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Related Concept Videos

Chronic Kidney Disease I: Introduction01:25

Chronic Kidney Disease I: Introduction

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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 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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The kidneys are intricate organs with millions of working units known as nephrons. Each nephron features two major structures: the renal corpuscle, which facilitates blood plasma filtration, and the renal tubule, which handles the glomerular filtrate. Blood supply is directly linked to the nephrons. The renal corpuscle consists of the glomerulus, a capillary network, and the Bowman's capsule, a double-walled epithelial structure that encases the glomerulus. The filtering of blood plasma...
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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.
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Renal failure occurs when the kidneys lose their ability to filter waste products from the blood effectively. It can be classified into two types: acute renal failure (ARF) and chronic renal failure (CRF).
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Chronic Kidney Disease (CKD) progressively impairs multiple body systems due to the accumulation of uremic toxins, which disrupt cellular functions across various organs.Neurologic symptomsNeurologic symptoms often arise early in CKD, as uremic toxin buildup drives changes in cognitive and motor functions. Patients frequently experience fatigue, headache, confusion, difficulty concentrating, and, in severe cases, seizures. Peripheral neuropathy commonly manifests as burning sensations in the...
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Related Experiment Video

Updated: Nov 2, 2025

Intravascular Delivery of Biologics to the Rat Kidney
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Progressive Cellular Senescence Mediates Renal Dysfunction in Ischemic Nephropathy.

Seo Rin Kim1,2, Amrutesh S Puranik1,3, Kai Jiang1

  • 1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.

Journal of the American Society of Nephrology : JASN
|June 17, 2021
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Summary

Cellular senescence contributes to kidney dysfunction and injury in renal artery stenosis. Senolytic treatments can improve kidney function and reduce damage, offering a potential therapeutic strategy for chronic ischemic renal injury.

Keywords:
dasatinibquercetinrenal artery stenosissenescencetranscriptome

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Area of Science:

  • Nephrology
  • Cellular Biology
  • Vascular Biology

Background:

  • Peripheral vascular diseases can cause chronic ischemia and cellular damage.
  • Cellular senescence, a stress response, can harm nearby cells.
  • The role and timing of cellular senescence in renal artery stenosis (RAS)-induced kidney dysfunction are unknown.

Purpose of the Study:

  • To investigate the role of cellular senescence in renal artery stenosis (RAS) and its impact on kidney function.
  • To determine the temporal pattern of cellular senescence in RAS-induced kidney injury.
  • To evaluate the efficacy of senolytic strategies in mitigating RAS-induced renal dysfunction and damage.

Main Methods:

  • Induction of chronic renal ischemia in mice via unilateral RAS.
  • Assessment of kidney function using in vivo micro-MRI and tissue damage.
  • Single-cell RNA-sequencing of healthy and stenotic mouse kidneys.
  • Investigation of cellular senescence in human stenotic kidneys for translational relevance.

Main Results:

  • Selective clearance of p16Ink4a-expressing cells improved stenotic-kidney function when initiated weeks after RAS, but not immediately.
  • The senolytic combination dasatinib and quercetin effectively cleared p21-positive cells and alleviated renal dysfunction and damage in RAS mice.
  • Single-cell RNA-sequencing revealed stenotic-kidney epithelial cells undergoing mesenchymal transition and senescence.
  • Human stenotic kidneys showed conserved cellular senescence, similar to mouse models.

Conclusions:

  • Maladaptive tubular cell senescence, marked by increased p16, p19, and p21 expression, is linked to renal dysfunction and injury in chronic ischemia.
  • These findings highlight cellular senescence as a key driver of chronic ischemic renal injury.
  • Senolytic strategies show promise for delaying or treating chronic ischemic renal injury.