Cystatin C-Properties and use as diagnostic marker
This chapter focuses on the most well characterized inhibitors—cystatin C—and provide some information on its structure, biochemical properties, its role in normal and abnormal physiological processes, as well as on its use as a diagnostic marker. A major part of the cysteine proteases are evolutionary related to the structurally well–defined cysteine protease papain and are called papain–like cysteine proteases. The biological roles and the cystatin superfamily inhibitors of papain–like cystein proteases are also discussed. The aminoacid sequence and schematic structure of human cystatin C is also presented. The evolutionary relationships among all known inhibitory active human cystatins and kininogen cystatin domains are diagrammatically represented. The distribution of cystatins in body fluids and additional functions attributed to cystatin C are described. The serum or plasma cystatin C is used as a marker for glomerular filtration rate (GFR). The urine cystatin C is used as a marker for proximal tubular damage. The two types of brain hemorrhage associated with Cystatin C amyloid deposits are also demonstrated. The conditions connected with deposition of amyloid β–protein in cystatin C and cerebral hemorrhage is also provided. [1]
Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C
BACKGROUND
Estimates of glomerular filtration rate (GFR) that are based on serum creatinine are routinely used; however, they are imprecise, potentially leading to the overdiagnosis of chronic kidney disease. Cystatin C is an alternative filtration marker for estimating GFR.
METHODS
Using cross-sectional analyses, we developed estimating equations based on cystatin C alone and in combination with creatinine in diverse populations totaling 5352 participants from 13 studies. These equations were then validated in 1119 participants from 5 different studies in which GFR had been measured. Cystatin and creatinine assays were traceable to primary reference materials.
RESULTS
Mean measured GFRs were 68 and 70 ml per minute per 1.73 m2 of body-surface area in the development and validation data sets, respectively. In the validation data set, the creatinine–cystatin C equation performed better than equations that used creatinine or cystatin C alone. Bias was similar among the three equations, with a median difference between measured and estimated GFR of 3.9 ml per minute per 1.73 m2 with the combined equation, as compared with 3.7 and 3.4 ml per minute per 1.73 m2 with the creatinine equation and the cystatin C equation (P=0.07 and P=0.05), respectively. Precision was improved with the combined equation (interquartile range of the difference, 13.4 vs. 15.4 and 16.4 ml per minute per 1.73 m2, respectively [P=0.001 and P<0.001]), and the results were more accurate (percentage of estimates that were >30% of measured GFR, 8.5 vs. 12.8 and 14.1, respectively [P<0.001 for both comparisons]). In participants whose estimated GFR based on creatinine was 45 to 74 ml per minute per 1.73 m2, the combined equation improved the classification of measured GFR as either less than 60 ml per minute per 1.73 m2 or greater than or equal to 60 ml per minute per 1.73 m2 (net reclassification index, 19.4% [P<0.001]) and correctly reclassified 16.9% of those with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 as having a GFR of 60 ml or higher per minute per 1.73 m2.
CONCLUSIONS
The combined creatinine–cystatin C equation performed better than equations based on either of these markers alone and may be useful as a confirmatory test for chronic kidney disease. [2]
Cystatin C: An Improved Estimator of Glomerular Filtration Rate?
Background: Glomerular filtration rate (GFR) is routinely assessed by measuring the concentrations of endogenous serum markers such as blood urea nitrogen and serum creatinine (SCr). Although widely used, these endogenous markers are not ideal and do not perform optimally in certain clinical settings. The purpose of this review is to critically review the potential utility of cystatin C (CysC), especially in patient populations in which CysC may have an advantage over routinely used endogenous markers of GFR.
Approach: In a narrative approach, we extensively review publications, primarily from the last 5 years, that address the development of methods to measure CysC, reference intervals, and the diagnostic accuracy of CysC to assess GFR. Between June 2000 and September 2001 Medline was searched using “cystatin c” as a textword, and articles that examined >75 individuals (except for renal transplant studies) and/or used accepted “gold standards” for assessing GFR were selected for inclusion. A total of 17 studies are reviewed that provide reference interval data for several populations. A total of 24 studies make conclusions about the utility of CysC vs SCr and/or creatinine clearance, with 20 providing data on the sensitivity and specificity of CysC for detecting impaired GFR. These publications are organized into subgroups that deal with specific patient populations or clinical situations.
