Serum cystatin C level is associated with left atrial enlargement, left ventricular hypertrophy and impaired left ventricular relaxation in patients with stage 2 or 3 chronic kidney disease

Sakuragi, Satoru; Ichikawa, Keishi; Yamada, Keiji; Tanimoto, Masafumi; Miki, Takashi; Otsuka, Hiroaki; Yamamoto, Kazuhiko; Kono, Kenji; Katayama, Yusuke; Tanakaya, Machiko; Itoh, Hiroshi

doi:10.1016/j.ijcard.2015.04.189

Cited by 11 publications

(10 citation statements)

References 30 publications

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“…Furthermore, with the increase of serum CysC, the incidence of eccentric and centripetal myocardial hypertrophy increased (P=0.0008). In particular, the incidence of concentric myocardial hypertrophy significantly increased (P=0.0187), and was independent of age, gender, history of hypertension, eGFR based on creatinine, medication use, and other factors (35).…”

Section: A B Cmentioning

confidence: 95%

“…Secondly, chronic renal insufficiency itself can also affect cardiac structure and function changes. Sakuragi et al found that 55% of patients with CKD stage 2-3 have LVH (35). The accumulation of uremic toxins during renal insufficiency can even occur within the normal range of eGFR, and participate in the occurrence of LVH and interstitial fibrosis (36,37).…”

Section: A B Cmentioning

confidence: 99%

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Pressure overload promotes cystatin C secretion of cardiomyocytes to regulate the MAPK signaling pathway and mediate cardiac hypertrophy

Shen

Zhang

et al. 2020

Ann Transl Med

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Background: This study aimed to compare serum cystatin C (CysC) levels between hypertensive and nonhypertensive patients, and to explore the correlation between serum CysC and left ventricular hypertrophy (LVH). We also investigated the effects of pressure overload on cardiac expression and secretion of CysC, and explored the direct effect of CysC on the hypertrophy of primary cardiomyocytes.Methods: Serum CysC was compared in patients with hypertension (634 patients) and those without hypertension (411 patients), and the correlation between serum CysC levels and LVH was explored. A transverse aortic constriction (TAC) mouse model and a mechanical stretch model of primary cardiomyocytes and fibroblasts were developed to compare cardiac expression and secretion of CysC under pressure overload.After intervention with exogenous CysC, we compared the cross-sectional area of primary cardiomyocytes, cardiac hypertrophy-associated gene expression, and phosphorylation of the MAPK signaling pathway.Results: In chronic kidney disease (CKD) stage 1 patients, serum CysC was higher in hypertensive patients independent of renal function. Serum CysC elevation was an independent predictor of LVH after correction for endogenous creatinine clearance rate (eCCr), left ventricular ejection fraction (LVEF), and NT-proBNP. Cardiac levels of CysC in TAC mice were elevated. CST3 gene expression was upregulated, and both intracellular and culture supernatant CysC levels increased after mechanical stretch of primary cardiomyocytes. After intervention with exogenous CysC, the cross-sectional area of primary cardiomyocytes increased, as well as the gene expression of Nppa, Nppb, and Myh7, and the phosphorylation of ERK, p38, and TAK1.Conclusions: Serum CysC levels were higher in hypertensive patients, and serum CysC elevation was an independent predictor of LVH after correction for eCCr. Pressure overload induced greater cardiomyocyte secretion of CysC. Exogenous CysC can enter cardiomyocytes, having a pro-hypertrophic effect on primary cardiomyocytes through regulation of the MAPK signaling pathways.

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Section: A B Cmentioning

confidence: 95%

Section: A B Cmentioning

confidence: 99%

Pressure overload promotes cystatin C secretion of cardiomyocytes to regulate the MAPK signaling pathway and mediate cardiac hypertrophy

Shen

Zhang

et al. 2020

Ann Transl Med

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“…При этом отмечается, что цистатин С оказывает влияние на неблагоприятное ремоделирование миокарда независимо от СКФ [13]. Ряд исследований подтверждают гипотезу о том, что цистатин С вносит вклад в развитие ФП у больных ХСН с сохраненной ФВ ЛЖ в основном за счет влияния на геометрию ЛП [14]. По некоторым данным этот эффект ассоциирован с женским полом [15], что косвенно подтверждается и нашим исследованием, включившим 65% женщин.…”

Section: Discussionunclassified

Peculiarities of chronic heart failure formation in patients with persistent atrial fi brillation depending on the renal dysfunction phenotype

