GFR Estimation

what is GFR?

-equal to the sum of the filtration rates in all of the functioning nephrons

GFR assessment is essential for

-patient care, research, and public health

what is a normal GFR?

-for healthy young adults: 90-120 mL/min/1.73m²

-expected age-related decline in GFR: ~1 mL/min/1.73m² per year beginning in the third decade of life

GFR is normalized to

-body surface area (BSA)

how to assess GFR

-direct measurement of GFR: EXOGENOUS filtration markers- most accurate, costly, cumbersome

-estimation of GFR: relies on ENDOGENOUS filtration markers (creatinine, cystatin C)- 24 hr urine for creatinine clearance, estimating equations

how to measure GFR

1) collect all urine entering Bowman’s space in a given time (impossible)

2) pick a substance that is freely filtered at the glomerulus BUT not reabsorbed, metabolized, or secreted (“ideal filtration marker”), measure its clearance form the blood or urine

measuring GFR

creatinine

-an endogenous, very good (non-ideal) filtration marker

-creatinine = waste product formed by normal breakdown of muscle

-released into circulation at relatively constant state

-freely filtered at the glomerulus

-not reabsorbed or metabolized by the kidney

-*there IS secretion by the proximal tubule

24hr urinary clearance of creatinine as estimate for GFR

relationship of GFR and plasma [Cr]

relationship of plasma [Cr] to GFR

GFR estimating equations

-for each patient in a large cohort: collect an abundance of clinical and demographic data and measure their GFRs

-apply stepwise multiple regression to find the fewest number of variables that most effectively predict the measured GFR

the MDRD eGFR equation

-1628 patients with measured GFR (iothalamate)

-mean age 50, 60% men, 80% white, mean GFR 40 ml/min/1.73²

-stepwise multiple regression to predict GFR

-clinical variables: weight, height, gender, race, age, diabetes, MAP, serum- creatinine/urea nitrogen/albumin/phos/calcium, urine- creatinine/urea nitrogen/protein/phos

the 4-variable MDRD eGFR equation

the 2009 CKD-EPI equation

problems with including race in GFR reporting

-race is a social construct, not a biologic determinant:

-the genetic variation found in the human species is not grouped into discrete, genetically distinct units scientists can identify as races

-race is an unreliable proxy for social determinants of health

-may normalize or perpetuate harmful beliefs about race and biology

-dichotomization of race is inappropriate

unifying approach for GFR estimation- recommendations of the NKF-ASN task force on reassessing the inclusion of race in diagnosing kidney disease

important caveats about Cr-based GFR estimating equations

-stable serum Cr is required (steady state!)

-eGFR: emphasis on the “estimate”

-equations will be less accurate in people with extremes of: muscle mass, animal protein intake

-equations will be less accurate in situations where tubular secretion of Cr is affected

eGFR- emphasis on “estimate”

limitations of SCr-based estimation equations- examples

-extremes of body composition: bodybuilder, lower extremity amputee

-dietary extremes of animal protein intake: high animal protein intake/creatinine supplements

-variability in tubular secretion: trimethoprim/sulfamethoxazole, cimetidine (inhibit tubular secretion of Cr)

-AKI with rapidly rising serum Cr

sometimes ____ is needed to better characterize GFR

-confirmatory testing

-when non-GFR determinants of PCr are prominent

-when the estimated GFR lies close to an inflection point that could change management (kidney donation, chemotherapy, clinical trial inclusion)

what tests can you order for confirmatory testing?

-cystatin C

-24h urine collection for creatinine clearance

-measured GFR with injectable filtration marker (ie iothalamate)

cystatin C

-endogenous filtration marker

-protein produced in all nucleated cells

-freely filtered at glomerulus

-catabolized and reabsorbed by tubular epithelial cells

-less affected by muscle mass and diet than serum Cr

-inflammation, smoking, thyroid abnormalities, and obesity may affect

eGFR equations that use cystatin C

-2012: CKD-EPI cystatin C (no race)

-2021: CKD-EPI creatinine-cystatin C (no race)

-equations that use BOTH Cr and cystatin C tend to be more accurate than either one alone

Cockcroft-Gault equation