The Difference Between Cystatin C- and Creatinine-Based Estimated GFR and Incident Frailty: An Analysis of the Cardiovascular Health Study (CHS).
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ABSTRACT:
SUBMITTER: Potok OA
PROVIDER: S-EPMC7967899 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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The Difference Between Cystatin C- and Creatinine-Based Estimated GFR and Incident Frailty: An Analysis of the Cardiovascular Health Study (CHS).
Potok O Alison OA Katz Ronit R Bansal Nisha N Siscovick David S DS Odden Michelle C MC Ix Joachim H JH Shlipak Michael G MG Rifkin Dena E DE
American journal of kidney diseases : the official journal of the National Kidney Foundation 20200716 6
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Project description:Rationale & objectiveLower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFRcys) and creatinine (eGFRcr) may differ substantially within an individual. The clinical implications of these differences for risk of HF among persons with chronic kidney disease (CKD) are unknown.Study designProspective cohort study.Setting & participants4,512 adults with CKD and without prevalent HF who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.ExposureDifference in GFR estimates (eGFRdiff; ie, eGFRcys minus eGFRcr).OutcomeIncident HF hospitalization.Analytical approachFine-Gray proportional subhazards regression was used to investigate the associations of baseline, time-updated, and slope of eGFRdiff with incident HF.ResultsOf 4,512 participants, one-third had eGFRcys and eGFRcr values that differed by over 15 mL/min/1.73 m2. In multivariable-adjusted models, each 15 mL/min/1.73 m2 lower baseline eGFRdiff was associated with higher risk of incident HF hospitalization (hazard ratio [HR], 1.20 [95% CI, 1.07-1.34]). In time-updated analyses, those with eGFRdiff less than -15 mL/min/1.73 m2 had higher risk of incident HF hospitalization (HR, 1.99 [95% CI, 1.39-2.86]), and those with eGFRdiff ≥15 mL/min/1.73 m2 had lower risk of incident HF hospitalization (HR, 0.67 [95% CI, 0.49-0.91]) compared with participants with similar eGFRcys and eGFRcr. Participants with faster declines in eGFRcys relative to eGFRcr had higher risk of incident HF (HR, 1.49 [95% CI, 1.19-1.85]) compared with those in whom eGFRcys and eGFRcr declined in parallel.LimitationsEntry into the CRIC Study was determined by eGFRcr, which constrained the range of baseline eGFRcr-but not eGFRcys-values.ConclusionsAmong persons with CKD who have large differences between eGFRcys and eGFRcr, risk for incident HF is more strongly associated with eGFRcys. Diverging slopes between eGFRcys and eGFRcr over time are also independently associated with risk of incident HF.
| S-EPMC9691565 | biostudies-literature
Project description:BackgroundThe difference between the estimated glomerular filtration rate (eGFR) calculated from cystatin C and creatinine (eGFRdiff) serves as a biomarker of kidney function impairment. However, the role of eGFRdiff in cardiovascular-kidney-metabolic (CKM) health and its impact on mortality in CKM syndrome patients has not yet been studied.MethodsThis study included 3,622 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004. Weighted ordinal logistic regression was used to explore the link between eGFRdiff and CKM health, while weighted Cox regression was used to examine the relationship between eGFRdiff and mortality in CKM syndrome patients. Restricted cubic splines (RCSs) were used to analyze the dose-response relationship.ResultsThe common odds ratio (cOR) per 10 mL/min/1.73m2 increase in eGFRdiff was 0.86 [95% confidence interval (CI), 0.81 to 0.91]. Compared to the midrange eGFRdiff, the cOR values for the negative and positive eGFRdiff were 1.88 [95% CI, 1.23 to 2.88] and 0.69 [95% CI, 0.58 to 0.83], respectively. During a median follow-up of 201 months, 853 participants died from all causes, while 265 died due to cardiovascular causes. The hazard ratios (HRs) per 10 mL/min/1.73m2 increase in eGFRdiff were 0.88 [95% CI, 0.83 to 0.93] for all-cause mortality and 0.90 [95% CI, 0.81 to 1.00] for cardiovascular mortality cases. Compared to the participants with a midrange eGFRdiff, those with negative eGFRdiff had a 48% higher risk of all-cause mortality, while those with positive eGFRdiff had a 30% lower risk. No significant non-linear associations were found in these regression analyses.ConclusionOur study found that eGFRdiff is associated with CKM health and stratified mortality risk in CKM syndrome patients.
