Clinical Background
Renal dysfunction occurs in a variety of diseases and scenarios, including the ICU (acute renal failure) and chronic disease states such as diabetes mellitus. Early detection of dysfunction may be important in prevention of further dysfunction.
Pathophysiology
- Tubular proteinuria results when glomerular function is normal but the proximal tubules have diminished absorbing capacity
- Detection of urinary microproteins can help detect renal abnormalities and may help differentiate various forms of renal and biological pathology
- Non-invasive markers
Several biomarkers detect tubular dysfunction - they are elevated in urine samples during disease
- Alpha-1-microglobulins (alpha1-MG)
- Occur during the course of nephritis or advanced diabetic nephropathy
- Occur after heavy metal exposure or treatment with nephrotoxic medications
- Occur in urinary tract infections, where elevated alpha1-MG concentrations signal renal involvement
- May be a promising candidate as a biomarker of acute renal failure
- Beta-2-microglobulins (Beta 2-MG)
- Occur during the course of advanced diabetic nephropathy
- May be useful as a marker of progressing idiopathic membranous nephropathy
- Alpha-2-macroglobulin (Alpha 2-MG)
- One of a family of protease inhibitors that includes Alpha-1-antitrypsin.
- Alpha 2-MG is a protease inhibitor capable of irreversibly binding and therefore inhibiting a wide variety of proteases, including plasmin, pepsin, trypsin, chymotrypsin and cathepsin-D
- The Alpha 2-MG molecule tends to remain intravascular due to its large size
- Alpha 2-MG is synthesized in the liver
- May be useful in detecting renal disease in diabetes mellitus
- May also be increased in
- Estrogen stimulation - pregnancy, contraceptives
- Nephrotic syndrome - retained by damaged glomerular membranes because of its large size
- Diabetes mellitus with renal disease
- Hepatorenal syndrome
- Interruption of blood/brain barrier; presence of Alpha 2-MG in CSF
- Urinary microalbumin
- Microalbuminuria 30-300 mg albumin/24 hours or 30 mg/g creatinine
- Sensitive marker of glomerular disease in diabetics
- NGAL
- Protein that is covalently bound to gelatinase from human neutrophils
- Expressed in kidney after ischemia and drug-induced toxicity; also increased in systemic and urinary tract infections
- May be useful as a marker for acute renal injury in certain situations
- Serum cystatin C
- Protease inhibitor that is freely filtered by the glomerulus and reabsorbed by tubular cells
- Marker is more specific than creatinine for assessing glomerular function
See Also
