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 – 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

Monitoring

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
  • GFR/BUN/creatinine (serum) – provide estimates of renal function
    • BUN/creatinine – biomarkers of protein metabolism
    • Estimated glomerular filtration rate (EGFR) is best measure since it accounts for age, BMI, and sex
  • Microalbumin (urine)
    • Very little normally excreted by the kidney
    • Microalbuminuria – 30-300 mg albumin/24 hours or 30 mg/g creatinine
    • Sensitive marker of glomerular disease in diabetics
      • Limited ability to predict disease progression
  • 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
  • Beta-2-microglobulins (urine)
    • Occur during the course of advanced diabetic nephropathy
    • May be useful as a marker of progressing idiopathic membranous nephropathy
  • 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
  • Cystatin-C (serum)
• Urinary micro proteins can help detect renal abnormalities and may help differentiate various forms of renal and biological pathology
  • Noninvasive markers
• Biomarkers of acute dysfunction
  • BUN/creatinine (serum)
  • EGFR
  • Fractional excretion of sodium (urine) (calculated)
    • Refer to FENa calculator
  • Cystatin C (serum)
    • Protease inhibitor that is freely filtered by glomeruli and reabsorbed by tubular cells – does not reenter bloodstream
      • Affected by steroid use and thyroid dysfunction
    • More specific than creatinine for assessing glomerular function
  • Novel
    • Neutrophil gelatinase-associated lipocalin (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 that may have a role in ischemic acute tubular necrosis
    • KIM-1 – transmembrane protein that is overexpressed in response to ischemic 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

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
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