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Related Concept Videos

Physiology of the Genitourinary System II: Tubular Reabsorption and Secretion01:22

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The kidneys maintain homeostasis through filtration, reabsorption, and secretion. Tubular reabsorption and secretion are crucial in forming urine and regulating electrolytes, water balance, and waste elimination.Tubular Reabsorption and Secretion ProcessesTubular reabsorption is the process that reclaims essential substances such as electrolytes, glucose, amino acids, and water from the glomerular filtrate back into the bloodstream. This is achieved through passive and active transport...
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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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Tubular Reabsorption and Secretion01:28

Tubular Reabsorption and Secretion

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Tubular secretion and reabsorption are two critical processes in the nephron tubule of the kidneys. When the fluid filtered from the glomerulus enters the proximal convoluted tubule, it is referred to as filtrate, and its composition changes due to tubular reabsorption and secretion.
Tubular reabsorption is a selective process that starts when the filtrate enters the proximal tubules. It involves substances traveling through the transcellular route (through the tubule cell and peritubular...
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Drug Elimination by Renal Route: Tubular Reabsorption01:22

Drug Elimination by Renal Route: Tubular Reabsorption

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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. However, the majority of drugs are either weak acids or weak bases, and their ionization level is dependent on pH. By altering the pH of urine, the...
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Renal Drug Excretion: Tubular Secretion01:28

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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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Physiology of Urine Formation01:24

Physiology of Urine Formation

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Urine formation is an essential function of the human body. It plays a critical role in maintaining homeostasis by regulating the volume and composition of body fluids. The kidneys, the primary organs involved in this process, filter blood to remove waste products and excess substances, ultimately producing urine.
Glomerular Filtration
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Proteinuria Increases Plasma Phosphate by Altering Its Tubular Handling.

Sophie de Seigneux1, Marie Courbebaisse2, Joseph M Rutkowski3

  • 1Service of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland; Laboratory of Renal Physiology and Physiopathology, Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland; sophie.deseigneux@hcuge.ch.

Journal of the American Society of Nephrology : JASN
|October 29, 2014
PubMed
Summary

Proteinuria, or excess protein in urine, elevates phosphate levels independently of kidney function. This occurs due to increased phosphate reabsorption in the kidneys, driven by reduced fibroblast growth factor 23 (FGF-23) activity.

Keywords:
chronic kidney diseasemineral metabolismphosphate uptake

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Area of Science:

  • Nephrology
  • Cardiovascular Medicine
  • Molecular Biology

Background:

  • Proteinuria and hyperphosphatemia are established cardiovascular risk factors.
  • Their independent contribution to cardiovascular disease risk, separate from glomerular filtration rate (GFR), necessitates further investigation.

Purpose of the Study:

  • To investigate the hypothesis that proteinuria increases phosphate retention through enhanced proximal tubule phosphate reabsorption.
  • To elucidate the molecular mechanisms linking proteinuria, phosphate handling, and cardiovascular risk.

Main Methods:

  • Studied phosphate handling in nephrotic children and a cohort of 1738 Chronic Kidney Disease (CKD) patients.
  • Analyzed plasma fibroblast growth factor 23 (FGF-23), phosphate levels, and tubular reabsorption.
  • Utilized animal models (rats and mice) with induced nephrotic proteinuria to examine renal protein expression of sodium-phosphate co-transporter NaPi-IIa and FGF-23 pathway components.

Main Results:

  • Nephrotic children showed increased plasma phosphate, FGF-23, and phosphate reabsorption during proteinuria.
  • In CKD patients, high albuminuria (≥300 mg/24 hours) predicted higher phosphate and FGF-23 levels, independent of GFR.
  • Animal models exhibited increased renal NaPi-IIa and decreased Klotho and FGF receptor substrate 2α phosphorylation.

Conclusions:

  • Proteinuria elevates plasma phosphate concentration independently of GFR.
  • This effect is mediated by increased proximal tubule NaPi-IIa expression due to diminished FGF-23 activity.
  • Proteinuria-induced elevations in phosphate and FGF-23 may contribute to cardiovascular disease risk.