Serum cystatin C: a practical alternative for renal function evaluation? Vantagens e desvantagens desse marcador foram aqui discutidas. Despite incontestable advances in medicine, it is still difficult to define precisely this test in clinical practice. Early markers of renal lesion are important, because glomerular filtration rate usually decreases before the first chronic renal failure symptoms or signs appear.
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The journal, published since , is the official publication of the Spanish Society of Cardiology and founder of the REC Publications journal family. Articles are published in both English an Spanish in its electronic edition. The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two receding years.
CiteScore measures average citations received per document published. Read more. SRJ is a prestige metric based on the idea that not all citations are the same. SJR uses a similar algorithm as the Google page rank; it provides a quantitative and qualitative measure of the journal's impact. SNIP measures contextual citation impact by wighting citations based on the total number of citations in a subject field.
Cardiovascular disease CVD is the main cause of death in western countries. Recent studies have shown that even mild renal impairment is related to this elevated risk, 3 and this fact has led to the idea that markers of renal function may be true sentinel indicators of CVR.
The best marker of renal function is the glomerular filtration rate GFR , but it is difficult to measure the GFR in daily practice. For this reason, the serum creatinine concentration or equations derived from this parameter have been used to calculate the estimated glomerular filtration eGF.
These estimations present limitations 4 that make it difficult to detect renal disease in the initial stages. Cystatin C CC is a low-molecular-weight 13 kDa , nonglycosylated protein from the family of cysteine protease inhibitors that closely approximates what could be considered an ideal marker of renal function.
This information is essential to improve the interpretation of CC values and enable their application in clinical practice. To determine the prevalence of elevated CC levels and the association between this finding and cardiovascular risk factors and cardiovascular disease in the general population. The patients analyzed had participated in a previous study designed to determine the prevalence of peripheral arterial disease in the general population.
All patients gave informed consent at the start of the study. Patients with end-stage disease and immobile patients were excluded. Patients who died, moved to another area, or refused to participate were considered lost and were not replaced.
Because there are no previous studies investigating elevated CC levels in the general population, we used the prevalence of CRD as a reference to calculate the minimum sample size, based on the idea that at least patients with this disease would have elevated CC, which is a very sensitive parameter for detecting CRD. The study was approved by the ethics committee for clinical research of our hospital. A protocol was designed to collect demographic data age, sex , clinical data weight, height, body mass index, systolic blood pressure, diastolic blood pressure , cardiovascular risk factors smoking, dyslipidemia, HT, diabetes, obesity and cardiovascular conditions ischemic heart disease, heart failure, cerebrovascular disease, peripheral arterial disease.
All patients underwent a comprehensive laboratory workup, including a complete blood count, and analysis of fibrinogen, glucose, creatinine, total cholesterol, high-density lipoproteins, triglycerides, uric acid, lipoprotein a , hemoglobin A 1c , homocysteine, C-reactive protein, and CC. In a single urine sample, the albumin:creatinine ratio was calculated.
Samples were processed according to the recommendations of the manufacturer of the analytical technique used. A smoker was defined as a person who had smoked in the previous month, and an ex-smoker was a person who had smoked at one time, but had not smoked in the previous year.
Cardiovascular comorbidity included ischemic heart disease angina and acute myocardial infarction , heart failure, cerebrovascular disease, and peripheral arterial disease, when documented during hospitalization or after a specialized study. To determine associations between CC and the various factors studied, the t test for independent samples was used. Analysis of variance was applied to compare the means of quantitative variables.
Logistic regression analysis was performed to determine which factors were independently associated with CC elevations. Significant variables in the univariate analysis were included in the model.
Results are expressed as the mean SD or as percentage. Statistical significance was established as P Cystatin C determinations were performed in patients women, The study group did not differ significantly from the randomly selected initial group in demographic characteristics or vascular risk factors. The demographic, clinical, and laboratory characteristics of the study group are presented in Table 1.
The prevalence of elevated CC values in the population was The distribution of CC values in the population studied are shown in Figure 1.
Figure 1. Distribution of cystatin C values in our population. The prevalence of elevated CC increased with advancing age. Elevated values were found in only 5. The prevalence was very similar between sexes up to age 70, after which time elevated CC levels became more prevalent in men than women Figure 2.
Figure 2. Prevalence of elevated cystatin C according to age and sex. Following stratification of CC concentrations into quartiles, a significant relationship was found for microalbuminuria and C-reactive protein and fibrinogen increases as well as high-density lipoprotein cholesterol HDL-C and eGF decreases, as CC values progressively increased Table 3.
We present the first study performed in Spain that determines the prevalence of elevated CC levels and their relationship with CVR factors in the general population.
Up to now, this issue has been examined mainly in specific populations, such as elderly persons 11 and patients with renal disease 12 or hypertension.
These differences in prevalence may be the result of differences in the populations studied, in the definitions of normal limits, or in the calibration of the analytical methods used, making comparisons between the studies difficult. Our data are similar to the findings of Parikh et al and are consistent with the estimated prevalence of CRD in our setting, which ranges from 7.
