The Impact of Interlaboratory Differences in Cystatin C Assay Measurement on Glomerular Filtration Rate Estimation

White, Christine A.; Rule, Andrew D.; Collier, Christopher M.; Akbari, Ayub; Lieske, John C.; Lepage, Nathalie; Doucette, Steve; Knoll, Greg

doi:10.2215/cjn.00130111

Cited by 30 publications

(18 citation statements)

References 29 publications

(33 reference statements)

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“…Given known variation in cystatin C calibrators over time, 17 our calibration of cystatin C concentrations over more than a decade of measurement was key to the implementation of this study, and it documents an approach that could be modeled by other longitudinal studies.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Changes in Estimated and Measured GFR in Type 1 Diabetes

Sun

Cleary

Lachin

et al. 2014

Journal of the American Society of Nephrology

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Estimation of GFR from serum concentrations of creatinine and cystatin C has been refined using crosssectional data from large numbers of people. However, the ability of the improved estimating equations to identify changes in GFR within individuals over time has not been rigorously evaluated, particularly within the normal range of GFR. In cross-sectional and longitudinal analyses of 1441 participants in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study with type 1 diabetes, we compared GFR estimated from creatinine (eGFR Cr ), cystatin C (eGFR Cys ), or both (eGFR Cr+Cys ) with iothalamate GFR (iGFR), including changes in each over time. Mean (SD) iGFR was 122.7 (21.0) ml/min per 1.73 m 2 . In cross-sectional analyses, eGFR Cr+Cys estimated iGFR with the highest correlation (r=0.48 versus 0.39-0.42), precision, and accuracy. In longitudinal analyses, change in eGFR Cr+Cys best estimated change in iGFR; however, differences between estimates were small, and no estimate accurately classified change in iGFR. Over a median 23 years of follow-up, mean rate of change in eGFR was similar across estimates of eGFR Cr , eGFR Cys , and eGFR Cr+Cys (21.37, 21.11, and 21.29 ml/min per 1.73 m 2 per year, respectively). Associations of BP and hemoglobin A1c with change in eGFR were strongest for eGFR Cys and eGFR Cr+Cys . Together, these results suggest that the addition of cystatin C to creatinine to estimate GFR may improve identification of the causes and consequences of GFR loss in type 1 diabetes, but may not meaningfully improve the tracking of GFR in clinical care. 25: 810-818, 201425: 810-818, . doi: 10.1681 Reduced GFR leads to ESRD and metabolic complications of CKD. Estimation of GFR from serum concentrations of creatinine and cystatin C has been refined using cross-sectional data from large numbers of people. 1 As a result, individuals with reduced GFR and increased risk of adverse clinical outcomes can be more accurately identified within populations. 1,2 However, the ability of the improved estimating equations to identify changes in GFR within individuals over time has not been rigorously evaluated, particularly within the normal range of GFR ($60 ml/min per 1.73 m 2 ). Detecting changes in GFR within individual patients is important to develop, evaluate, and implement strategies to prevent CKD. J Am Soc NephrolIdentifying changes in GFR within individuals may be particularly useful in type 1 diabetes. Patients with type 1 diabetes often have GFR higher than normal early in the course of disease (hyperfiltration). 3 Over many years of follow-up, some of these patients develop overtly reduced GFR (,60 ml/min per 1.73 m 2 ). 4 Tracking GFR during this interval is challenging, because large changes in GFR may cause only small changes in serum creatinine and cystatin C concentrations. In addition, it is now clear that macroalbuminuria (urine albumin excretion$300 mg/d) is not a sensitive marker of early GFR loss. Rather, some patients...

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Section: Discussionmentioning

confidence: 99%

Longitudinal Changes in Estimated and Measured GFR in Type 1 Diabetes

Sun

Cleary

Lachin

et al. 2014

Journal of the American Society of Nephrology

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“…Laboratory drift in the cystatin C assay has proved substantial, even when measured using the same assay from the same manufacturer, and our results underscore the importance of careful calibration of cystatin C measurements in NHANES. 27, 28 In addition, we used cystatin C-based GFR estimating equations developed in a diverse population and which include age and sex, rather than equations developed in a CKD population that did not use these terms. 11, 13 …”

Section: Discussionmentioning

confidence: 99%

Trends in the Prevalence of Reduced GFR in the United States: A Comparison of Creatinine- and Cystatin C−Based Estimates