| S-EPMC11774968 | biostudies-literature
Project description:Rationale & objectiveIn prior research and in practice, the difference between estimated glomerular filtration rate (eGFR) calculated from cystatin C level and eGFR calculated from creatinine level has not been assessed for clinical significance and relevance. We evaluated whether these differences contain important information about frailty.Study designA cohort analysis of the Systolic Blood Pressure Intervention Trial (SPRINT).Setting & participants9,092 hypertensive SPRINT participants who had baseline measurements of serum creatinine, cystatin C, and frailty.ExposureeGFRs calculated using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (eGFRcys and eGFRcr), and eGFRDiff, calculated as eGFRcys-eGFRcr.OutcomesA validated 35-item frailty index that included questionnaire data for general and physical health, limitations of activities, pain, depression, sleep, energy level, self-care, and smoking status, as well as medical history, cognitive assessment, and laboratory data. We defined frailty as frailty index score>0.21 (range, 0-1). The incidence of injurious falls, hospitalizations, cardiovascular events, and mortality was also recorded.Analytical approachWe used logistic regression to model the cross-sectional association of baseline eGFRDiff with frailty among all SPRINT participants. Adjusted proportional hazards regression was used to evaluate the association of eGFRDiff with adverse outcomes and mortality.ResultsMean age was 68±9 (SD) years, mean eGFRcys and eGFRcr were 73±23 and 72±20mL/min/1.73m2, and mean eGFRDiff was 0.5±15mL/min/1.73m2. In adjusted models, each 1-SD higher eGFRDiff was associated with 24% lower odds of prevalent frailty (OR, 0.76; 95% CI, 0.71-0.81), as well as with lower incidence rate of injurious falls (HR, 0.84; 95% CI, 0.77-0.92), hospitalization (HR, 0.91; 95% CI, 0.88-0.95), cardiovascular events (HR, 0.89; 95% CI, 0.81-0.97), and all-cause mortality (HR, 0.71; 95% CI, 0.63-0.82); P<0.01.LimitationsGold-standard measure of kidney function and assessment of muscle mass were not available.ConclusionsThe difference between eGFRcys and eGFRcr is associated with frailty and health status. Positive eGFRDiff is strongly associated with lower risks for longitudinal adverse outcomes and mortality, even after adjusting for chronic kidney disease stage and baseline frailty.
| S-EPMC8896529 | biostudies-literature
Project description:Rationale & objectiveUse of cystatin C in addition to creatinine to estimate glomerular filtration rate (estimated glomerular filtration rate based on cystatin C [eGFRcys] and estimated glomerular filtration rate based on creatinine [eGFRcr], respectively) is increasing. When eGFRcr and eGFRcys are discordant, it is not known which is more accurate, leading to uncertainty in clinical decision making.Study designCross-sectional analysis.Setting & participantsFour thousand fifty participants with measured glomerular filtration rate (mGFR) from 12 studies in North America and Europe.ExposuresSerum creatinine and serum cystatin C.OutcomesPerformance of creatinine-based and cystatin C-based glomerular filtration rate estimating equations compared to mGFR.Analytical approachWe evaluated the accuracy of eGFRcr, eGFRcys, and the combination (eGFRcr-cys) compared to mGFR according to the magnitude of the difference between eGFRcr and eGFRcys (eGFRdiff). We used CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations to estimate glomerular filtration rate. eGFRdiff was defined as eGFRcys minus eGFRcr and categorized as less than -15, -15 to <15, and ≥15 mL/min/1.73 m2 (negative, concordant, and positive groups, respectively). We compared bias (median of mGFR minus eGFR) and the percentage of eGFR within 30% of mGFR.ResultsThirty percent of participants had discordant eGFRdiff (21.0% and 9.6% negative and positive eGFRdiffs, respectively). In the concordant eGFRdiff group, all equations displayed similar accuracy. In the negative eGFRdiff groups, eGFRcr had a large overestimation of mGFR (-13.4 [-14.5 to -12.2] mL/min/1.73 m2) and eGFRcys had a large underestimation (9.9 [9.1-11.2] mL/min/1.73m2), with opposite results in the positive eGFRdiff group. In both negative and positive eGFRdiff groups, eGFRcr-cys was more accurate than either eGFRcr or eGFRcys. These results were largely consistent across age, sex, race, and body mass index.LimitationsFew participants with major comorbid conditions.ConclusionsDiscordant eGFRcr and eGFRcys are common. eGFR using the combination of creatinine and cystatin C provides the most accurate estimates among persons with discordant eGFRcr or eGFRcys.