Other authors 17 have described CC elevations with advancing age and have attributed them to progressive deterioration of renal function, although the lack of direct measures of glomerular filtration in the present study and in others is an obstacle to precise determination of this relationship. It is known that the prevalence of CRD increases considerably after the age of 70, and it is precisely at this age when CC concentrations began to show substantial increases in this study and in others.
Our results also coincide in that elderly men present higher CC values than elderly women; nevertheless, in younger patients, we found similar values in both sexes. In contrast to other studies, 18 higher CC levels were not found in our population of smokers, and decreased eGF was associated with the lowest use of tobacco.
This association disappeared after adjusting for CVD, however, and it can be explained by the fact that patients with heart disease tend to smoke less and usually have a lower eGF. Patients with established CVD presented the highest prevalence of elevated CC levels, and, as is well recognized, these patients are at a high risk of experiencing new cardiovascular events. Shlipak et al 6 have described the relationship between CC and proinflammatory parameters, such as C-reactive protein and fibrinogen in the elderly population.
Our findings support the idea that this close association is maintained in the younger general population, and that it is gradual and progresses with the CC rise. In the Multi-Ethnic Study of Atherosclerosis MESA , Keller et al 21 reaffirm these data and show that CC is associated with an extensive battery of inflammatory and procoagulant markers in all aspects of renal function, whereas eGF only shows a relationship when its decreases reach One explanation for this situation could be that the GFR is linearly associated with inflammation, and because CC is a more sensitive marker than the GFR, it would show a closer association with these molecules.
Another possible explanation is that CC is associated with inflammation regardless of renal function, as some authors have suggested, 18,21 although the majority, including those reporting two meta-analyses, 5,22 agree that CC is a very sensitive marker of small decreases in renal function.
In our population, patients with elevated CC levels showed more associations with CVR factors than patients with eGF decreases, and it was seen that C-reactive protein and fibrinogen increases and HDLc decreases were associated with elevated CC, but not with decreased eGF.
The factors that were independently associated with elevated CC levels in the general population were diabetes, male sex, and decreased eGF. This metabolic disease is a classic example of an early, silent kidney disease that confers an elevated CVR. In patients older than 60, C-reactive protein and advanced age, together with other factors that accompany ageing, were the variables most closely related to elevated CC levels. Based on this background, it can be suggested that CC measurement may identify persons in the general population with mild vascular injury, a condition that often precedes diseases such as diabetes and HT, and whose identification would be very useful for establishing appropriate treatment and, particularly, prevention measures.
It seems that the patients who would most benefit from this test would be older persons, women, and diabetic patients with normal renal function, in whom creatinine analysis, GFR formulas, or microalbuminuria do not always reveal alterations.
Only CC elevation could alert the physician to the increased vascular risk in these patients. Our study has some limitations. First, because of its descriptive, epidemiologic, cross-sectional design, we can only propose a hypothesis about the potential usefulness and advantages of CC determination.
We cannot demonstrate these advantages because the study was designed to investigate the prevalence of elevated CC levels, but not associations with the various CVR factors. Prospective studies designed to determine the true cause of the association between CC and CVD would be needed.
The study focused on the general population older than 49 years because it is the group at the highest risk of renal and vascular disease, in which the greatest diagnostic yield was expected. Thus, the findings are only applicable to this population group. The lack of standardized creatinine and CC measurement methods also makes extrapolation of the results difficult.
The fact that only one measure of eGF and microalbuminuria was available may imply some bias in the classification of patients, but we believe that the large number of individuals included may mitigate these possible errors, so they would not have a substantial influence on the final results. CC concentration can be affected by several factors, such as thyroid disease and corticoid use, 17 which were not excluded from our study; nonetheless, because of the low prevalence of these factors in the general population, we also believe that they would not significantly alter the final results.
In our setting, we found a high prevalence of individuals with elevated CC concentrations, which were related to classic cardiovascular risk factors such as diabetes, CRD and HT, and with emergent CVR markers such as C-reactive protein, homocysteine, and fibrinogen.
If the association between CC and CVD is confirmed in other studies, this test could become a useful tool in screening for vascular diseases, facilitating early diagnosis and adequate treatment and leading to a considerable improvement in the management of these diseases and in reducing their morbidity and mortality.
Additional studies are needed in the general population to confirm these data and to provide more information on the possible advantages of CC determination versus other tests. Correspondence: Dr.
Cepeda Piorno. Hospital Santos Reyes. Ruperta Baraya, 6. Received March 28, Accepted for publication November 30, Home Articles in press Current Issue Archive. ISSN: Previous article Next article. Issue 4. Pages April Download PDF. This item has received. Article information. TABLE 1. TABLE 2. TABLE 3. Show more Show less. Introduction and objectives. Cystatin C has been proposed as a novel marker of renal function and as a predictor of cardiovascular risk in the elderly.
Cystatin C: A Promising Marker of Renal Function in Patients With Systemic Lupus Erythematosus?
The journal, published since , is the official publication of the Spanish Society of Cardiology and founder of the REC Publications journal family. Articles are published in both English an Spanish in its electronic edition. The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two receding years. CiteScore measures average citations received per document published. Read more.
The journal, published since , is the official publication of the Spanish Society of Cardiology and founder of the REC Publications journal family. Articles are published in both English an Spanish in its electronic edition. The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two receding years. CiteScore measures average citations received per document published.