Home Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values
Article
Licensed
Unlicensed Requires Authentication

Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values

  • Yao Ma , Zhenzhu Yong , Lu Wei , Haichuan Yuan , Lihong Wan , Xiaohua Pei , Feng Zhang , Guohua Wen , Cheng Jin , Yan Gu , Qun Zhang EMAIL logo , Weihong Zhao EMAIL logo and Bei Zhu EMAIL logo
Published/Copyright: January 12, 2024

Abstract

Objectives

Glomerular filtration rate (GFR) estimating equations based on rescaled serum creatinine (SCr/Q) have shown better performance, where Q represents the median SCr for age- and sex-specific healthy populations. However, there remains a scarcity of investigations in China to determine this value. We aimed to develop Chinese age- and sex-specific reference intervals (RIs) and Q-values for SCr and to validate the equations incorporating new Q-values.

Methods

We included 117,345 adults from five centers for establishing RIs and Q-values, and 3,692 participants with reference GFR (rGFR, 99mTc-DTPA renal dynamic imaging measurement) for validation. Appropriate age partitioning was determined using the decision tree method. Lower and upper reference limits and medians were calculated using the refineR algorithm, and Q-values were determined accordingly. We evaluated the full age spectrum (FAS) and European Kidney Function Consortium (EKFC) equations incorporating different Q-values considering bias, precision (interquartile range, IQR), and accuracy (percentage of estimates within ±20 % [P20] and ±30 % [P30] of rGFR).

Results

RIs for males were: 18–79 years, 55.53–92.50 μmol/L; ≥80 years, 54.41–96.43 μmol/L. RIs for females were: 18–59 years, 40.42–69.73 μmol/L; 60–79 years, 41.16–73.69 μmol/L; ≥80 years, 46.50–73.20 μmol/L. Q-values were set at 73.82 μmol/L (0.84 mg/dL) for males and 53.80 μmol/L (0.61 mg/dL) for females. After validation, we found that the adjusted equations exhibit less bias, improved precision and accuracy, and increased agreement of GFR categories.

Conclusions

We determined Chinese age- and sex-specific RIs and Q-values for SCr. The adjustable Q-values provide an effective alternative to obtain valid equations for estimating GFR.


Corresponding authors: Qun Zhang, MD, Health Management Center, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, P.R. China, E-mail: ; and Weihong Zhao, MD, PhD and Bei Zhu, MD, Division of Nephrology, Department of Geriatrics, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, P.R. China, E-mail: (W. Zhao), (B. Zhu)
Qun Zhang, Weihong Zhao, and Bei Zhu share senior authorship.

Award Identifier / Grant number: 82171585

Funding source: Jiangsu Province Graduate Training Innovation Project

Award Identifier / Grant number: SJCX21_0620

Funding source: Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital

Award Identifier / Grant number: JSPH-MC-2022-22

Award Identifier / Grant number: BJ17018

Award Identifier / Grant number: LX2021003

  1. Research ethics: The study was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University and conducted in accordance with the Declaration of Helsinki, registration number 2021-SR-508.

  2. Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: Authors state no conflict of interest.

  5. Research funding: This study was supported by the grants from the National Key R&D Program of China (2018YFC2002100, 2018YFC2002102), National Natural Science Foundation of China (82171585), Jiangsu Province Older Adults Health Introduction New Technique Project (LX2021003), Jiangsu Province Hospital Clinical Ability Improvement Project (JSPH-MC-2022-22), Jiangsu Province Graduate Training Innovation Project (SJCX21_0620), Jiangsu Province Cadres Health Care Project (BJ17018).

