Serum cystatin C as a predictor for cardiovascular events in end-stage renal disease patients at the initiation of dialysis

Shin, Min Ji; Song, Sang Heon; Kwak, Ihm Soo; Lee, Soo Bong; Lee, Jun Young; Seong, Eun Young; Kim, Il Young; Rhee, Harin; Lee, Naria

doi:10.1007/s10157-011-0583-1

Cited by 15 publications

(12 citation statements)

References 49 publications

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“…Although there is a growing body of literature on the use of BTP as an endogenous filtration marker, to our knowledge, no studies have analyzed the association between serum BTP levels and outcomes in dialysis patients. In a recent small study (n=66), higher cystatin C levels, measured immediately before dialysis initiation, were associated with a higher risk of cardiovascular events in the follow-up period (38). In our study, higher serum BTP levels were independently associated with all-cause and CVD mortality.…”

Section: Discussionsupporting

confidence: 58%

Serum β-Trace Protein and Risk of Mortality in Incident Hemodialysis Patients

Shafi¹,

Parekh²,

Jaar³

et al. 2012

Clinical Journal of the American Society of Nephrology

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Summary Background and objectives Residual kidney function in dialysis patients is associated with better survival, but there are no simple methods for its assessment. β-Trace protein is a novel endogenous filtration marker of kidney function that is not removed during hemodialysis and may serve as a marker for residual kidney function similar to serum creatinine in patients not on dialysis. The objective of this study was to determine the association of serum β-trace protein with mortality in incident hemodialysis patients. Design, setting, participants, & measurements Serum β-trace protein was measured in baseline samples from 503 participants of a national prospective cohort study of incident dialysis patients with enrollment during 1995–1998 and follow-up until 2004. Outcomes were all-cause and cardiovascular disease mortality analyzed using Cox regression adjusted for demographic, clinical, and treatment factors. Results Serum β-trace protein levels were higher in individuals with no urine output compared with individuals with urine output (9.0±3.5 versus 7.6±3.1 mg/L; P<0.001). There were 321 deaths (159 deaths from cardiovascular disease) during follow-up (median=3.3 years). Higher β-trace protein levels were associated with higher risk of mortality. The adjusted hazard ratio and 95% confidence interval for all-cause mortality per doubling of serum β-trace protein was 1.36 (1.09–1.69). The adjusted hazard ratios (95% confidence intervals) for all-cause mortality in the middle and highest tertiles compared with the lowest tertile were 0.95 (0.69–1.32) and 1.72 (1.25–2.37). Similar results were noted for cardiovascular disease mortality. Conclusions The serum level of β-trace protein is an independent predictor of death and cardiovascular disease mortality in incident hemodialysis patients.

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Section: Discussionsupporting

confidence: 58%

Serum β-Trace Protein and Risk of Mortality in Incident Hemodialysis Patients

Shafi¹,

Parekh²,

Jaar³

et al. 2012

Clinical Journal of the American Society of Nephrology

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“…Cystatin C was less influenced by factors other than glomerular filtration rate (24), and is considered to be a significant predictor of all-cause mortality and CV events in non-dialysis chronic kidney disease patients (6) and incident dialysis patients (24). In our study, 77.9% of the subjects exhibited urinary volumes of <100 mL/day, and the addition of cystatin C to the base model did not improve the model's ability to predict 2-year all-cause or CV mortality in prevalent HD patients with depleted renal function.…”

Section: Discussionmentioning

confidence: 92%

Addition of Novel Biomarkers for Predicting All‐Cause and Cardiovascular Mortality in Prevalent Hemodialysis Patients

