Box 2.
NKF-ASN Task Force Agreed-Upon Statements of Evidence and Value
| Equity and Disparities | |
| (1) | Equitya in kidney health and kidney health care is a fundamental and important goal. (V) |
| (2) | Disparities in kidney health and kidney health care should not exist. (V) |
| (3) | Equity in health care, as defined by the NAM, is care that does not vary in quality on the basis of personal characteristics, such as sex, race/ ethnicity, geographic location, or socioeconomic status.43 (E) |
| (4) | A disparity in health care, as defined by NAM, is a difference in care that arises through operation of the health care system; legal or regulatory climate; or discrimination, biases, stereotyping, and uncertainty; but is not due to clinical appropriateness or patient preference.44 (E) |
| (5) | A variety of factors influence kidney health across racial and ethnic groups, including delivery of health care, clinical/health policies, environment, genetics, and health behaviors.45–51 (E) These factors act with a different degree of influence along the life span of individuals and along the continuum from health to kidney disease.45–49 (E) There are gaps in our understanding of these influences and how to interrupt their effect on creating health disparities.52 (E) To eliminate disparities, multifaceted initiatives beyond an examination of estimating equations must be developed. (V) |
| (6) | Differences in health exist across racial and ethnic groups in the United States, and not all of these differences are accounted for by socioeconomic status, geographic regions (including urban versus rural setting), insurance, lifestyle, and clinical factors.53 (E) Disparities in health care exist across racial and ethnic groups and geographic regions (including urban versus rural setting) in the United States, even after accounting for insurance status, income, age, and disease severity.44,54 (E) |
| (7) | Disparities across racial and ethnic groups in the United States exist in kidney disease. These disparities exist with regard to kidney disease risk factors, comorbidities, and progression to kidney failure.2,5,55 (E) Disparities across racial and ethnic groups in the United States exist in kidney disease care, including diabetes and BP control, nephrology referral, dialysis modality, and transplantation, and with regard to both living and deceased kidney donation.56–58 (E) Disparities across racial and ethnic groups in the United States in health care exist for diagnostics and therapeutics that rely on GFR assessment (eg, radiocontrast administration; metformin, anticoagulant, and chemotherapeutic use).59–62 (E) |
| (8) | Racial and ethnic diversity in participants in health and health care research is an important component of equity for studies and their data to be useful and generalizable to decisions in routine clinical practice.17,63,64 (E) Research studies should focus on a diversity of racial and ethnic groups to allow for greater generalizability. (V) |
| Race and Racism | |
| (9) | Race is defined as a construct of human variability based on perceived differences in biology, physical appearance, and behavior.65 (E) Race and ethnicity are social and not biological constructs.17,66,67 (E) |
| (10) | Racism is defined as an organized system, rooted in an ideology of inferiority that categorizes, ranks, and differentially allocates societal resources to human population groups.68 (E) Racism can be internalized, personal, or institutional.40 (E) As such, racism can be a part of the environment/behavior, delivery of health care, and clinical/health policy factors, respectively.69 (E) Racism can impede prevention and clinical care along the continuum from healthy kidneys, to kidney disease, to treatment.39,70 (E) Implicit bias has also been shown to negatively affect patient outcomes, particularly among African American patients in the United States.71 (E) Approaches proven to minimize implicit bias in health care delivery should be used. (V) The effects of racism can be long lasting and this effect may even be carried forward over generations.72–74 (E) |
| (11) | Although race and genetic ancestry are related, race captures factors beyond genetic ancestry. The relation between race, ancestry, and observed biology is poorly understood.17 (E) Research is ongoing to elucidate the relation between genetic ancestry and race.17 (E) |
| (12) | According to 2019 US Census population estimates, the self-identified racial and ethnic composition of individuals was 76.3% White, 13.4% African Americans, 5.9% Asian, 1.3% American Indian/Native American and Alaskan Native, 0.2% Native Hawaiian and Other Pacific Islander, with approximately 18.5% Hispanic/Latinx ethnicity.75 (E) Approximately 2.9% of US individuals self-identified as being of mixed racial background.75 (E) The complexity of changing racial and ethnic makeup makes the use of race in the practice of medicine challenging and potentially problematic. (V) |
| GFR Measurement, Estimation, and Equation Performance | |
| (13) | Creatinine and cystatin C are the most commonly used and studied filtration markers for use in estimating GFR.13 (E) Creatinine is used more commonly, is more widely available, and has a longer history of study than cystatin C.8,10,76 (E) The determinants of serum concentrations of creatinine are not completely understood, and those of cystatin C are even less well understood.77 (E) Assays for cystatin C have greater analytical variation than do assays for creatinine.78 (E) |
| (14) | Over 250 million serum creatinine measurements are performed each year in the United States. The measurement cost for serum creatinine is currently low relative to serum cystatin C (Medicare reimbursement rates in 2020, $5.12 and $18.52, respectively).79 (E) With more widespread adoption and use of cystatin C, costs could decrease. (V) |
