Serum Cys Research Articles

Clinical studies of dynamic changes on the renal injury indicators of acute paraquat poisoning

To investigate the clinical significance of dynamic changes of blood urea nitrogen (BUN), serum creatinine (Cr), serum cystatin (Cys C) and urinary protein on renal injury with paraquat poisoning. According to the clinical manifestation and curative effect, the clinical information was analyzed retrospectively in 35 cases of acute paraquat poisoning, survival after eight weeks as the standard. Poisoning patients were taken a fasting blood 5 ml and the middle of urinary on the 1st day, 3rd day, 7th day, 14th day, 21st day and 8 weeks after the poisoning. Then the levels of serum BUN, Cr, Cys C and urinary protein were detected by automatic biochemistry analyzer. 30 cases healthy subjects were randomly selected as normal control group, and discharged kidney disease and other diseases of urinary system history. The same laboratory subjects have been done. The level of serum Bun, Cr, Cys C of survival group increased significantly compared with control group within 21 days (P < 0.05). The level of serum BUN, Cr Cys C decreased on the 14th day. The decreased level of serum Cys C was lower than that of serum BUN and Cr. The renal function of 29 cases among 35 cases survival patients recovered on 21st day. The renal function of 31 cases among 35 cases survival patients recovered 8 weeks late. The positive rate of urinary protein of survival patients was high in the early intoxication (76.9%). Serum Cys C is sensitive indicator to reveal the kidney injury on paraquat poisoning patients and have higher value of clinical applications in the diagnosis of the kidney injury of paraquat poisoning, which sensitivity is higher than serum BUN and Cr. The kidney injury caused by paraquat poisoning is reversible.

Transient elevation of serum cystatin C concentrations during perioperative cisplatin-based chemotherapy in esophageal cancer patients

In the present study, the time-concentration profile of platinum (Pt) in plasma was compared to that of serum cystatin C (Cys C) in Japanese esophageal cancer patients receiving perioperative cisplatin-based chemotherapy. Five male and one female patients receiving 2 successive cycles of cisplatin-based chemotherapy combined with 5-fluorouracil, the treatment for esophageal squamous cell carcinoma, participated in this study. The pharmacokinetic parameters in each patient were calculated from the individual plasma Pt concentration-time curve after intravenous infusion of cisplatin using the one-compartment model. Within a week of starting the first cycle of chemotherapy, serum Cys C concentrations increased in all patients from 122.6 to 143.0%, subsequently returning to baseline levels in approximately 10 days. A similar increase in serum Cys C levels also occurred during the second treatment cycle. However, no increase in serum creatinine levels was observed during either treatment cycle. In addition, the concentration of plasma Pt 2 days after treatment in the first and second cycles did not correlate with those of either serum Cys C or creatinine. Finally, the half-life of Pt in plasma during the first treatment cycle was not significantly different from that in the second cycle. These findings suggest that concentration fluctuations in serum Cys C are unlikely to correlate with Pt elimination from the plasma and that renal function estimates based on serum Cys C concentration might be underestimated during perioperative cisplatin-based chemotherapy for esophageal cancer.

Comparison of Serum Creatinine and Cystatin C for Early Diagnosis of Contrast-Induced Nephropathy after Coronary Angiography and Interventions

The diagnostic accuracy of serum creatinine and cystatin C (Cys) as early predictors of contrast-induced nephropathy (CIN) has been debated. We investigated the diagnostic sensitivities, diagnostic specificities, and variations from baseline for serum creatinine and Cys in CIN. We prospectively evaluated 166 patients at risk for CIN at baseline, and at 12, 24, and 48 h after exposure to contrast media. CIN occurred in 30 patients (18%). Changes (Δ) compared to baseline in serum creatinine and Cys were evaluated at the predefined time points. ROC curve analysis was performed for the Δ 12-h basal serum creatinine and Cys. The Δ serum creatinine at 12 h from baseline was the earliest predictor of CIN [area under the ROC curve (AUC) = 0.80; P < 0.001]. The Δ serum creatinine 15% variation [0.15 mg/dL (13.2 μmol/L)] yielded 43% diagnostic sensitivity and 93% diagnostic specificity. The ΔCys at 12 h from baseline performed significantly worse than serum creatinine (AUC = 0.48; P = 0.74). Variations from the serum creatinine baseline offer better diagnostic accuracy for predicting CIN at an earlier stage than similar variations in Cys. An additional diagnostic value of Cys over the determination of serum creatinine in the setting of CIN was not observed.