  6. Data availability: The data underlying this article will be shared on reasonable request to the corresponding author.

References

1. GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020;396:1204–22. https://doi.org/10.1016/s0140-6736(20)30925-9.Search in Google Scholar PubMed PubMed Central

2. GBD Chronic Kidney Disease Collaboration. Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2020;395:709–33. https://doi.org/10.1016/S0140-6736(20)30045-3.Search in Google Scholar PubMed PubMed Central

3. Delanaye, P, Schaeffner, E, Ebert, N, Cavalier, E, Mariat, C, Krzesinski, JM, et al.. Normal reference values for glomerular filtration rate: what do we really know? Nephrol Dial Transplant 2012;27:2664–72. https://doi.org/10.1093/ndt/gfs265.Search in Google Scholar PubMed

4. Ma, Y, Shen, X, Yong, Z, Wei, L, Zhao, W. Comparison of glomerular filtration rate estimating equations in older adults: a systematic review and meta-analysis. Arch Gerontol Geriatr 2023;114:105107. https://doi.org/10.1016/j.archger.2023.105107.Search in Google Scholar PubMed

5. Hsu, CY, Yang, W, Parikh, RV, Anderson, AH, Chen, TK, Cohen, DL, et al.. Race, genetic ancestry, and estimating kidney function in CKD. N Engl J Med 2021;385:1750–60. https://doi.org/10.1056/nejmoa2103753.Search in Google Scholar

6. Pottel, H, Hoste, L, Martens, F. New insights in glomerular filtration rate formulas and chronic kidney disease classification. Clin Chim Acta 2010;411:1341–7. https://doi.org/10.1016/j.cca.2010.05.031.Search in Google Scholar PubMed

7. Ceriotti, F, Henny, J. Are my laboratory results normal?" Considerations to be made concerning reference intervals and decision limits. EJIFCC 2008;19:106–14.Search in Google Scholar

8. Pottel, H, Hoste, L, Martens, F. A simple height-independent equation for estimating glomerular filtration rate in children. Pediatr Nephrol 2012;27:973–9. https://doi.org/10.1007/s00467-011-2081-9.Search in Google Scholar PubMed

9. Hoste, L, Dubourg, L, Selistre, L, De Souza, VC, Ranchin, B, Hadj-Aïssa, A, et al.. A new equation to estimate the glomerular filtration rate in children, adolescents and young adults. Nephrol Dial Transplant 2014;29:1082–91. https://doi.org/10.1093/ndt/gft277.Search in Google Scholar PubMed

10. Pottel, H, Hoste, L, Dubourg, L, Ebert, N, Schaeffner, E, Eriksen, BO, et al.. An estimated glomerular filtration rate equation for the full age spectrum. Nephrol Dial Transplant 2016;31:798–806. https://doi.org/10.1093/ndt/gfv454.Search in Google Scholar PubMed PubMed Central

11. Pottel, H, Bjork, J, Courbebaisse, M, Couzi, L, Ebert, N, Eriksen, BO, et al.. Development and validation of a modified full age spectrum creatinine-based equation to estimate glomerular filtration rate : a cross-sectional analysis of pooled data. Ann Intern Med 2021;174:183–91. https://doi.org/10.7326/m20-4366.Search in Google Scholar

12. Delanaye, P, Vidal-Petiot, E, Bjork, J, Ebert, N, Eriksen, BO, Dubourg, L, et al.. Performance of creatinine-based equations to estimate glomerular filtration rate in White and Black populations in Europe, Brazil and Africa. Nephrol Dial Transplant 2023;38:106–18. https://doi.org/10.1093/ndt/gfac241.Search in Google Scholar PubMed

13. Ma, Y, Wei, L, Yong, Z, Yu, Y, Chen, Y, Zhu, B, et al.. Validation of the European Kidney Function Consortium (EKFC) equation in Chinese adult population: an equation standing on the shoulders of predecessors. Nephron 2023. https://doi.org/10.1159/000531030.Search in Google Scholar PubMed

14. Pottel, H, Vrydags, N, Mahieu, B, Vandewynckele, E, Croes, K, Martens, F. Establishing age/sex related serum creatinine reference intervals from hospital laboratory data based on different statistical methods. Clin Chim Acta 2008;396:49–55. https://doi.org/10.1016/j.cca.2008.06.017.Search in Google Scholar PubMed

15. Pottel, H, Bjork, J, Rule, AD, Ebert, N, Eriksen, BO, Dubourg, L, et al.. Cystatin C-based equation to estimate GFR without the inclusion of race and sex. N Engl J Med 2023;388:333–43. https://doi.org/10.1056/nejmoa2203769.Search in Google Scholar PubMed

