Development and Validation of Residual Kidney Function Estimating Equations in Dialysis Patients

Dominik Steubl, Li Fan, Wieneke M. Michels, Lesley A. Inker, Hocine Tighiouart, Friedo W. Dekker, Raymond T. Krediet, Andrew L. Simon, Meredith C. Foster, Amy B. Karger, John H. Eckfeldt, Hongyan Li, Jiamin Tang, Yongcheng He, Minyan Xie, Fei Xiong, Hongbo Li, Hao Zhang, Jing Hu, Yunhua LiaoXudong Ye, Tariq Shafi, Wei Chen, Xueqing Yu, Andrew S. Levey

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Rationale & Objective: Measurement of residual kidney function is recommended for the adjustment of the dialysis prescription, but timed urine collections are difficult and prone to errors. Equations to calculate residual kidney function from serum concentrations of endogenous filtration markers and demographic parameters would simplify monitoring of residual kidney function. However, few equations to estimate residual kidney function using serum concentrations of small solutes and low-molecular-weight proteins have been developed and externally validated. Study Design: Study of diagnostic test accuracy. Setting & Participants: 823 Chinese peritoneal dialysis (PD) patients (development cohort) and 826 PD and hemodialysis patients from the Netherlands NECOSAD study (validation cohort). Tests Compared: Equations to estimate residual kidney function (estimated clearance [eCl]) using serum creatinine, urea nitrogen, cystatin C, β2-microglobulin (B2M), β-trace protein (BTP), and combinations, as well as demographic variables (age, sex, height, and weight). Equations were developed using multivariable linear regression analysis in the development cohort and then tested in the validation cohort. Equations were compared with published validated equations. Outcomes: Residual kidney function measured as urinary clearance (mCl) of urea nitrogen (mClUN) and average of creatinine and urea nitrogen clearance (mClUN-cr). Results: In external validation, bias (difference between mCl and eCl) was within ± 1.0 unit for all equations. Accuracy (percent of differences within ± 2.0 units) was significantly better for eClBTP, eClB2M, and eClBTP-B2M than eClUN-cr for both mClUN (78%, 80%, and 81% vs 72%; P < 0.05 for all) and mClUN-cr (72%, 78%, and 79% vs 68%; P < 0.05 for all). The area under the curve for predicting mClUN > 2.0 mL/min was highest for eClB2M (0.853) and eClBTP-B2M (0.848). Results were similar for other validated equations. Limitations: Development cohort only consisted of PD patients, no gold-standard method for residual kidney function measurement. Conclusions: These results confirm the validity and extend the generalizability of residual kidney function estimating equations from serum concentrations of low-molecular-weight proteins without urine collection.

Original languageEnglish (US)
Pages (from-to)104-114
Number of pages11
JournalKidney Medicine
Volume1
Issue number3
DOIs
StatePublished - May 1 2019

Bibliographical note

Funding Information:
Grant 2002B60118 from Guangdong Provincial Key Laboratory of Nephrology , Guangzhou, China; Key Laboratory of Nephrology, Guangdong Province, Guangzhou, China; Operational grant 2017B030314019 of Guangdong Provincial Key Laboratory ; Guangdong Provincial Programme of Science and Technology , grant 2017A050503003 ; Paul Teschan Research Fund – Dialysis Clinic Inc (“Monitoring PD Adequacy Using Serum Levels of Endogenous Filtration Marker“); Siemens Healthcare (“Monitoring PD Adequacy Using Serum Levels of Endogenous Filtration Marker). None of the funders of this study had any role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication.

Funding Information:
Dr Eckfeldt was a consultant for Gentian AS until December 2017; Dr Inker receives grant support from Retrophin, Reata, and Omeros Corp; Dr Michels received payment for a PD advisory counsil 06/2018. The remaining authors declare that they have no relevant financial interests.

Funding Information:
Dominik Steubl, MD, Li Fan, MD, PhD, Wieneke M. Michels, MD, PhD, Lesley A. Inker, MD, MS, Hocine Tighiouart, MS, Friedo W. Dekker, PhD, Raymond T. Krediet, MD, PhD, Andrew L. Simon, ScM, Meredith C. Foster, ScD, MPH, Amy B. Karger, MD, PhD, John H. Eckfeldt, MD, PhD, Hongyan Li, MD, Jiamin Tang, RN, Yongcheng He, MD, Minyan Xie, MD, Fei Xiong, MD, Hongbo Li, MD, Hao Zhang, MD, Jing Hu, MD, PhD, Yunhua Liao, MD, PhD, Xudong Ye, MD, Tariq Shafi, MBBS, MHS, Wei Chen, MD, PhD, Xueqing Yu, MD, PhD, and Andrew S. Levey, MD. Research idea and study design: LAI, XYu, ASL; data acquisition: LF, WMM, FWD, RTK, HL, JT, YH, MX, FX, HL, HZ, JH, YL, XYe, WC; data analysis/interpretation: DS, LF, LAI, HT, ALS, MCF, TS, XYu, ASL; biomarker measurement: ABK, JHE. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. Grant 2002B60118 from Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China; Key Laboratory of Nephrology, Guangdong Province, Guangzhou, China; Operational grant 2017B030314019 of Guangdong Provincial Key Laboratory; Guangdong Provincial Programme of Science and Technology, grant 2017A050503003; Paul Teschan Research Fund ? Dialysis Clinic Inc (?Monitoring PD Adequacy Using Serum Levels of Endogenous Filtration Marker?); Siemens Healthcare (?Monitoring PD Adequacy Using Serum Levels of Endogenous Filtration Marker). None of the funders of this study had any role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication. Dr Eckfeldt was a consultant for Gentian AS until December 2017; Dr Inker receives grant support from Retrophin, Reata, and Omeros Corp; Dr Michels received payment for a PD advisory counsil 06/2018. The remaining authors declare that they have no relevant financial interests. We express our appreciation to the nurses in the PD center of the First Affiliated Hospital, Sun Yat-sen University, who collected demographic and clinical characteristics and follow-up data for patients, as well as all patients enrolled in the Guangzhou PD Study. Received December 20, 2018. Evaluated by 2 external peer reviewers and a statistician, with editorial input from an Acting Editor-in-Chief (Editorial Board Member Roberto Minutolo, MD, PhD). Accepted in revised form April 15, 2019. The involvement of an Acting Editor-in-Chief to handle the peer-review and decision-making processes was to comply with Kidney Medicine's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies.

Publisher Copyright:
© 2019 The Authors

Keywords

  • Residual kidney function
  • creatinine
  • hemodialysis
  • low-molecular-weight proteins
  • peritoneal dialysis

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