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Cystatin C provides a better estimate of the effect of glomerular filtration rate on serum human epididymis protein 4 concentrations

  • Simona Ferraro EMAIL logo , Sara Pasqualetti , Assunta Carnevale and Mauro Panteghini
Published/Copyright: April 19, 2016
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 54 Issue 10

Abstract

Background:

We evaluated the effect of kidney glomerular function on serum concentrations of human epididymis protein 4 (HE4) using creatinine (Cr), cystatin C (CysC) and related chronic kidney disease epidemiology collaboration (CKD-EPI) equations.

Methods:

We enrolled 101 women aged ≤56 years with a glomerular filtration rate (GFR) (estimated by CKD-EPI eGFRCr) ranging from 60 to 120 mL/min/1.73 m2, free of any disease and biological and life-style factors known to influence serum HE4 concentrations, and we measured serum Cr, CysC and HE4 concentrations. Cr and CysC values were included in the three CKD-EPI equations to obtain GFR estimates.

Results:

A statistically significant increase in HE4 median concentrations was detected in subjects with an eGFRCr between 60 and 74 mL/min/1.73 m2 when compared with those with an eGFR >90 mL/min/1.73 m2 (54.2 vs. 42.2 pmol/L, p=0.003). Regression models showed that CysC measurement per se and eGFRCysC were the most sensitive markers to catch HE4 increases due to a mild decrease in renal function [adjusted r2, 0.38 (p=0.00003) and 0.37 (p=0.0004), respectively]. By assuming baseline CysC and eGFRCysC at 0.80 mg/L and 101.5 mL/min/1.73 m2, an increase of 0.10 mg/L in CysC concentrations and a decrease of 10 mL/min of eGFRCysC implied an average (±SE) increase in serum HE4 concentrations of 9.2 (±1.2) and 8.8 (±1.1) pmol/L, respectively.

Conclusions:

Our study shows that a better estimate of the effect of GFR on serum HE4 is obtained by measuring CysC in serum or using CKD-EPI eGFRCysC equation.

Keywords: biological variation; glomerular filtration; human epididymis protein 4; kidney; ovarian cancer; tumor marker

Acknowledgments:

We thank Abbott Diagnostics for the gift of HE4 and CysC reagents to carry out the study.

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

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplemental Material:

The online version of this article (DOI: 10.1515/cclm-2015-1272) offers supplementary material, available to authorized users.

Received: 2015-12-29
Accepted: 2016-3-10
Published Online: 2016-4-19
Published in Print: 2016-10-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2015-1272
Keywords for this article
biological variation; glomerular filtration; human epididymis protein 4; kidney; ovarian cancer; tumor marker

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Serum myoglobin immunoassays: obsolete or still clinically useful?
  4. Reviews
  5. Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management
  6. What do we know about homocysteine and exercise? A review from the literature
  7. Mini Review
  8. Osteocalcin as a potential risk biomarker for cardiovascular and metabolic diseases
  9. Opinion Paper
  10. Statistical approach for optimization of external quality assurance (EQA) studies of molecular and serological viral diagnostics
  11. EFLM Article
  12. Sample collections from healthy volunteers for biological variation estimates’ update: a new project undertaken by the Working Group on Biological Variation established by the European Federation of Clinical Chemistry and Laboratory Medicine
  13. General Clinical Chemistry and Laboratory Medicine
  14. Analyte stability during the total testing process: studies of vitamins A, D and E by LC-MS/MS
  15. Improvement in the predictive ability of the Intermountain Mortality Risk Score by adding routinely collected laboratory tests such as albumin, bilirubin, and white cell differential count
  16. Cystatin C provides a better estimate of the effect of glomerular filtration rate on serum human epididymis protein 4 concentrations
  17. Verification of the harmonization of human epididymis protein 4 assays
  18. Clinical utility of urinary liver-type fatty acid binding protein measured by latex-enhanced turbidimetric immunoassay in chronic kidney disease
  19. Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa
  20. Reference Values and Biological Variations
  21. Distribution of antiphospholipid antibodies in a large population-based German cohort
  22. Cardiovascular Diseases
  23. Serum protein S100 as marker of postoperative delirium after off-pump coronary artery bypass surgery: secondary analysis of two prospective randomized controlled trials
  24. Infectious Diseases
  25. Copeptin predicts 10-year all-cause mortality in community patients: a 10-year prospective cohort study
  26. Clinical and laboratory findings in the diagnosis of right lower quadrant abdominal pain: outcome analysis of the APPAC trial
  27. Letters to the Editor
  28. Why a new algorithm using high-sensitivity cardiac troponins for the rapid rule-out of NSTEMI is not adapted to routine practice
  29. Optimal collection tubes for plasma glucose determination: confusion reigns supreme
  30. Long-term stability of serum samples positive for carbohydrate deficient transferrin (CDT) routinely stored at −20 °C
  31. Seasonal variations in plasma free metanephrine concentrations are not evident in the West of Ireland
  32. Potential errors in the determination of urinary ammonium by formol titration
  33. Interference by biological anti-cancer drugs in electrophoretic and immunofixation techniques
  34. A point mutation in the thiopurine S-methyltransferase gene that led to exon 5 deletion in the transcribed mRNA
  35. Detection of the heterozygote of hemoglobin Constant Spring by α-thalassemia immunochromatographic strip test
  36. Automated CH50 liposome-based immunoassay: consideration in dilution and validation of reference interval
  37. Theranos phenomenon – Part 5: Theranos’ presentation at the American Association for Clinical Chemistry Annual Conference 2016
  38. Congress Abstracts
  39. 58th National Congress of the Hungarian Society of Laboratory Medicine
  40. The 4th Joint EFLM-UEMS Congress “Laboratory Medicine at the Clinical Interface” Warsaw, Poland, 21th–24th September, 2016
  41. Congress of Clinical Chemistry and Laboratory Medicine
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