Renal Function and Solitary Kidney Disease: Wilms Tumour Survivors versus Patients with Unilateral Renal Agenesis

Aims: To test the hypothesis that Wilms tumour survivors (WTs) experience increased disturbance in renal function, even after prompt treatment, compared to patients with unilateral renal agenesis (URA). Methods: To assess the renal function of 30 WTs and 17 individuals with URA, the estimated glomerular filtration rate (eGFR) was calculated using the Schwartz and Filler formulas as well as the new Schwartz equation for chronic kidney disease. To measure kidney damage, serum levels and urine excretion of β₂-microglobulin (B2M), cystatin C (Cys C), neutrophil gelatinase-associated lipocalin (NGAL) were tested, N-acetyl-β-glucosaminidase (NAG), and albumin urine excretion and urine sediment were examined. Blood pressure was measured. Results: No differences were found between the groups in terms of eGFR, serum Cys C, B2M and NGAL concentrations. The urine excretion of Cys C, NGAL and NAG was similar in both groups. URA patients had higher B2M excretion than WTs. Arterial hypertension was present in 7/30 (23%) WTs and 1/17 (6%) patients with URA. Conclusions: WTs have similar eGFR to individuals with URA and are more likely to have arterial hypertension. The patients with URA have signs of tubular damage. This study demonstrates the need for nephrological monitoring of individuals with a single kidney.

The Significance of Serum Cystatin C Accompanied by a Normal Serum Creatinine Level in Pediatric Patients With Chronic Kidney Disease

To evaluate the significance of serum cystatin C (Cys C) levels in pediatric patients with chronic kidney disease (CKD) diagnosed by renal biopsy and who show normal serum creatinine (Cr) levels. The patient group was composed of 167 males (M) and 119 females (F) with CKD enrolled from the Department of Pediatrics at Kyung Hee Medical Center from July 2009 to May 2010. The serum Cys C, Cr, and C-reactive protein (CRP) were tested using a chemical analyzer (Toshiba, Nasushiobara, Japan). The mean age of the total patients was 11.72 years, and the mean body weight was 32.24 kg. The mean Cys C value was 0.84 mg/L, and 24 patients (3 Henoch-Schönlein purpura nephritis [HSPN], 3 IgA nephropathy [IgAN], 10 mesangial proliferative nephritis [MesPN], and 8 nephritic syndrome [NS]) showed increased Cys C levels (range: 1.0–1.6 mg/L). In this study, 95% of the patients showed only slightly increased Cys C levels (0.5∼1.1 mg/L) from the upper normal limit of the reference range (0.9 mg/L). Therefore, we carefully suggest that mildly increased Cys C without increased Cr might not have clinical significance.

Serum and urinary markers of early impairment of GFR in chronic kidney disease patients: diagnostic accuracy of urinary β-trace protein

The screening for chronic kidney diseases (CKD) patients with impaired GFR needs the measurement of serum creatinine (SCr) or cystatin C (SCys). GFR can also be predicted from SCr or SCys with different formulas. The aim of this study, performed in a group of CKD patients with different levels of GFR, was to evaluate the possibility to select the patients with a GFR <90 ml·min(-1)·1.73 m(-2) by means of serum levels and urinary excretion of different low-molecular-weight proteins (LMWP), cystatin C (Cys), β2-microglobulin (β2M), retinol-binding protein (RBP), β-trace protein (BTP), and derived prediction equations for GFR. In the 295 CKD patients (137 women), at all stages of GFR impairment a very high correlation was found between GFR ((99m)Tc-DTPA) and serum Cr, Cys, β2M, and BTP. All these serum markers showed a similar accuracy as indicators of different GFR impairments. RBP had the lowest correlation with GFR and was also significantly less accurate. The different prediction formulas derived from gender, anthropometric data and SCr or S-LMWP had a diagnostic accuracy similar to that of serum Cr, Cys, β2M, and BTP. Urinary albumin was inadequate as an indicator of any level of GFR impairment. Urinary excretion of Cys and β2M increased significantly only in patients with a GFR <30 ml·min(-1)·1.73 m(-2), while urinary BTP increased already at GFR <90 ml·min(-1)·1.73 m(-2). In this selected group of CKD patients, the positive predictive value of urinary BTP for a GFR <90 ml·min(-1)·1.73 m(-2) was 85%, indicating that, in CKD patients, a urine-based test can predict a slight GFR impairment.

