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PubMed2003

Interest of cystatin C in screening diabetic patients for early impairment of renal function.

We compared cystatin C, creatinine, and the Cockroft formula for assessment of early renal failure, defined as a (51)Cr-EDTA clearance < 80 mL/min, in 89 diabetic patients with various degrees of renal impairment (glomerular filtration rate [GFR], 11.4 to 196.5 mL/min). The relationships between cystatin C, creatinine, and (51)Cr-EDTA clearance were linearized by plotting the reciprocals of the values, and correlation coefficients were determined. Sensitivity and specificity for the diagnosis of early renal failure were calculated from receiver operating characteristic (ROC) curves. Over the whole population, cystatin C was as well correlated with GFR (r =.74) as was creatinine (r =.67) or the Cockroft formula (r =.88). Moreover, its diagnostic accuracy was comparable to that of the 2 other parameters. Its sensitivity (86.8%) was better than that of creatinine (77.4%) for screening GFR < 80 mL/min, although the Cockroft formula was more sensitive (96.2%). The study of albuminuric diabetics (n = 63) led to similar conclusions, except for a poor sensitivity of cystatin C. In the 36 patients whose plasma creatinine was < 1 mg/dL, 10 (27.7%) had GFR < 80 mL/min. The correlation of creatinine with GFR, its diagnostic accuracy, and sensitivity were significantly lower than those of cystatin C. In this population of patients with normal creatinine levels, the correlation coefficient of cystatin C, its sensitivity, and its diagnostic accuracy were comparable to those of the Cockroft formula. A moderate reduction in GFR may be present in diabetic patients with low creatinine levels. Although Cockroft formula remains the most reliable and the less expensive tool for the evaluation of renal function, cystatin C is a more reliable criterion for screening and assessment than creatinine and represents a useful alternative to the Cockcroft-Gault formula.

Adult↗

PubMed2003

Cystatin C as a cerebrospinal fluid biomarker for pain in humans.

Through a process of subtraction cloning and differential hybridization, we previously identified several new genes whose expression was induced by peripheral inflammation. One of these coded for cystatin C, a secreted cysteine protease inhibitor in the cystatin superfamily. We hypothesized that, concurrent with increased expression in dorsal horn, increased secretion would elevate the cystatin C content in cerebrospinal fluid (CSF) during active pain states. Alterations were assessed by immunoassay and by surface enhanced laser desorption ionization (SELDI) mass spectrometry with either reverse phase or immobilized anti-cystatin C antibody surfaces using CSF from ten age-matched obstetrical patients at term. Five control subjects were scheduled for an elective caesarian section and were not in pain. Another five subjects were in labor for 8.9+/-1h and were in severe pain as assessed with a visual analog scale and the McGill short form questionnaire. The level of cystatin C as measured by immunoassay in the non-pain patients was 2.77+/-0.75 microg/ml and in the pain patients 5.36+/-0.92 microg/ml (P<0.02). The elevation occurred without significant change in total CSF protein or beta-endorphin content. The cystatin C increase also was detectable by SELDI with either raw CSF or after antibody capture. These data are consistent with our previous animal study and the idea that persistent pain induces the synthesis and release of cystatin C in dorsal spinal cord, the surplus of which overflows into the CSF.

Adult↗

PubMed2000

Increased cystatin C immunoreactivity in the skin in amyotrophic lateral sclerosis.

OBJECTIVES: Several abnormalities of skin have been described in patients with amyotrophic lateral sclerosis (ALS). Bunina bodies, which are small eosinophilic intraneuronal inclusions in the remaining lower motor neurons in ALS, are the only pathologically specific hallmark of ALS. It has been demonstrated that Bunina bodies were positive for anti-cystatin C serum. However, cystatin C in the skin of ALS has not been investigated. MATERIAL AND METHODS: We studied cystatin C immunoreactivity of skin in ALS patients, and the results were compared with those of control subjects. RESULTS: The epidermis of ALS was immunohistochemically strongly positive for cystatin C as compared with that of controls. The optical density of cystatin C immunostaining reactivity in ALS patients was significantly higher than in controls, and was significantly increased with duration of illness. CONCLUSION: These data suggest that a metabolic alteration of cystatin C may take place in the skin of ALS and the increased cystatin C in skin is likely to be related to the disease process in ALS.

Aged↗

PubMed2006

Colocalization of cystatin M/E and cathepsin V in lamellar granules and corneodesmosomes suggests a functional role in epidermal differentiation.

