What’s the Best Approach for Evaluating GFR in Living Kidney Donors?

Why is it important to precisely evaluate glomerular filtration rate (GFR) in kidney donor candidates?

A: Kidney transplants from living donors are widely recognized as the optimal approach for treating end-stage renal disease (ESRD). They lead to improved graft and patient survival rates. However, the procedure increases the donor’s risk of kidney and cardiovascular diseases. Precisely assessing GFR in living kidney-donor candidates helps identify individuals with preexisting kidney dysfunction, ensuring they are excluded from the donor pool. It also guarantees the selection of candidates with minimal risk of developing ESRD, thereby optimizing the overall success of kidney transplantation for both donors and recipients.

What clinical methodologies are available for assessing GFR? What are their pros and cons?

GFR can be either measured—for example, by assessing creatinine, iothalamate, or iohexol clearance—or estimated based on the serum or plasma concentration of creatinine and/or cystatin C.

Estimated GFR (eGFR) is a widely used screening approach that calculates GFR based on serum creatinine and/or cystatin C concentrations, as well as the patient’s age and sex. The recommended eGFR equations are the 2021 CKD-EPI creatinine, 2012 CKD-EPI cystatin C, and the 2021 CKD-EPI combined creatinine-cystatin equations.

A key advantage of using creatinine-based eGFR is the widespread availability of creatinine measurements, making this method simple, cost-effective, and standardizable. However, creatinine levels can be affected by factors other than GFR, such as muscle mass and diet—which may lead to inaccuracies, particularly in individuals with normal or mildly reduced GFR. Significant deviations from true GFR may be observed in individual patients.

Cystatin C, an endogenous filtration marker like creatinine, is not influenced by muscle mass or diet, potentially making it more reliable. Combining measurements of creatinine and cystatin C in eGFR equations has been shown to improve accuracy compared to eGFR based on either marker alone. However, the superiority of cystatin C-based eGFR over creatinine-based eGFR has not been unequivocally established.

With measured GFR (mGFR), endogenous or exogenous filtration markers such as creatinine, iothalamate, or iohexol are used to directly measure GFR. Iothalamate and iohexol are administered to patients intravenously, and plasma and/or urine clearance of the markers is measured to determine GFR. Creatinine clearance (CrCl) is calculated by measuring creatinine in a 24-hour urine sample and comparing that to the patient’s serum creatinine concentration.

While CrCl is more reliable than eGFR using serum creatinine alone, it can overestimate GFR by 10−20% due to distal tubular secretion of creatinine. Inaccurate urine collections can also lead to errors, further compromising the reliability of CrCl.

Measured GFR using exogenous markers is considered the gold standard for assessing GFR due to its high accuracy and sensitivity to changes in renal function. However, mGFR methods require specialized facilities, expertise, and analytical methods. The administration of exogenous markers and the collection of samples for plasma or urine clearance measurements can be time-consuming, invasive, and costly. Additionally, variations in the timing and number of samples collected can affect the accuracy of the measurement.

Which method is most appropriate for evaluating living kidney-donor candidates?

The most accurate method is mGFR using exogenous markers. Although convenient, eGFR equations lack the necessary accuracy for donor evaluations and should be used cautiously. Creatinine clearance often overestimates GFR and is susceptible to errors in collection.

Using mGFR ensures a reliable assessment of GFR, while eGFR equations and creatinine clearance can provide supplementary information. It is essential for clinicians to carefully consider the advantages and limitations of each method when making decisions regarding donor eligibility.

Sarrah Lahorewala, BDS, PhD, is a clinical chemistry fellow at Houston Methodist Hospital, Houston, Texas. +Email: [email protected].