Content: This review focuses on two areas: (a) the evolution of immunoassays used to determine the concentration of CysC in serum, their analytic sensitivity, and reference intervals; and (b) the diagnostic performance of CysC against other renal markers in the general population and in specific subpopulations of patients.
Summary: Studies of reference intervals for CysC overwhelmingly demonstrated that CysC values in blood are independent of age and sex. Of the 24 studies that examined clinical utility, 15 concluded that CysC is superior to SCr, whereas 9 concluded that CysC is equivalent but provides no advantage. Summary ROC plot analysis of 20 studies that provide sensitivity and specificity data strongly suggests that CysC will be superior to SCr for detecting impaired GFR. Taken together, it is clear that CysC performs at least as well as SCr in the population at large and that it is likely to be superior to SCr in specific patient populations. [3]
Profound Study for Functions of Antimicrobial Peptides in Prevention of Oral Disease
Antimicrobial peptides (AMPs) have a widespread distribution in human body and have antimicrobial activity against microorganisms with wide-range class of host-defense molecules. These are small cationic peptides that play an important role in the development of innate immunity with activity against gram-positive and negative bacteria, parasites, fungi and some viruses.
In the oral cavity, the AMPs are produced by the salivary glands and the oral epithelium and serve as defensive purposes. At least forty-five identifiable antimicrobial gene products found in saliva are secreted from oral epithelial cells, salivary glands and neutrophils. AMPs also serve as effective biological molecules in immune response activation, inflammation and wound healing.The aim of this review was to discuss the types and functions of oral AMPs and their role in combating microorganisms and infections in the oral cavity.
AMPs have a promising potential to be used against oral microbes in order to control their growth and biofilm formation. There are many challenges that need to be overcome in order to design and synthesize AMPs that have the ability to with stand the unique and harsh oral environment. AMPs are expected in the future to be used as models for developing effective oral microbial antibiotics. [4]
Paraquat Poisoning Management in Iran (Isfahan): Devising a Protocol
Background: Paraquat poisoning has been a health concern in many developing countries. Management of it is not standardized and varies from center to center. This study is aimed at devising an available evidence-based comprehensive protocol for parquat poisoning management in Isfahan, Iran, to reduce unnecessary variations in practice.
Materials and Methods: A narrative search in electronic databases was performed. Several peer-reviewed articles, guidelines, and textbooks were reviewed and practical details were extracted from 1967 till now.
The simple, available and wide-ranged descriptive protocol was developed.
Then, it was finally discussed with expert physicians specialized to be optimized for the diagnostic tools and treatments used in this setting by supplementing other specific considerations.
Results: The final version of the protocol was designed in six steps. The algorithm consists of a planned are based on the severity of the toxicity. It comprised of supportive treatments based on Resuscitation, Gastrointestinal decontamination, Elimination enhancement, and other treatment options for PQ lung injury.
Conclusion: Paraquat poisoning is a clinical toxicologic emergency, which needs to be diagnosed and treated in an organized manner, although its mortality rate is great. [5]
Reference
[1] Grubb, A.O., 2001. Cystatin C-properties and use as diagnostic marker. Advances in clinical chemistry, 35, pp.63-99.
[2] Inker, L.A., Schmid, C.H., Tighiouart, H., Eckfeldt, J.H., Feldman, H.I., Greene, T., Kusek, J.W., Manzi, J., Van Lente, F., Zhang, Y.L. and Coresh, J., 2012. Estimating glomerular filtration rate from serum creatinine and cystatin C. New England Journal of Medicine, 367(1), pp.20-29.
[3] Laterza, O.F., Price, C.P. and Scott, M.G., 2002. Cystatin C: an improved estimator of glomerular filtration rate?. Clinical chemistry, 48(5), pp.699-707.
[4] Alalwani, M., Kharma, M. and Aws, G. (2016) “Profound Study for Functions of Antimicrobial Peptides in Prevention of Oral Disease”, Journal of Advances in Medicine and Medical Research, 14(5), pp. 1-10. doi: 10.9734/BJMMR/2016/24528.
[5] Hedaiaty, M., Sabzghabaee, A., Gheshlaghi, F. and Eizadi Mood, N. (2016) “Paraquat Poisoning Management in Iran (Isfahan): Devising a Protocol”, Journal of Advances in Medicine and Medical Research, 16(5), pp. 1-10. doi: 10.9734/BJMMR/2016/23987.
