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Related Concept Videos

Renal Drug Excretion: Tubular Secretion01:28

Renal Drug Excretion: Tubular Secretion

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Active tubular secretion is a robust, energy-demanding process that utilizes carrier systems to transport drugs into renal tubules. The active renal secretion systems include the organic anion transporter (OAT) for weak acids and the organic cation transporter (OCT) for weak bases. Structurally similar drugs can compete for the same transporter, potentially leading to drug accumulation and toxicity. However, this principle can be exploited therapeutically. One example is probenecid (Probalan),...
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Acute Kidney Injury IV: Diagnostic Studies and Prevention01:30

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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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Drug Accumulation During Multiple Dosing: Intermittent IV Infusions01:24

Drug Accumulation During Multiple Dosing: Intermittent IV Infusions

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Intermittent intravenous (IV) infusion is a method of drug administration where medications are delivered over short infusion periods followed by intervals of no drug delivery. This approach helps to prevent sustained high drug concentrations in the bloodstream, reducing the risk of adverse effects associated with prolonged exposure. Unlike continuous infusion, steady-state concentrations may not be achieved during a single dosing cycle but can be reached through repeated...
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Renal Drug Excretion: Tubular Reabsorption01:25

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Tubular reabsorption, a process occurring post-glomerular filtration of drugs in the renal tubule, is a critical determinant of drug half-life. During the process of renal excretion, as the glomerular filtrate progresses to the distal convoluted tubule (DCT), drugs that are highly permeable, lipophilic, and nonionized undergo passive reabsorption from the tubular fluid into the surrounding peritubular capillaries. This reabsorption process restricts their elimination through the kidneys. This...
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Renal Drug Clearance: Overview01:06

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Renal clearance is a crucial parameter in pharmacokinetics that quantifies the rate at which the kidneys excrete a drug. It represents a constant fraction of the central volume of distribution containing the drug that the kidney eliminates per unit of time.
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Renal Drug Excretion: Overview01:15

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As primary excretory organs, the kidneys maintain homeostasis by removing waste substances from the bloodstream. They comprise over a million units called nephrons, which serve as the kidney's functional units.
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Iptacopan in IgA Nephropathy - Final 24-Month Data.

Jonathan Barratt1,2, Necmi Eren3, Naoki Kashihara4

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Iptacopan significantly slowed kidney function decline in IgA nephropathy patients compared to placebo. This complement factor B inhibitor demonstrated a slower annualized estimated glomerular filtration rate slope, reducing kidney failure risk.

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Area of Science:

  • Nephrology
  • Immunology
  • Pharmacology

Background:

  • Alternative complement pathway overactivation is implicated in IgA nephropathy (IgAN) pathogenesis and glomerular inflammation.
  • Iptacopan, an oral complement factor B inhibitor, targets this pathway.
  • Previous interim analysis showed iptacopan reduced proteinuria in IgAN patients.

Purpose of the Study:

  • To evaluate the efficacy and safety of iptacopan in adults with IgA nephropathy.
  • To assess the effect of iptacopan on the rate of kidney function decline over 24 months.
  • To determine the impact of iptacopan on kidney failure events.

Main Methods:

  • Phase 3, randomized, double-blind, placebo-controlled trial involving 477 adults with IgAN.
  • Patients received oral iptacopan (200 mg) or placebo twice daily.
  • Primary endpoint: annualized total eGFR slope over 24 months. Secondary endpoint: composite kidney-failure event rate.

Main Results:

  • Iptacopan demonstrated a significantly slower annualized eGFR slope (-3.10 ml/min/1.73 m² per year) versus placebo (-6.12 ml/min/1.73 m² per year).
  • The composite kidney-failure event rate was lower in the iptacopan group (21.4%) compared to placebo (33.5%).
  • Adverse event rates were similar; serious infections were more frequent with iptacopan (6.7%) vs. placebo (2.1%).

Conclusions:

  • Iptacopan therapy resulted in a significantly slower decline in kidney function compared to placebo in patients with IgAN.
  • Iptacopan represents a potential therapeutic option for slowing IgAN progression.
  • The study met its primary and secondary endpoints, supporting iptacopan's efficacy.