Cystatin M/E is a cysteine protease inhibitor with two distinct binding sites for papain-like cysteine proteases (family C1) and the asparaginyl endopeptidase (AEP) legumain of family C13. We have previously demonstrated that deficiency of cystatin M/E in mice causes ichthyosiform skin changes and barrier disruption, which could be caused by unrestrained AEP activity. Recently, we provided biochemical evidence that human cathepsin V (CTSV) and cathepsin L (CTSL) are additional biological targets for human cystatin M/E. To address the possible role of these three proteases and their inhibitor in epidermal differentiation, we investigated the localization of these proteins in normal human skin. Whereas CTSL and AEP were broadly expressed in epithelial cells of the skin, we found a specific colocalization of cystatin M/E and CTSV in the stratum granulosum and in the root sheets of the hair follicle, using immunofluorescence microscopy. Immunoelectron microscopy revealed that cystatin M/E and CTSV are separately transported within the lamellar granules. Cystatin M/E was also found in the extracellular space in the stratum corneum associated with corneodesmosomes, where it was closely associated with CTSV. Based on the striking stratum-specific colocalization of cystatin M/E and CTSV, we propose that these molecules could have an important role in epidermal differentiation and desquamation.

Cathepsins↗

PubMed2004

Cystatin M suppresses the malignant phenotype of human MDA-MB-435S cells.

Proteases are involved in many aspects of tumor progression, including cell survival and proliferation, escape from immune surveillance, cell adhesion and migration, remodeling and invasion of the extracellular matrix. Several lysosomal cysteine proteases have been cloned and shown to be overexpressed in cancer; yet, despite the great potential for development of novel therapeutics, we still know little about the regulation of their proteolytic activity. Cystatins such as cystatin M are potent endogenous protein inhibitors of lysosomal cysteine proteases. Cystatin M is expressed in normal and premalignant human epithelial cells, but not in many cancer cell lines. Here, we examined the effects of cystatin M expression on malignant properties of human breast carcinoma MDA-MB-435S cells. Cystatin M was found to significantly reduce in vitro: cell proliferation, migration, Matrigel invasion, and adhesion to endothelial cells. Reduction of cell proliferation and adhesion to an endothelial cell monolayer were both independent of the inhibition of lysosomal cysteine proteases. In contrast, cell migration and matrix invasion seemed to rely on lysosomal cysteine proteases, as both recombinant cystatin M and E64 were able to block these processes. This study provides the first evidence that cystatin M may play important roles in safeguarding against human breast cancer.

Breast Neoplasms↗

PubMed1990

Structure and expression of the human cystatin C gene.

The structural organization of the gene for the human cysteine-proteinase inhibitor cystatin C was studied. Restriction-endonuclease digests of human genomic DNA hybridized with human cystatin C cDNA and genomic probes produced patterns consistent with a single cystatin C gene and, also, the presence of six closely related sequences in the human genome. A 30 kb restriction map covering the genomic region of the cystatin C gene was constructed. The positions of three polymorphic restriction sites, found at examination of digests of genomic DNA from 79 subjects, were localized in the flanking regions of the gene. The gene was cloned and the nucleotide sequence of a 7.3 kb genomic segment was determined, containing the three exons of the cystatin C structural gene as well as 1.0 kb of 5'-flanking and 2.0 kb of 3'-flanking sequences. Northern-blot experiments revealed that the cystatin C gene is expressed in every human tissue examined, including kidney, liver, pancreas, intestine, stomach, antrum, lung and placenta. The highest cystatin C expression was seen in seminal vesicles. The apparently non-tissue-specific expression of this cysteine-proteinase inhibitor gene is discussed with respect to the structure of its 5'-flanking region, which shares several features with those of housekeeping genes.

Amino Acid Sequence↗

PubMed2002

Renal dysfunction in falciparum--malaria is detected more often when assessed by serum concentration of cystatin C instead of creatinine.

