유지 투석 개시시 혈청 Cystatin C의 의의: 혈청 Creatinine과 계산된 사구체 여과율과의 비교

최혜민 ( Hye Min Choi ),김혜원 ( Hye Won Kim ),이재원 ( Jae Won Lee ),현영율 ( Young Youl Hyun ),박상원 ( Sang Won Lee ),이지은 ( Ji Eun Lee ),권영주 ( Young Joo Kwon ),표희정 ( Heui Jung Pyo ) 대한신장학회 2007 Kidney Research and Clinical Practice Vol.26 No.1

목적: 혈청 cystatin C (Cys-C)는 혈청 creatinine (Cr)과는 달리 비신성 요인에 의한 영향이 적어 사구체 여과율을 더 정확하게 반영할 수 있을 것이라는 보고가 많이 있었다. 특히 조기 신기능 저하 또는 신이식 환자에서 Cr보다 신기능을 예민하게 반영한다는 연구 결과들이 발표된 바 있으나, 말기 신질환 환자에서 Cys-C에 대한 연구는 거의 없다. 저자들은 말기 신부전 환자에서 투석 개시시 혈청 Cys-C를 측정한 후 혈청 Cr, 24시간 Cr 청소율 (G (Ccr)) 및 C&G formula, MDRD formula로 계산한 사구체 여과율 (각각 G (C&G), G (MDRD1), G (MDRD2))과 비교하고, 비신성 요인의 영향을 살펴보며, 혈청 Cys-C를 투석 개시시 객관적 혈청 지표로 활용할 수 있는지 알아보고자 하였다. 방법: 말기 신부전 환자 163명을 대상으로, 투석 개시시 혈청 Cys-C 및 Cr을 측정하였다. 이후 Pearson 상관 분석으로 G (Ccr), G (C&G), G (MDRD1), G (MDRD2)와의 상관계수를 구하였으며, 다중 회귀 분석을 이용하여 성별, 연령, 체중, 당뇨병성 신증 유무와 같은 비신성 요인의 영향을 확인해 보았다. 또한 ROC curve를 통해 혈청 Cys-C 수치로 응급 혈액 투석 가능성을 예측할 수 있는지 검토하였다. 결과: 1/Cys-C는 G (Ccr), G (C&G), G (MDRD1), G (MDRD2)와 의미 있는 상관 관계를 보였다. 다중 회귀분석에서 혈청 Cr은 고령, 저체중, 당뇨병성 신증과 각각 독립적으로 유의한 음의 관계가 있었고, 혈청 Cys-C는 성별, 체중, 당뇨병성 신증 여부와는 유의한 관계가 없었으나 연령이 증가함에 따라 감소하는 경향을 보였다. 투석 개시시 요독증상이 심해 응급 혈액 투석을 시행한 경우를 기준으로 그려본 ROC 곡선에서 아래 영역 면적은 혈청 Cr, Cys-C가 각각 0.684±0.043, 0.644±0.044로서, 응급 혈액 투석을 예견하며 조속한 투석개시를 요구할 수 있는 혈청 표지자로서 Cys-C는 Cr보다 우월하지 않았다. 결론: Cys-C는 말기 신질환 환자에서 투석 개시시 Cr 을 기초로 한 사구체 여과율과 연관 관계가 있었다. 혈청 Cys-C는 체중, 성별에 대해선 혈청 Cr보다 영향을 받지 않았으나, 독립적으로 연령의 영향을 받았다. 이상으로 혈청 Cys-C는 투석 개시시 및 응급 혈액 투석을 예측하는 혈청 표지자로서 혈청 Cr 보다 우월하지 않았다. Purpose: Cystatin-C is produced at a constant rate, and has been known to be unaffected by non-renal factors. However, there are limited data on its superiority to serum creatinine as a marker of renal function in ESRD population. The aims of our study were to compare serum cystatin-C and serum creatinine with estimated GFR in ESRD patients at the initiation of dialysis, whether the non-renal factors may influence on serum cystatin-C levels, and whether serum cystatin-C may be a useful marker of the start of dialysis. Methods: This study was cross-sectional about 163 ESRD patients. We measured serum cystatin-C and serum creatinine levels at the initiation of dialysis, and determined GFR from 24 hour urine collection [G (Ccr)], Cockcroft-Gault [G (C&G)], and the modification of diet in renal disease [G (MDRD)] formula. We considered age, gender, body weight and diabetic nephropathy as non-renal factors. Results: The mean serum cystatin-C was 5.0±0.9 mg/dL, serum creatinine 11.4±5.9 mg/dL, G (Ccr) 5.0±2.9 mL/min/1.73m2, G (C&G) 7.5±3.1 mL/min/1.73m2, G (MDRD1) 5.7±2.9 mL/min/1.73m2, and G (MDRD2) 5.5±2.5 mL/min/1.73m2. We found significant correlation between estimated GFR and serum cystatin-C. However, comparing to serum creatinine, serum cystatin-C had no merits in estimating renal function and in predicting urgent hemodialysis. In the multivariate linear regression models, serum cystatin-C had no significant correlation with gender, body weight, and diabetic nephropathy, but decreased with the age. Conclusion: Serum cystatin-C is not superior to serum creatinine for estimating renal function and predicting urgent hemodialysis in ESRD patients. Besides, serum cystatin-C seems to be influenced by non-renal factors, age.

