eGFR Testing around the World: Justice, Access, and Accuracy : Clinical Journal of the American Society of Nephrology

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eGFR Testing around the World: Justice, Access, and Accuracy

Jha, Vivekanand1,2,3; Modi, Gopesh K.4

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CJASN 16(6):p 963-965, June 2021. | DOI: 10.2215/CJN.16001020
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Alongside a broad social and racial justice movement in United States, the use of the race coefficient for eGFR from serum creatinine (eGFRcr) in Black individuals has raised a robust debate, especially around how it might create systematic discrimination in health care for this population (1,2). Many university laboratories have stopped using the coefficient, thus eliminating race-based eGFR reporting. The rationale behind this approach and the implications on clinical practice in the United States have been discussed elsewhere (2,3). There is also increasing momentum to develop race-neutral markers for estimating GFR.

What does this debate mean for the rest of the world, in particular the Global South? The great racial and ethnic diversity around the world is obvious. The race coefficient represents a correction factor to account for the observation that the measured GFR using a gold standard method was higher in Black than in non-Black individuals of the same age, sex, and serum creatinine. This difference can be attributed to differences in the non-GFR determinants of serum creatinine between Black and non-Black individuals, such as differences in creatinine generation by muscle or diet, kidney tubular secretion, or extrarenal elimination of creatinine. Researchers in some countries with populations ethnically different from White and Black individuals have also proposed population-specific coefficients (4) to improve the accuracy of eGFR measurement with respect to actual GFR value, but these factors are not widely used in clinical practice.

Populations in many Asian countries are not ethnically/racially homogeneous. For example, people living in India represent a large mix of ethnicities from a diverse ancestry. Many Southeast Asian countries have multiethnic populations. Populations in Africa are equally diverse. The current equations have been found to be inaccurate in populations from these regions (5,6). It is likely impossible to develop a single accurate ethnicity-specific equation or correction factor that would allow precise eGFRcr reporting in all populations in different countries. Further, race and ethnicity are likely oversimplified social constructs with an assortment of superficial biologic attributes (7). Research is needed to identify whether genetic variations influence non-GFR determinants of serum creatinine or any other filtration marker and thus have an effect on GFR estimation.

How do we ensure equitable access to measures of kidney health for all populations around the world? The Global Kidney Health Atlas has documented that serum creatinine testing and eGFRcr reporting in primary care settings were available in only 33% and 0% of low-income countries and 50% and 20% of lower middle–income countries, respectively (8). Therefore, the primary concern for these countries is ensuring consistent access to cheap and reliable testing that allows GFR estimation. Equations and their accuracy do not matter if testing is not available or if the methodology is flawed.

When CKD is detected early, an important management goal is prevention of kidney failure (9). Despite the caveats in accuracy arising from the different race-ethnicity or diet-body composition variables, the currently available creatinine-based eGFR reporting does facilitate monitoring of progression of kidney disease in routine clinical practice.

We suggest prioritizing actions that will bring the biggest gains in kidney health when resources are limited. At this time, they include ensuring access to serum creatinine testing using standard methodology to those who need it and the opportunity to receive appropriate preventative treatment for those identified as having potentially progressive kidney disease—all in the overall context of non-communicable disease (NCD) prevention and control rather than as a separate program vertical. When eGFRcr is reported, the equation used should be specified alongside the creatinine testing methodology. Any equation, applied consistently, will allow evaluation of trends. Finally, clinicians should clearly communicate results to patients and emphasize the value of serial testing for clinical decision making.

Appropriate drug dosing is one argument for having accurate knowledge of GFR. It bears remembering that most of the dosing recommendations have been on the basis of creatinine clearance derived by the Cockcroft–Gault formula. Moreover, dosing is guided by a broad range of GFR values. Another area that raises concern is participation in international clinical trials because regulatory agencies, trial networks, and several journals are unclear about the use of correction factors other than those specified in the original Chronic Kidney Disease Epidemiology Collaboration equations.

As shown in Figure 1, precision or accuracy in eGFR is of paramount importance in a small proportion of patients or situations. GFR should be measured where accuracy is critical—for example, in evaluating a kidney donor with borderline eGFR values, listing for kidney transplantation, or in ascertainment of some clinical trial end points. Research should indeed continue on in finding a race-neutral marker. However, even if a new marker, such as cystatin C, was recommended, it will need to be tested for accuracy in diverse populations around the world. Next, there would be challenges in getting the test laboratories in resource-poor countries (especially in primary care settings) to replace the existing hardware to incorporate new technology. Third, the new test is likely to be way more expensive than creatinine testing, and the opportunity costs from the gains made in accuracy in terms of change in clinical practice might be hard to justify. It is also important to point out that when it becomes available, the test will likely deepen the existing inequities around access to care in low-resource economies. It is therefore important to develop affordable assay technologies that increase the likelihood of uptake in resource-poor regions.

fig1
Figure 1.:
Hierarchy of practical GFR measures in population health and clinical practice. eGFRcr fulfills most of the requirements for day-to-day clinical practice and population health. More accurate estimation may be needed in special situations. eGFRcr, eGFR from serum creatinine; eGFRcys, eGFR from serum cystatin C; mGFR, measured GFR.

One final point is especially relevant to South Asian populations. Several studies from the region have shown lower GFR values in otherwise healthy individuals even when GFR was measured using gold standard methods. Should these individuals be classified as having CKD, as is currently done? Should they be excluded from donating a kidney? It is not at all clear whether these low values, in the absence of other health issues and normal urinalysis, indicate a long-term adverse health risk as shown in other populations. The 2012 Kidney Disease Improving Global Outcomes guidelines emphasize the need to interpret abnormal eGFR values in light of their implication on health. Longitudinal studies that measure GFR and carefully and accurately define prognosis in this population are needed to inform the definition and staging of CKD.

In conclusion, accurate eGFR reporting has theoretical appeal for all populations around the world, but knowledge around how clinicians can make best use of such a report in routine clinical practice is uncertain. Despite limitations imposed by racial and ethnic variations, health systems in low-resource settings should prioritize increasing population-level access to standardized creatinine testing and more widespread implementation of eGFRcr reporting, enable follow-up testing as necessary, and ensure access to care. Finally, we should recognize and decipher the overall health effect of global variations in true GFR and study their overall effect on health.

Disclosures

V. Jha reports employment with George Institute for Global Health India. He has received grant funding from Baxter Healthcare and GSK and consultancy incomes from Biocon, NephroPlus, and Zydus; all funds come to the organization. He has also received honoraria from AstraZeneca and Baxter Healthcare. G.K. Modi received consultancy income from Intas Pharmaceuticals and Vyapitus Life Sciences.

Funding

This work was supported by Department of Biotechnology, Ministry of Science and Technology grant BT/PR3150/MED/97/345/2016 (to V. Jha).

Published online ahead of print. Publication date available at www.cjasn.org.

Acknowledgments

The content of this article reflects the personal experience and views of the author(s) and should not be considered medical advice or recommendation. The content does not reflect the views or opinions of the American Society of Nephrology (ASN) or CJASN. Responsibility for the information and views expressed herein lies entirely with the author(s).

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Keywords:

chronic kidney disease; glomerular filtration rate; equity

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