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Cystatin C and the misdiagnosis of CKD in older adults

The use of cystatin C-inclusive equations will continue to propagate the unnecessary overdiagnosis of chronic kidney disease (CKD) in older people. Cystatin C is less biologically specific for CKD than is serum creatinine, inflates the risks of adverse outcomes compared to measured glomerular filtration rate, and does not establish chronicity at a single time point.

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Fig. 1: The risk of a cardiovascular (CV) event or mortality by eGFR after adjusting for measured GFR among kidney transplant recipients.


  1. Eriksen, B. O. et al. GFR in healthy aging: an individual participant data meta-analysis of iohexol clearance in European population-based cohorts. J. Am. Soc. Nephrol. 31, 1602–1615 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 105, S117–S314 (2024).

    Article  Google Scholar 

  3. Liu, P. et al. Accounting for age in the definition of chronic kidney disease. JAMA Intern. Med. 181, 1359–1366 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Jonsson, A. J., Lund, S. H., Eriksen, B. O., Palsson, R. & Indridason, O. S. The prevalence of chronic kidney disease in Iceland according to KDIGO criteria and age-adapted estimated glomerular filtration rate thresholds. Kidney Int. 98, 1286–1295 (2020).

    Article  CAS  PubMed  Google Scholar 

  5. Kleeman, S. O. et al. Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy. Cell Genomics 3, 100347 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Keddis, M. T. et al. GFR estimated with creatinine rather than cystatin C is more reflective of the true risk of adverse outcomes with low GFR in kidney transplant recipients. Nephrol. Dial. Transplant. 38, 1898–1906 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Rule, A. D., Bailey, K. R., Lieske, J. C., Peyser, P. A. & Turner, S. T. Estimating the glomerular filtration rate from serum creatinine is better than from cystatin C for evaluating risk factors associated with chronic kidney disease. Kidney Int. 83, 1169–1176 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Fu, E. L. et al. Association of low glomerular filtration rate with adverse outcomes at older age in a large population with routinely measured cystatin C. Ann. Intern. Med. 177, 269–279 (2024).

    Article  PubMed  Google Scholar 

  9. Asghar, M. S. et al. Age-based versus young-adult thresholds for nephrosclerosis on kidney biopsy and prognostic implications for CKD. J. Am. Soc. Nephrol. 34, 1421–1432 (2023).

    Article  PubMed  Google Scholar 

  10. Denic, A. et al. An improved method for estimating nephron number and the association of resulting nephron number estimates with chronic kidney disease outcomes. J. Am. Soc. Nephrol. 34, 1264–1278 (2023).

    Article  PubMed  Google Scholar 

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The authors’ work is supported with funding from the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK090358).

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Correspondence to Andrew D. Rule.

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Rule, A.D., Glassock, R.J. Cystatin C and the misdiagnosis of CKD in older adults. Nat Rev Nephrol (2024).

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