Initial GFR estimation in a living kidney donor candidate

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A 32-year-old woman is evaluated for potential kidney donation to her sister. She does not have any chronic medical conditions; her only medication is an over-the-counter multivitamin. Her physical examination is normal. Her BP is 120/78 mm Hg and heart rate 72/min, and she weighs 58 kg. Laboratory data include the following: sodium 141 mEq/L (reference 136–145); potassium 4.7 mEq/L (3.5–5.0); chloride 106 mEq/L (98–106); total CO₂ 23 mEq/L (23–28); BUN 10 mg/dL (8–20); creatinine 0.7 mg/dL (0.5–1.1). Which of the following is the BEST initial method for estimating her GFR?

  1. A.Iothalamate I-125 GFR
  2. B.Cockcroft-Gault
  3. C.Abbreviated Modification of Diet in Renal Disease (MDRD)
  4. D.Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI)Correct

Explanation

The best initial method to estimate this patient's GFR is the CKD-EPI formula. The MDRD equation was developed in 1999 in patients with non-diabetic CKD and proteinuria who were part of a randomized study on the effects of dietary protein restriction and BP control on CKD progression. The original equation had six variables (age, sex, race, creatinine, albumin, and BUN) but was reduced to four variables in 2000. In 2006, the equation was revised for use with standardized creatinine measurements. The 2006 MDRD equation was found to be more accurate than the Cockcroft-Gault equation, with more patients' eGFR within 30% of measured GFR by iothalamate clearance (83% versus 69%). The CKD-EPI equation was derived in a more diverse population, including patients without CKD. Although the overall accuracy of CKD-EPI versus MDRD is similar, it performs better in people with higher GFR, particularly GFR ≥90 mL/min/1.73 m². Conversely, in patients with GFR 15–29 mL/min/1.73 m², MDRD may predict actual GFR better than CKD-EPI. In a meta-analysis of 12 studies including nearly 13,000 patients, the overall bias was smaller for the CKD-EPI creatinine equation than the MDRD equation in patients with a higher eGFR but larger at a lower eGFR. Both equations previously used race as a factor in the estimation equation, but a joint statement by the National Kidney Foundation and the American Society of Nephrology in 2022 recommended against the use of race in estimation equations. Many labs no longer report a race-based eGFR and race is no longer a required variable for web-based calculators. Lastly, the inclusion of cystatin C with creatinine to estimate eGFR has been demonstrated to increase accuracy. Although measurement of GFR by methods such as iothalamate I-125 is the gold standard, this is an expensive, cumbersome technique not readily available at most centers. Therefore, it is not commonly used as the initial method for assessment of GFR. Rather, it is more often used when results of estimation equations are borderline or the prospective donor is of extreme age or size, or has other characteristics that might make the prediction equation less reliable.

Why each option

A.
Measured iothalamate clearance is the gold standard but is costly and cumbersome, reserved for confirmation when estimates are borderline or unreliable.
B.
Cockcroft-Gault estimates creatinine clearance rather than GFR and was less accurate than MDRD against iothalamate (69% versus 83% within 30%).
C.
MDRD was derived in patients with CKD and underestimates GFR above 60 mL/min/1.73 m², making it less accurate for healthy donor candidates.
D.
Correct. CKD-EPI was derived in a broader population including people without CKD and is more accurate at higher GFR, as in donor candidates.

Reference: KDIGO 2017 Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors; Inker LA, N Engl J Med 2021 (race-free CKD-EPI creatinine and cystatin C equations)

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