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Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...
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  6. Endogenous Adenine Mediates Kidney Injury In Diabetic Models And Predicts Diabetic Kidney Disease In Patients

Endogenous adenine mediates kidney injury in diabetic models and predicts diabetic kidney disease in patients

Kumar Sharma1,2, Guanshi Zhang1,2, Jens Hansen3

  • 1Center for Precision Medicine and.

The Journal of Clinical Investigation
|August 24, 2023

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Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
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Assessment of Kidney Function in Mouse Models of Glomerular Disease
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View abstract on PubMed

Summary
This summary is machine-generated.

Urine adenine/creatinine ratio (UAdCR) may predict end-stage kidney disease (ESKD) in diabetic kidney disease (DKD) patients. Lowering UAdCR with empagliflozin and inhibiting adenine production reduced kidney injury in mice, suggesting adenine

Keywords:
Chronic kidney diseaseDiabetesFibrosisNephrology

Related Experiment Videos

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212
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Assessment of Kidney Function in Mouse Models of Glomerular Disease
09:16

Assessment of Kidney Function in Mouse Models of Glomerular Disease

Published on: June 30, 2018

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Area of Science:

  • Nephrology
  • Metabolomics
  • Molecular Biology

Background:

  • Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease (ESKD) and mortality.
  • Current biomarkers for high-risk DKD patients, particularly those without macroalbuminuria, are limited.
  • Understanding mechanistic biomarkers is crucial for early intervention in DKD.

Purpose of the Study:

  • To investigate urine adenine/creatinine ratio (UAdCR) as a mechanistic biomarker for ESKD in diabetic patients.
  • To explore the role of adenine in DKD pathogenesis.
  • To assess the effect of empagliflozin on UAdCR in nonmacroalbuminuric individuals.

Main Methods:

  • Analysis of UAdCR in large diabetic cohorts (CRIC, SMART2D, American Indian Study).
  • Spatial metabolomics and single-cell transcriptomics to localize adenine and identify related pathways.
  • In vivo studies using diabetic mice treated with adenine production inhibitors.

Main Results:

  • Highest UAdCR tertiles were associated with increased risk of ESKD and mortality in CRIC and SMART2D cohorts.
  • This association persisted in patients without macroalbuminuria across all three studies.
  • Empagliflozin reduced UAdCR in nonmacroalbuminuric participants; adenine was localized to kidney pathology and implicated mTOR pathway.

Conclusions:

  • Urine adenine/creatinine ratio is a potential mechanistic biomarker for predicting ESKD in diabetic kidney disease.
  • Endogenous adenine may play a causative role in DKD progression, potentially via the mTOR pathway.
  • Targeting adenine production could be a novel therapeutic strategy for diabetic kidney disease.