OBJECTIVES: To estimate the frequency of renal dysfunction in falciparum malaria by serum concentration of cystatin C, a new sensitive indicator of the glomerular filtration rate (GFR). METHODS: Retrospective study of stored sera and patient files. Assessment of renal function by serum concentration of creatinine and cystatin C and comparison of the results from both indicators of GFR. RESULTS: A total of 108 adult patients with falciparum malaria were included in the study. Concentration of creatinine and cystatin C correlated well (r = 0.706; P < 0.001). Elevated cystatin C was more frequent than elevated creatinine (54.6%vs. 20.4%; P < 0.001). Patients older than 50 years developed renal dysfunction more often (P < 0.05) than younger ones. Results from cystatin C and creatinine were concordant in 63 (58.3%) and contradictory in 45 (41.6%) cases. Four (3.7%) patients had elevated creatinine but normal cystatin C levels, hence 63 patients (58.3%) showed elevation of at least one indicator of GFR. The frequency of elevated cystatin C and elevated creatinine was unrelated to body weight, gender or bilirubin level. CONCLUSIONS: The prevalence of impaired renal function in patients with falciparum malaria seems to have been underestimated in the past. Using a sensitive marker, 55% of the patients have a reduced GFR.

Adolescent↗

PubMed2003

The human cystatin M/E gene (CST6): exclusion candidate gene for harlequin ichthyosis.

Cystatin M/E is a recently discovered cysteine proteinase inhibitor whose expression is largely confined to cutaneous epithelia. In human skin it is expressed in sweat glands, hair follicles, and stratum granulosum of the epidermis where it presumably acts as a substrate for transglutaminase. Very recently we reported that a null mutation in the mouse cystatin M/E gene (Cst6) causes the murine ichq phenotype, which is characterized by abnormalities in cornification and desquamation, demonstrating an essential role for cystatin M/E in the final stages of epidermal differentiation. We here obtained the complete sequence of the human cystatin M/E gene (CST6), which provides a tool to investigate CST6 as a candidate gene in skin diseases characterized by abnormal cornification. The involvement of CST6 in harlequin ichthyosis in humans was evaluated by sequencing the entire coding region and intron-exon boundaries for mutations in 11 sporadic harlequin ichthyosis patients. No CST6 mutations were detected in this group, which comprised type 1 and type 2 harlequin ichthyosis patients. Disturbed transcription/translation due to mutations in regulatory and noncoding regions of cystatin M/E was unlikely because cystatin M/E protein expression was observed in all patients examined, as assessed by immunohistochemistry. Although our results indicate that CST6 is not a major gene contributing to type 1 and 2 harlequin ichthyosis, these data may facilitate further analysis of the role of cystatin M/E in normal human skin and other genetic disorders of cornification.

Animals↗

PubMed2000

Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment.

Cystatin C is a nonglycosylated basic protein produced at a constant rate by all investigated nucleated cells. It is freely filtered by the renal glomeruli and primarily catabolized in the tubuli (not secreted or reabsorbed as an intact molecule). Because serum cystatin C concentration is independent of age, sex, and muscle mass, it has been postulated to be an improved marker of glomerular filtration rate (GFR) compared with serum creatinine level. We compared serum cystatin C level with other markers of GFR, such as serum creatinine level and creatinine clearance, and analyzed their variations based on iothalamate labeled with iodine 125 ((125)I-iothalamate) clearance ((125)I-ICl), used as the gold standard for GFR. The concentrations of the two different markers of GFR in patients with impaired renal function were classified according to (125)I-ICl. Twenty individuals with normal renal function ((125)I-ICl, 128 +/- 23 mL/min/1.73 m(2)) were used as the control group. Serum cystatin C level showed a greater sensitivity (93.4%) than serum creatinine level (86.8%). Also, serum cystatin C showed the greatest proportion of increased values in patients with impaired renal function (100%) compared with serum creatinine level (92.15%). Serum cystatin C levels started to increase to greater than normal values when GFR was 88 mL/min/1.73 m(2), whereas serum creatinine level began to increase when GFR was 75 mL/min/1.73 m(2). These data suggest that measurement of serum cystatin C may be useful to estimate GFR, especially to detect mild reductions in GFR, and therefore may be important in the detection of early renal insufficiency in a variety of renal diseases for which early treatment is critical.

Biomarkers↗

PubMed2005

Cystatin C and the risk of death and cardiovascular events among elderly persons.

