GFR Estimation Using a Panel of Filtration Markers in Shanghai and Beijing

Nan Chen, Hao Shi, Luxia Zhang, Li Zuo, Jingyuan Xie, Danshu Xie, Amy B. Karger, Shiyuan Miao, Hong Ren, Wen Zhang, Weiming Wang, Yujing Pan, Wei Minji, Zhun Sui, Aghogho Okparavero, Andrew Simon, Juhi Chaudhari, John H. Eckfeldt, Lesley A. Inker, Andrew S. Levey

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Rationale & Objectives: Estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys) may be less accurate compared to measured GFR (mGFR) in China than in North America, Europe, and Australia due to variation across regions in their non-GFR determinants. The non-GFR determinants of β2-microglobulin (B2M) and β-trace protein (BTP) differ from those of creatinine and cystatin C. Thus, the average eGFR using all 4 markers (eGFRavg) could be more accurate than eGFRcr-cys in China. Study Design: Diagnostic test study. Setting & Participants: 1,066 participants in Shanghai and Beijing with creatinine and cystatin C and 666 participants with all 4 filtration markers. Tests Compared: Index tests were previously developed equations for eGFR using creatinine, cystatin C, B2M, and BTP and combinations. The reference test was mGFR using plasma clearance of iohexol. We compared the performance of eGFRavg to eGFRcr-cys using the proportion of participants with errors in eGFR >30% of mGFR (1 − P30) and root mean square error (RMSE) of the regression of eGFR on mGFR on the logarithmic scale. We also compared classification and reclassification of mGFR categories using eGFRavg compared to eGFRcr-cys. Outcomes: Accuracy was significantly better for eGFRavg (1 − P30 of 10.4% and RMSE of 0.214) compared to eGFRcr-cys (1 − P30 of 13.8% and RMSE of 0.232; P = 0.004 and P = 0.006, respectively). However, improvements in accuracy did not generally translate into significant improvement in classification or reclassification of mGFR categories. Limitations: Study population may not be generalizable to clinical settings other than large urban medical centers in China. Conclusions: A panel of endogenous filtration markers including B2M and BTP in addition to creatinine and cystatin C may improve GFR estimation in China. Further study is necessary to determine whether GFR estimation using B2M and BTP can be improved and whether these improvements lead to useful clinical applications.

Original languageEnglish (US)
Pages (from-to)172-180
Number of pages9
JournalKidney Medicine
Volume2
Issue number2
DOIs
StatePublished - Mar 1 2020

Bibliographical note

Funding Information:
Research grant of international collaborative research from Science and Technology Commission of Shanghai Municipality (no. 13430720800 ) to Shanghai Jiao Tong University School of Medicine , Multi-Center Clinical Research Project (no.: DLY201510 ); “Optimizing the Management of Chronic Kidney Disease : Timing of RRT, a randomized controlled clinical trial” (grant ID: 201502010 ) National Health and Health Council (previously Ministry of Health ), from 2015 through 2018; National Natural Science Foundation of China (grant nos. 81771938 , 91846101 , 81301296 ), from Peking University (grant nos. BMU2018MX020 , PKU2017LCX05 ), the National Key Technology R&D Program of the Ministry of Science and Technology of the People's Republic of China ( 2016YFC1305400 ); National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK097020 “Estimating GFR from a Panel of Endogenous Filtration Markers” and Siemens Healthcare grant “Monitoring PD Adequacy Using Serum Levels of Endogenous Filtration Markers“ to Tufts Medical Center. Funders of this study had no role in study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.

Funding Information:
Dr Zhang reports grant support from AstraZeneca. Dr Karger reports National Institutes of Health (NIH) grant funding for multiple clinical trials and research studies, serving as principal or co-investigator for clinical laboratory testing and grants from Siemens Healthcare Diagnostics, for research collaborations. Dr Zuo reports grant funding from National Health and Health Council (previously Ministry of Health). Dr Eckfeldt reports consulting fees from Gentian. Dr Inker reports funding from NIH, National Kidney Foundation, Retrophin, Omeros, Dialysis Clinic, Inc, and Reata Pharmaceuticals. Dr Levey reports grant support from NIH, National Kidney Foundation, and Siemens. Drs Inker and Levey have a provisional patent (filed Aug 15, 2014; precise estimation of GFR from multiple biomarkers, patent no. PCT/US2015/044567). The remaining authors declare that they have no relevant financial interests.

Keywords

  • China
  • Estimated GFR
  • beta-2 microglobulin
  • beta-trace protein
  • creatinine
  • cystatin C

PubMed: MeSH publication types

  • Journal Article

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