Understanding Kidney Function Test Parameters
Kidney function tests primarily measure two critical parameters: glomerular filtration rate (GFR) and albuminuria/proteinuria, which together determine kidney health, disease severity, and predict outcomes including mortality and progression to kidney failure. 1
Core Parameters of Kidney Function Testing
Glomerular Filtration Rate (GFR)
GFR is the single best overall measure of kidney function and represents the flow rate of filtered fluid through the kidneys. 2 It cannot be measured directly in clinical practice, so estimation methods are used. 3, 2
GFR Categories (G1-G5)
The KDIGO guidelines classify GFR into six categories, regardless of whether kidney disease is present: 1
- G1 (Normal to increased): ≥90 ml/min per 1.73 m² 1
- G2 (Mildly reduced): 60-89 ml/min per 1.73 m² 1
- G3a (Moderately reduced): 45-59 ml/min per 1.73 m² 1
- G3b (Moderately reduced): 30-44 ml/min per 1.73 m² 1
- G4 (Severely reduced): 15-29 ml/min per 1.73 m² 1
- G5 (Kidney failure): <15 ml/min per 1.73 m² or treated by dialysis 1
Methods of GFR Assessment
Estimated GFR (eGFR) using prediction equations is the recommended method rather than measured creatinine clearance. 4, 3 The estimating equation (such as CKD-EPI or MDRD) and filtration markers (creatinine, cystatin C, or both) must be specified. 1
Both measured and estimated GFR should be indexed to body surface area of 1.73 m². 1
Albuminuria and Proteinuria
Albumin measurement is preferred over total protein because it can be standardized and is more accurate in the lower range, though both are widely used. 1
Albuminuria Categories (A1-A3)
The KDIGO guidelines define three categories: 1
- A1 (Normal to mildly increased): ACR <30 mg/g (<3 mg/mmol) or AER <30 mg/d 1
- A2 (Moderately increased): ACR 30-300 mg/g (3-30 mg/mmol) or AER 30-300 mg/d 1
- A3 (Severely increased): ACR >300 mg/g (>30 mg/mmol) or AER >300 mg/d 1
Measurement Methods
Albumin-to-creatinine ratio (ACR) or protein-to-creatinine ratio (PCR) from spot urine samples has replaced 24-hour collections as the preferred method. 4 This corrects for variations in urinary concentration due to hydration status. 4
For ACR and PCR measurements, specify whether from timed or spot collections, and note the time of day for spot collections. 1 First-morning spot collections are best for children and adolescents to avoid orthostatic proteinuria effects. 4
Additional Tubular Function Parameters
Beyond glomerular filtration, kidney function tests may assess: 1
- Tubular secretion (TS): Requires specification of rate, clearance, or fraction compared to filtered load 1
- Tubular reabsorption (TR): Requires specification of rate, clearance, or fraction compared to filtered load 1
- Fractional excretion (FE): Most commonly sodium (FENa) 1
- Fractional reabsorption (FR): Most commonly sodium (FRNa) 1
The CGA Classification System
Assessment of kidney disease severity and prognosis requires both GFR and albuminuria together—GFR alone is generally not acceptable. 1 The CGA classification combines: 1
- C: Cause of disease
- G: GFR category (G1-G5)
- A: Albuminuria category (A1-A3)
These categories are grouped into four risk levels (low, moderately high, high, very high) based on associations with all-cause mortality, cardiovascular mortality, kidney failure requiring replacement therapy, acute kidney injury, and CKD progression. 1
Critical Pitfalls to Avoid
Never assess kidney function using serum creatinine alone without considering GFR estimation or urine parameters. 4 Serum creatinine is affected by muscle mass, age, race/ethnicity, and does not directly reflect kidney function. 4
Incomplete 24-hour urine collections are a common source of error when measuring creatinine clearance, which is why spot urine ratios are now preferred. 4
Do not use terms like "microalbuminuria" or "macroalbuminuria"—these are outdated. Use the standardized A1-A3 categories instead. 1
Creatinine clearance and GFR are not synonymous and should not be used interchangeably. 1
Practical Collection Guidelines
For optimal urine specimen collection: 4
- Patients should refrain from vigorous exercise for 24 hours before collection
- Samples should be refrigerated and assayed the same or next day
- One freeze is acceptable if necessary, but avoid repeated freeze-thaw cycles
- In adults, random spot urine samples are generally acceptable for ACR/PCR measurements