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07.03.2012  
Markers for renal function and toxicity
 
ELISAs, Antibodies, Proteins  
Highly tissue-specific, non-invasive Biomarkers to detect early signs of renal damage and to efficiently prioritize drug compounds.
 
  • Cell specific biomarkers can identify toxic compounds earlier and at lower doses
  • They can provide information on sites of injury and optimal dosing
  • Combining biomarkers increases the value of testing
 
 

Alpha-1-Microglobulin
An increase in the urinary concentration of alpha-1-microglobulin indicates proximal tubule injury and/or impaired proximal tubular function.
 
  Glutathione S-Transferase Mu1 (Yb1)
GST's play an important role in defense against electrophilic chemicals generated by cellular oxidative reactions catalyzed by e.g. cytochrome P450.
  Alpha-2-Macroglobulin
A2M is a major plasma protein with various functions. Elevated levels are seen in cirrhosis, nephrotic syndrome, severe burns and diabetes.
 
  Interleukin-6
Interleukin 6 is released by leukocytes in response to a number of inciting stimuli. Among others, IL-6 is elevated in alcoholic cirrhosis and chronic renal failure.
  Angiotensin II
The angiotensins act as vasoconstricting agents. ACE converts angiotensin to its activated form (called angiotensin II) enabling it to function.
 
  KIM-1: Kidney Injury Molecule-1
KIM-1 serves as a biomarker for renal proximal tubule injury facilitating the early diagnosis of the disease and serving as a diagnostic discriminator.
  Angiotensin-Converting Enzyme
ACE is an ideal target in the treatment of high blood pressure, heart failure, diabetic nephropathy and type 2 diabetes mellitus.
 
  NGAL: Neutrophil Gelatinase-Associated Lipocalin
NGAL forms a disulfide bond-linked heterodimer with MMP-9.
  Beta-2-Microglobulin
High Beta-2-Microglobulin plasma levels occur in renal failure, inflammation, and neoplasms, especially those associated with B-lymphocytes.
 
  Osteopontin
OPN is synthesized within the kidney and is present in human urine at levels that can effectively inhibit Calcium oxalate crystallization.
  Calbindin
In the kidney, Calbindin (28kD) is involved in Ca2+ transport of distal tubular cells and cortical collecting tubules.
 
  Proguanylin
Proguanylin regulates kidney function and is a marker for renal insufficiency since plasma levels increase in chronic renal failure.
  Clusterin
Clusterin is a marker for the severity of renal tubular damage. Urinary clusterin may help to differentiate between tubular and glomerular proteinuria.
 
  Prorenin
In renal juxtaglomerular cells, sequential cleavage of the N-terminal 20 and 46 amino acids of preprorenin produces prorenin and active renin, respectively.
  Cystatin-C
Cystatin C is removed from the bloodstream by glomerular filtration . If kidney function and glomerular filtration rate decline, the blood levels of cystatin C rise.
 
  Prostaglandin D Synthase
The serum and urinary levels of Lipocalin–type prostaglandin D synthase are a marker for various renal diseases and renal transplant patients.
  Complement C3
Quantitation of C3 is used in lupus erythematosus, chronic active hepatitis, chronic infections, and glomerulonephritis.
 
  Tamm-Horsfall Urinary Glycoprotein
It is the most abundant protein present in the urine of healthy subjects and has been shown to decrease in individuals with kidney stones.
  Connective Tissue Growth Factor
Upregulation of CTGF mRNA and protein levels have been observed in diabetic nephropathy and in glomerular and tubulo-interstitial lesions of the kidney.
 
  TIMP-1
Tissue inhibitor of metalloproteinases 1 is a major regulator of extracellular matrix synthesis and degradation.
  Erythropoietin
Erythropoietin (EPO), produced primarily by the kidney, is the factor regulating red blood cell (RBC) production by changes in oxygen availability.
 
  Trefoil Factor 3
Urinary TFF3 protein levels are markedly reduced in renal tubular injury. Urinary TFF3 enables sensitive and robust diagnosis of acute renal tubular injury.

Glutathione S-Transferase alpha
Glutathione S-Transferase alpha (GSTalpha) plays a key role in the detoxification carcinogens, therapeutic drugs, and products of oxidative stress.
 
  Vascular Endothelial Growth Factor
VEGF is important in the pathophysiology of neuronal and other tumors, probably functioning as a potent promoter of angiogenesis.
     
 
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