Chronic kidney disease, cardiovascular risk markers and total mortality in older men: cystatin C versus creatinine

BackgroundIt remains uncertain whether cystatin C is a superior marker of renal function than creatinine in older adults. We have investigated the association between estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations based on creatinine (CKD-EPIcr) and cystatin C (CKD-EPIcys), and cardiovascular risk markers and mortality in older adults.MethodsThis is a cross-sectional and prospective study of 1639 British men aged 71–92 years followed up for an average of 5 years for mortality. Cox survival model and receiving operating characteristic analysis were used to assess the associations.ResultsThe prevalence of chronic kidney disease (CKD) was similar using the two CKD-EPI equations, although cystatin C reclassified 43.9% of those with stage 3a CKD (eGFR 45–59 mL/min/1.732, moderate damage) to no CKD. However, CKD stages assessed using both CKD-EPIcr and CKD-EPIcys were significantly associated with vascular risk markers and with all-cause and cardiovascular disease mortality. In all men with CKD (eGFR <60 mL/min/1.732), the HRs (95% CI) for all-cause mortality after adjustment for cardiovascular risk factors compared with those with no CKD were 1.53 (1.20 to 1.96) and 1.74 (1.35 to 2.23) using CKD-EPIcr and CKD-EPIcys, respectively. Comparisons of the two CKD equations showed no significant difference in their predictive ability for mortality (difference in area under the curve p=0.46).ConclusionDespite reclassification of CKD stages, assessment of CKD using CKD-EPIcys did not improve prediction of mortality in older British men >70 years. Our data do not support the routine use of CKD-EPIcys for identifying CKD in the elderly British male population.

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Contribution of cystatin C- and creatinine-based definitions of chronic kidney disease to cardiovascular risk assessment in 20 population-based and 3 disease cohorts: the BiomarCaRE project

BMC Medicine ◽

10.1186/s12916-020-01776-7 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Dietrich Rothenbacher ◽

◽

Martin Rehm ◽

Licia Iacoviello ◽

Simona Costanzo ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Risk Factor ◽

Cardiovascular Risk ◽

Kidney Disease ◽

Cystatin C ◽

Total Mortality ◽

Population Based ◽

Cox Proportional Hazards ◽

Adverse Outcomes ◽

Ckd Stage

Abstract Background Chronic kidney disease has emerged as a strong cardiovascular risk factor, and in many current guidelines, it is already considered as a coronary heart disease (CHD) equivalent. Routinely, creatinine has been used as the main marker of renal function, but recently, cystatin C emerged as a more promising marker. The aim of this study was to assess the comparative cardiovascular and mortality risk of chronic kidney disease (CKD) using cystatin C-based and creatinine-based equations of the estimated glomerular filtration rate (eGFR) in participants of population-based and disease cohorts. Methods The present study has been conducted within the BiomarCaRE project, with harmonized data from 20 population-based cohorts (n = 76,954) from 6 European countries and 3 cardiovascular disease (CVD) cohorts (n = 4982) from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for the Systematic COronary Risk Evaluation (SCORE) variables and study center. Main outcome measures were cardiovascular diseases, cardiovascular death, and all-cause mortality. Results The overall prevalence of CKD stage 3–5 by creatinine- and cystatin C-based eGFR, respectively, was 3.3% and 7.4% in the population-based cohorts and 13.9% and 14.4% in the disease cohorts. CKD was an important independent risk factor for subsequent CVD events and mortality. For example, in the population-based cohorts, the HR for CVD mortality was 1.72 (95% CI 1.53 to 1.92) with creatinine-based CKD and it was 2.14 (95% CI 1.90 to 2.40) based on cystatin-based CKD compared to participants without CKD. In general, the HRs were higher for cystatin C-based CKD compared to creatinine-based CKD, for all three outcomes and risk increased clearly below the conventional threshold for CKD, also in older adults. Net reclassification indices were larger for a cystatin-C based CKD definition. Differences in HRs (between the two CKD measures) in the disease cohorts were less pronounced than in the population-based cohorts. Conclusion CKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of creatinine- and cystatin C-based CKD differed considerably between low- and high-risk populations. Especially in low-risk settings, the use of cystatin C-based CKD may result in more accurate risk estimates and have better prognostic value.

