Sepsis-associated acute kidney injury in mice and humans elicits heterogeneous renal microvascular microRNA responses

Matthijs Luxen1,2, Tamar J van der Aart3, Rianne M Jongman1,4

  • 1Department of Pathology and Medical Biology, Medical Biology section, University Medical Center Groningen, University of Groningen, 5617 Hanzeplein 1, Groningen, 9713 GZ, the Netherlands.

Scientific Reports
|October 2, 2025
PubMed

Insights

MicroRNAs, including miR-21-5p, are altered in sepsis-associated acute kidney injury (SA-AKI). Elevated miR-21-5p in plasma may serve as an early biomarker and potential therapeutic target for SA-AKI.

Area of Science:

  • Renal physiology and pathology
  • Molecular biology
  • Biomarker discovery

Background:

  • Sepsis-associated acute kidney injury (SA-AKI) involves microvascular endothelial cells.
  • MicroRNAs (miRNAs) are crucial regulators of cellular processes and are implicated in disease.
  • Identifying novel biomarkers and therapeutic targets for SA-AKI is critical.

Purpose of the Study:

  • To investigate changes in microvascular miRNAs in SA-AKI.
  • To identify potential druggable miRNA targets and early biomarkers for SA-AKI.
  • To elucidate the role of specific miRNAs, such as miR-21-5p, in SA-AKI pathogenesis.

Main Methods:

  • Small RNA sequencing was employed to profile miRNA expression in the renal microvasculature of SA-AKI models.
  • In vitro functional assays were conducted to assess the role of hsa-miR-21-5p in endothelial cells.
  • Plasma hsa-miR-21-5p levels were measured in patients with SA-AKI and sepsis without AKI.

Main Results:

  • Forty differentially expressed miRNAs were identified in the renal microvasculature during SA-AKI.
  • miR-21-5p levels were significantly increased across the renal microvasculature in both mice and humans with SA-AKI.
  • Inhibition of hsa-miR-21-5p worsened endothelial inflammatory activation, indicating a protective role.
  • Elevated plasma hsa-miR-21-5p levels were observed in SA-AKI patients compared to sepsis patients without AKI.

Conclusions:

  • Microvascular miRNA dysregulation is a feature of SA-AKI.
  • hsa-miR-21-5p demonstrates a protective role in endothelial cells during SA-AKI.
  • hsa-miR-21-5p is a promising candidate for an early plasma biomarker and a potential therapeutic target for SA-AKI.

Related Concept Videos

Acute Kidney Injury II: Pathophysiology01:29

Acute Kidney Injury II: Pathophysiology

Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
899
Acute Kidney Injury I: Introduction01:22

Acute Kidney Injury I: Introduction

Introduction:Acute Kidney Injury (AKI) describes a swift decrease in kidney function occurring over hours to days, characterized by the kidneys' failure to remove waste products from the bloodstream. This leads to dangerous complications like metabolic acidosis, fluid overload, and electrolyte imbalances, such as hyperkalemia, which can cause life-threatening arrhythmias. AKI is common in both hospital and outpatient settings, often triggered by dehydration, sepsis, or exposure to nephrotoxic...
577
Acute Kidney Injury IV: Diagnostic Studies and Prevention01:30

Acute Kidney Injury IV: Diagnostic Studies and Prevention

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...
260
Acute Kidney Injury III: Clinical Manifestations01:29

Acute Kidney Injury III: Clinical Manifestations

Acute Kidney Injury (AKI) progresses through distinct clinical phases: the oliguric, diuretic, and recovery phases, each marked by unique manifestations and challenges.Oliguric Phase:The oliguric phase is the initial stage of AKI, typically lasting 10 to 14 days. This phase is marked by a significant reduction in urine output, usually less than 400 mL per day, indicating decreased kidney function. Fluid retention is a prominent feature, leading to symptoms such as edema, hypertension, and...
825