BACKGROUND: Cystatin C is a serum measure of renal function that appears to be independent of age, sex, and lean muscle mass. We compared creatinine and cystatin C levels as predictors of mortality from cardiovascular causes and from all causes in the Cardiovascular Health Study, a cohort study of elderly persons living in the community. METHODS: Creatinine and cystatin C were measured in serum samples collected from 4637 participants at the study visit in 1992 or 1993; follow-up continued until June 30, 2001. For each measure, the study population was divided into quintiles, with the fifth quintile subdivided into thirds (designated 5a, 5b, and 5c). RESULTS: Higher cystatin C levels were directly associated, in a dose-response manner, with a higher risk of death from all causes. As compared with the first quintile, the hazard ratios (and 95 percent confidence intervals) for death were as follows: second quintile, 1.08 (0.86 to 1.35); third quintile, 1.23 (1.00 to 1.53); fourth quintile, 1.34 (1.09 to 1.66); quintile 5a, 1.77 (1.34 to 2.26); 5b, 2.18 (1.72 to 2.78); and 5c, 2.58 (2.03 to 3.27). In contrast, the association of creatinine categories with mortality from all causes appeared to be J-shaped. As compared with the two lowest quintiles combined (cystatin C level, < or =0.99 mg per liter), the highest quintile of cystatin C (> or =1.29 mg per liter) was associated with a significantly elevated risk of death from cardiovascular causes (hazard ratio, 2.27 [1.73 to 2.97]), myocardial infarction (hazard ratio, 1.48 [1.08 to 2.02]), and stroke (hazard ratio, 1.47 [ 1.09 to 1.96]) after multivariate adjustment. The fifth quintile of creatinine, as compared with the first quintile, was not independently associated with any of these three outcomes. CONCLUSIONS: Cystatin C, a serum measure of renal function, is a stronger predictor of the risk of death and cardiovascular events in elderly persons than is creatinine.

Aged↗

PubMed2001

Fetal serum concentrations of cystatin C and beta2-microglobulin as predictors of postnatal kidney function.

OBJECTIVES: Cystatin C and beta(2)-microglobulin are established serum markers of renal function in children and adults. In contrast to creatinine, diaplacental exchange is minimal. The aim of the study was to establish reference values in fetal serum and to test their efficiency in predicting postnatal kidney function. STUDY DESIGN: This was a prospective noninterventional study measuring cystatin C and beta(2)-microglobulin by particle-enhanced immunoturbidimetry in excess serum from 129 cordocenteses performed in 84 fetuses. Reference intervals (mean +/- 1.96 SD) were calculated in a subgroup of 54 fetuses without evidence of kidney disease, and these reference values were evaluated in 75 sera from 55 fetuses. RESULTS: Mean cystatin C was 1.66 +/- 0.202 mg/L (upper limit 2.06), and mean beta(2)-microglobulin was 4.25 +/- 0.734 mg/L. Unlike cystatin C, beta(2)-microglobulin decreased significantly with gestational age so that the upper reference limit was 7.19-0.052 x gestational age in weeks. beta(2)-Microglobulin had higher sensitivity (90.0% vs 63.6%) and cystatin C a higher specificity (91.8% vs. 85.5%) for the prediction of impaired renal function; diagnostic efficiency was equal (87.6% vs. 86.1%). Fetuses with impaired renal function at birth or who were aborted for renal malformations had higher cystatin C concentrations than those in a control group. beta(2)-Microglobulin was increased only in fetuses who were aborted. CONCLUSION: Fetal serum cystatin C and beta(2)-microglobulin concentrations may be useful predictors of postnatal kidney function.

Cordocentesis↗

PubMed1996

Cystatins up-regulate nitric oxide release from interferon-gamma-activated mouse peritoneal macrophages.

Up-regulation of nitric oxide (NO) production by activated murine macrophages was observed during infection by Trypanosoma cruzi, the etiological agent of Chagas' disease. Cell infection by T. cruzi depends at least in part on cruzipain, a membrane-associated papain-related proteinase which is sensitive to inhibition by synthetic inhibitors of cysteine proteinases. Using the natural cysteine proteinase inhibitor chicken cystatin, a representative member of cystatin family 2, to investigate the effect of cruzipain on macrophage infection and NO release, we found that the inhibitor alone up-regulated NO release from interferon-gamma-activated macrophages. A 12-fold increase in NO production was observed in the presence of 1 microM chicken cystatin. This overproduction was concentration-dependent and could be detected at concentrations as low as 10 nM and remained in the presence of polymyxin B. Representative members of the other cystatin families, i.e. stefin B (family 1), T-kininogen, and its inhibitory domains (family 3), were also able to enhance NO production from interferon-gamma-activated macrophages. Neither E64, an irreversible inhibitor of cysteine proteinases, nor inhibitors of aspartyl and serine proteinases (aprotinin, pepstatin, and soybean trypsin inhibitor) enhanced NO production. Upon complexation with saturating amounts of reduced-alkylated papain, cystatins still remained active in increasing NO production, suggesting that the cystatin inhibitory site was not involved in the mechanism. The results demonstrate that members of all 3 cystatin families share another common property unrelated to their function of cysteine proteinase inhibitors, i.e. up-regulation of NO production, which biological significance remains to be elucidated.