Yamashita

Mizuiri²,

Nishizawa³

et al. 2017

Ther Apher Dial

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Novel biomarkers might improve the prediction of mortality in hemodialysis (HD) patients. We simultaneously measured the levels of conventional and novel biomarkers [serum N-terminal pro-brain natriuretic peptide (NT-proBNP), intact fibroblast growth factor-23 (FGF23), β2-microglobulin (β2MG), cystatin C, and high-sensitivity C-reactive protein (hsCRP)] in 307 prevalent Japanese HD patients. There were 66 all-cause deaths, and 25 cardiovascular (CV) deaths during 2 years, which were assessed using Cox models and concordance (C)-statistics. The addition of NT-proBNP alone (P < 0.05) or NT-proBNP, hsCRP, and β2MG as a panel (C-statistics: 0.834 vs. 0.776, P < 0.01) to a conventional risk model composed of age, diabetes, and the serum albumin level significantly improved the prediction of 2-year all-cause mortality, and the addition of NT-proBNP and hsCRP as a panel to a conventional risk model composed of age significantly improved the prediction of 2-year CV mortality (P < 0.05) in Japanese prevalent HD patients. Neither FGF23 nor cystatin C improved mortality prediction.

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“…Basic, unbiased search of the PubMed database yields over 2800 hits for “cystatin C” as a subject, most of them focused on clinical application of this protein as a valuable biomarker of various disease states. The original application of cystatin C as a measure of the glomerular filtration rate (Grubb et al, 1985) and a marker of kidneys function (Grubb, 1992; Page et al, 2000; Curhan, 2005) has expanded and now hCC is investigated also as a prognostic marker of cardiovascular events (Zethelius et al, 2008; Taglieri et al, 2009; Shin et al, 2012), as well as several forms of cancer (Turk et al, 2008). Another branch of the research is focused on the role of cystatin C in Alzheimer's disease, as both a biomarker and potential target for therapy (Levy, 2008; Zerovnik, 2009; Craig-Schapiro et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Influence of point mutations on the stability, dimerization, and oligomerization of human cystatin C and its L68Q variant

Szymańska¹,

Jankowska²,

Orlikowska³

et al. 2012

Front. Mol. Neurosci.

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Human cystatin C (hCC) is a small but very intriguing protein. Produced by all nucleated cells is found in almost all tissues and body fluids where, at physiological conditions, plays a role of a very potent inhibitor of cysteine proteases. Biologically active hCC is a monomeric protein but during cellular trafficking it forms dimers, transiently losing its inhibitory activity. In vitro, dimerization of cystatin C was observed for the mature protein during crystallization trials, revealing that the mechanism of this process is based on the three dimensional swapping of the protein domains. In our work we have focused on the impact of two proposed “hot spots” in cystatin C structure on its conformational stability. Encouraged by promising results of the theoretical calculations, we designed and produced several hCC hinge region point mutation variants that display a variety of conformational stability and propensity for dimerization and aggregation. A similar approach, i.e., rational mutagenesis, has been also applied to study the amyloidogenic L68Q variant to determine the contribution of hydrophobic interactions and steric effect on the stability of monomeric cystatin C. In this overview we would like to summarize the results of our studies. The impact of a particular mutation on the properties of the studied proteins will be presented in the context of their thermal and mechanical stability, in vitro dimerization tendency as well as the outcome of crystallization. Better understanding of the mechanism and, especially, factors affecting conformational stability of cystatin C and access to stable monomeric and dimeric versions of the protein opens new perspectives in explaining the role of dimers and the domain swapping process in hCC oligomerization, as well as designing potential inhibitors of this process.

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Serum cystatin C as a predictor for cardiovascular events in end-stage renal disease patients at the initiation of dialysis

Abstract: Serum cystatin C might be an independent marker of cardiovascular events in incident dialysis patients. Furthermore, eGFR(cysC) based on measured serum cystatin C could have a new role in predicting cardiovascular events beyond the estimation of true GFR.

Cited by 15 publications

References 49 publications

Serum β-Trace Protein and Risk of Mortality in Incident Hemodialysis Patients

Serum β-Trace Protein and Risk of Mortality in Incident Hemodialysis Patients

Addition of Novel Biomarkers for Predicting All‐Cause and Cardiovascular Mortality in Prevalent Hemodialysis Patients

Influence of point mutations on the stability, dimerization, and oligomerization of human cystatin C and its L68Q variant

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