Identification of the Cysteine Proteinase Inhibitor, Cystatin, in Mungbean (Vigna radiata [L.] wilczek)

Park, Kwang-Sook,Bae, Young-Joo,Kim, Min-Chong,Yoo, Da-Woon,Kang, Soon-Ja 한국유전학회 2003 Genes & Genomics Vol.25 No.3

We have identified and analyzed the cysteine proteinase inhibitor (CPI), cystatin, in mungbean (Vigna radiata). Cystatin cDNA encoding an 89 amino acid coding region was isolated using RT-PCR and sequenced (GenBank Acession Number AF454396). The cystatin sequences from C. chinensis-resistant and susceptible lines showed a high degree of similarity, 90 - 95%. The cystatin uncleotide sequence from Jangan mungbean, a resistant breeding line, shows 95%, 86%, and 74% homology compared to that of cowpea, oryza, and soybean respectively. The deduced coding region contains a QXVXG putative reactive domain in the central region and a PW motif near the C-terminus, both of which are conserved among members of the cystatin superfamily. No signal sequence motif was found in the N-terminal region, indication that mungbean systatin may be an intracellular protein similar to cowpea cystatin and oryzacystatin. Using 3'-RACE PCR analysis, a polyadenylation signal was detected in the 3' UTR. Quantitative RT-PCR and Northern blot analysis from mature seeds of resistant and susceptible mungbean lines showed similar cystatin mRNA expression levels. These results strongly suggested that cystatin is expressed in mungbean seeds during maturation. Southern blot analysis of the cystatin gene using BamHI, EcoRI, PstI, HindIII and XhoI performed on both resistant, and susceptible mungbean lines showed no significant difference. We concluded that mungbean cystatin functions in plant regulation rather than for defense as in the ase of the cowpea cystatin.

Identification and molecular profiling of a novel homolog of cystatin C from rock bream (Oplegnathus fasciatus) evidencing its transcriptional sensitivity to pathogen infections

Don Anushka Sandaruwan Elvitigala,Jehee Lee 제주대학교 해양과학연구소 2021 해양과환경연구소 연구논문집 Vol.45 No.-

Cystatins are reversible inhibitors of cysteine proteases which show an omnipresent distribution in the life on earth. Although, cystatins with mammalian origin were well characterized and their roles in physiology were reported in details, those from teleostean origin are still underrepresented in literature. However, role of cystatins in fish physiology and immune defense is highlighted in few recent reports. In this study, a cystatin C holmologue from rock bream (Oplegnathus fasciatus); termed RbCytC was identified and molecularly characterized. The complete coding sequence of RbCytC was 387 bp in length, which codes for a polypeptide with 129 amino acids, including a signal peptide of 19 amino acids. The consensus cystatin family signatures including a G residue, turning up towards the N-terminus region, QVVAG motif, locating at the middle of the sequence and the PW motif at the c terminal region was found to be well conserved in RbCytC. Phylogenetic analysis using different cystatin counterparts affirmed the close evolutionary relationship of RbCytC with its teleostan homologs which belong to family 2 cystatins. The predicted molecular model of RbCytC resembled most of the structural features of empirically elucidated tertiary structures for chicken egg white cystatin. According to the qPCR assays, RbCytC showed detectable expression in all fish tissues used in the experiment, with markedly pronounced expression level in liver. Moreover, its basal mRNA expression was up-regulated in liver and spleen tissues by experimental rock bream iridovirus infection, whereas down regulated in the same tissues, post live Edwardsiella tarda injection. Collectively, outcomes of our study validate the structural homology of RbCytC with known cystatin C similitudes, especially those of teleosts and suggest its potential roles in proteolytic processes of rock bream physiology as well as in host immune defense mechanisms.

