Living donor kidney transplantation (LDKT) offers better quality of life and clinical outcomes, including patient survival, compared with remaining on dialysis or receiving a deceased donor kidney transplant. Although LDKT education within transplant centers for both potential recipients and living donors is very important, outreach and education to kidney patients in settings other than transplant centers and to the general public is also critical to increase access to this highly beneficial treatment. In June 2014, the American Society of Transplantation's Live Donor Community of Practice, with the support of 10 additional sponsors, convened a consensus conference to determine best practices in LDKT, including a workgroup focused on developing a set of recommendations for optimizing outreach and LDKT education outside of transplant centers. Members of this workgroup performed a structured literature review, conducted teleconference meetings, and met in person at the 2-day conference. Their efforts resulted in consensus around the following recommendations. First, preemptive transplantation should be promoted through increased LDKT education by primary care physicians and community nephrologists. Second, dialysis providers should be trained to educate their own patients about LDKT and deceased donor kidney transplantation. Third, partnerships between community organizations, organ procurement organizations, religious organizations, and transplant centers should be fostered to support transplantation. Fourth, use of technology should be improved or expanded to better educate kidney patients and their support networks. Fifth, LDKT education and outreach should be improved for kidney patients in rural areas. Finally, a consensus-driven, evidence-based public message about LDKT should be developed. Discussion of the effect and potential for implementation around each recommendation is featured, particularly regarding reducing racial and socioeconomic disparities in access to LDKT. To accomplish these recommendations, the entire community of professionals and organizations serving kidney patients must work collaboratively toward ensuring accurate, comprehensive, and up-to-date LDKT education for all patients, thereby reducing barriers to LDKT access and increasing LDKT rates.

Background

Current equations for estimated glomerular filtration rate (eGFR) that use serum creatinine or cystatin C incorporate age, sex, and race to estimate measured GFR. However, race in eGFR equations is a social and not a biologic construct.

Methods

We developed new eGFR equations without race using data from two development data sets: 10 studies (8254 participants, 31.5% Black) for serum creatinine and 13 studies (5352 participants, 39.7% Black) for both serum creatinine and cystatin C. In a validation data set of 12 studies (4050 participants, 14.3% Black), we compared the accuracy of new eGFR equations to measured GFR. We projected the prevalence of chronic kidney disease (CKD) and GFR stages in a sample of U.S. adults, using current and new equations.

Results

In the validation data set, the current creatinine equation that uses age, sex, and race overestimated measured GFR in Blacks (median, 3.7 ml per minute per 1.73 m² of body-surface area; 95% confidence interval [CI], 1.8 to 5.4) and to a lesser degree in non-Blacks (median, 0.5 ml per minute per 1.73 m²; 95% CI, 0.0 to 0.9). When the adjustment for Black race was omitted from the current eGFR equation, measured GFR in Blacks was underestimated (median, 7.1 ml per minute per 1.73 m²; 95% CI, 5.9 to 8.8). A new equation using age and sex and omitting race underestimated measured GFR in Blacks (median, 3.6 ml per minute per 1.73 m²; 95% CI, 1.8 to 5.5) and overestimated measured GFR in non-Blacks (median, 3.9 ml per minute per 1.73 m²; 95% CI, 3.4 to 4.4). For all equations, 85% or more of the eGFRs for Blacks and non-Blacks were within 30% of measured GFR. New creatinine-cystatin C equations without race were more accurate than new creatinine equations, with smaller differences between race groups. As compared with the current creatinine equation, the new creatinine equations, but not the new creatinine-cystatin C equations, increased population estimates of CKD prevalence among Blacks and yielded similar or lower prevalence among non-Blacks.

Conclusions

New eGFR equations that incorporate creatinine and cystatin C but omit race are more accurate and led to smaller differences between Black participants and non-Black participants than new equations without race with either creatinine or cystatin C alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

Rationale and objective

Glomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFR_cr-cys) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFR_cr or eGFR_cys, respectively), but the inclusion of creatinine in eGFR_cr-cys requires specification of a person's race. β₂-Microglobulin (B2M) and β-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine is.

Study design

Study of diagnostic test accuracy.

Setting and participants

Development in a pooled population of 7 studies with 5,017 participants with and without chronic kidney disease. External validation in a pooled population of 7 other studies with 2,245 participants.

Tests compared

Panel eGFR using B2M and BTP in addition to cystatin C (3-marker panel) or creatinine and cystatin C (4-marker panel) with and without age and sex or race.

Outcomes

GFR measured as the urinary clearance of iothalamate, plasma clearance of iohexol, or plasma clearance of [⁵¹Cr]EDTA.

Results

Mean measured GFRs were 58.1 and 83.2 mL/min/1.73 m², and the proportions of Black participants were 38.6% and 24.0%, in the development and validation populations, respectively. In development, addition of age and sex improved the performance of all equations compared with equations without age and sex, but addition of race did not further improve the performance. In validation, the 4-marker panels were more accurate than the 3-marker panels (P < 0.001). The 3-marker panel without race was more accurate than eGFR_cys (percentage of estimates greater than 30% different from measured GFR [1 - P₃₀] of 15.6% vs 17.4%; P = 0.01), and the 4-marker panel without race was as accurate as eGFR_cr-cys (1 - P₃₀ of 8.6% vs 9.4%; P = 0.2). Results were generally consistent across subgroups.

Limitations

No representation of participants with severe comorbid illness and from geographic areas outside of North America and Europe.

Conclusions

The 4-marker panel eGFR is as accurate as eGFR_cr-cys without requiring specification of race. A more accurate race-free eGFR could be an important advance.

Introduction

Much of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (APOL1). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)-sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes.

Methods

APOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys.

Results

The United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses.

Conclusion

This article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are common, heterogeneous, and morbid diseases. Mechanistic characterization of CKD and AKI in patients may facilitate a precision-medicine approach to prevention, diagnosis, and treatment. The Kidney Precision Medicine Project aims to ethically and safely obtain kidney biopsies from participants with CKD or AKI, create a reference kidney atlas, and characterize disease subgroups to stratify patients based on molecular features of disease, clinical characteristics, and associated outcomes. An additional aim is to identify critical cells, pathways, and targets for novel therapies and preventive strategies. This project is a multicenter prospective cohort study of adults with CKD or AKI who undergo a protocol kidney biopsy for research purposes. This investigation focuses on kidney diseases that are most prevalent and therefore substantially burden the public health, including CKD attributed to diabetes or hypertension and AKI attributed to ischemic and toxic injuries. Reference kidney tissues (for example, living-donor kidney biopsies) will also be evaluated. Traditional and digital pathology will be combined with transcriptomic, proteomic, and metabolomic analysis of the kidney tissue as well as deep clinical phenotyping for supervised and unsupervised subgroup analysis and systems biology analysis. Participants will be followed prospectively for 10 years to ascertain clinical outcomes. Cell types, locations, and functions will be characterized in health and disease in an open, searchable, online kidney tissue atlas. All data from the Kidney Precision Medicine Project will be made readily available for broad use by scientists, clinicians, and patients.