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Higher Levels of Cystatin C Are Associated with Worse Cognitive Function in Older Adults with Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort Cognitive Study

Journal of the American Geriatrics Society ◽

10.1111/jgs.12986 ◽

2014 ◽

Vol 62 (9) ◽

pp. 1623-1629 ◽

Cited By ~ 20

Author(s):

Kristine Yaffe ◽

Manjula Kurella-Tamura ◽

Lynn Ackerson ◽

Tina D. Hoang ◽

Amanda H. Anderson ◽

...

Keyword(s):

Older Adults ◽

Chronic Kidney Disease ◽

Cognitive Function ◽

Kidney Disease ◽

Renal Insufficiency ◽

Cystatin C ◽

Chronic Renal Insufficiency ◽

Cognitive Study

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Association of kidney function-related dietary pattern, weight status, and cardiovascular risk factors with severity of impaired kidney function in middle-aged and older adults with chronic kidney disease: a cross-sectional population study

Nutrition Journal ◽

10.1186/s12937-019-0452-4 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 8

Author(s):

Adi Lukas Kurniawan ◽

Chien-Yeh Hsu ◽

Hsiao-Hsien Rau ◽

Li-Yin Lin ◽

Jane C.-J. Chao

Keyword(s):

Risk Factors ◽

Older Adults ◽

Chronic Kidney Disease ◽

Cardiovascular Risk ◽

Kidney Disease ◽

Cardiovascular Risk Factors ◽

Kidney Function ◽

Dietary Pattern ◽

Weight Status ◽

Cross Sectional

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Hospitalization Risk among Older Adults with Chronic Kidney Disease

American Journal of Nephrology ◽

10.1159/000501539 ◽

2019 ◽

Vol 50 (3) ◽

pp. 212-220 ◽

Cited By ~ 2

Author(s):

Eugenia Wong ◽

Shoshana H. Ballew ◽

Natalie Daya ◽

Junichi Ishigami ◽

Casey M. Rebholz ◽

...

Keyword(s):

Older Adults ◽

Chronic Kidney Disease ◽

High Risk ◽

Kidney Disease ◽

Cystatin C ◽

Negative Binomial ◽

Incidence Rates ◽

Hospitalization Rates ◽

Increased Risk ◽

Very High

Introduction: Chronic kidney disease (CKD) risk staging is based on estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR). However, the relationship between all-cause hospitalization risk and the current CKD staging system has not been well studied among older adults, despite a high prevalence of CKD and a high risk of hospitalization in old age. Methods: Among 4,766 participants of the Atherosclerosis Risk in Communities study, CKD was staged according to Kidney Disease Improving Global Outcomes (KDIGO) criteria, using creatinine-based eGFR (eGFRcr) and ACR. Incidence rates of all-cause hospitalization associated with each CKD risk group were analyzed using negative binomial regression. Additionally, cause-specific hospitalization risks for cardiovascular, infectious, kidney, and other diseases were estimated. The impacts of using cystatin C-based eGFR (eGFRcys) to estimate the prevalence of CKD and risks of hospitalization were also quantified. Results: Participants experienced 5,548 hospitalizations and 29% had CKD. Hospitalization rates per 1,000 person-years according to KDIGO risk categories were 208–223 (“low risk”), 288–376 (“moderately increased risk”), 363–548 (“high risk”), and 499–1083 (“very high risk”). The increased risk associated with low eGFR and high ACR persisted in adjusted analyses, examinations of cause-specific hospitalizations, and when CKD was staged by eGFRcys or eGFRcr-cys, a combined equation based on both creatinine and cystatin C. In comparison to eGFRcr, staging by eGFRcys increased the prevalence of CKD to 50%, but hospitalization risks remained similarly high. Discussion/Conclusion: In older adults, decreased eGFR, increased ACR, and KDIGO risk stages based on a combination of these measures, were strong risk factors for hospitalization. These relationships were consistent, regardless of the marker used to estimate GFR, but the use of cystatin C resulted in a substantially higher prevalence of CKD than the use of creatinine. Older adults in the population with very high risk stages of CKD have hospitalization rates exceeding 500 per 1,000 person-years.

