acute lung injury. We developed a murine model mimicking the generation of respiratory failure following acute kidney injury. To identify interorgan crosstalk mediators involved, we performed scRNAseq of mouse kidneys and lungs after AKI. We then applied ligand-receptor (L-R) pairing analysis across cells residing in kidney (ligands) or lung (receptors) to identify kidney-released circulating osteopontin (OPN) as a novel mediator of AKI-induced ALI (AKI-ALI). OPN release very early after AKI largely from tubule cells triggered neutrophil and macrophage infiltration into lungs associated with endothelial leakage, interstitial edema, and functional impairment. Pharmacological or genetic inhibition of OPN prevented AKI-ALI. Transplantation of ischemic wt kidneys into wt mice caused AKI-ALI, while transplantation of ischemic OPN-global-knockout kidneys failed to induce lung endothelial leakage and AKI-ALI, identifying circulating kidney-released OPN as sufficient to cause AKI-ALI in vivo. We show that AKI in humans results in elevations in OPN levels in the serum. Increased serum OPN levels in patients with multiorgan failure have been shown to positively correlate with reduced kidney function, respiratory failure, and mortality. Thus, our results identifying OPN as a mediator of AKI-ALI may have important therapeutic implications in human AKI-ALI and multiorgan failure.

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Development of a Biomarker Panel to Distinguish Risk of Progressive Chronic Kidney Disease

Cited by 11 publications

References 56 publications

Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease

Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease

Identification of kidney injury–released circulating osteopontin as causal agent of respiratory failure

Circulating osteopontin released by injured kidneys causes pulmonary inflammation and edema

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