Animals↗

PubMed1999

Relationships among serum cystatin C, serum creatinine, lean tissue mass and glomerular filtration rate in healthy adults.

In an effort to increase our knowledge of the optimal use of serum cystatin C and creatinine as glomerular filtration rate (GFR) markers, these variables, as well as lean tissue mass and GFR, were determined in a population of 42 healthy young adults (men and women with normal GFR). Dual-energy X-ray absorptiometry and measurement of the plasma clearance of iohexol were used to measure lean tissue mass and GFR, respectively. Serum creatinine was significantly correlated to lean tissue mass (r=0.65; p < 0.0001) but not to GFR (1/creatinine vs. GFR: r=0.11; p=0.106). In contrast, serum cystatin C correlated with GFR (1/cystatin C vs. GFR: r=0.32; p=0.0387), especially in men (1/cystatin C vs. GFR: r=0.64; p=0.0055), but not to lean tissue mass. These results might explain previous observations that serum cystatin C seems to be a better marker for GFR than serum creatinine, particularly for individuals with small to moderate decreases in GFR. However, the results also show that the serum concentrations of both creatinine and cystatin C are determined not only by GFR, but also by other factors. Since these additional factors differ for cystatin C and creatinine, it seems justified to use serum creatinine and cystatin C in conjunction to estimate GFR, at least until it is known in what situations serum creatinine or cystatin C is the preferable marker.

Absorptiometry, Photon↗

PubMed1990

Direct radioimmunoassay of rat cystatin C: increased urinary excretion of this cysteine proteases inhibitor during chromate nephropathy.

Rat cystatin C was purified to apparent homogeneity from rat urine after induction of a tubular dysfunction with sodium chromate. The two-steps purification procedure included a Carboxymethyl-papain affinity chromatography and anion exchange chromatography. The purified protein was identified as rat cystatin C by the following criteria: firstly retained on a Cm-papain affinity column, secondly an apparent molecular weight of 15 kDa and pI of 10.2. Antisera raised in rabbits against our purified rat cystatin C did not cross-react with other urinary proteins such as rat albumin and rat kallikrein, but partially cross-reacted with human cystatin C. A direct radioimmunoassay was developed and it enabled 8.32 fmol/ml of rat cystatin C to be detected. The detection range was between 0.125 and 62.5 ng/ml, with 10% intra-assay variation and 14% inter-assay variation. Physiological rat cystatin C excretion (40 +/- 18 micrograms/24 h) was found by the direct assay. In the chromate-intoxicated rat, urinary excretion increased twenty-fivefold (1017 +/- 391 micrograms/24 h) and returned to normal level one week after intoxication. This RIA will allow the study of rat cystatin C metabolism particularly during renal dysfunction.

Acute Kidney Injury↗

PubMed1989

A rapid two-step purification of rat cystatin C, one major inhibitor of cysteine proteinases.

Rat cystatin C was purified to apparent homogeneity from rat urine after induction of a tubular dysfunction with sodium chromate. Twentyfold concentrated urine was chromatographed by a rapid purification procedure. A two-step purification including affinity chromatography on carboxymethyl papain- Sepharose and high-resolution anion exchange chromatography was developed. The purified protein has an apparent molecular mass of 15 kDa and pI of 10.2; its aminoacid composition was similar to human cystatin C. As opposed to previous data, purified urinary rat cystatin C did not contain significant amounts of carbohydrate. Antisera against rat cystatin C, raised in rabbits, partially cross-reacted with human and mouse cystatin C, indicating their antigenic similarities. Like human cystatin C, native rat cystatin C, named slow form, is degraded into a more acidic form, called fast form, by a loss of N-terminal amino acids; fast form displayed a pI of 9.4.

Amino Acid Sequence↗

PubMed1989

Stroke in Icelandic patients with hereditary amyloid angiopathy is related to a mutation in the cystatin C gene, an inhibitor of cysteine proteases.

