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

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.

Renal markers and risks of all cause and cardiovascular mortality from the Taichung community based cohort study

“…Most studies that explored the relationship between renal-related biomarkers and mortality 7 – 15 had been conducted in special populations, such as persons with diabetes 2 , persons with CKD 7 , 9 , persons undergoing percutaneous intervention 8 , persons with hypertension 12 , or persons participating in comprehensive health screening programs 15 . By contrast, studies that focused on general populations are few 10 , 11 , 13 , 14 , 16 , 17 . These studies evaluated the associations of urine albumin-to-creatinine ratio (UACR) 14 , estimated glomerular filtration rate (eGFR) 10 , 11 , 16 , 17 , or both 13 with mortality with or without adjustment for metabolic syndrome-related markers.…”

“…By contrast, studies that focused on general populations are few 10 , 11 , 13 , 14 , 16 , 17 . These studies evaluated the associations of urine albumin-to-creatinine ratio (UACR) 14 , estimated glomerular filtration rate (eGFR) 10 , 11 , 16 , 17 , or both 13 with mortality with or without adjustment for metabolic syndrome-related markers. The results of investigations on renal-related biomarkers with mortality are inconsistent.…”

Cystatin C predicts renal function impairment after partial or radical tumor nephrectomy

“…Moreover, multiple studies showed a better accuracy of cystatin C (CysC), relative to serum creatinine, to estimate kidney function through eGFR in surgically and non-surgically treated patients [13][14][15]. Several studies showed that CysC predicts short-term postoperative AKI and long-term kidney impairment [15][16][17][18]. Additionally, it was also found that creatinine, which is used in hospital standard routine, may over-and underestimate kidney function regarding patients' age category [19].…”

Nomogram to predict risk of incident chronic kidney disease in high-risk population of cardiovascular disease in China: community-based cohort study

“…CKD has long been proven a strong cardiovascular risk factor. 21 Since Professor Bright established the concept of ‘renal origin of CVD’ which means renal disease is the primary disorder and cardiovascular changes are secondary. 22 Many studies have confirmed and extended this association.…”