Accessible Unlicensed Requires Authentication Published online by De Gruyter October 3, 2020

Critical appraisal and meta-analysis of biological variation estimates for kidney related analytes

Niels Jonker, Berna Aslan, Beatriz Boned, Fernando Marqués-García, Carmen Ricós, Virtudes Alvarez, William Bartlett, Federica Braga ORCID logo, Anna Carobene, Abdurrahman Coskun, Jorge Diaz-Garzón, Pilar Fernández-Calle, Elisabet Gonzalez-Lao, Joana Minchinela, Carmen Perich, Margarita Simón, Sverre Sandberg, Aasne K. Aarsand and on behalf of theEuropean Federation of Clinical Chemistry and Laboratory Medicine Working Group on Biological Variation and Task Group for the Biological Variation Database



Kidney markers are some of the most frequently used laboratory tests in patient care, and correct clinical decision making depends upon knowledge and correct application of biological variation (BV) data. The aim of this study was to review available BV data and to provide updated BV estimates for the following kidney markers in serum and plasma; albumin, creatinine, cystatin C, chloride, potassium, sodium and urea.


Relevant studies were identified from a historical BV database as well as by systematic literature searches. Retrieved publications were appraised by the Biological Variation Data Critical Appraisal Checklist (BIVAC). Meta-analyses of BIVAC compliant studies with similar design were performed to deliver global estimates of within-subject (CVI) and between-subject (CVG) BV estimates. Out of the 61 identified papers, three received a BIVAC grade A, four grade B, 48 grade C, five grade D grade and one was not appraised as it did not report numerical BV estimates. Most studies were identified for creatinine (n=48). BV estimates derived from the meta-analysis were in general lower than previously reported estimates for all analytes except urea. For some measurands, BV estimates may be influenced by age or states of health, but further data are required.


This review provides updated global BV estimates for kidney related measurands. For all measurands except for urea, these estimates were lower than previously reported.


For the measurands analyzed in this review, there are sufficient well-designed studies available to publish a trustworthy estimate of BV. However, for a number of newly appearing kidney markers no suitable data is available and additional studies are required.

Corresponding author: Dr. Niels Jonker, Certe-Wilhelmina Ziekenhuis Assen, Europaweg-Zuid 1, 9401 RK, Assen, The Netherlands, E-mail:


The authors acknowledge Thomas Roraas for his invaluable advice and assistance in performing all statistical analysis required for this study.

  1. Research funding: None declared.

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

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

  4. Informed consent: Informed consent was obtained from all individuals included in this study.


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2020-07-30
Accepted: 2020-08-24
Published Online: 2020-10-03

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