16. Jeong, TD, Cho, EJ, Lee, W, Chun, S, Hong, KS, Min, WK. Accuracy assessment of five equations used for estimating the glomerular filtration rate in Korean adults. Ann Lab Med 2017;37:371–80. https://doi.org/10.3343/alm.2017.37.5.371.Search in Google Scholar PubMed PubMed Central

17. Haeckel, R, Wosniok, W, Arzideh, F, Zierk, J, Gurr, E, Streichert, T. Critical comments to a recent EFLM recommendation for the review of reference intervals. Clin Chem Lab Med 2017;55:341–7. https://doi.org/10.1515/cclm-2016-1112.Search in Google Scholar PubMed

18. Barai, S, Gambhir, S, Jain, S, Rastogi, N. Evaluation of basal renal function in treatment-naive patients with malignancy and comparison with age matched healthy control. World J Nucl Med 2016;15:148–52. https://doi.org/10.4103/1450-1147.167602.Search in Google Scholar PubMed PubMed Central

19. Eriksen, BO, Palsson, R, Ebert, N, Melsom, T, van der Giet, M, Gudnason, V, et al.. GFR in healthy aging: an individual participant data meta-analysis of iohexol clearance in European population-based cohorts. J Am Soc Nephrol 2020;31:1602–15. https://doi.org/10.1681/asn.2020020151.Search in Google Scholar PubMed PubMed Central

20. Shang, H, Wang, YS, Shen, ZS. National Guide to ClinicalLaboratory procedure, 4th ed. Beijing: People’s Medical Publishing House; 2015.Search in Google Scholar

21. Zhu, X, Wang, K, Zhou, Q, Guo, W, Jia, Y, Xu, J. Age- and sex-specific pediatric reference intervals of serum electrolytes in Jilin province of China using the a priori approach. Am J Clin Pathol 2020;154:708–20. https://doi.org/10.1093/ajcp/aqaa093.Search in Google Scholar PubMed PubMed Central

22. Speybroeck, N. Classification and regression trees. Int J Public Health 2012;57:243–6. https://doi.org/10.1007/s00038-011-0315-z.Search in Google Scholar PubMed

23. Harris, EK, Boyd, JC. On dividing reference data into subgroups to produce separate reference ranges. Clin Chem 1990;36:265–70. https://doi.org/10.1093/clinchem/36.2.265.Search in Google Scholar

24. Lahti, A. Are the common reference intervals truly common? Case studies on stratifying biochemical reference data by countries using two partitioning methods. Scand J Clin Lab Invest 2004;64:407–30. https://doi.org/10.1080/00365510410006027.Search in Google Scholar PubMed

25. Ammer, T, Schutzenmeister, A, Prokosch, HU, Rauh, M, Rank, CM. refineR: a novel algorithm for reference interval estimation from real-world data. Sci Rep 2021;11:16023. https://doi.org/10.1038/s41598-021-95301-2.Search in Google Scholar PubMed PubMed Central

26. Jiangsu Provincial Bureau of Statistics. Office of the leading group of Jiangsu province for the seventh national population census. Jiangsu population census yearbook 2020. Beijing: China Statistics Press; 2020.Search in Google Scholar

27. Ammer, T, Schutzenmeister, A, Prokosch, HU, Zierk, J, Rank, CM, Rauh, M. RIbench: a proposed benchmark for the standardized evaluation of indirect methods for reference interval estimation. Clin Chem 2022;68:1410–24. https://doi.org/10.1093/clinchem/hvac142.Search in Google Scholar PubMed

28. Waters, DL, Baumgartner, RN, Garry, PJ. Sarcopenia: current perspectives. J Nutr Health Aging 2000;4:133–9.Search in Google Scholar

29. Carrero, JJ, Hecking, M, Chesnaye, NC, Jager, KJ. Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease. Nat Rev Nephrol 2018;14:151–64. https://doi.org/10.1038/nrneph.2017.181.Search in Google Scholar PubMed