| S-EPMC10518599 | biostudies-literature
Project description:Rationale & objectiveEstimation of glomerular filtration rate (eGFR) and staging of chronic kidney disease (CKD) are essential to guide management. Although creatinine is routinely used, a recent national task force recommended the use of cystatin C for confirmation. The objective of this study was to examine the following parameters: (1) how cystatin C correlates with creatinine eGFR; (2) how it indicates differences in CKD staging; and (3) how it may affect kidney care delivery.Study designRetrospective observational cohort study.Setting & participants1,783 inpatients and outpatients who had cystatin C and creatinine levels drawn within 24 hours at Brigham Health-affiliated clinical laboratories.PredictorsSerum creatinine levels, basic clinical/sociodemographic variables, and reasons for ordering cystatin C from a structured partial chart review.Analytical approachUnivariate and multivariable linear and logistic regression.ResultsCystatin C-based eGFR was very strongly correlated with creatinine-based eGFR (Spearman correlation ρ = 0.83). Cystatin C eGFR resulted in a change to a later CKD stage in 27%, an earlier stage in 7%, and no change in 66% of patients. Black race was associated with a lower likelihood of change to a later stage (OR, 0.53; 95% CI [0.36, 0.75]; P < 0.001), whereas age (OR per year OR, 1.03; 95% CI [1.02, 1.04]; P < 0.001) and Elixhauser score (OR per point OR, 1.22; 95% CI [1.10, 1.36]; P < 0.001) were associated with a higher likelihood of change to a later stage.LimitationsSingle center, no direct measurement of clearance for comparison, and inconsistent self-identification of race/ethnicity.ConclusionsCystatin C eGFR correlates strongly with creatinine eGFR but can have a substantial effect on CKD staging. As cystatin C is adopted, clinicians must be informed on this impact.
| S-EPMC9984886 | biostudies-literature
Project description:Rationale & objectiveSerum creatinine and cystatin C are used to estimate glomerular filtration rate, but creatinine-based estimated glomerular filtration rate (eGFRcr), cystatin C-based estimated glomerular filtration rate (eGFRcys), and combined creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) are often divergent, particularly in older adults. We investigated which estimated glomerular filtration rate (eGFR) was more accurate and less biased compared with measured glomerular filtration rate (mGFR).Study designA diagnostic test study from the Berlin Initiative Study.Setting & participantsThe study population included 657 individuals aged 70 years or older with iohexol plasma clearance (mGFR) and serum creatinine and cystatin C measurements: 567 community-dwelling participants and 90 with a serum creatinine of ≥1.5 mg/dL.Tests comparedWe defined 3 groups on the basis of the difference eGFRcys - eGFRcr: whether < -5 mL/min/1.73 m2 (lower eGFRcys), within 5 mL/min/1.73 m2 (reference), or ≥ 5 mL/min/1.73 m2 (lower eGFRcr). eGFRcr, eGFRcys, and eGFRcr-cys were compared to mGFR to assess bias and accuracy.OutcomeMedian bias (eGFR minus mGFR) with 95% CIs and accuracy (percentage of eGFR values within ±30% of mGFR).ResultsThe mean ± standard