Cystatin C is an inhibitor of lysosomal cysteine proteases and consists of 120 amino acids. A variant of cystatin C lacking the first NH2-terminal residues and having one amino acid substitution at position 68 forms amyloid deposits mainly in the walls of brain arteries, causing fatal strokes in Icelandic patients with familial cerebral hemorrhage secondary to a form of an autosomal dominant amyloidosis. To understand the molecular basis of the genetic defect, the gene encoding cystatin C was isolated from genomic DNA libraries made from normal tissue and the brain of an Icelandic patient with hereditary cerebral hemorrhage with amyloidosis (HCHWA-I). The data indicate that the cystatin C gene encodes a polypeptide of 146 amino acids, of which the first 26 correspond to a secretory peptide signal sequence. The gene contains two intervening sequences that interrupt the coding region at amino acids 55 and 93. Comparison with genes encoding salivary cystatins and kininogen proteins show sequence homology and conservation of exon-intron structure. Except for a mutation in the second exon (CAG instead of CTG in the normal gene, resulting in the substitution of glutamine for a leucine residue), the gene cloned from the brain of the Icelandic patient is identical to the normal cystatin C gene. Thus, HCHWA-I is the first familial type of amyloidosis related to a point mutation in a gene encoding for an inhibitor. The mutation in the structural gene encoding cystatin C appears to be the primary defect in this inherited disorder causing amyloid fibril formation and accumulation followed by cerebral hemorrhage.

Amino Acid Sequence↗

PubMed2002

A null mutation in the cystatin M/E gene of ichq mice causes juvenile lethality and defects in epidermal cornification.

Cystatin M/E (CST6 ), a new member of the cystatin gene family, has a restricted expression pattern in humans, which is largely limited to cutaneous epithelia. Although cystatin M/E possesses two distinct biochemical properties, being a cysteine proteinase inhibitor and a substrate for transglutaminase, its physiological function is unknown. Here we report the isolation and characterization of the mouse Cst6 orthologue and the assignment of the chromosomal localization to the proximal end of mouse chromosome 19. This region corresponds to the locus of the spontaneous harlequin ichthyosis (ichq) mouse mutation, for which no causative gene has been identified so far. We found a nonsense mutation in the Cst6 gene of BALB/cJ-ichq/+ mice, which precludes the synthesis of functional protein. Immunohistochemistry confirmed the absence of cystatin M/E at the protein level in ichq/ichq mice. Mice that are homozygous for two null alleles display a hyperplastic, hyperkeratotic epidermis and abnormal hair follicles, and die between 5 and 12 days of age. In wild-type mice, cystatin M/E was found in the stratum granulosum and in the infundibulum of the hair follicle indicating that the anatomical site in the skin where cystatin M/E is normally expressed correlates with the abnormalities at the tissue level in ichq/ichq mice. Our data provide evidence that cystatin M/E is required for viability and for correct formation of cornified layers in the epidermis and hair follicles. The ichq mouse mutation may serve as a model for human type 2 harlequin ichthyosis.

Amino Acid Sequence↗

PubMed2007

Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis in middle-aged adults.

BACKGROUND: Cystatin C, a marker of renal function, has been shown to be an independent predictor of cardiovascular disease (CVD) in older adults, but few data are available in middle-aged adults. Moreover, no study has compared cystatin C and microalbuminuria as risk factors for CVD outcomes in middle-aged adults, and it is not known whether cystatin C is related to an early stage of atherosclerosis. METHODS: We evaluated the relationships between serum creatinine, estimated glomerular filtration rate (GFR), serum cystatin C (all divided into tertiles), microalbuminuria and carotid atherosclerosis in a population-based random sample of 523 adults aged 35-64 years from the Seychelles (Indian Ocean). GFR was estimated using the modification of diet in renal disease (MDRD) equation. Intima-media thickness (IMT) was assessed by B-mode ultrasound. RESULTS: The mean age of the study sample was 52 years, and 55% were women. Carotid IMT was higher in participants with microalbuminuria (802 vs 732 microm, P<0.001) and was inversely associated with GFR tertiles (from 728 to 809 microm, P for trend=0.002). IMT was not associated with cystatin C or creatinine (P for trend=0.10 and 0.16, respectively). In multivariate analyses adjusted for cardiovascular risk factors, the association between microalbuminuria and IMT remained (P=0.047), while the association between GFR and IMT disappeared (P for trend=0.33). CONCLUSIONS: Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis beyond traditional cardiovascular risk factors among middle-aged adults. Cystatin C does not have a stronger relationship with carotid atherosclerosis in middle-aged adults than creatinine.

Adult↗