Renal Function Markers - Kidney Disease

Diagnosis

Indications for Testing

  • Any risk factors for chronic kidney disease
  • Assess diabetics for early renal function abnormalities

Laboratory Testing

  • Serum creatinine, BUN, and estimated glomerular filtration rate – use for initial diagnosis of acute or chronic disease
  • Urine microalbumin – initial test in diabetes to assess renal function
  • Other biomarkers – usefulness in assessing renal function has not been determined; studies are ongoing

Differential Diagnosis

  • See Risk Factors section in Clinical Background

Screening

  • Estimated glomerular filtration rate (using creatinine) and microalbumin testing in individuals with hypertension, diabetes mellitus, cardiovascular disease, and family history of cardiovascular disease (CVD)

Monitoring

  • Urinary microalbumin – use to monitor renal function in diabetes

Clinical Background

Renal dysfunction occurs in a variety of diseases and scenarios. Acute kidney injury results from trauma to the kidney during an accident or a medical procedure, including ICU acute renal failure. Chronic kidney disease results from another disease, such as diabetes mellitus, or from an inherited syndrome. Early detection of dysfunction may be important in prevention of further dysfunction.

Epidemiology

  • Prevalence
    • Acute kidney injury – 5-20% of patients in ICU
    • Chronic kidney disease – >10 million in U.S.

Risk Factors

  • Acute kidney injury
    • Trauma
    • Sepsis
    • Blood loss
    • Hypotension
    • Contrast induced
  • Chronic kidney disease
    • Hypertension
    • Diabetes mellitus
    • Atherosclerotic vascular disease
    • Nephrotoxic drugs
      • Nonsteroidal anti-inflammatory drugs
      • Radiocontrast
    • Familial disease
    • Polycystic kidney disease

Pathophysiology

  • Tubular proteinuria results when glomerular function is normal but the proximal tubules have diminished absorbing capacity
  • Biomarkers of chronic tubular dysfunction – acute and chronic
    • GFR/BUN/creatinine (serum) – provide estimates of renal function
      • BUN/creatinine – biomarkers of protein metabolism
      • Estimated glomerular filtration rate (EGFR) is best measure – accounts for age, BMI, and sex
      • Useful in both acute and chronic renal failure
    • Microalbumin (urine)
      • Normally very little excreted by the kidney
      • Microalbuminuria – 30-300 mg albumin/24 hours or 30 mg/g creatinine
      • Sensitive marker of glomerular disease in patients with diabetes, chronic kidney disease
      • Limited ability to predict disease progression
    • Cystatin-C (serum and urine)
      • Cysteine protease inhibitor is a marker of GFR
      • Not influenced by changes in muscle mass
      • Urine test measures proximal tubular injury
      • Affected by steroid use and thyroid dysfunction
    • Beta-2-microglobulins (urine)
      • Filtered freely in the glomerulus and nearly completely reabsorbed – normally <1% appears in urine 
      • Occur during the course of advanced diabetic nephropathy
      • May be useful as a marker of progressing idiopathic membranous nephropathy
    • Alpha-1-microglobulins (α1-MG) (urine)
      • 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
    • Alpha-2-macroglobulin (α2-MG) (urine)
      • 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
      • α2-MG molecule tends to remain intravascular due to its large size
      • α2-MG is synthesized in the liver
      • May also be increased in the following
        • Estrogen stimulation due to 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 micro proteins can help detect renal abnormalities and may help differentiate various forms of renal and biological pathology
    • Noninvasive markers
    • Novel biomarkers
      • Neutrophil gelatinase-associated lipocalin (NGAL) (urine)
        • 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
      • IL18 (urine)
        • Proinflammatory cytokine
        • May have a role in ischemic acute tubular necrosis
      • KIM-1
        • Transmembrane protein expressed in low levels by normal kidney 
        • Overexpressed in response to ischemic or nephrotoxic injury

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
Urea Nitrogen, Serum or Plasma 0020023
Method: Quantitative Spectrophotometry
Initial diagnostic test for renal disease    
Creatinine, Serum or Plasma 0020025
Method: Quantitative Enzymatic

Initial diagnostic test for renal disease

   
Microalbumin, Urine 0050203
Method: Quantitative Immunoturbidimetry
Monitor diabetic nephropathy in insulin-dependent diabetes mellitus    
Glomerular Filtration Rate, Estimated 0020725
Method: Quantitative Enzymatic

Estimate renal function and use as monitoring tool

(Test reports serum creatinine reference intervals)

   
Cystatin C, Serum 0095229
Method: Quantitative Nephelometry

May assist as a marker of renal disease

Lacks specificity

 
Beta-2-Microglobulin, Urine 0080432
Method: Quantitative Chemiluminescent Immunoassay

May indicate renal involvement in patients with diabetic nephropathy, cadmium toxicity, or progressing idiopathic membranous nephropathy

   
Alpha-1-Microglobulin, Urine 0050043
Method: Quantitative Nephelometry

May indicate renal involvement in patients with urinary tract infections or diabetes mellitus

   
Alpha-2-Macroglobulin 0050005
Method: Quantitative Nephelometry

May be used as a marker of membrane permeability in urine

Limited clinical use

 
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Renal Function Panel 0020144
Method: Quantitative Chemiluminescent Immunoassay/Quantitative Enzyme-Linked Immunosorbent Assay

Panel includes albumin, calcium, carbon dioxide, creatinine, chloride, glucose, phosphorous, potassium, sodium, and urea nitrogen

Protein, Total, Urine 0020479
Method: Quantitative Spectrophotometry
Myoglobin, Urine 0020223
Method: Quantitative Electrochemiluminescent Immunoassay