Related Experiment Videos

Quantification of cleaved beta2-microglobulin in serum from patients undergoing chronic hemodialysis

Dorthe B Corlin1, Jette W Sen, Søren Ladefoged

  • 1Department of Autoimmunology, Statens Serum Institut, Copenhagen, Denmark.

Clinical Chemistry
|May 14, 2005
PubMed
Abstract

Insights

Dialysis patients develop a specific cleaved beta(2)-microglobulin (beta(2)M) variant in their circulation. This variant, linked to amyloid deposits, is not cleared by dialysis and is higher with less biocompatible membranes.

Area of Science:

  • Biochemistry
  • Nephrology
  • Proteomics

Background:

  • Patients undergoing chronic hemodialysis are susceptible to beta(2)-microglobulin (beta(2)M) amyloid deposits in osteoarticular tissues.
  • Beta(2)M amyloid fibrils contain structurally intact and modified forms of beta(2)M, but the circulating beta(2)M population's state remains uncharacterized.
  • High-resolution methods are needed to analyze the circulating beta(2)M population.

Purpose of the Study:

  • To investigate the presence and structure of modified beta(2)M in the circulation of hemodialysis patients.
  • To develop and apply a novel immunoassay for quantifying a specific cleaved beta(2)M variant.

Main Methods:

  • Immunoaffinity-liquid chromatography-mass spectrometry (LC-MS) was used to analyze serum samples for modified beta(2)M.
  • A novel immunoassay employing monoclonal antibodies was developed to quantify a cleaved beta(2)M variant in biological fluids.
  • The immunoassay was applied to serum samples from dialysis patients and controls.

Main Results:

  • A specific alteration, lysine-58-cleaved and truncated beta(2)M (DeltaK58-beta(2)M), was identified in 20%-40% of dialysis patient sera, but not in controls or Alzheimer's disease patients.
  • Dialysis significantly reduced total beta(2)M but did not alter DeltaK58-beta(2)M concentrations.
  • Patients dialyzed with less biocompatible membranes (cuprophane) showed significantly higher serum concentrations of cleaved beta(2)M compared to those using polysulfone membranes or controls.

Conclusions:

  • This study provides the first structural characterization of a specific beta(2)M variant in the sera of dialysis patients.
  • The identified DeltaK58-beta(2)M variant is conformationally unstable in vitro.
  • The DeltaK58-beta(2)M variant may play a role in in vivo amyloidogenesis in hemodialysis patients.

Related Concept Videos

Drug Dosing in Renal Diseases: Measurement of Serum Creatinine Concentration and Clearance01:25

Drug Dosing in Renal Diseases: Measurement of Serum Creatinine Concentration and Clearance

In healthy individuals, serum creatinine levels remain stable due to a balance between its constant production—primarily from muscle metabolism—and renal excretion. Creatinine is freely filtered by the glomeruli, making it a valuable marker for estimating renal function. When the glomerular filtration rate (GFR) decreases, the kidneys can only eliminate less creatinine, causing serum levels to rise.Serum creatinine concentration is widely used to estimate creatinine clearance (Clcr), a...
Drug Dosing in Renal Diseases: Measurement of Glomerular Filtration Rate01:25

Drug Dosing in Renal Diseases: Measurement of Glomerular Filtration Rate

The glomerular filtration rate (GFR) is a critical indicator of kidney health, reflecting how well the kidneys filter blood. Changes in GFR can signal potential kidney impairment, necessitating accurate measurement methods to monitor kidney function effectively.Various molecules can serve as markers for GFR measurement, with the ideal marker meeting several specific criteria. It must freely filter at the glomerulus, avoid reabsorption or secretion by the renal tubules, remain unmetabolized, not...
Drug Dosing in Renal Diseases: Estimation of Glomerular Filtration Rate Based on Serum Creatinine Concentration01:28

Drug Dosing in Renal Diseases: Estimation of Glomerular Filtration Rate Based on Serum Creatinine Concentration

Glomerular filtration rate (GFR) can be estimated from serum creatinine using the modification of diet in renal disease (MDRD) formula or the chronic kidney disease–epidemiology collaboration (CKD–EPI) equation. Both methods are widely used in clinical practice to assess kidney function and guide treatment decisions.The MDRD equation does not require weight or height measurements and is normalized to the body surface area of 1.73 m², considered the average adult surface area. This equation is...
Factors Affecting Renal Clearance: Renal Impairment01:17

Factors Affecting Renal Clearance: Renal Impairment

Renal dysfunction significantly impairs the renal clearance of drugs, leading to potential complications in drug therapy. Renal failure, which can be caused by various factors, poses a significant challenge in the elimination of drugs from the body.
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...
Serum Studies: Renal Function Tests01:24

Serum Studies: Renal Function Tests

Renal function tests are crucial for assessing kidney health, monitoring disease progression, and evaluating the kidneys' efficiency in waste elimination, fluid balance, and electrolyte regulation. These tests offer critical insights into kidney function, even though routine measurements may appear normal until there is a significant decline in the glomerular filtration rate or GFR. Typically, signs of kidney impairment only become evident when the GFR falls to about 50% of its normal level.
Renal Clearance01:23

Renal Clearance

The glomerular filtration rate (GFR) is a critical marker of kidney function, reflecting the efficiency of filtration by the glomeruli. Renal clearance of specific substances, such as inulin or creatinine, is commonly used to measure GFR.
Renal clearance refers to the volume of plasma cleared of a specific substance, such as creatinine, per unit of time. To measure clearance, urine samples are collected over a 24-hour period during each bladder voiding, followed by a single blood sample at the...