Prognostic Performance of MELD Score after Substitution of Creatinine by Cystatin C: Preliminary Study

( Gwang Hyeon Choi ),( Ju Hyun Shim ),( Seheon Chang ),( Ji Hyun An ),( Danbi Lee ),( Kang Mo Kim ),( Young-suk Lim ),( Yung Sang Lee ),( Han Chu Lee ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Renal dysfunction is a strong prognostic predictor in cirrhotic patients and the model of end stage liver disease (MELD) score contains creatinine to reflect the renal dysfunction. Conversely, Serum cystatin C is a more surrogate marker of renal function than serum creatinine in the patients with liver cirrhosis. The aim of this study was to assess the substitution of creatinine by cystatin C improves the prognostic performance of the models. Methods: This prospective study had been enrolled 92 decompensated cirrhotic patients with Child-Pugh class B and C from August 2014 to October 2016 at Asan Medical Center [age (56 ± 12; mean ± standard deviation), sex (65/27; M/F), etiology (Alcohol/HBV/Alcohol+HBV/HCV/others; 42/19/13/7/11), and Child-Pugh class (B/C 41/51)]. Patients who had a history of hepatocellular carcinoma or had other malignant condition or had a severe cardiopulmonary disease which can affect the prognosis or had a history of prior liver or kidney transplantation were excluded. We compared the predictive power of the 90-day mortality (which was defined as death of urgent LT) of cystatin C substitution model and MLED model using ROC curve. Results: Median follow-up duration was 134 days (64-195; range), 29 patients were expired and 8 patient patients undergone urgent LT. In multivariate Cox regression, both cystatin C and creatinine were not independent predictors (HR, 1.47; 95% CI, 0.44-4.93; p=0.53, and 2.40; 0.67-8.55; 0.18, respectively). The 90-day mortality AUCs for the MELD, MELD-Na, cystatin-MELD, cystatin-MELD-Na were 0.80, 0.83, 0.82, 0.82. These differences did not reach statistical significance. Conclusions: Substitution of creatinine by cystatin C might not improve the predictive power of MELD. Additional large scale study which could show statistical difference is needed to confirm the result.

A Correlation Analysis of Serum Creatinine Based eGFR and Serum Cystatin C Based eGFR with Thyroid Dysfunction Patients

임구,박형두,성호중,Lim, Gu,Park, Hyung-Doo,Sung, Ho Joong Korean Society for Clinical Laboratory Science 2017 대한임상검사과학회지(KJCLS) Vol.49 No.3

Serum creatinine-based eGFR and serum cystatin C-based eGFR are the most popular methods for measuring renal function. Thyroid hormone is known to affect serum creatinine-based eGFR and serum cystatin C-based eGFR; however, the clinical significance of thyroid dysfunctional patients of renal function evaluation has not been fully elucidated to date. This study examined the effect of thyroid hormone on serum creatinine-based eGFR and serum cystatin C-based eGFR. Moreover, we also evaluated the correlation analysis between serum creatinine-based eGFR and serum cystatin C-based eGFR in patients with thyroid dysfunction. A total of 442 patients with hypothyroidism and 284 patients with hyperthyroidism were investigated. A correlation analysis between thyroid hormone and serum creatinine- (and cystatin C-) based eGFR was performed. A correlation analysis between thyroid hormone and serum cystatin-C based eGFR indicated that serum cystatin-C based eGFR is more of an independent biomarker than serum creatinine-based eGFR in thyroid dysfunction patients. Therefore, serum cystatin C-based eGFR more accurately reflects renal function than serum creatinine-based eGFR in thyroid dysfunction patients.