Prediction of acute kidney injury complicated by sepsis with neutronphil gelatinase-associated lipocalin as an early marker

Objective To investigate the accuracy of NGAL in prediction of acute kidney injury (AKI) complicated by sepsis. Methods Blood and urine samples were collected at different time points in 74 sepsis patients, and 17 AKI patients were got from them.Cysteine Cys C levels were detected with Latex enhanced turbidimetric immunoassay (LETIA). Urine NGAL and Scr levels were detected with solid-phase sandwich enzyme-linked immunosorbent assay and creatinine enzymatic assay respectively. At the same time, 57 non-AKI patients were set as controls. Dynamic changes of urine NGAL and Scr were observed in sepsis patients in test and control group. ROC curve was used to evaluate the performance of AKI diagnosis by urinary NGAL.Results The Scr base line was (59. 38 ±16. 72) μmol/L.The median time of diagnose of AKI was 24 (12, 48) h past-sepsis diagnosis, while the Scr was(100. 35± 28. 26) μmol/L. Of the group, 17 cases of sepsis were diagnosed with AKI, accounting for 23% (17/74) prevalence. In sepsis group, base line value[(0. 61 ± 0. 15) mg/L] of serum Cys C was not upregulated at 2, 4 and 6 h, which was (0. 63 ± 0. 14) mg/L, (0. 68 ± 0. 16) mg/L and (0.65±0. 14) mg/L respectively. As to 8 h [(0. 85 ± 0. 22) mg/L], a slight upregulation was found with no significant difference (t = 1.63, P ＞ 0. 05).A trend of gradual increase of serum Cys C levels was found in sepsis AKI group at 12, 18, 24, 36, 48 and 72 h. A significant difference was found compared with base line (t = 2. 81, 2.98, 3.05, 3.11, 3. 38,3. 17,P ＜0.01). NGAL level[(96.21 ±45.32) μg/L] was significantly higher than base line value [(4. 98 ± 1.65) μg/L]. Subsequently, in each time point from the 2 h to 48 h, a trend of gradual increase in urinary NGAL levels was showed. The differences were significant compared with the baseline values (t =2. 74,2. 83,2. 91,3.04,3.15,3.22,3. 31,3.45,3.57 ,P ＜0. 01). Urinary NGAL levels of sepsis AKI group were significantly higher than those in non-AKI group at different time points with significant difference (t =2. 69,2. 73,2. 84,2. 96,3.02,3. 13,3.29,3.43,3.54,3.22,P ＜0. 01). ROC curve was selected to analyze diagnostic performance of urinary NGAL levels in AKI patients 2 h post-sepsis. Area under ROC curve was obtained as 0. 935, 95% confidence interval was 0. 683-0. 971. When cut-off value of urinary NGAL for patients 2 h post-sepsis was 50 μg/L, the sensitivity, specificity and accuracy were 94. 4%, 87. 5% and 96. 8% in AKI diagnosis respectively. Conclusions The occurrence of AKi can be accurately predicted by urinary NGAL levels 2 h post-sepsis , and its AKI diagnosis time is earlier than that of Scr. Urine NGAL can be used as early marker of AKI complicated by sepsis. Key words: Sepsis; Renal insufficiency, acute; Acute-phase proteins; Proto-oncogene proteins; Lipocalins; Biological markers

