Estimation of Kidney Function

Richard C. Walls07-16-2013

Importance of Kidney Function

• Kidney responsible (in part/whole) for excretion of many medications from the body

• t1/2 of renally cleared medications prolonged with decreasing kidney function– Vancomycin: 5-11 hours w/normal function– Vancomycin: 8-10 days in ESRD

• Potential for medication error– Drug accumulation & toxicity– Overly rapid clearance & subtherapeutic doses

Importance of Kidney Function

• Medications often require dose adjustment when eGFR < 60

• ≈40% of adults >70 years old have eGFR < 60

• This population uses 34% of all prescription drugs

Estimating Kidney Function

• Creatinine• Freely filtered• Minimally reabsorbed• Some secretion

– Creatine Clearance estimates glomerular filtration rate

• 24-hour urine collection gold standard

– Time consuming– Logistically difficult

Estimating Kidney Function

• Equations estimating CrCl based on SCr alone desirable for convenience

• Cockcroft-Gault Equation

– FDA reports 1998-2007: CG equation specifically mentioned as the basis for 25% of renal adjustments for drugs reviewed

– In elderly patients w/SCr < 1.0, common practice is to round SCr to 1.0 to compensate for reduced Cr production

Estimating Kidney Function• Modification of Diet in Renal Disease (MDRD)

– Designed and tested to more accurately estimate GFR than CG– eGFR ≈ 186a * Scr

-1.154 * Age-0.204(*1.212 if black)(*0.742 if female)

• Chronic Kidney Disease Epidemiology Study (CKD-EPI)– eGFR ≈ 141 * min(,1)α * max()-1.209 * 0.993Age (*1.018 if female)(*1.159 if black)– κ = 0.7 for females; 0.9 for males– α = -0.329 for females; -0.411 for males– More representative of actual GFR than MDRD in GFR > 60

• Recently National Kidney Disease Education Program has recommended eGFR equations be used interchangeably with CG for CrCl estimation

Dowling Study

• Objective: To evaluate how accurately different estimates of renal function reflect actual creatinine clearance.

• Retrospective review of data collected as a part of the Baltimore Longitudinal Study of Aging

Dowling Study

• CrCl estimated/measured via– Measured 24-hour creatinine clearance (mClCr)– Cockcroft-Gault (CG)– Cockcroft-Gault SCr < 1.0 rounded to 1.0 (r-CG)– Modification of Diet in Renal Disease (MDRD)– Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

• Estimates compared for– Bias from mClCr

– Variance ratio to mClCr

– Dosage discordances from CG labeling

Dowling Study - Population

• Patients: 269 total– 140 women– 129 men

• Age, yrs: 81 ± 6• SCr: 1.1 ± 0.4– 103 subjects < 1.0– Avg 8.0 ± 0.1

• Race: 85% white• BMI– Only 28 patients > 30– No patients > 40

• Overt signs of renal failure/dialysis excluded

Dowling Study - ResultsMeasurement Returned Value Bias from mClCr Variance Ratio to mClCr

mClCr 52.8 ± 12.6 n/a n/a

CG 49.6 ± 14.3 -3.2 ± 14.1 1.3

MDRD 65.5 ± 18.5 12.8 ± 15.1 2.2

CKD-EPI 59.9 ± 16.1 7.1 ± 15.1 1.63

Dowling Study - Results

• Patients w/SCr < 1.0Measurement Returned Value

mClCr 56.2 ± 11.5

CG 55.8 ± 15.0

r-CG 44.1 ± 10.2

Dowling Study - Results