Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to investigate circulating levels of cystatin C (an important endogenous marker of renal function) in mothers, fetuses, and neonates from intrauterine growth-restricted (IUGR; characterized by impaired nephrogenesis) and appropriate-for-gestational-age (AGA) pregnancies. Serum cystatin C levels were measured by enzyme immunoassay in 40 parturients and their 20 IUGR (<or=3rd customized centile, due to gestational pathology) and 20 AGA fetuses and neonates on postnatal day 1 (N1) and 4 (N4). Comparatively, creatinine and urea concentrations were determined in the same samples. Fetal cystatin C levels were higher in the AGA than the IUGR group (P = .001). In both groups, maternal cystatin C levels were lower than fetal (P < .001), N1 (P < .001), and N4 (P < .001) levels. Fetal levels were higher than N1 (P < .001) and N4 (P < .001), and N1 levels were higher than N4 (P = .007) ones. In both groups, no correlation existed between maternal and fetal levels, but positive correlations were found between cystatin C, creatinine, and urea levels in maternal and neonatal samples (in all cases, r >or= 0.376 and P <or= .045). Cystatin C levels did not correlate with gestational age and did not differ between males and females. Fetal cystatin C serum levels are lower in the IUGR group, significantly decrease after birth, and do not correlate with maternal levels in both groups. In addition, serum cystatin C levels positively correlate with respective creatinine and urea levels in the perinatal period.
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PMID:Serum cystatin C in pregnancies with normal and restricted fetal growth. 1763 14

Drug-induced kidney injury is a serious and not uncommon adverse event which needs to be considered during drug development. The current standards used to monitor kidney function, such as blood urea nitrogen and serum creatinine, are late indicators of kidney injury and thus do not allow for timely intervention before loss of function. Improving the diagnosis and monitoring of kidney damage goes hand-in-hand with the identification of new biomarkers and the development of technologies that enable their sensitive and specific measurements. In order to move beyond restriction to internal company decisions, every entity that demonstrates the qualities of a biomarker must gain acceptance by health authorities if it is to be used for regulatory decision making in preclinical studies and clinical trials. This review focuses on the most promising achievements of new technologies applied to monitoring drug-induced nephrotoxicity (eg, gene expression, imaging, in vitro screening, protein assays) and on the use and implications of peripheral biomarkers such as the urinary protein biomarkers glutathione S-transferase-alpha, N-acetyl-beta-d-glucosaminidase, total protein, cystatin C, beta2-microglobulin, KIM-1, lipocalin-2 and serum cystatin C. Finally, the associated regulatory processes for use in clinics are also discussed.
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PMID:Monitoring kidney safety in drug development: emerging technologies and their implications. 1817 68

Acute renal failure (ARF) is an acute loss of kidney function that occurs over days to weeks and results in an inability to appropriately excrete nitrogenous wastes and creatinine (Cre). ARF is diagnosed by elevations of blood urea nitrogen and serum Cre level, which is classified as prerenal, intrinsic and postrenal according to their mechanisms. However, discriminate diagnosis of these types by blood biochemistry findings is difficult. Recently, cystatin C (Cys-C), a basic protein having isoelectric point 9.3 with a molecular weight of 13.3 kDa, is freely filtered at the level of the glomerulus and virtually all is reabsorbed and metabolized by the proximal tubular cells. Therefore, assuming constant cellular production, serum Cys-C level has the potential to be an excellent surrogate marker of glomerular filtration rate. Because Cre is electrically charged neutrally, there is a possibility that the permeation of Cys-C, which is positively charged, is diffluent from that of Cre through glomerular basement membrane due to the type of the renal failure. We determined blood concentrations of Cys-C and Cre in a patients with prerenal renal failure (17 patients), intrinsic renal failure (232 patients) and postrenal renal failure (13 patients) as compared with healthy subjects (n = 771). We found that patients with postrenal renal failure displayed significantly elevated Cre/Cys-C ratio (mean +/- standard deviation) (8.3 +/- 8.0, p < 0.001) as compared with healthy subjects (1.1 +/- 0.2), prerenal (0.6 +/- 0.2) and intrinsic (1.6 +/- 0.5). These findings suggest that measurement of Cys-C concentration and Cre/Cys-C ratio may be useful for the discriminate diagnosis of postrenal renal failure.
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PMID:[Plasma creatinine and cystatin C ratio is useful for discriminate diagnosis of postrenal renal failure]. 1840 24