Plasma Cystatin C Concentration Reflects the Severity of Coronary Artery Disease in Patients Without Chronic Kidney Disease

This study examines whether the serum concentration of cystatin C (Cys C) correlates with the severity of coronary artery disease (CAD) and whether it provides additional information on the risk for CAD in patients without chronic kidney disease (CKD) estimated by the creatinine-based glomerular filtration rate (GFR). The relationship between serum Cys C and the severity of CAD in 526 patients was investigated. Based on GFR, patients were divided into those with and without CKD. The relationship of serum Cys C with the severity of CAD was examined. Serum Cys C was closely correlated with GFR in all cases and in CKD patients, but not in non-CKD patients. The average number of stenotic coronary arteries was significantly higher in the quartiles of higher concentration of Cys C as well as in those of GFR. In 348 patients (66%) the GFR was ≥60 ml · min(-1)·1.73 m(-2). Those patients with increased Cys C (>0.90 mg/L, 143 patients) had a significantly larger number of stenotic coronary arteries than those patients with normal Cys C. Among patients considered to be at low risk based on the estimated GFR using serum creatinine, those with high concentrations of Cys C could have severe CAD. Besides CKD, Cys C might serve as a marker of CAD severity.

Application of cystatin C as an efficacious marker of renal function in kidney transplant recipients

目的 探讨血清半胱氨酸蛋白酶抑制剂C(Cys C)在肾移植术后,尤其是感染和排斥时,监测肾功能的临床应用价值.方法 同时检测65例肾移植患者术前、术后1个月内、感染或排斥发生时及次日血清中Cys C和血清肌酐(Scr)的浓度,并测定30名健康人和30例非移植感染患者的Cys C和Scr作为对照.结果 健康人与非肾移植感染患者的Cys C浓度差异无统计学意义(P=0.32).移植后肾功能稳定组(n=36)术后前3 d内Cys C分别较术前下降了69.2%、74.7%、75.8%(P＜0.01),Scr相应的下降了38.4%、74.5%、81.4%(P＜0.01).移植术后感染组(n=13)肾功能异常时,Cys C比Scr早(4.4±1.5)d升高,升高幅度分别为39.4%和35.3%(P=0.43);排斥组(n=16)Cys C比Scr早(2.7±1.8)d升高,升高幅度分别为148.9%和43.9%(P=0.0069).与肾功能稳定组作横向比较,术后感染组和排斥组的Cys C分别升高了38.7%和108.5%(P＜0.001),Scr分别升高了34.2%和89.5%(P＜0.001).所有肾移植患者术后3～28 d之间,Cys C与Scr呈线性正相关(r=0.785,P＜0.0001).根据ROC曲线确定Cys C和Scr在术后排斥时的临界值分别为1.79 mg/L和122 μmol/L.排斥组Cys C的敏感度、特异度、阳性预测值、阴性预测值、符合率以及曲线下面积(AUC)均优于Scr(均P＜0.05).结论 Cys C优于Scr,是一个能早期、灵敏、准确判断移植肾功能变化的血清标志物。

β-Trace Protein Is an Alternative Marker for Glomerular Filtration Rate in Renal Transplantation Patients

Careful monitoring of graft function after renal transplantation (RTx) is necessary for short- and long-term success. Because of the many difficulties in performing serial measurements of glomerular filtration rate (GFR) by use of exogenous substances such as inulin, 51Cr-EDTA, or technetium-diethylenetriaminepentaacetic acid (99mTc-DTPA), graft function is often estimated from serum creatinine concentrations. Tubular secretion as well as various nonrenal factors may alter creatinine concentrations, thus rendering it an imprecise marker for GFR (1). Cystatin C (Cys C) is at least as good as creatinine as a marker of renal function (2)(3)(4), but corticosteroid treatment can alter serum Cys C concentrations (5)(6)(7), making it potentially less useful in RTx patients. β-Trace protein (BTP), also known as prostaglandin D synthase, is a 23- to 29-kDa enzyme that has been proposed as an alternative marker for GFR in children and in persons with diabetes or various renal diseases (8)(9)(10)(11), but it has not been examined as an endogenous renal function marker in RTx patients. The aim of this study was to compare the diagnostic performances of BTP, Cys C, and creatinine as estimates of GFR in RTx patients. We prospectively performed GFR measurements in 85 consecutive RTx patients (34 females and 51 males) who attended our outpatient department. GFR was determined by 99mTc-DTPA clearance with a single-injection technique based on the method described by Russell et al. (12). Patients included into the study were in “steady-state” conditions, defined as the lack of increases or decreases >15% in creatinine within 2 weeks before and after the investigation. The mean (SD) patient age was 49.6 (13.3) years (range, 19–72 years), and the time frame of investigation was 75.7 (71.2) months after transplantation (range, 3–240 months; 21 patients …

