Why Routine Lab eGFR Falls Short in Living Kidney Donor Assessment

Xin Yi, PhD, DABCC, FADLM, Houston Methodist Hospital, Associate Professor, Weill Cornell Medical College;

Sarrah Lahorewala, BDS, PhD, DABCC, Baylor St. Luke's Medical Center, Assistant Professor, Baylor College of Medicine

Editor: Jing Cao, PhD, DABCC, FADLM, Associate Professor, UT Southwestern Medical Center; Jada Yu Zhang, PhD, DABCC, FADLM, Assistant Professor, UT MD Anderson Cancer Center.

About 815,896 people in the United States are living with end-stage kidney disease. Roughly 1 in 3 are living with a functioning kidney transplant. The number of patients on the kidney transplant waiting list continues to grow steadily, underscoring the gap between organ demand and availability. 

In the US, about 1/4 of all kidney transplants are from living donors (LDKT), and in some large academic centers the figure can approach 50%. Compared to deceased-donor kidney transplantation, LDKT consistently offers shorter waiting times, improved long-term graft and overall survival, making LDKT a cornerstone of modern kidney replacement therapy. When considering LDKT, donor safety remains a critical concern. Donation is not risk-free, and strict evaluation criteria are in place to minimize long-term donor harm. Assessing baseline kidney function and estimating long-term risk of chronic kidney disease (CKD) are central to this process. The question is: how well does routine laboratory estimation of glomerular filtration rate (GFR) support these critical clinical decisions?

Dr. Xin Yi’s recent study examined this issue in depth. The authors analyzed 1,210 living donor candidates evaluated between 2019 and 2023, using iohexol-based measured GFR (mGFR) as the reference method. A wide range of estimated GFR (eGFR) equations were compared. The findings revealed significant gaps. No eGFR equation reliably rejected ineligible donors, and all had <35% positive predictive value for identifying donors below the Kidney Disease: Improving Global Outcomes (KDIGO) threshold of <60 mL/min/1.73 m². The 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine–cystatin C equation was most reliable for identifying acceptable donors across racial and age groups, with cystatin C adding value particularly in Black donor candidates. In contrast, the newer European Kidney Function Consortium (EKFC) equations showed no advantage in older donors and performed poorly in discriminating between eligibility categories. Importantly, applying age-adjusted thresholds, as adopted in the United

Kingdom (UK), improved performance across all equations, reducing false exclusions compared to fixed KDIGO cutoffs.

Their study highlights an urgent reality: no eGFR equation can be solely relied upon to determine living donor eligibility. The limitations of eGFR, especially its inability to confidently reject ineligible donors carry profound implications for donor qualification. Overreliance on equations risks either excluding healthy donors or, more concerning, approving donors at risk of long-term harm. While KDIGO guidelines still allow the use of eGFR for donor assessment, United Network for Organ Sharing (UNOS) policy mandates mGFR, underscoring the high stakes involved. Understanding and respecting these limitations is critical to safeguarding donor health while ensuring fair and evidence-based access to transplantation.

 

活体肾移植捐献者中肾功能检测的考量

在美国，目前有超过81万名患者患有终末期肾病，其中约三分之一依赖肾移植维持生命，其余大多需要长期接受透析治疗。随着等待肾移植的患者数量持续攀升，器官供需之间的差距日益显著。 在这一背景下，活体肾移植发挥着不可替代的作用。全美约有四分之一的肾移植来自活体捐献者，而在一些大的医学中心，该比例甚至接近50%。与逝世后捐献相比，活体肾移植不仅能显著缩短等待时间，还可提高移植肾的长期存活率及患者整体生存率，因而成为肾脏替代治疗中至关重要的组成部分。 然而，我们在关注患者获益的同时，也必须高度重视捐献者的长期安全。肾脏捐献并非零风险行为，因此需通过严格的评估标准尽可能降低捐献者面临的潜在健康威胁，其中包括准确评估其基线肾功能，并科学预测其未来发生慢性肾脏病（CKD）的风险。在此过程中，一个关键问题浮出水面：常规实验室用于估算肾小球滤过率（eGFR）的方法，是否足以支撑这类高风险临床决策？ 

易欣教授和团队近期开展的一项研究对这一问题进行了深入探讨。该研究纳入2019至2023年间1210名活体捐献者候选人，以碘海醇清除率测得的实测肾小球滤过率（mGFR）作为金标准，系统比较了多种 eGFR 估算公式的表现。 结果显示出明显的局限性：所有 eGFR 公式均无法可靠地排除不符合捐献标准的供者， 在识别肾功能低于 KDIGO 指南所设阈值（＜60 mL/min/1.73 m²）的个体时，各类公式的阳性预测值均低于35%。在不同种族和年龄层中，2021版CKD-EPI creat-cys 在识别合格供者方面表现最佳，其中胱抑素C在黑人群组中的贡献尤为突出。相比之下，较新的EKFC并未在老年人群中展现出优势，其在捐献者类别中的判别能力也较差。值得关注的是，当采用英国所使用的年龄校正阈值时，所有 eGFR 公式的分类准确性均有所提升，假阳性排除率也比固定的KDIGO截断值更低。

该研究揭示出一个极需重视的现实：现有 eGFR 估算公式均不应作为判定活体供者资格的单一依据。eGFR 在排除不合格供者方面的能力有限，这一局限对捐献者评估具有深远影响。过度依赖这些公式，既可能导致健康候选人被错误排除，更严重的是，可能使部分存在长期健康风险的捐献者不适当的捐献。尽管KDIGO指南允许将 eGFR 作为筛查工具，但美国器官共享网络（UNOS）政策仍强制要求供者必须进行 mGFR 测定，这进一步凸显出问题的严峻性。充分认识并尊重 eGFR 的局限性，对于保障供者安全、推动移植实践的公平性与循证决策至关重要。

1.      Sarrah Lahorewala, Zheng Yin, Jacob Kinskey, Shane A Bobart, Angelina Edwards, Paul Christensen, Roger L Bertholf, Xin Yi, eGFR Inaccuracy in the Assessment of Living Kidney Transplant Donor Eligibility, Clinical Chemistry, Volume 71, Issue 8, August 2025, Pages 870–883.

2.    Lentine KL, Kasiske BL, Levey AS, Adams PL, Alberú J, Bakr MA, et al. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation 2017;101:S1-S109.

3.    Organ Procurement and Transplantation Network (OPTN). OPTN Policies, Policy 14: Living Donation, section 14.4.B. Additional Requirements for the Medical Evaluation of Living Kidney Donors. https://optn.transplant.hrsa.gov/media/eavh5bf3/optn_policies.pdf. (Accessed January 2025).