This is the first report from Saudi Arabia studying the normal reference intervals in adult Saudi subjects and evaluating serum cystatin C as a prospective marker for the assessment of the glomerular filtration rate (GFR). Three hundred healthy adult Saudi subjects including 156 males (52%) and 144 females (48%), with a mean age of 31.21 +/- 9.82 years were prospectively studied to establish normal reference ranges for cystatin C. A total of 68.34% of the study patients were in the age-group of 21-40 years. The mean serum cystatin C in the 300 healthy subjects was 0.751 +/- 0.11 mg/L (0.50 - 1.09), increasing gradually with age: it was 0.738 +/- 0.11 mg/L (0.51 - 1.09) in the age-group 21 - 30 years and 0.807 +/- 0.12 (0.51 - 1.09) among subjects who were > 50 years of age. The mean serum cystatin C in females (0.778 +/- 0.118 mg/L) was significantly hig-her than in males (0.726 +/- 0.095 mg/L) (p < 0.0001). The serum cystatin C level was within the defined reference range of 0.53 - 0.95 mg/L in 95% of the subjects with a mean value of 0.74 +/- 0.097 mg/L, and was falling within the 95% confidence interval of 0.73865 - 0.7637 mg/L, and with 98.84% area under the curve (AUC). All the other renal function markers (urea, serum creatinine, calculated GFR, BMI) among the studied subjects were within the normal reference ranges for adult Saudi population. The serum cystatin C level had a significant correlation with the body mass index (BMI) (r = 0.155; p = 0.007) and a correlation with serum creatinine as well (r = 0.009; p = 0.873). It showed a negative correlation with calculated GFR as per Cockroft-Gault equation (r = - 0.101; p = 0.083).
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PMID:Normal reference levels of serum cystatin C in Saudi adults. 1844 94

As the US population has continued to age, the number of patients with chronic kidney disease (CKD) has dramatically increased. Faced with this increase, clinicians need a better understanding of what an elevated serum creatinine level represents and a simple codified approach to evaluating renal failure. Creatinine, a muscle waste product, has an imperfect but predictable association with the glomerular filtration rate (GFR). Although other markers of GFR exist, including cystatin C, urea, inulin, and radioisotopic methods, their role in estimating GFR remains a matter for debate, especially that of cystatin C. Diagnosis and management of CKD are challenges for the nonspecialist. We describe a systematic approach that can be used by the nonspecialist to identify most but not all causes of renal insufficiency. Although this approach should allow for earlier recognition of treatable causes of CKD, it does not eliminate the involvement of a nephrologist in the care and management of the conditions causing the renal insufficiency. The nonspecialist should also be able to recognize the 9 therapies that are helpful in preservation of renal function in all patients with CKD.
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PMID:Diagnosis and management of chronic kidney disease. 1877 6

The Schwartz formula was devised in the mid-1970s to estimate GFR in children. Recent data suggest that this formula currently overestimates GFR as measured by plasma disappearance of iohexol, likely a result of a change in methods used to measure creatinine. Here, we developed equations to estimate GFR using data from the baseline visits of 349 children (aged 1 to 16 yr) in the Chronic Kidney Disease in Children (CKiD) cohort. Median iohexol-GFR (iGFR) was 41.3 ml/min per 1.73 m(2) (interquartile range 32.0 to 51.7), and median serum creatinine was 1.3 mg/dl. We performed linear regression analyses assessing precision, goodness of fit, and accuracy to develop improvements in the GFR estimating formula, which was based on height, serum creatinine, cystatin C, blood urea nitrogen, and gender. The best equation was: GFR(ml/min per 1.73 m(2))=39.1[height (m)/Scr (mg/dl)](0.516) x [1.8/cystatin C (mg/L)](0.294)[30/BUN (mg/dl)](0.169)[1.099](male)[height (m)/1.4](0.188). This formula yielded 87.7% of estimated GFR within 30% of the iGFR, and 45.6% within 10%. In a test set of 168 CKiD patients at 1 yr of follow-up, this formula compared favorably with previously published estimating equations for children. Furthermore, with height measured in cm, a bedside calculation of 0.413*(height/serum creatinine), provides a good approximation to the estimated GFR formula. Additional studies of children with higher GFR are needed to validate these formulas for use in screening all children for CKD.
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PMID:New equations to estimate GFR in children with CKD. 1915 56

To evaluate whether cystatin C levels can be a surrogate marker of creatinine clearance and reflect the characteristics of peritoneal membrane in dialysis patients, we performed peritoneal equilibration tests (PET) in 18 anuric adult chronic peritoneal dialysis (PD) patients with a mean age of 39.7 +/- 20 years. All the samples were analyzed for urea, creatinine, and cystatin C. Peritoneal transport, mass transfer, and peritoneal clearance of cystatin C were calculated. Correlation and regression analysis was done using cystatin C as a dependent variable and age, sex, height, weight, body surface area, and creatinine as independent variables. Cystatin C demonstrated a significant time dependent increase of dialysate concentration and decline in the serum concentrations during PET, and a strong correlation between serum creatinine and serum cystatin C concentrations(r: 0.62, p= 0.008). The trans-peritoneal clearance (mL/min/1.73 m 2 ) of cystatin C was related to its serum concentration and was similar to creatinine in its pattern but of smaller magnitude. Peritoneal mass transfer (mg/4 hr per 1.73 m 2 ) for cystatin C serum creatinine was 1.68 +/- 0.67 and 73.3 +/- 29.8, respectively. The dialysis/plasma D/P cystatin C concentration was > or = 0.1 at 4 hrs of PET denoted high peritoneal transport, while the values of < 0.1 denoted low transport type. We conclude that cystatin C follows the same pattern of peritoneal exchange as creatinine but the magnitude of transfer is many folds lower than creatinine. At present clinical utility of cystatin C in the evaluation of solute clearance is probably limited due to the minute amounts transferred across the membrane and the high renal clearance in the presence of residual renal function.
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PMID:Serum cystatin C: a surrogate marker for the characteristics of peritoneal membrane in dialysis patients. 1923 9

