How to Measure Kidney Function
Kidney function should be measured using estimated glomerular filtration rate (eGFR) calculated from serum creatinine-based prediction equations (such as the MDRD equation), combined with assessment of proteinuria using spot urine albumin-to-creatinine or protein-to-creatinine ratios—never rely on serum creatinine alone. 1
Primary Assessment: eGFR Calculation
Do not use serum creatinine concentration as the sole measure of kidney function. 1 Serum creatinine is affected by multiple non-GFR factors including muscle mass, age, diet, creatinine secretion, and generation, making it insensitive to detecting early kidney disease—GFR must decline to approximately half of normal before serum creatinine rises above the upper limit of normal. 1
Recommended Prediction Equations
Use the MDRD (Modification of Diet in Renal Disease) study equation as the preferred method for estimating GFR in adults, which incorporates serum creatinine, age, sex, and race without requiring height or weight measurements. 1
The abbreviated MDRD equation is: GFR (mL/min/1.73 m²) = 186 × (serum creatinine)^-1.154 × (age)^-0.203 × (0.742 if female) × (1.212 if African American). 1
The Cockcroft-Gault equation is an acceptable alternative, particularly for drug dosing decisions, though it is less accurate than MDRD for GFR <90 mL/min/1.73 m². 1
Clinical laboratories should automatically report eGFR whenever serum creatinine is measured, with values >60 mL/min/1.73 m² reported as ">60 mL/min/1.73 m²" rather than a precise figure due to reduced accuracy at higher GFR levels. 1
Important Caveats for eGFR
The MDRD equation has not been validated in several populations where direct GFR measurement may be necessary: 1
- Extremes of age (<18 years or >70 years)
- Extremes of body size (severe malnutrition, obesity, or unusual muscle mass)
- Skeletal muscle diseases, paraplegia, or quadriplegia
- Vegetarian diet
- Rapidly changing kidney function
- Pregnancy
- When calculating doses of potentially toxic renally-excreted drugs
Assessment of Kidney Damage: Proteinuria Testing
Screening Approach
Use untimed (spot) urine samples for albumin-to-creatinine ratio (ACR) or protein-to-creatinine ratio (PCR) as the preferred method—this has replaced 24-hour urine collections for routine assessment. 1
First morning void specimens are preferred but random samples are acceptable. 1
For patients at increased risk (diabetes, hypertension, African American race, family history of kidney disease), begin screening with an albumin-specific dipstick followed by quantitative ACR if positive (≥1+). 1
Confirming Persistent Proteinuria
Two or more positive quantitative tests over 3 months are required to establish persistent proteinuria and diagnose chronic kidney disease. 1
Normal ACR is <30 mg/g; abnormal is ≥30 mg/g in diabetic patients. 2
Microalbuminuria: 30-299 mg/g; macroalbuminuria: ≥300 mg/g. 2
Nephrotic-range proteinuria: >3500 mg/g (equivalent to >3.5 g/24 hours). 2
When 24-Hour Urine Collection Is Still Needed
Avoid routine 24-hour urine collections—they are inconvenient, frequently inaccurate, and prediction equations provide more accurate GFR estimates than measured creatinine clearance. 1 However, 24-hour collections remain appropriate for: 1
- Extremes of body size or muscle mass
- Severe malnutrition or obesity
- Rapidly changing kidney function
- Calculating toxic drug dosages
- Confirming nephrotic syndrome when precise quantification affects management decisions 2
Screening Frequency for High-Risk Populations
Annual screening is recommended for patients with: 1
- Diabetes mellitus
- Hypertension
- African American race
- Age >60 years
- Family history of chronic kidney disease
- HIV infection (especially with CD4 <200 cells/µL or HIV RNA ≥4000 copies/mL)
- Hepatitis C coinfection
Laboratory Standardization Requirements
Clinical laboratories must calibrate serum creatinine assays to international standards—differences in calibration can cause errors in eGFR estimates as high as 20%, particularly problematic in patients with near-normal creatinine levels. 1
Laboratories should calibrate to the same standard used in developing the MDRD equation. 1
Staging Chronic Kidney Disease
Once eGFR and proteinuria are measured, stage kidney disease as follows: 1
- Stage 1: Kidney damage with GFR ≥90 mL/min/1.73 m²
- Stage 2: GFR 60-89 mL/min/1.73 m²
- Stage 3: GFR 30-59 mL/min/1.73 m²
- Stage 4: GFR 15-29 mL/min/1.73 m²
- Stage 5: GFR <15 mL/min/1.73 m² or dialysis
When to Use Direct GFR Measurement
For situations where prediction equations are unreliable, measure GFR directly using exogenous filtration markers (iohexol, iothalamate, or inulin clearance). 1, 3, 4 This provides the gold standard measurement but is reserved for special circumstances due to cost and complexity. 4, 5
Common Pitfalls to Avoid
Never interpret serum creatinine in isolation—elderly patients may have significantly reduced GFR despite "normal" creatinine due to decreased muscle mass. 1
Do not use measured creatinine clearance from 24-hour collections as a routine alternative to eGFR—it is less accurate than prediction equations. 1
Ensure proteinuria testing avoids false positives by: collecting specimens when patients are not febrile, avoiding vigorous exercise 24 hours prior, treating urinary tract infections before testing, and avoiding collection during menses. 2
Be aware that certain medications (cobicistat, dolutegravir, trimethoprim) can elevate serum creatinine by blocking tubular secretion without affecting actual kidney function. 1