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Examining the utility of cystatin C as a confirmatory test of chronic kidney disease across the age range in middle-aged and older community-dwelling adults
  1. Mark Canney1,2,
  2. Donal J Sexton1,2,
  3. Neil O’Leary1,
  4. Martin Healy3,
  5. Rose Anne Kenny1,
  6. Mark A Little2,
  7. Conall M O’Seaghdha4
  1. 1 The Irish Longitudinal Study on Ageing, Trinity College Dublin, Dublin, Ireland
  2. 2 Trinity Health Kidney Centre, Tallaght Hospital, Dublin, Ireland
  3. 3 Department of Biochemistry, St. James’ Hospital, Dublin, Ireland
  4. 4 Department of Renal Medicine, Beaumont Hospital, Dublin, Ireland
  1. Correspondence to Dr Mark Canney, The Irish Longitudinal Study on Ageing, University of Dublin Trinity College, Dublin 2, Ireland; mcanney{at}


Background Cystatin C has been proposed as a confirmatory test of chronic kidney disease (CKD). This is most applicable to older individuals with CKD, the majority of whom have a creatinine-based estimated glomerular filtration rate (eGFR) of 45–59 mL/min/1.73 m2 (CKD stage 3a). We sought to examine the utility of cystatin C as a confirmatory test of CKD across the age range in the general population of older adults.

Methods Cross-sectional analysis of 5386 participants from The Irish Longitudinal Study on Ageing, a cluster-sampled national cohort of community-dwelling adults aged ≥50 years. Cystatin C and creatinine were measured simultaneously using standardised assays. Using generalised additive models, we modelled the distributions of creatinine and cystatin C per year of age from four distributional parameters: location, dispersion, skewness, kurtosis. Among participants with CKD stage 3a, we estimated the predicted probability of cystatin C eGFR <60 mL/min/1.73 m2 (‘confirmed CKD’) as a function of age.

Results Median age was 62 years, 53% were female and median cystatin C eGFR was 80 mL/min/1.73 m2. We observed progressive variability in cystatin C with increasing age. Compared with creatinine, cystatin C levels rose sharply beyond the age of 65. Among participants with CKD stage 3a (n=463), the predicted probability of ‘confirmed CKD’ increased steadily with age, from 15% at age 50 to 80% at age 80.

Conclusions The clinical utility of cystatin C may be maximised in middle-aged individuals, in whom the distribution of cystatin C is less variable than older adults, and the pretest probability of confirming CKD is lower.

  • Ageing
  • , Biostatistics
  • , Epidemiology of chronic diseases
  • , renaL

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  • Contributors Study conception or design: MC, DJS, RAK, MAL, CMOS; statistical analysis: MC, NOL; data interpretation: all authors; manuscript drafting or revision: all authors; provided intellectual content: all authors; final approval of submitted manuscript: all authors.

  • Funding This work was supported by the Health Research Board of Ireland (grant numbers HPF/2014/540 (to MC), HRB/RL/2013/7). TILDA was funded by the Irish Government and The Atlantic Philanthropies, along with support from Irish Life in the form of a charitable gift.

  • Competing interests None declared.

  • Ethics approval Research Ethics Committee of Trinity College Dublin.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The anonymised TILDA dataset is publicly available to researchers who meet the criteria for access, at no monetary cost, from the Irish Social Science Data Archive (ISSDA) at University College Dublin ( and the Interuniversity Consortium for Political and Social Research (ICPSR) at the University of Michigan (