3 - Estimating Renal Filtration

What are the two types markers of renal filtration?

Exogenous

Endogenous

Exogenous markers?

Filtered with little or no tubular handling → like secretion or reabsorption

Ex → Inulin, iothalamate, and iohexol

Endogenous markers?

Serum creatinine → muscle creatine metabolism

Cystatin C → nucleated cells

Not typically used in clinical practice

Measured GFR (mGFR)?

Uses exogenous filtration markers

Marker clearance directly measures GFR

Reference standard

Measured CrCl?

Timed urine collection

Affected by collection error and tubular creatinine secretion

Estimated GFR (eGFR) and CrCl (eCrCl) ?

Uses endogenous biomarkers in estimating equations

Used in clinical practice

Why does accuracy matter when measuring renal filtration?

Overestimate kidney function → excessive drug exposure/toxicity

Underestimate kidney function → subtherapeutic dosing/treatment failure

Why was the Cockcroft-Gault equation developed?

Timed urine creatinine clearance was inconvenient and prone to urine collection errors

Cockcroft-Gault estimates → creatinine clearance using patient characteristics and serum creatinine

What variables does Cockcroft-Gault use?

Variables → Serum creatinine (SCr), age, weight, and sex

Output → Estimated creatinine clearance (eCrCl) → in mL/min

Why is Cockcroft-Gault still commonly used?

Many historical drug studies and dosing recommendations use Cockcroft-Gault estimated creatinine clearance (eCrCl)

The Cockcroft-Gault equation?

eCrCl = [(140 – age) × weight in kg × (0.85 if female)] / (72 × serum creatinine)

CKD-EPI equations?

Contemporary equations used to estimate GFR in adults

Estimate GFR → not creatinine clearance

Usually reported as → mL/min/1.73 m²

Increasingly used for medication-related decisions

What are the three major CKD-EPI equations?

2021 eGFRcr → Creatinine

2012 eGFRcys → Cystatin C

2021 eGFRcr-cys → Both creatinine and cystatin C

2021 eGFRcr ?

Creatinine

2012 eGFRcys ?

Cystatin C

2021 eGFRcr-cys ?

Uses both creatinine and cystatin C

When can low creatinine production make renal estimates misleading?

Low muscle mass or major muscle loss

Advanced liver disease or other changes in creatinine production

Both decrease creatinine production → so any creatinine based estimates may overestimate filtration

Which medications inhibit creatinine secretion?

Ex → Trimethoprim, cimetidine, cobicistat

Inhibit creatinine secretion → increases SCr without a true decreased GFR → estimates may underestimate filtration

When are creatinine-based renal estimates less reliable?

When creatinine production or secretion is abnormal

Calculated renal filtration estimates may be less reliable

Advantages of Cystatin C?

Less affected by muscle mass than creatinine

Can add information when creatinine-based estimates may be inaccurate

What non-GFR determinants can increase cystatin C?

Systemic glucocorticoids

Hyperthyroidism

Inflammation

Higher adiposity/obesity

What non-GFR determinants can decrease cystatin C?

Hypothyroidism

Why are creatinine- and cystatin C–based estimates unreliable during AKI?

Equations assume kidney function is relatively stable

SCr and cystatin C lag behind changes in true GFR

Estimates are less reliable during AKI development and recovery

What should you do when kidney-function estimates disagree?

Identify whether each estimate uses creatinine, cystatin C, or both

Check patient factors that may make either marker misleading

Determine whether eGFR is indexed or absolute

Key idea → Look for an explanation; don't assume one equation is always correct

Indexed eGFR?

Normalized to a standard BSA of 1.73 m²

Reported as mL/min/1.73 m²

Absolute eGFR?

Adjusted to the patient's actual BSA

Reported as mL/min

Difference from indexed eGFR increases as patient BSA differs from 1.73 m²

What is the difference between indexed and absolute GFR?

Indexed → standard body size

Absolute → actual body size

What is the difference between absolute eGFR and eCrCl?

Both are reported in mL/min

Absolute eGFR → Estimates GFR

eCrCl → Estimates creatinine clearance