The purpose of this study was to investigate the effect of iloprost, a cytoprotective prostacyclin analog, on renal injury during unilateral renal I/R in rats and to determine whether the levels of serum cystatin C (CyC) and beta2-microglobulin (B2M), as markers of glomerular function, might denote this injury. Thirty-two Wistar rats were randomized into four groups (n = 8) as follows: control (sham laparotomy), renal I/R (60-min left renal ischemia and 120-min reperfusion), renal I/R + iloprost (20 ng kg(-1) min(-1) infusion during renal I/R period, i.v.), and control + iloprost. Blood and kidney tissue samples were obtained for biochemical and histological analysis from all rats. Serum urea, creatinine, CyC, and B2M levels were evaluated for biochemical analysis. Histopathological changes in renal structure were examined for histological analysis. Serum urea, creatinine, and CyC levels were significantly increased in the renal I/R group. Iloprost treatment decreased these three markers in the renal I/R + iloprost group. beta2-Microglobulin levels were not significantly changed in any group. Histological analyses showed that renal I/R elicited significant renal injury, whereas iloprost significantly decreased I/R-induced renal injury. Serum CyC level is one of the good indicators of acute renal damage due to I/R produced by renal artery occlusion. In contrast, we have shown that there are no significant changes in the levels of serum B2M levels that would make it an accurate diagnostic tool for detecting acute changes in renal injury subject to renal I/R in rats.
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PMID:The effect of iloprost on renal dysfunction after renal I/R using cystatin C and beta2-microglobulin monitoring. 1929 92

We initiated the present work to explore whether neutrophil gelatinase-associated lipocalin (NGAL) could be used to predict the progression of diabetic nephropathy in type-2 diabetic patients. Seventy-four type-2 diabetic patients were divided into normo-, micro- and macro-albuminuria groups according to their 24 h-urinary albumin excreting rate. Serum and urine NGAL, and other clinical parameters were detected. Patients were followed and measurements were repeated 1 year later. An increased tendency of urine NGAL and a decreased tendency of serum NGAL were detected, from normo-albuminuria group to macro-albuminuria group. Serum NGAL was found to rise after follow-up. Moreover, urine NGAL was found to be correlated positively with cystatin C, urea nitrogen, and serum creatinine (SCr), and inversely with glomerular filtration rate (GFR), while serum NGAL correlated negatively with cystatin C and urea nitrogen, at both baseline and follow-up levels. The results indicate that NGAL correlates closely with renal function. Both serum and urine NGAL are sensitive for predicting the progression of type-2 diabetic nephropathy but they may change differently. Serum NGAL may be more useful in early detection and urine NGAL may be more meaningful in renal function assessment.
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PMID:Changes of serum and urine neutrophil gelatinase-associated lipocalin in type-2 diabetic patients with nephropathy: one year observational follow-up study. 1939 Sep 97

Oxidative stress has been considered as one of the possible mechanisms of ischemia/ reperfusion (I/R) injury in the kidney. The aim of this study was to analyze the possible protective effect of dietary ginger (Zingiber officinals Rosc), a free radical scavenger, on renal I/R injury in rats. The protective effect of ginger against the damage inflicted by reactive oxygen species (ROS) during renal I/R was investigated in Wistar albino rats using histopathological and biochemical parameters. Thirty rats were randomly divided into five experimental groups (i.e., control, sham-operated, ginger, I/R, and I/R + ginger groups, n = 6 each). The ginger and I/R + ginger groups were fed on the test diet containing 5% ginger. The rats were subjected to bilateral renal ischemia followed by reperfusion in I/R and I/R + ginger groups. At the end of the reperfusion period, rats were sacrificed, and kidney function tests, serum and tissue oxidants and antioxidants, and renal morphology were evaluated. Serum urea, creatinine, and cystatin C (CYC) levels were significantly elevated in the ischemia group, but these levels remained unchanged in the ginger + I/R group compared to the I/R group. Reduction of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) enzyme activity was significantly improved by the treatment with ginger compared to I/R group. Administration of ginger resulted in significant reduction levels of tissue malondialdehyde (MDA), NO, protein carbonyl contents (PCC) in the ginger + I/R group compared with the I/R group. Ginger supplementation in the diet before I/R injury resulted in higher total antioxidant capacity (TAC) and lower total oxidant status (TOS) levels than I/R group. The ginger supplemented diet prior to I/R process demonstrated marked reduction of the histological features of renal injury. The findings imply that ROS play a causal role in I/R-induced renal injury, and ginger exerts renoprotective effects probably by the radical scavenging and antioxidant activities.
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PMID:The effect of dietary ginger (Zingiber officinals Rosc) on renal ischemia/reperfusion injury in rat kidneys. 1946 72


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