30. Ceriotti, F, Boyd, JC, Klein, G, Henny, J, Queralto, J, Kairisto, V, et al.. Reference intervals for serum creatinine concentrations: assessment of available data for global application. Clin Chem 2008;54:559–66. https://doi.org/10.1373/clinchem.2007.099648.Search in Google Scholar PubMed

31. Auyeung, TW, Lee, SW, Leung, J, Kwok, T, Woo, J. Age-associated decline of muscle mass, grip strength and gait speed: a 4-year longitudinal study of 3018 community-dwelling older Chinese. Geriatr Gerontol Int 2014;14:76–84. https://doi.org/10.1111/ggi.12213.Search in Google Scholar PubMed

32. Perrone, RD, Madias, NE, Levey, AS. Serum creatinine as an index of renal function: new insights into old concepts. Clin Chem 1992;38:1933–53. https://doi.org/10.1093/clinchem/38.10.1933.Search in Google Scholar

33. Wang, X, Xu, G, Li, H, Liu, Y, Wang, F. Reference intervals for serum creatinine with enzymatic assay and evaluation of four equations to estimate glomerular filtration rate in a healthy Chinese adult population. Clin Chim Acta 2011;412:1793–7. https://doi.org/10.1016/j.cca.2011.05.033.Search in Google Scholar PubMed

34. Li, H, Zheng, H, Deng, Q, Li, J, Wang, Z, Li, H, et al.. New comprehensive reference values for kidney function indexes across adult and geriatric ages in Chinese population. Heliyon 2022;8:e11919. https://doi.org/10.1016/j.heliyon.2022.e11919.Search in Google Scholar PubMed PubMed Central

35. Wei, DZ, Ge, M, Wang, CX, Lin, QY, Li, MJ, Li, P. Geographical distribution of the Serum creatinine reference values of healthy adults. Nan Fang Yi Ke Da Xue Xue Bao 2016;36:1555–60.Search in Google Scholar

36. Ma, G, Shao, M, Xu, B, Tian, J, Chen, Y. Establish new formulas for the calculation of renal depth in both children and adults. Clin Nucl Med 2015;40:e357–62. https://doi.org/10.1097/rlu.0000000000000808.Search in Google Scholar PubMed

37. Pan, XF, Wang, L, Pan, A. Epidemiology and determinants of obesity in China. Lancet Diabetes Endocrinol 2021;9:373–92. https://doi.org/10.1016/s2213-8587(21)00045-0.Search in Google Scholar

38. Inker, LA, Eneanya, ND, Coresh, J, Tighiouart, H, Wang, D, Sang, Y, et al.. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med 2021;385:1737–49. https://doi.org/10.1056/nejmoa2102953.Search in Google Scholar

39. Zelnick, LR, Leca, N, Young, B, Bansal, N. Association of the estimated glomerular filtration rate with vs. without a coefficient for race with time to eligibility for kidney transplant. JAMA Netw Open 2021;4:e2034004. https://doi.org/10.1001/jamanetworkopen.2020.34004.Search in Google Scholar PubMed PubMed Central

40. Zingano, CP, Escott, GM, Rocha, BM, Porgere, IF, Moro, CC, Delanaye, P, et al.. 2009 CKD-EPI glomerular filtration rate estimation in Black individuals outside the United States: a systematic review and meta-analysis. Clin Kidney J 2023;16:322–30, https://doi.org/10.1093/ckj/sfac238.Search in Google Scholar PubMed PubMed Central

41. Delanaye, P, Cavalier, E, Pottel, H, Stehle, T. New and old GFR equations: a European perspective. Clin Kidney J 2023;16:1375–83. https://doi.org/10.1093/ckj/sfad039.Search in Google Scholar PubMed PubMed Central


Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2023-1421).