Grams

Juraschek

Selvin

et al. 2013

American Journal of Kidney Diseases

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Background The US prevalence of reduced estimated glomerular filtration rate (eGFR) based on serum creatinine increased over the decade ending in 2002. National Health and Nutrition Examination Survey (NHANES) cystatin C measurements were recently calibrated to the international standard, allowing for an independent test of the trend in prevalence of reduced eGFR using cystatin C. Study Design Cross-sectional surveys performed during two periods. Setting & Participants Nationally representative subsamples of adult participants from NHANES III (1988–1994) and the NHANES 1999–2002 surveys. Predictor Survey period. Outcomes Prevalence of reduced GFR, defined as eGFR<60ml/min/1.73m2 based on serum creatinine, cystatin C, or both (eGFRcr, eGFRcys, eGFRcr-cys), using estimating equations developed by the Chronic Kidney Disease Epidemiology Collaboration (CKDEPI). Measurements Serum cystatin C, measured from stored samples in 2006, calibrated to the international standard in 2012. Results Between 1988–1994 and 1999–2002, the prevalence of reduced eGFRcr, eGFRcys and eGFRcr-cys increased from 4.7% (95% CI, 4.1%–5.3%) to 6.5% (95% CI, 5.9%–7.1%; p<0.001), from 5.5% (95% CI, 4.6%–6.5%) to 8.7% (95% CI, 7.5%–10.0%; p<0.001), and from 4.4% (95% CI, 3.7%–5.2%) to 7.1% (95% CI, 6.2%–8.0%; p<0.001), respectively. The higher prevalence of reduced GFR in the later period was observed in all subgroups of age, race, sex, and GFR categories. After adjusting for changes in the US population by age, sex, race, diabetes, hypertension, and body mass index, the prevalence ratio of reduced GFR in the later versus earlier survey was 1.24 (95% CI, 1.09–1.45), 1.34 (95% CI, 1.15–1.67), and 1.33 (95% CI, 1.17–1.65) using eGFRcr, eGFRcys, and eGFRcr-cys, respectively. Limitations Likely under-ascertainment of persons with GFR<15 ml/min/1.73m2; GFR was estimated and not measured; comparability of laboratory assays based on a calibration subsample. Conclusions The prevalence of reduced eGFRcys in the US civilian, non-institutionalized population increased between 1988–1994 and 1999–2002, confirming the increase observed in the prevalence of reduced eGFRcr.

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“…Thus, the application of these eGFRcys in elderly, obese patients with type 2 diabetes seems to lead to an incorrect estimation of GFR. In addition, there is no standardisation between assays and laboratories for cystatin C [33]. We used published results to calibrate our measurements of cystatin C to other methods [23], but this calibration worsened the results for almost all eGFRcys.…”

Section: Discussionmentioning

confidence: 99%

Glomerular filtration rate estimation in patients with type 2 diabetes: creatinine- or cystatin C-based equations?

et al. 2011

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Aims/hypothesis It is argued that GFR estimation (eGFR) using cystatin C-based equations (eGFRcys) is superior to that using creatinine-based equations (eGFRcre). We investigated whether eGFRcys are superior to eGFRcre in patients with type 2 diabetes. Methods GFR was measured in 448 type 2 diabetic patients using 51 Cr-EDTA-measured GFR (mGFR) as the reference standard. Bias, precision and accuracy of eGFRcys and eGFRcre were compared. Results The most accurate eGFRcre equation (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]), which produced the highest proportion of estimates that were within 30% and 10% of the reference standard (80.7% and 38.0% of samples, respectively) had a bias of 7.1 and precision of 12.0 ml min −1 1.73 m −2 . The calibrated eGFRcys with the highest accuracy (Tan-C), which produced the highest proportion of estimates that were within 30% (78.8%) and within 10% (39.0%) of the reference standard had a bias of −3.5 and precision of 18.0 ml min ) and moderate (mGFR <60 ml min −1 1.73 m −2

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The Impact of Interlaboratory Differences in Cystatin C Assay Measurement on Glomerular Filtration Rate Estimation

Cited by 30 publications

References 29 publications

Longitudinal Changes in Estimated and Measured GFR in Type 1 Diabetes

Longitudinal Changes in Estimated and Measured GFR in Type 1 Diabetes

Trends in the Prevalence of Reduced GFR in the United States: A Comparison of Creatinine- and Cystatin C−Based Estimates

Glomerular filtration rate estimation in patients with type 2 diabetes: creatinine- or cystatin C-based equations?

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