Cystatin C for managing diuretic-induced kidney dysfunction in MMVD dogs

Donghyun Han,Jae Hyeon Cho,Chung Hui Kim 한국동물위생학회 2023 韓國家畜衛生學會誌 Vol.46 No.3

Cystatin C, a low-molecular-weight protein synthesized by cells, is being explored as a valuable biomarker for assessing renal function in veterinary medicine. Although the relationship between cystatin C and heart disease remains unclear, some studies suggest a possible association. This retrospective case-control study aimed to investigate the role of cystatin C as a biomarker for heart disease and its correlation with diuretic use in veterinary clinical practice. A total of 39 dogs were included in this study, comprising 9 control dogs without a predisposition to heart disease and 30 dogs in the study group diagnosed with heart disease. Among the 30 dogs with heart disease, 18 exhibited symptoms indicative of heart failure. Results showed significantly higher cystatin C levels in the heart disease group compared to the control group (P<0.05). However, no significant differences were observed among different stages of heart disease severity in the control group. Furthermore, cystatin-C showed statistically positive correlations with BUN (r =0.478, P<0.01), creatinine (r =0.506, P<0.01), and furosemide (r =0.338, P<0.05). Diuretics are essential for managing congestive heart failure, and the observed associations between cystatin C and furosemide suggest potential impacts of diuretic use on renal function in dogs with heart failure. Monitoring renal function markers, such as cystatin C, can aid in predicting and managing potential renal complications, ultimately improving the overall health and quality of life of dogs with heart disease.

AvCystatin, a novel cysteine protease inhibitor from spider (Araneus ventricosus) venom

Hu Wan,Tinghao Kang,김보연,이광식,Jianhong Li,진병래 한국응용곤충학회 2015 Journal of Asia-Pacific Entomology Vol.18 No.1

Cystatins are involved in various physiological and cellular processes, including immune responses, protein homeostasis, signaling pathways, and apoptosis. Thus far, no Cystatins have been identified from spider venom. In this study, we report the cloning and characterization of a spider venom-derived Cystatin fromAraneus ventricosus (AvCystatin). The AvCystatin gene contains an open reading frame of 405 bp encoding a predicted protein of 134-amino acids with a 16-amino acid signal peptide. Sequence alignment and structural modeling indicated that AvCystatin is closely related to family 2 Cystatins. Endogenous AvCystatin was present as an 18-kDa peptide in spider venom. Recombinant AvCystatin, expressed in baculovirus-infected insect cells, showed inhibitory activity against papain (Ki 86.73 nM), but not trypsin and chymotrypsin, defining a role for AvCystatin as a spider venom-derived cysteine protease inhibitor. Furthermore, recombinant AvCystatin exhibited stability against high temperatures and pH extremes, but had no effects on the growth of the entomopathogenic fungi Beauveria bassiana. These data demonstrate that AvCystatin is a novel member of the family 2 Cystatins and provide new insight for the future investigations of spider venom-derived Cystatins.

Genomic characterization and expression profiles upon bacterial infection of a novel cystatin B homologue from disk abalone (Haliotis discus discus)

Premachandra, H.K.A.,Wan, Q.,Elvitigala, D.A.S.,De Zoysa, M.,Choi, C.Y.,Whang, I.,Lee, J. Pergamon Press ; Elsevier Science Ltd ; Pergamon 2012 DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY Vol.38 No.4

