Extrahepatic Synthesis of Acute Phase Proteins
Andrzej Mackiewicz, Irving Kushner, Heinz Baumann in Acute Phase Proteins, 2020
Cystatin C is the extracellular brain protein with the highest ratio of the concentration in cerebrospinal fluid over that in blood plasma (for data on the human, see Reference 107). The primary structure of the cDNA has been reported for human cystatin C.108 Oligonucleotide probes were synthesized based on the sequence of human cystatin C cDNA and found to cross-hybridize with the corresponding mRNA in the rat.109,110 In the rat, the tissue with the highest cystatin C mRNA level was found to be the choroid plexus.109 Cystatin C mRNA was also detected in lower levels in other areas of the brain, in testis, epididymis, seminal vesicles, prostate, ovary, submandibular gland, and, in trace amounts, in liver.109 Choroid plexus pieces incubated with radioactive leucine secreted radioactive cystatin C.109 Possibly, the function of cystatin C is the inhibition of extracellular proteinases, such as those released from destroyed or dying cells. Thus, cystatin C could be important in maintaining the integrity of cell-surface proteins in the brain. The presence of large numbers of lysosomes, cell organelles rich in proteinases, has been described for neuronal cells.111
Renal diseases in pregnancy
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
Cystatin C is a low–molecular weight (MW) protein, which has been recently studied in the general population in an attempt to find a better endogenous marker that could be used for more accurate estimation of GFR (17). Studies have found that while serum creatinine levels decrease in pregnancy, cystatin C levels were higher for pregnant women as compared with healthy nonpregnant women (18) and also significantly higher in twin as compared with singleton pregnancies (18). Cystatin C levels increase during pregnancy in relationship to gestational age, being highest in the third trimester (19). Its actual role in pregnancy is very interesting, as cystatin C is a member of the cystatin superfamily of cysteine protease inhibitors. Proteinases and their inhibitors regulate the trophoblast invasion, and the serum concentration of cystatin C has been found in several studies to be increased not only in late pregnancy but also in pre-eclampsia (18–20). Based on the available data, it is unlikely that cystatin C will have any utility in monitoring kidney function in pregnancy but might prove useful in the early detection of patients who will develop pre-eclampsia (21).
Polypharmacy
Medha N. Munshi, Lewis A. Lipsitz in Geriatric Diabetes, 2007
Elimination involves a drug’s exit from the body. Renal clearance is the most common pathway for the elimination of drugs, although hepatobiliary clearance is also an important pathway for some medications. Elimination can involve removal of the parent compound or metabolites of the parent compound. On average, aging is associated with a linear decline in renal function, such that the average reduction in glomerular filtration rate from young adulthood to old age is roughly one-third. However, it is important to realize that there can be significant heterogeneity in the decline of renal function with age—some subjects have minimal changes in renal function with aging, and a few subjects even appear to have improvements in renal function over time. Thus, the effects of age on renal function can be quite variable in individual patients. This is especially true of diabetic patients, who are at risk for subtle and overt nephropathy. Serum creatinine measurements provide a limited perspective on the level of renal function. Cystatin C, a non-glycosylated basic protein that is freely filtered by the glomerulus, is under investigation as a possible alternative to serum creatinine for estimating the glomerular filtration rate (18). At present, however, cystatin C measurements are not commonly available for clinical use. Several formulae have been suggested to better estimate renal function. For example, the Cockcroft–Gault formula (19) is one useful approach for estimating renal function and requires only a few easily obtained measurements:
Expression of urinary exosomal miRNA-615-3p and miRNA-3147 in diabetic kidney disease and their association with inflammation and fibrosis
Published in Renal Failure, 2023
Jiaxin Wang, Yiying Tao, Fan Zhao, Tong Liu, Xiahong Shen, Ling Zhou
As a traditional inflammatory indicator, Cystatin C not only reflects the degree of renal damage but is also one of the important indicators of the micro-inflammatory state in DKD patients [46]. Cystatin C is a low molecular weight protein (13KD) produced by all nucleated human cells and is primarily catabolized by proximal tubular cells [47]. As an endogenous inhibitor of cysteine protein, it is not affected by age, gender, muscle mass, or protein intake [48]. However, studies [46] have shown that serum Cystatin C is positively correlated with the micro-inflammatory state of DKD and related inflammatory factors. Cystatin C is not only correlated with eGFR and other indicators of renal function damage but also in evaluating the degree and progression of inflammatory response in the course of DKD. The present study provided evidence that the expression level of urinary exosomal miRNA-615-3p correlated with serum Cystatin C, so urinary exosomal miRNA-615-3p might be useful as a marker of the inflammatory response and the progression of kidney damage in DKD.
Early serum cystatin C-enhanced risk prediction for acute kidney injury post cardiac surgery: a prospective, observational, cohort study
Published in Biomarkers, 2020
Xudong Wang, Xinghui Lin, Bo Xie, Ritai Huang, Yucheng Yan, Shang Liu, Mingli Zhu, Renhua Lu, Jiaqi Qian, Zhaohui Ni, Song Xue, Miaolin Che
Cystatin C (CyC) is a 13-kDa endogenous cysteine proteinase inhibitor which plays an important role in intra-cellular catabolism of proteins and peptides. Some studies have shown that it is a better indicator of kidney function compared to creatinine (Dharnidharka et al.2002, Odutayo and Cherney 2012), but still no widespread recommendations exist for its use (Yong et al.2017). Arun et al. (2015) showed that measurement of serum cystatin C (sCyC) within 24 h of completion of cardiac surgery significantly improved the prediction of AKI. This is an important observation and could be widely applicable as sCyC is readily available in clinical practice. Our previous study corroborated this finding, demonstrating a significant rise in sCyC 10–72 h after ICU admission following cardiac surgery in AKI patients (Che et al.2010).
Cystatin C and mortality risk in the general population: systematic review and dose response meta-analysis
Published in Biomarkers, 2022
Eujene Jung, Young Sun Ro, Hyun Ho Ryu, So Yeon Kong, Sang Do Shin, Sung Oh Hwang
In recent years, cystatin C has been proposed as a more reliable marker of renal failure than creatinine, particularly for the detection of small reduction of GFR (Dharnidharka et al.2002). Cystatin C is a small (13-kDa) protein and cysteine protease inhibitor produced by nearly all cells and excreted into the bloodstream, Cystatin C is, freely filtered by the glomerulus, then metabolized by the proximal tubule. Therefore, cystatin C has potential merit over serum creatinine for estimating GFR as its production is independent of muscle mass (Coll et al.2000). In addition, it is not affected by age, fever, or other exogenous agents (Newman et al.1995). As a result, cystatin C has been suggested as a more accurate estimation tool of GFR than serum creatinine based equations and in predicting early decline in renal function (Shlipak et al.2006).
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