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Related Concept Videos

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Nephrotic Syndrome I : Introduction

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Nephrotic Syndrome is a chronic kidney disorder defined by clinical findings such as severe proteinuria, hypoalbuminemia, hyperlipidemia, and edema. These symptoms result from damage to the glomeruli, the kidney’s filtering units, increasing their permeability to proteins.Definition and Meaning:Proteinuria, defined as the loss of more than 3.5 grams of protein per day in adults, is a crucial feature of nephrotic syndrome. This condition is often accompanied by edema, the accumulation of...
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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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The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
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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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Nephrotic Syndrome II : Assessment and Medical Management01:26

Nephrotic Syndrome II : Assessment and Medical Management

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IntroductionNephrotic syndrome is a kidney disorder marked by excessive protein loss in the urine, leading to various systemic complications. This condition often results from damage to the glomeruli—the kidney's filtering units—causing proteinuria, low blood protein levels, and fluid retention. Understanding the assessment, diagnosis, and management of nephrotic syndrome is essential for effective treatment and prevention of further kidney damage.AssessmentPatient History: Document...
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Chronic Kidney Disease II: Clinical Manifestations01:24

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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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Liddle syndrome is a genetically inherited form of hypertension characterized by the overactivity of epithelial sodium channels in the nephron, the functional unit of the kidney. This heightened activity leads to increased sodium reabsorption and excessive excretion of potassium. To counteract this, potassium-sparing diuretics such as amiloride are used. They function by blocking these sodium channels, thereby reducing the influx of sodium into the epithelial cells and minimizing the loss of...
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Single-channel Analysis and Calcium Imaging in the Podocytes of the Freshly Isolated Glomeruli
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SuPAR mediates viral response proteinuria by rapidly changing podocyte function.

Changli Wei1, Prasun K Datta2, Florian Siegerist3,4

  • 1Department of Medicine, Rush University Medical Center, Chicago, IL, USA. changli_wei@rush.edu.

Nature Communications
|July 21, 2023
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Summary

Elevated soluble urokinase receptor (suPAR) and proteinuria are linked to COVID-19 severity. This study identifies viral response proteinuria (VRP) as an innate immune mechanism involving suPAR and podocyte integrins, offering new therapeutic targets.

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Area of Science:

  • Nephrology
  • Virology
  • Immunology

Background:

  • Elevated soluble urokinase receptor (suPAR) and proteinuria are common in severe COVID-19.
  • The exact mechanism linking viral infections to kidney damage, specifically proteinuria, requires further elucidation.
  • Distinct SARS-CoV-2 variants may exhibit different pathogenic mechanisms.

Purpose of the Study:

  • To characterize a novel form of proteinuria resulting from viral infections.
  • To investigate the role of suPAR and SARS-CoV-2 spike proteins in inducing proteinuria.
  • To explore potential therapeutic interventions targeting the suPAR-integrin pathway.

Main Methods:

  • Utilizing African green monkeys and a suPAR-expressing mouse model for SARS-CoV-2 inoculation and spike protein exposure.
  • Administering suPAR antibodies and SARS-CoV-2 vaccination to assess blockade of proteinuria.
  • Analyzing suPAR levels and proteinuria in a large cohort of COVID-19 patients across different variants.

Main Results:

  • SARS-CoV-2 inoculation increased suPAR levels and caused glomerulopathy in monkeys.
  • Inhaled SARS-CoV-2 spike S1 protein induced proteinuria in mice, preventable by suPAR antibody or vaccination.
  • A stepwise association between suPAR and proteinuria was observed in non-Omicron COVID-19 infections but not Omicron.

Conclusions:

  • Viral response proteinuria (VRP) is an innate immune mechanism involving suPAR and podocyte integrins.
  • Biophysical and functional differences exist between SARS-CoV-2 variants' spike proteins and their interaction with podocyte integrins.
  • Targeting the suPAR-integrin axis presents a potential therapeutic strategy for viral-induced kidney injury.