Полянская

Козиолова

2020

SMJ

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Aim. To study the features of chronic heart failure (CHF) formation in patients with persistent atrial fibrillation (AF) depending on the phenotype of renal dysfunction.Material and Methods. The study included 60 patients with persistent AF and CHF. To diagnose CHF, echocardiography study was performed and the concentrations of NT-pRoBNP and sST2 in the blood serum were determined. Renal filtration function was assessed by glomerular filtration rate (GFR) calculated based on creatinine and cystatin C. Plasma NGAL concentration was determined to assess tubular dysfunction. Three phenotypes of renal damage were identified. Group 1 included 14 individuals (23.3%) with isolated tubular dysfunction assessed by NGAL; group 2 included 14 patients (23.3%) with isolated glomerular dysfunction assessed by GFR (CKD-EPIcys); group 3 comprised 32 patients (53.3%) with a combination of tubular and glomerular dysfunction.Results. The GFR value (CKD-EPIcre) below 60 mL/min/1.73 m2 was found in 36.7% of patients from groups 2 and 3. The concentration of cystatin C significantly diff ered between groups and was the highest in group 3. The value of GFR (CKDEPIcys) below 60 mL/min/1.73 m2 was detected in 76.7% of patients from all groups. The value of GFR (CKD-EPIcys) significantly diff ered between groups and was the lowest in group 3. When comparing serum creatinine and cystatin C in group 1, eight patients (57.1%) showed latent glomerular dysfunction, which manifested only in the concentration of cystatin C. A relationship was found between the level of DBP and NGAL (r = 0.44; p < 0.05). The correlations were identified between the parameters of left ventricular (LV) diastolic function and indicators of filtration function and tubular apparatus of the kidneys, namely: between E/e’ and NGAL concentration (r = 0.31; p < 0.05); between E/e’ and cystatin C concentration (r = 0,30; p < 0.05); between E/A and NGAL concentration (r = –0.36; p < 0.05); and between septal e’ and cystatin C concentration (r = –0.30; p < 0.05). Relationships were found between the concentrations of NGAL and sST2 (r = 0.44; p < 0.05) and between the concentrations of cystatin C and TIMP-1 (r = 0.39; p < 0.05).Conclusion. The use of blood cystatin C to assess kidney filtration function allowed to detect latent glomerular dysfunction in 57.1% of patients with heart failure and persistent AF, which could not be determined by GFR (CKD-EPIcre). Patients with persistent AF developed CHF with preserved LV EF regardless of the phenotype of renal dysfunction. The severities of glomerular filtration and kidney tubular apparatus abnormalities correlated with the severity of diastolic dysfunction. Unlike clinical indicators and blood concentration of NT-proBNP, sST2 levels allowed to detect the diff erences in heart failure severity in patients with persistent AF depending on the phenotype of renal dysfunction: the lowest severity was observed in the presence of glomerular dysfunction; the highest severity was found in the presence of combined dysfunction. Glomerular dysfunction in patients with CHF and persistent AF was associated with the impaired collagen formation and TIMP-1 activation.

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“…По данным крупных исследований (Heart and Soul Study, MESA Study, Cardiovascular Health Study, Dallas Heart Study, CKiD Study), отмечалась связь между повышением уровня цистатина C в сыворотке крови и наличием структурных изменений миокарда ЛЖ, тогда как для нарушения функции сердца такая закономерность прослеживалась не всегда [10,11,28,29]. Продемонстрировано независимое влияние повышения цистатина C на увеличение ИММЛЖ, объема левого предсердия и нарушение релаксации ЛЖ у пациентов с II-Ⅲ стадиями ХБП без признаков СН [30]. У подростков с незначительно и умеренно сни-женной СКФ повышение концентрации сывороточного цистатина C на 1 мг/л ассоциировано с увеличением ИММЛЖ в среднем на 7,7% и снижением диастолического расслабления миокарда ЛЖ на 4,7% [31].…”

Section: ìàòåðèàëû è ìåòîäûunclassified

Risk factors for diastolic left ventricular myocardial dysfunction in patients with chronic kidney disease

Rudenko

Vasilyeva

et al. 2018

Terapevticheskii arkhiv

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Purpose of the study. To examine the frequency and risk factors for the development of diastolic dysfunction (DD) of the left ventricle (LV) of the heart in patients with chronic kidney disease (CKD). Materials and methods. The study included 225 patients with stage I-CKD of non-diabetic etiology (median age 47.0 years, 50.2% of women). Depending on the degree of decrease in the glomerular filtration rate (GFR), all patients were divided into 3 groups. Group 1 (n=70) consisted of patients with GFR 89-45 ml / min / 1.73 m2, group 2 (n=120) - patients with GFR 44-15 ml / min / 1.73 m2, group 3 (n=35) - patients with GFR

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Serum cystatin C level is associated with left atrial enlargement, left ventricular hypertrophy and impaired left ventricular relaxation in patients with stage 2 or 3 chronic kidney disease

Cited by 11 publications

References 30 publications

Pressure overload promotes cystatin C secretion of cardiomyocytes to regulate the MAPK signaling pathway and mediate cardiac hypertrophy

Pressure overload promotes cystatin C secretion of cardiomyocytes to regulate the MAPK signaling pathway and mediate cardiac hypertrophy

Peculiarities of chronic heart failure formation in patients with persistent atrial fi brillation depending on the renal dysfunction phenotype

Risk factors for diastolic left ventricular myocardial dysfunction in patients with chronic kidney disease

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