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
Creators: name: Rothenbacher, Dietrich
name: Rehm, Martin
name: Iacoviello, Licia
name: Costanzo, Simona
name: Tunstall-Pedoe, Hugh
name: Belch, Jill J. F.
name: Söderberg, Stefan
name: Hultdin, Johan
name: Salomaa, Veikko
name: Jousilahti, Pekka
name: Linneberg, Allan
name: Sans, Susana
name: Padró, Teresa
name: Thorand, Barbara
name: Meisinger, Christa
name: Kee, Frank
name: McKnight, Amy Jayne
name: Palosaari, Tarja
name: Kuulasmaa, Kari
name: Waldeyer, Christoph Andreas Johannes Wolfgang
name: Zeller, Tanja
name: Blankenberg, Stefan
name: König, Wolfgang
Publisher: name: Universität Ulm
Year: 2020
Subjects: subject: Chronic kidney disease
subject: Estimated glomerular filtration rate
subject: Adverse outcome
subject: DDC 610 / Medicine &amp; health
subject: Renal insufficiency, Chronic
subject: Creatinine
subject: Cystatin C
subject: Cohort studies
subject: Nierenkrankheit
subject: Creatinin-Clearance
subject: Cystatine
subject: Kohortenanalyse

description: 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.