Related Experiment Video
Updated: May 26, 2026
11:47
Using 2-Photon Microscopy to Quantify the Effects of Chronic Unilateral Ureteral Obstruction on Glomerular Processes
Published on: March 4, 2022
An update on protein-bound uremic retention solutes
Raymond Vanholder1, Eva Schepers, Anneleen Pletinck
1Nephrology Section, Department of Internal Medicine, University Hospital, Ghent, Belgium. raymond.vanholder@ugent.be
Summary
Protein-bound uremic toxins like p-cresyl sulfate and indoxyl sulfate harm kidney health and cardiovascular outcomes. The sorbent AST-120 shows promise in reducing these toxins, but large trials are needed.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Toxicology
Background:
- Protein-bound uremic retention solutes (PBURS) are a major category of toxins in chronic kidney disease (CKD).
- P-cresyl sulfate (PCS) and indoxyl sulfate (IS) are key PBURS linked to cardiovascular disease and CKD progression.
- Elevated PCS and IS levels correlate with inflammation, vascular issues, and poorer survival in CKD patients.
Purpose of the Study:
- To review the impact of PBURS on CKD.
- To evaluate strategies for reducing PBURS, including dialysis and intestinal adsorbents.
- To assess the efficacy of AST-120 in lowering PBURS and improving outcomes.
Main Methods:
- Review of in vitro, ex vivo, and in vivo studies on PBURS.
- Analysis of data on the removal of PCS and IS by various dialysis techniques.
- Evaluation of studies investigating the sorbent AST-120 for PBURS management.
Main Results:
- High-flux hemodialysis has limited efficacy in removing PCS and IS; convection offers some improvement.
- The sorbent AST-120 has demonstrated the ability to reduce PCS and IS concentrations in controlled studies.
- Pilot studies suggest AST-120 may offer superior outcomes compared to placebo, pending larger trials.
Conclusions:
- PBURS, particularly PCS and IS, significantly contribute to CKD complications.
- Reducing intestinal generation and absorption of PBURS is a potential therapeutic strategy.
- AST-120 shows promise for managing PBURS, but further large-scale randomized trials are necessary before clinical recommendation.
Related Concept Videos
01:28Renal Drug Excretion: Tubular Secretion
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),...
01:22Drug Elimination by Renal Route: Tubular Reabsorption
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...
01:26Nephrotic 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 any history...
01:29Drug Distribution: Plasma Protein Binding
Drugs predominantly attach to plasma proteins, with only a small percentage remaining unbound. The unbound portion can be calculated as one minus the bound fraction. Acidic drugs form large, inactive complexes by reversibly binding to plasma albumin, which prevents them from diffusing across biological barriers. These drug-protein complexes act as reservoirs for the drugs. As the concentration of unbound drugs decreases, these complexes quickly dissociate to release the free drug, maintaining...
01:25Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant
In patients with renal disease, dosage adjustments are necessary to maintain therapeutic plasma drug concentrations and prevent toxicity or subtherapeutic exposure. Renal impairment alters drug pharmacokinetics, especially in conditions like uremia, where changes such as prolonged elimination half-life and altered apparent volume of distribution can significantly affect drug disposition. These changes require careful modification of the dosing regimen to achieve the desired clinical...
01:25Renal Drug Excretion: Tubular Reabsorption
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...