Related Experiment Video

Updated: Mar 7, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

1.0K

BRAF Signaling Pathway Inhibition, Podocyte Injury, and Nephrotic Syndrome

Luca Perico1, Mario Mandalà2, Arrigo Schieppati3

  • 1IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy.

American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
|March 1, 2017
PubMed

Insights

Dabrafenib and trametinib, used for metastatic melanoma, can cause nephrotic syndrome, a rare kidney injury. Prompt drug withdrawal and monitoring are crucial for patients undergoing this targeted therapy.

Area of Science:

  • Oncology
  • Nephrology
  • Pharmacology

Background:

  • Dabrafenib and trametinib are targeted therapies for metastatic melanoma.
  • Their nephrotoxicity is not well-characterized, with tubulointerstitial injury being the most common renal side effect.
  • Nephrotic syndrome has not been previously reported with these agents.

Observation:

  • A patient with metastatic melanoma developed nephrotic syndrome during treatment with dabrafenib and trametinib.
  • Kidney biopsy revealed diffuse podocyte injury, foot-process effacement, and glomerular endothelial damage.
  • Renal function and ultrastructural changes improved after discontinuing the medications.

Findings:

  • BRAF inhibition in vitro reduced podocyte PLCε1 and nephrin expression, increasing albumin permeability.
  • These targeted therapies inhibited the podocyte-VEGF system.
  • The study identified a novel mechanism for drug-induced nephrotic syndrome.

Implications:

  • This case highlights a previously unreported renal side effect of dabrafenib and trametinib.
  • Understanding the mechanism involving podocyte injury and VEGF inhibition is crucial for nephrotic syndrome pathophysiology.
  • Close monitoring for glomerular damage is recommended for patients receiving these melanoma therapies.
Keywords:
BRAF inhibitorBRAF signaling pathwayDabrafenibMEK inhibitorPLCε1case reportglomerulopathymelanomanephrotic syndromenephrotoxicitypodocyte injuryproteinuriarenal biopsytargeted cancer therapytrametinib

More Related Videos

Induction of Nephrotic Syndrome in Mice by Retrobulbar Injection of Doxorubicin and Prevention of Volume Retention by Sustained Release Aprotinin07:38

Induction of Nephrotic Syndrome in Mice by Retrobulbar Injection of Doxorubicin and Prevention of Volume Retention by Sustained Release Aprotinin

Published on: May 6, 2018

8.9K
Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease08:15

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease

Published on: May 10, 2024

1.0K

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.5K
Nephrotic Syndrome I : Introduction01:24

Nephrotic Syndrome I : Introduction

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...
789
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.8K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.2K
Nephrotic Syndrome II : Assessment and Medical Management01:26

Nephrotic Syndrome II : Assessment and Medical Management

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...
286
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.8K