deviation age was 78 ± 6 years; the mean eGFRcys, eGFRcr, and eGFRcr-cys were 59 ± 23, 64 ± 20, and 61 ± 22 mL/min/1.73 m2, respectively, and the mean mGFR was 56 ± 19 mL/min. Half of the participants were in the lower eGFRcys group (n=337, 51%). Among them, the median bias for eGFRcys was the lowest (median bias, -2.7; 95% CI, -3.8 to -1.9) compared with the other eGFR equations. Conversely, in the lower eGFRcr group (n=121, 18%), the median bias for eGFRcr was the lowest compared with those for eGFRcys and eGFRcr-cys (2.9; [95% CI, 0.9-4.8] vs 13.8 [95% CI, 11.4-15.6] and 9.5 [95% CI, 7.7-11.0], respectively). Accuracy (percentage of eGFR values within ±30% of mGFR) was 93% for eGFRcr in the lower eGFRcr group and 92% for eGFRcys and 94% for eGFRcr-cys in the lower eGFRcys group.LimitationsUntested generalizability in younger populations.ConclusionsAmong older adults, the lower eGFR between eGFRcys and eGFRcr was a more accurate and less biased estimate of mGFR when comparing the groups.
| S-EPMC10165149 | biostudies-literature
Project description:Rationale & objectiveLarge differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) occur commonly. A comprehensive evaluation of factors that contribute to these differences is needed to guide the interpretation of discrepant eGFR values.Study designCohort study.Setting & participants468,969 participants in the UK Biobank.ExposuresCandidate sociodemographic, lifestyle factors, comorbidities, medication usage, and physical and laboratory predictors.OutcomeseGFRdiff, defined as eGFRcys minus eGFRcr, categorized into 3 levels: lower eGFRcys (eGFRdiff, less than -15 mL/min/1.73 m2), concordant eGFRcys and eGFRcr (eGFRdiff, -15 to < 15 mL/min/1.73 m2), and lower eGFRcr (eGFRdiff, ≥15 mL/min/1.73 m2).Analytical approachMultinomial logistic regression models were constructed to identify predictors of lower eGFRcys or lower eGFRcr. We developed 2 prediction models comprising 375,175 participants: (1) a clinical model using clinically available variables and (2) an enriched model additionally including lifestyle variables. The models were internally validated in an additional 93,794 participants.ResultsMean ± standard deviation of eGFRcys was 88 ± 16 mL/min/1.73 m2, and eGFRcr was 95 ± 13 mL/min/1.73 m2; 25% and 5% of participants were in the lower eGFRcys and lower eGFRcr groups, respectively. In the multivariable enriched model, strong predictors of lower eGFRcys were older age, male sex, South Asian ethnicity, current smoker (vs never smoker), history of thyroid dysfunction, chronic inflammatory disease, steroid use, higher waist circumference and body fat, and urinary albumin-creatinine ratio >300 mg/g. Odds ratio estimates for these predictors were largely inverse of those in the lower eGFRcr group. The model's area under the curve was 0.75 in the validation set, with good calibration (1.00).LimitationsLimited generalizability.ConclusionsThis study highlights the multitude of demographic, lifestyle, and health characteristics that are associated with large eGFRdiff. The clinical model may identify individuals who are likely to have discrepant eGFR values and thus should be prioritized for cystatin C testing.
