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Related Concept Videos

Acute Kidney Injury I: Introduction01:22

Acute Kidney Injury I: Introduction

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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...
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Chronic Kidney Disease I: Introduction01:25

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Chronic Kidney Disease (CKD) arises when the kidneys progressively lose their ability to function, ultimately leading to end-stage renal disease. At this advanced stage, the kidneys can no longer filter waste or maintain essential body functions, requiring renal replacement therapy (RRT) through dialysis or a kidney transplant for survival.Early-stage chronic kidney disease and detection challengesIn CKD's early stages, symptoms often remain absent because healthy nephrons compensate for...
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Acute Kidney Injury IV: Diagnostic Studies and Prevention01:30

Acute Kidney Injury IV: Diagnostic Studies and Prevention

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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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Chronic kidney disease (CKD) requires collaborative and comprehensive management. CKD progresses through stages and can lead to end-stage kidney disease (ESKD) if untreated. Interprofessional collaboration and patient education are crucial, enabling patients to manage their health and improve their quality of life.Diagnostic approach for chronic kidney diseaseThe diagnosis of CKD primarily focuses on the glomerular filtration rate (GFR), which assesses kidney function by measuring how well...
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Acute Kidney Injury II: Pathophysiology01:29

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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...
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Renal Corpuscle01:20

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The glomerulus and Bowman's capsule are two essential components of the nephron, which is the functional unit of the kidney. These microscopic structures play a critical role in the process of blood filtration to produce urine.
Glomerulus: Structure and Function
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RIPK3 and kidney disease.

Juan Guerrero-Mauvecin1, Miguel Fontecha-Barriuso1, Ana M López-Diaz1

  • 1Department of Nephrology and Hypertension, IIS-Fundacion Jimenez Diaz UAM, 28040 Madrid, Spain.

Nefrologia
|May 7, 2023
PubMed
Summary

Receptor interacting protein kinase 3 (RIPK3) is crucial for cell death and inflammation. Targeting RIPK3 shows potential for kidney diseases, but understanding its complex roles is key for safe clinical development.

Keywords:
Acute kidney injuryChronic kidney diseaseEnfermedad renal crónicaHiperosmolaridadHyperosmolarityInflamaciónInflammationInsuficiencia renal agudaNecroptosisRIPK3

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Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • Receptor interacting protein kinase 3 (RIPK3) is an intracellular kinase regulating cell death and inflammation.
  • RIPK3 possesses a RIP homotypic interaction motif (RHIM) domain for protein interactions and a kinase domain for phosphorylation.
  • RIPK3 activation occurs via RHIM-dependent or independent pathways, influencing necroptosis, NFκB, and inflammasome activation.

Purpose of the Study:

  • To explore the role of RIPK3 in kidney injury, including acute kidney injury (AKI) and chronic kidney disease (CKD).
  • To investigate the potential of RIPK3 inhibition as a therapeutic strategy for inflammatory kidney diseases.
  • To address challenges in clinical translation, particularly concerning RIPK3 inhibitor-induced apoptosis.

Main Methods:

  • Preclinical in vivo studies using RIPK3-deficient mice.
  • Evaluation of small molecule RIPK3 inhibitors.
  • Analysis of RIPK3's role in inflammation and kidney injury progression.
  • Investigating RIPK3 conformational changes and their impact on apoptosis.

Main Results:

  • RIPK3 deficiency or inhibition reduced inflammation in preclinical kidney injury models.
  • Therapeutic benefits on kidney injury were context-dependent.
  • Some small molecule RIPK3 inhibitors can induce apoptosis due to conformational changes.
  • RIPK3 targeting decreased inflammation but kidney injury improved only in some contexts.

Conclusions:

  • RIPK3 plays a significant role in kidney inflammation and injury, with preclinical evidence supporting its targeting.
  • Clinical development of RIPK3 inhibitors is hindered by off-target apoptotic effects.
  • Further research into RIPK3 conformational changes and development of dual inhibitors or repurposed kinase inhibitors is needed for therapeutic advancement in inflammatory diseases, including kidney diseases.