Thyroid function differently affects serum cystatin Cand creatinine concentrations

Cystatin C (Cys C) is a cysteine protease inhibitor produced at a constant rate by nucleated cells, filtered through the glomerular membrane and reabsorbed by kidney tubular cells. Aim of this cross-sectional and longitudinal study was to assess serum Cys C and creatinine (Crea) concentrations in thyroid dysfunction. One hundred and eighty-one patients, 26 with untreated non-toxic nodular goiter, 58 with hyperthyroidism, 31 on L-T4 suppressive therapy for non-toxic nodular goiter, 35 with short-term hypothyroidism after L-T4 withdrawal to perform whole body scan for thyroid cancer, 11 with long-term hypothyroidism due to chronic autoimmune thyroiditis and 20 patients with mild hypothyroidism were enrolled in the study. Fifty-seven age- and sex-matched normal subjects served as controls. Serum Cys C, Crea, free T4 (FT4), FT3 and TSH were assessed. Thirty hyperthyroid patients and 35 short-term hypothyroid patients were followed prospectively until euthyroidism was reached by methimazole or L-T4 therapy. The cross-sectional study showed that mean serum Crea concentrations were significantly reduced in overt hyperthyroid or subclinical hyperthyroid patients, while it was increased in overt hypothyroid patients, but not in mild hypothyroidism. Conversely, serum Cys C levels were significantly increased in overt hyperthyroid patients compared to controls (p<0.05), and significantly decreased in short-term, long-term and mild hypothyroids (p<0.05, p<0.05, p<0.01, respectively). However, 36 (62%) hyperthyroid patients and 50 (76%) hypothyroid patients had normal serum Cys C values. In the prospective study, restoration of euthyroidism by either methimazole or L-T4 therapy was associated with normalization of mean serum Cys C concentrations. In conclusion, thyroid dysfunction affects serum Cys C concentration, possibly influencing the production rate of the protein. However, the observation that hyper- or hypothyroid patients have normal serum Cys C levels limits its use as a marker of peripheral thyroid hormone effect.

Beta2-microglobulin and cystatin C in type 2 diabetes: assessment of diabetic nephropathy.

Changes in glomerular filtration rate (GFR) provide a valuable indicator of the progression of diabetic nephropathy (DN). This study was designed to demonstrate the clinical values of serum cystatin C (Cys C) and beta2-microglobulin in the assessment of renal function in type 2 diabetics by comparing them with the GFR, estimated from the uptake phase of 99 m technetium dimetiltriamino pentaacetic acid renogram (GFR-DTPA) and creatinine clearances. 68 type 2 diabetic patients with (urinary albumin excretions (UAE) 30 - 300 mg/24 h) (n = 39) and without (UAE < 30 mg/24 h) (n = 29) microalbuminuria and 32 controls were enrolled in the study. Serum Cys C, beta2-microglobulin, creatinine, urinary microalbumin levels, creatinine clearances and GFR-DTPA values were determined in all groups. Non-parametric ROC curves, using a cut-off GFR-DTPA of 60 mL/min/1.73 m (2), were obtained for these markers. Serum Cys C, beta2-microglobulin, glucose and HbA1c concentrations were significantly higher in the group with diabetes compared to controls. In the patients with microalbuminuria, serum Cys C and glucose concentrations increased significantly in comparison to patients with normoalbuminuria, while no differences were observed for beta2-microglobulin levels. Serum creatinine concentrations, GFR-DTPA values and creatinine clearances were not different between both diabetic groups and controls. Cys C was positively correlated with beta2-microglobulin and creatinine and negatively with GFR values; beta2-microglobulin was also positively correlated with serum creatinine in microalbuminurics. A significant inverse correlation was found between beta2-microglobulin and GFR values in both microalbuminurics and normoalbuminurics. Increased Cys C and beta2-microglobulin in diabetics may be early indicators of incipient DN. The diagnostic accuracies of Cys C and beta2-microglobulin are superior to that of serum creatinine in distinguishing between mild and moderately reduced GFR.