| (15) | Multiple studies among the US population, including national health statistics studies across age groups, show African American men and African American women have higher serum creatinine concentrations than their White counterparts. Not all factors that might affect serum creatinine concentrations were accounted for in these studies.7,80 (E) Studies have also shown African Americans have higher serum creatinine concentrations than White individuals at the same measured GFR in the United States.81 (E) The reasons for these differences are not understood.81 (E) |
| (16) | Studies have shown the proportion of African ancestry is related to the level of creatinine in US adults.82,83 (E) Studies have not examined the relation of genetic ancestry to measured GFR. (E) These studies are desired. (V) |
| (17) | All estimates of GFR are subject to bias, imprecision, and inaccuracy.8,10,76,84 (E) Equations should not differentially induce bias and inaccuracy by age, sex, or race; ie, they should not have disproportionate bias, imprecision, or inaccuracy for a particular group according to age, sex, or race. (V) |
| (18) | Clinical algorithms to assess eGFR with additional predictors are a better indicator of GFR than serum creatinine concentration alone.13 (E) |
| (19) | Individual studies of adults with measured GFR and eGFRcr or eGFRcys have been limited in the diversity of participants with regard to age, sex, race, ethnicity, geography, socioeconomic status, comorbidity, and other risk factors for kidney disease. These individual studies have also been limited in diversity of participants with regard to absence, severity, and etiology of kidney disease.8,10,76,81 (E) Individual studies of adults are also limited in measurements of body composition and chronic or acute illness.8,12,76 (E) Future studies should seek more diversity in participants with regard to many patient characteristics (age; sex; race; ethnicity; geography; socioeconomic status; comorbidity; risk factors for kidney disease; absence, severity, and etiology of kidney disease; diet; and body composition). (V) |
| (20) | Estimating equations that were not developed in diverse populations (including race and ethnicity) leads to questions as to how applicable they are to populations not included in the developmental phase without further validation. (V) |
| (21) | To estimate GFR, it is useful to pool data on participants from individual studies (ie, meta-analysis) to obtain a more comprehensive and diverse sample of people (age; sex; race; ethnicity; geography; socioeconomic status; comorbidity; risk factors for kidney disease; absence, severity, and etiology of kidney disease; and body composition) for whom eGFR can be applied in clinical practice. (V) |
| (22) | To approximate measured GFR with greater accuracy and to minimize bias in all groups, creatinine-based estimating equations (MDRD and CKD-EPI eGFRcr or eGFRcr-cys) have included a coefficient for age, sex, and race; whereas cystatin C-based equations (CKD-EPI) have included coefficients for age and sex alone.12 (E) |
| (23) | Data in adult ambulatory outpatients show that the most validated equations (CKD-EPI; eGFRcr, eGFRcys, and eGFRcr-cys) perform with different degrees of bias and accuracy.12 (E) With regard to accuracy, CKD-EPI 2012 eGFRcr-cys has the highest available accuracy (P30 at 91.5%), with similar accuracy for CKD-EPI 2009 eGFRcr (at 87.2%) and CKD-EPI 2012 eGFRcys (at 86.9%).12 (E) Precision (interquartile range) is best for eGFRcr-cys (13.4) and less for eGFRcr (15.4) and eGFRcys (16.4), all in mL/min/1.73 m2.12 (E) Bias (measured minus estimated GFR) is similar among equations: eGFRcr-cys (3.9), GFRcr (3.7), and eGFRcys (3.4), all in mL/min/1.73 m2.12 (E) Bias and inaccuracy of estimated GFR equations are greater at higher measured GFR.12 (E) There is no differential accuracy, precision, or bias in equations between Black and non-Black individuals using these equations.12 (E) |
| (24) | Inclusion of height and total body weight did not improve performance of eGFR estimation in adults.11,85 (E) Validated equations for use in children include height, serum creatinine, cystatin C, and SUN, but do not include race.86 (E) Although methods for measuring body composition have been useful in research settings, no single method has been widely standardized and adapted for routine clinical use for adults in the United States or evaluated for use with eGFR equations. (V) |
| Laboratory Standardization | |
| (25) | Standardization of measurement and reporting of GFR in the United States is important. (V) |
| (26) | Standardization can be achieved through issuance and adherence to clinical practice guidelines.87 (E) |
| (27) | Reference materials, methods, and accounting for interfering substances are important in achieving assay equivalence.1,88,89 (E) Results for analytes used to estimate GFR should be standardized. (V) |
| (28) | Implementation efforts to achieve standardization, and adoption and adherence to practice guidelines, are important for uniform practices. (V) |
| (29) | Clinical laboratories and the manufacturers of laboratory equipment and supplies must be engaged to achieve standardization. (V) |
| Patients’ Perspective | |
| (30) | Patients prefer to have shared decision making with their physician, rather than the patient or the physician being the sole decision maker.90 (E) Given the diversity of the patient populations within and across health care settings, patient education on the clinical implications of eGFR should include a discussion on how the equation was derived, its limitations, and how it applies to them. (V) |
The task force actively participated in constructing the statements of evidence (E) and value (V), the statements then underwent scrutiny and revision by all of the members of the task force. The task force went through a series of iterations regarding content, language, and perspective.
Abbreviations: BP, blood pressure; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; eGFRcr, estimated GFR from creatinine; eGFRcr-cys, estimated GFR from creatinine and cystatin C; eGFRcys, estimated GFR from cystatin C; MDRD, Modification of Diet in Renal Disease (Study); NAM, National Academy of Medicine; P30, accuracy measured as the percentage of estimates within 30% of measured GFR; SUN, serum urea nitrogen.
a
See Item S2 for terms and definitions.