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Disease Categories > Renal Disease

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Renal Function Markers - Kidney Disease

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 (α1-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 α1-MG concentrations signal renal involvement
- May be a promising candidate as a biomarker of acute renal failure
Beta-2-microglobulins (ß2-MG)
- Occur during the course of advanced diabetic nephropathy
- May be useful as a marker of progressing idiopathic membranous nephropathy
Alpha-2-macroglobulin (α2-MG)
- One of a family of protease inhibitors that includes alpha-1-antitrypsin.
- α2-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 α2-MG molecule tends to remain intravascular due to its large size
- α2-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 α2-MG in CSF
Urinary microalbumin
- Microalbuminemia 30-300 mg albumin/24 hours
- Good monitoring test for 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

Diabetes Mellitus Monitoring

Test Name and Number	Recommended Use	Limitations
Alpha-1-Microglobulin, Urine 0050043 Method: Nephelometry	May indicate renal involvement in patients with urinary tract infections or diabetes mellitus
Beta-2 Microglobulin, Urine 0080432 Method: Chemiluminescent Immunoassay	May indicate renal involvement in patients with diabetic nephropathy, cadmium toxicity, or progressing idiopathic membranous nephropathy
Alpha-2-Macroglobulin 0050005 Method: Nephelometry	May be used as a marker of membrane permeability in serum and fluids	Limited clinical use
Microalbumin, Urine 0050203 Method: Immunoturbidimetric	May be used as a screening test Useful in monitoring diabetic nephropathy in insulin-dependent diabetes mellitus
Cystatin C, Serum 0095229 Method: Nephelometry	May be assistive as a marker of renal disease; however, test lacks specificity

General References

Basi S, Fesler P, Mimran A, Lewis JB. Microalbuminuria in type 2 diabetes and hypertension: a marker, treatment target, or innocent bystander?. Diabetes Care. 2008;31 Suppl 2:S194-S201. (Link to PubMed)

Endre ZH, Westhuyzen J. Early detection of acute kidney injury: emerging new biomarkers. Nephrology (Carlton ). 2008;13(2):91-98. (Link to PubMed)

Hong CY, Chia KS. Markers of diabetic nephropathy. J Diabetes Complications. 1998;12(1):43-60. (Link to PubMed)

Honore PM, Joannes-Boyau O, Boer W, Janvier G, Gressens B. Acute kidney injury in the ICU: time has come for an early biomarker kit!. Acta Clin Belg Suppl. 2007;(2):318-321. (Link to PubMed)

Ritchie RF, Palomaki GE, Neveux LM, Navolotskaia O, Ledue TB, Craig WY. Reference distributions for alpha2-macroglobulin: a practical, simple and clinically relevant approach in a large cohort. J Clin Lab Anal. 2004;18(2):139-147. (Link to PubMed)

Schaefer U, Brucker B, Elbers A, Neugebauer E. The capacity of alpha2-macroglobulin to inhibit an exogenous protease is significantly increased in critically ill and septic patients. Shock. 2004;22(1):16-22. (Link to PubMed)

Tayade C, Esadeg S, Fang Y, Croy BA. Functions of alpha 2 macroglobulins in pregnancy. Mol Cell Endocrinol. 2005;245(1-2):60-66. (Link to PubMed)

Trof RJ, Di Maggio F, Leemreis J, Groeneveld AB. Biomarkers of acute renal injury and renal failure. Shock. 2006;26(3):245-253. (Link to PubMed)

Reviewed by

Delgado, Julio C., M.D., M.S. Medical Director, Protein Immunology at ARUP Laboratories; Associate Director, Histocompatibility and Immunogenetics Laboratory and Assistant Professor, Clinical Pathology, University of Utah

Hill, Harry R., M.D. Group Medical Director, Laboratory of Immunology, ARUP Laboratories, and Executive Director of the ARUP Institute for Clinical and Experimental Pathology; Professor and Division Head, Clinical Pathology, University of Utah

Roberts, William L. , M.D., Ph.D. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor, Pathology, University of Utah

Comprehensive Review: July 2008
Last Update: July 2008

Renal Function Markers - Kidney Disease

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