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FP280THE ROLE OF CYSTATIN C AND CYSTATIN C-BASED GFR MARKERS FOR PREDICTION OF MORTALITY IN ELDERLY PATIENTS WITH CHRONIC KIDNEY DISEASE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfy104.fp280 ◽

2018 ◽

Vol 33 (suppl_1) ◽

pp. i126-i126

Author(s):

Sebastjan Bevc ◽

Nina Hojs ◽

Masa Knehtl ◽

Nejc Piko ◽

Robert Ekart ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Elderly Patients ◽

Cystatin C ◽

Prediction Of Mortality

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Abstract P296: Age-related Differences in Risk Factors for Mortality Among Individuals with Chronic Kidney Disease: The REGARDS Study

Circulation ◽

10.1161/circ.129.suppl_1.p296 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Rikki M Tanner ◽

Barrett Bowling ◽

Monika M Safford ◽

Orlando Gutiérrez ◽

Lisandro D Colantonio ◽

...

Keyword(s):

Risk Factors ◽

Older Adults ◽

Chronic Kidney Disease ◽

Cardiovascular Risk ◽

Kidney Disease ◽

Cardiovascular Risk Factors ◽

Older Individuals ◽

Increased Risk ◽

Regards Study

At younger ages, chronic kidney disease (CKD) is a progressive disorder associated with an increased risk for end-stage renal disease (ESRD). Older individuals with CKD are 10 to 20 times more likely to die than progress to ESRD. We hypothesized that, among individuals with CKD, the association between traditional cardiovascular risk factors with mortality would be weaker and the association between psychosocial risk factors with mortality would be stronger for individuals ≥ 75 years of age compared to those < 75 years of age. We included 5,924 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants with CKD without ESRD at baseline. CKD was defined as an albumin-to-creatinine ratio ≥ 30 mg/g or an estimated glomerular filtration rate < 60 mL/min/1.73m2. The 12-item Short Form Health Survey (SF-12) was administered and low physical and mental component scores (PCS and MCS) were defined as scores in the lowest quintile. Mortality was assessed through biannual telephone follow-up and contact with proxies provided by the study participant upon recruitment. Date of death was confirmed through death certificates, National Death Index, or Social Security Death Index. Over a median follow-up of 5.0 years, 1,255 deaths occurred. The mortality rate was 30.9 (95% CI: 28.6 - 33.4) and 74.8 (95% CI: 69.2 - 80.8) per 1,000 person-years for individuals < 75 years and ≥ 75 years of age, respectively. Diabetes, history of stroke, and systolic blood pressure were associated with an increased risk for mortality among individuals < 75 years of age but not among those ≥ 75 years of age (Table 1). Low PCS was associated with a higher risk for mortality for both younger and older adults. Symptoms of depression and low MCS were not associated with mortality in either age group. In conclusion, some cardiovascular risk factors are associated with an increased risk for mortality among younger but not older individuals with CKD. These data suggest approaches to reduce mortality risk may differ for younger and older adults with CKD.

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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

Journal of Epidemiology & Community Health ◽

10.1136/jech-2017-209864 ◽

2018 ◽

Vol 72 (4) ◽

pp. 287-293 ◽

Cited By ~ 3

Author(s):

Mark Canney ◽

Donal J Sexton ◽

Neil O’Leary ◽

Martin Healy ◽

Rose Anne Kenny ◽

...

Keyword(s):

Older Adults ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Cystatin C ◽

Community Dwelling ◽

Confirmatory Test ◽

Middle Aged ◽

Predicted Probability ◽

Ckd Stage ◽

Age Range

BackgroundCystatin 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.MethodsCross-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.ResultsMedian 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.ConclusionsThe 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.

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