| S-EPMC10986041 | biostudies-literature
Project description: Not available
| S-EPMC11284434 | biostudies-literature
Project description:BackgroundHigher serum cystatin C level is associated with an increased risk of hip fracture in postmenopausal white women, but there is a paucity of data for men. Whether estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) is superior in predicting hip fracture risk to eGFR based on creatinine (eGFRcr) or the combination (eGFR(cr-cys)) also is uncertain.Study designNested case-cohort.Setting & participantsParticipants enrolled in the Osteoporotic Fractures in Men (MrOS) Study (5,994 men aged ≥ 65 years from 6 US centers) including a random subcohort of 1,602 men and 168 men with incident hip fractures (51 of whom were in the subcohort).PredictoreGFR(cys), eGFR(cr), and eGFR(cr-cys) computed using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations and expressed in categories of <60, 60-74, and ≥ 75 mL/min/1.73 m(2) (referent group).OutcomeIncident hip fracture ascertained by participant contacts every 4 months and confirmed with radiographic reports.ResultsMedian eGFR(cys) was 72.9 (IQR, 60.5-85.7) mL/min/1.73 m(2). In unadjusted models, all measures of eGFR were associated with increased hip fracture risk. However, after adjustment for age, race, site, and body mass index, the association of lower eGFR(cys) (but not lower eGFR(cr) or lower eGFR(cr-cys)) with higher hip fracture risk remained: for <60 versus ≥ 75 mL/min/1.73 m(2), HRs were 1.96 [95% CI, 1.25-3.09], 0.84 [95% CI, 0.52-1.37], and 1.08 [95% CI, 0.66-1.77] for eGFR(cys), eGFR(cr), and eGFR(cr-cys), respectively. Similarly, after adjustment for age, race, site, and body mass index, eGFR < 60 mL/min/1.73 m(2) defined by eGFR(cys), but not eGFR(cr) or eGFR(cr-cys), was associated with higher hip fracture risk. The association between eGFR(cys) and hip fracture was not explained by levels of calciotropic hormones or inflammatory markers, but the relationship was attenuated and no longer reached significance (for <60 vs ≥ 75 mL/min/1.73 m(2): HR, 1.43; 95% CI, 0.88-2.34) after consideration of additional clinical risk factors and bone mineral density.LimitationsFindings not generalizable to other populations; residual confounding may exist.ConclusionsOlder community-dwelling men with lower eGFR(cys) have an increased risk of hip fracture that is explained in large part by greater burden of risk factors among men with lower eGFR(cys). In contrast, lower eGFR(cr) or lower eGFR(cr-cys) was not associated with a higher age-adjusted hip fracture risk.
| S-EPMC3833961 | biostudies-literature
Project description:BackgroundSerum cystatin C-based estimated glomerular filtration rate (eGFRcys) generally associates with clinical outcomes better than serum creatinine-based eGFR (eGFRcr) despite similar precision in estimating measured GFR (mGFR). We sought to determine whether the risk of adverse outcomes with eGFRcr or eGFRcys was via GFR alone or also via non-GFR determinants among kidney transplant recipients.MethodsConsecutive adult kidney transplant recipients underwent a standardized GFR assessment during a routine follow-up clinic visit between 2011 and 2013. Patients were followed for graft failure or the composite outcome of cardiovascular (CV) events or mortality through 2020. The risk of these events by baseline mGFR, eGFRcr and eGFRcys was assessed unadjusted, adjusted for mGFR and adjusted for CV risk factors.ResultsThere were 1135 recipients with a mean baseline mGFR of 55.6, eGFRcr of 54.8 and eGFRcys of 46.8 ml/min/1.73 m2 and a median follow-up of 6 years. Each 10 ml/min/1.73 m2 decrease in mGFR, eGFRcr or eGFRcys associated with graft failure [hazard ratio (HR) 1.79, 1.68 and 2.07, respectively; P < .001 for all) and CV events or mortality outcome (HR 1.28, 1.19 and 1.43, respectively; P < .001 for all). After adjusting for mGFR, eGFRcys associated with graft failure (HR 1.57, P < .001) and CV events or mortality (HR 1.49, P < .001), but eGFRcr did not associate with either. After further adjusting for CV risk factors, risk of these outcomes with lower eGFRcys was attenuated.ConclusioneGFRcr better represents the true relationship between GFR and outcomes after kidney transplantation because it has less non-GFR residual association. Cystatin C is better interpreted as a nonspecific prognostic biomarker than is eGFR in the kidney transplant setting.
| S-EPMC10387404 | biostudies-literature