Received: 2023-12-11
Accepted: 2024-01-02
Published Online: 2024-01-12
Published in Print: 2024-05-27

© 2024 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. SARS-CoV-2 is here to stay: do not lower our guard
  4. Reviews
  5. SARS-CoV-2 subgenomic RNA: formation process and rapid molecular diagnostic methods
  6. Prognostic value of anti-SARS-CoV-2 antibodies: a systematic review
  7. Presence of SARS-CoV-2 RNA in COVID-19 survivors with post-COVID symptoms: a systematic review of the literature
  8. Opinion Papers
  9. Harmonizing the post-analytical phase: focus on the laboratory report
  10. Blood-based biomarkers in Alzheimer’s disease – moving towards a new era of diagnostics
  11. A comprehensive review on PFAS including survey results from the EFLM Member Societies
  12. General Clinical Chemistry and Laboratory Medicine
  13. Report from the HarmoSter study: different LC-MS/MS androstenedione, DHEAS and testosterone methods compare well; however, unifying calibration is a double-edged sword
  14. An LC–MS/MS method for serum cystatin C quantification and its comparison with two commercial immunoassays
  15. CX3CL1/Fractalkine as a biomarker for early pregnancy prediction of preterm premature rupture of membranes
  16. Elevated S100B urine levels predict seizures in infants complicated by perinatal asphyxia and undergoing therapeutic hypothermia
  17. The correlation of urea and creatinine concentrations in sweat and saliva with plasma during hemodialysis: an observational cohort study
  18. Tubular phosphate transport: a comparison between different methods of urine sample collection in FGF23-dependent hypophosphatemic syndromes
  19. Reference Values and Biological Variations
  20. Monocyte distribution width (MDW): study of reference values in blood donors
  21. Data mining of reference intervals for serum creatinine: an improvement in glomerular filtration rate estimating equations based on Q-values
  22. Hematology and Coagulation
  23. MALDI-MS in first-line screening of newborns for sickle cell disease: results from a prospective study in comparison to HPLC
  24. Cardiovascular Diseases
  25. To rule-in, or not to falsely rule-out, that is the question: evaluation of hs-cTnT EQA performance in light of the ESC-2020 guideline
  26. Temporal biomarker concentration patterns during the early course of acute coronary syndrome
  27. Diabetes
  28. Proteomic analysis of diabetic retinopathy identifies potential plasma-protein biomarkers for diagnosis and prognosis
  29. Infectious Diseases
  30. Serum biomarkers of inflammation and vascular damage upon SARS-Cov-2 mRNA vaccine in patients with thymic epithelial tumors
  31. A high throughput immuno-affinity mass spectrometry method for detection and quantitation of SARS-CoV-2 nucleoprotein in human saliva and its comparison with RT-PCR, RT-LAMP, and lateral flow rapid antigen test
  32. Evaluation of inflammatory biomarkers and vitamins in hospitalized patients with SARS-CoV-2 infection and post-COVID syndrome
  33. The CoLab score is associated with SARS-CoV-2 viral load during admission in individuals admitted to the intensive care unit: the CoLaIC cohort study
  34. Development and evaluation of a CRISPR-Cas13a system-based diagnostic for hepatitis E virus
  35. Letters to the Editor
  36. Crioplast® is a reliable device to ensure pre-analytical stability of adrenocorticotrophin (ACTH)
  37. Falsely decreased Abbott Alinity-c gamma-glutamyl transferase-2 result from paraprotein and heparin interference: case report and subsequent laboratory experiments
  38. Impact of hemolysis on uracilemia in the context of dihydropyrimidine dehydrogenase deficiency testing
  39. Value of plasma neurofilament light chain for monitoring efficacy in children with later-onset spinal muscular atrophy under nusinersen treatment
  40. Analytical evaluation of the Snibe β-isomerized C-terminal telopeptide of type I collagen (β-CTX-I) automated method
  41. Acute myeloid leukemia with blue-green neutrophilic inclusions have different outcomes: two cases and review of the literature
  42. Congress Abstracts
  43. The 10+1 Santorini Conference
  44. 14th National Congress of the Portuguese Society of Clinical Chemistry, Genetics and Laboratory Medicine
  45. 15th National Congress of the Portuguese Society of Clinical Chemistry, Genetics and Laboratory Medicine
  46. ISMD2024 Thirteenth International Symposium on Molecular Diagnostics
Downloaded on 13.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2023-1421/html?lang=en
Scroll to top button