Serum cystatin C is superior to serum creatinine as a marker of kidney function: A meta-analysis

Background: Serum cystatin C (Cys C) has been proposed as a simple, accurate, and rapid endogenous marker of glomerular filtration rate (GFR) in research and clinical practice. However, there are conflicting reports regarding the superiority of Cys C over serum creatinine (Cr), with a few studies suggesting no significant difference. Methods: We performed a meta-analysis of available data from various studies to compare the accuracy of Cys C and Cr in relation to a reference standard of GFR. A bibliographic search showed 46 articles until December 31, 2001. We also retrieved data from eight other studies presented and published in abstract form. Results: The overall correlation coefficient for the reciprocal of serum Cys C (r = 0.816; 95% confidence interval [CI], 0.804 to 0.826) was superior to that of the reciprocal of serum Cr (r = 0.742; 95% CI, 0.726 to 0.758; P < 0.001). Similarly, receiver operating characteristic (ROC)-plot area under the curve (AUC) values for 1/Cys C had greater identity with the reference test for GFR (mean ROC-plot AUC for Cys C, 0.926; 95% CI, 0.892 to 0.960) than ROC-plot AUC values for 1/Cr (mean ROC-plot AUC for serum Cr, 0.837; 95% CI, 0.796 to 0.878; P < 0.001). Immunonephelometric methods of Cys C assay produced significantly greater correlations than other assay methods (r = 0.846 versus r = 0.784; P < 0.001). Conclusion: In this meta-analysis using currently available data, serum Cys C is clearly superior to serum Cr as a marker of GFR measured by correlation or mean ROC-plot AUC. © 2002 by the National Kidney Foundation, Inc.

A study of preoperative methionine-depleting parenteral nutrition plus chemotherapy in gastric cancer patients.

AIM:To investigate the interference of methionine-free parenteral nutrition plus 5-Fu (-MetTPN+5-Fu) in gastric cancer cell kinetics and the side effects of the regimen.METHODS:Fifteen patients with advanced gastric cancer were randomly divided intotwo groups, 7 patients were given preoperatively a seven-day course of standard parenteral nutrition in combination with a five-day course of chemotherapy (sTPN+5-Fu), while the other 8 patients were given methionine-deprived parenteral nutrition and 5-Fu (-MetTPN+5-Fu). Cell cycles of gastric cancer and normal mucosa were studied by flow cytometry (FCM). Blood samples were taken to measure the serum protein, methionine (Met) and cysteine (Cys) levels, and liver and kidney functions.RESULTS:As compared with the results obtained before the treatment, the percentage of G(0)/G(1) tumor cells increased and that of S phase decreased in the -MetTPN+5-Fu group, while the contrary was observed in the sTPN+5-Fu group. Except that the ALT, AST and AKP levels were slightly increased in a few cases receiving -MetTPN+5-Fu, all the other biochemical parameters were within normal limits. Serum Cys level decreased slightly after the treatment in both groups. Serum Met level of patients receiving sTPN+5-Fu was somewhat higher after treatment than that before treatment; however, no significant change occurred in the -MetTPN+5-Fu group, nor operative complications in both groups.CONCLUSION:-MetTPN+5-Fu exerted a suppressive effect on cancer cell proliferation, probably through a double mechanism of creating a state of "Met starvation" adverse to the tumor cell cycle, and by allowing 5-Fu to kill specifically cells in S phase. Preoperative shortterm administration of -MetTPN+5-Fu had little undesirable effect on host metabolism.