Cystatins are a large family of cysteine proteinase inhibitors which are involved in diverse biological and pathological processes. In the present study, we identified a gene related to cystatin superfamily, AbCyt B, from disk abalone Haliotis discus discus by expressed sequence tag (EST) analysis and BAC library screening. The complete cDNA sequence of AbCyt B is comprised of 1967 nucleotides with a 306bp open reading frame (ORF) encoding for 101 amino acids. The amino acid sequence consists of a single cystatin-like domain, which has a cysteine proteinase inhibitor signature, a conserved Gly in N-terminal region, QVVAG motif and a variant of PW motif. No signal peptide, disulfide bonds or carbohydrate side chains were identified. Analysis of deduced amino acid sequence revealed that AbCyt B shares up to 44.7% identity and 65.7% similarity with the cystatin B genes from other organisms. The genomic sequence of AbCyt B is approximately 8.4Kb, consisting of three exons and two introns. Phylogenetic tree analysis showed that AbCyt B was closely related to the cystatin B from pacific oyster (Crassostrea gigas) under the family 1.Functional analysis of recombinant AbCyt B protein exhibited inhibitory activity against the papain, with almost 84% inhibition at a concentration of 3.5μmol/L. In tissue expression analysis, AbCyt B transcripts were expressed abundantly in the hemocyte, gill, mantle, and digestive tract, while weakly in muscle, testis, and hepatopancreas. After the immune challenge with Vibrio parahemolyticus, the AbCyt B showed significant (P<0.05) up-regulation of relative mRNA expression in gill and hemocytes at 24 and 6h of post infection, respectively. These results collectively suggest that AbCyst B is a potent inhibitor of cysteine proteinases and is also potentially involved in immune responses against invading bacterial pathogens in abalone.

Molecular Characteristics and Potent Immunomodulatory Activity of Fasciola hepatica Cystatin

Kai Zhang,Yucheng Liu,Guowu Zhang,Xifeng Wang,Zhiyuan Li,Yunxia Shang,Chengcheng Ning,Chunhui Ji,Xuepeng Cai,Xianzhu Xia,Jun Qiao,Qingling Meng 대한기생충학ㆍ열대의학회 2022 The Korean Journal of Parasitology Vol.60 No.2

Cystatin, a cysteine protease inhibitor found in many parasites, plays important roles in immune evasion. This study analyzed the molecular characteristics of a cystatin from Fasciola hepatica (FhCystatin) and expressed recombinant FhCystatin (rFhcystatin) to investigate the immune modulatory effects on lipopolysaccharide-induced proliferation, migration, cytokine secretion, nitric oxide (NO) production, and apoptosis in mouse macrophages. The FhCystatin gene encoded 116 amino acids and contained a conserved cystatin-like domain. rFhCystatin significantly inhibited the activity of cathepsin B. rFhCystatin bound to the surface of mouse RAW264.7 cells, significantly inhibited cell proliferation and promoted apoptosis. Moreover, rFhCystatin inhibited the expression of cellular nitric oxide, interleukin-6, and tumor necrosis factor-α, and promoted the expression of transforming growth factor-β and interleukin-10. These results showed that FhCystatin played an important role in regulating the activity of mouse macrophages. Our findings provide new insights into mechanisms underlying the immune evasion and contribute to the exploration of potential targets for the development of new drug to control F. hepatica infection.

Cr-51 EDTA GFR 검사 결과의 분석 및 의의

임수연,문형호,유선희,조시만,Lim, Soo-Yeon,Moon, Hyoung-Ho,Yoo, Seon-Hee,Cho, Shee-Man 대한핵의학기술학회 2009 핵의학 기술 Vol.13 No.1

Purpose: Correct estimation of Glomerular filtration rate (GFR) is very important for an accurate clinical assessment of the kidney function. This study compares four GFR markers, a serum creatinine-based estimation using MDRD formula, Cystatin-C, Cr-51 EDTA 2 samples and 6 samples. Materials and Methods: Serum creatinine concentrations, Cystatin-C serum concentrations and Cr-51 EDTA clearance are measured in 43 patients who received or donated kidney. Results: The correlation coefficient between serum based estimated GFR (MDRD) and Cr-51 EDTA 6 samples was 0.817 (p<0.01). The correlation coefficient between Cystatin-C based GFR and EDTA 6 samples was 0.7322 (p<0.01). Regression analysis showed a statistically significant correlation between Cr-51 EDTA 2 samples and 6 samples (r=0.971, p<0.01). Mean value and ${\pm}2SD$ for the difference between Cr-51 EDTA 2 samples and 6 samples were 4.7 mL/min and ${\pm}9.3$ respectively. Conclusions: The estimation of two samples Cr-51 EDTA showed that the method can be simplified by reducing blood samples without losing its high accuracy.