Biophotonic sensor for the detection of creatinine concentration in blood serum based on 1D photonic crystal

A new biophotonic sensor based on photonic crystal (PC) has been designed for the detection of creatinine concentration in blood, and is considered an important small molecule biomarker of renal dysfunction. Based on the transfer matrix method (TMM), we theoretically investigated the transmittance spectra of a one dimensional alternating dielectric photonic crystal (PC) designed as (AB)⁷/C/(AB)⁷ made of MgF₂ (A), CeO₂ (B) and creatinine concentration present in blood (C). The transmission spectra exhibit resonant peaks within the photonic band gap (PBG) indicative of so-called defect modes, which depend on parameters, such as concentration of creatinine in blood, thickness of defect layer and incident angle. The proposed sensor can determine the physiological levels of creatinine in human blood serum samples. The estimated parameters realize an efficient biophotonic sensor wherein sensitivity was tuned from 136.4 nm per RIU to 306.25 nm per RIU and is very useful for the detection of creatinine.

A new biophotonic sensor based on photonic crystal (PC) has been designed for the detection of creatinine concentration in blood, and is considered an important small molecule biomarker of renal dysfunction.     

Predictive performance of serum digoxin concentration in patients with congestive heart failure by a hyperbolic model based on creatinine clearance

OBJECTIVES: To formulate a simple equation for determining the daily dose requirements of digoxin by inclusion of creatinine clearance (Ccr) values as an explanatory variable. METHODS: We included 235 routine monitoring and clinical laboratory test data (steady-state serum digoxin concentration and Ccr values), obtained from hospitalized patients receiving digoxin for treatment of congestive heart failure. The 107 data sets were fitted to a hyperbolic model to account for the relation between the ratio of serum digoxin level to the daily dose (L/D) and the Ccr values determined by six methods. Their correlation coefficients (r) were computed by non-linear regression analysis. To evaluate the validity of the best-fitting model, the predictive performance of the L/D ratios was compared with those given by seven reference models previously published, using another 128 data sets. RESULTS: The hyperbolic model involving the Ccr values estimated by Cockcroft and Gault's equation showed the closest correlation (r = 0.81) between the actual and estimated Ccr values. Mean prediction error (ME), a measure of bias, of the L/D ratio (0.018 ng/mL) was almost negligible when other data were fitted to the proposed model, and this ME value proved to be much smaller than those calculated from the previously published prediction models. Mean absolute prediction error, a measure of precision, by the proposed model was also satisfactory for prediction. CONCLUSION: The newly developed model provided good predictive performance of serum digoxin level. Taking simplicity in practical use into account, the clinical application of the proposed model will allow for accurate and rapid determination of the initial maintenance dosing regimen of digoxin based on the individual Ccr value, without actual measurement of its serum concentration.     

马来酸罗格列酮造成肌酐苦味酸法检测结果假性增高

目的 探讨马来酸罗格列酮(RM)对肌酐(Cr)苦味酸法测定的干扰及其机制.方法 将不同饱和度RM溶液加入Cr标准溶液中,采用苦味酸法对混合液进行Cr浓度检测;绘制RM溶液及其与苦味酸的反应产物吸收曲线,分析其干扰Cr检测的可能机制.结果 RM可导致Cr检测结果假性增高,干扰程度与RM浓度呈正相关(r2=0.996);RM溶液在苦味酸法Cr检测采用的510 nm波长附近无吸收峰,但RM与苦味酸的反应产物在480 nm处有吸收峰.结论 RM以造成肌酐检测结果假性增高,并呈良效依赖关系;应避免在患者服用RM后立即进行Cr检测,以减少对检测结果的干扰.     

同位素稀释质谱法测定血清肌酐浓度的不确定度评定

目的探讨同位素稀释质谱法(ID-MS)测量血清肌酐浓度的不确定度评定方法。方法应用ID-MS建立测定血清肌酐浓度的参考测量程序,严格按照《测量不确定度表示指南》(简称GUM)评定不确定度,即严格根据测量模型对各不确定度分量进行详细分析和定量,加减项用绝对值、乘除项用相对值合成各标准不确定度分量;同时,用传统评定方法和蒙特卡洛方法(MCM)分别对血清肌酐浓度测量结果进行不确定度评定。结果对特定血清进行赋值,其肌酐浓度为347.4μmol/L。按照ID-MS测量模型,并严格应用GUM原理进行不确定度评定,其合成标准不确定度的相对值为0.89%,而传统方法评定结果为0.93%,较GUM法高4.8%;采用MCM评定各不确定度分量,其合成标准不确定度的相对值为0.64%,较严格GUM法低27.9%,其测量结果的95%可信区间为343.1~351.8μmol/L。结论与GUM法评定结果比较,传统评定方法结果偏高,而MCM偏低,3种评定方法存在差异。建议采用GUM法,根据测量模型对各不确定度分量进行定量和合成。有条件的话,可用MCM评定不确定度。     

A new enzymatic serum creatinine measurement based on an endogenous creatine-eliminating system

We describe a new colorimetric determination of serum creatinine which does not require a blank to correct for endogenous creatine. In the first reaction, creatinase (creatinase amidinohydrolase EC 3.5.3.3) and sarcosine oxidase (sarcosine: oxygen oxidoreductase (demethylating) EC 1.5.3.1) were used in the enzymatic hydrolysis of endogenous creatine to produce hydrogen peroxide. In the presence of horseradish peroxidase, 2,4-dichlorophenolsulfonate (2,4-DCPS) was converted to a colorless polymer by hydrogen peroxide. In the second reaction, creatininase (creatinine amidohydrolase EC 3.5.2.10) and 4-aminoantipyrine (4-AA) were added, and only the creatine generated from creatinine by creatininase was hydrolyzed sequentially by creatinase and sarcosine oxidase to produce hydrogen peroxide. This newly-formed hydrogen peroxide was measured at 510 nm in a coupled reaction catalyzed by peroxidase, with 2,4-DCPS/4-AA as a chromogen. The standard curve was linear up to 20 mg/dl; 40 microliter of serum and 20 min were required for determination. Analytical recovery of creatinine added to either normal or abnormal sera averaged 98.5%. Within-day and day-to-day studies gave CV values of less than or equal to 2.9% and less than or equal to 4.8%, respectively. No significant interferences were observed with the proposed method. The results obtained by the present method correlated well with those obtained by the Jaffé procedure.     

Gentamicin binding to serum and plasma proteins

Gentamicin binding to serum proteins was studied by equilibrium dialysis at 37 degrees C and pH 7.4 in the presence of both physiologic and adjusted concentrations of ionized calcium and magnesium. The percentage of bound drug was inversely related to the concentration of these two divalent cations, raning from 27% bound with no calcium and magnesium present to 17% bound in the presence of four times physiologic concentrations. No significant difference in the extent of drug-protein binding was noted in a comparison of sera from healthy and uremic subjects. Heparin also was found to affect gentamicin binding. Increasing heparin concentration in serum increased apparent gentamicin-protein binding to 34% in the presence of physiologic amounts of calcium and magnesium. Buffered heparin solutions without plasma proteins bound up to 65% of total drug concentration. Gentamicin-protein binding may have implications regarding pharmacokinetics and renal cortical uptake.     

Low baseline serum creatinine concentration predicts mortality in critically ill patients independent of body mass index

OBJECTIVE: Malnutrition and low muscle mass reduce the ability of patients to fight critical illness. Low serum creatinine is a better surrogate marker of low muscle mass than a low body mass index and has been associated with poor outcome in some patient populations. We hypothesized that low baseline serum creatinine would predict poor outcome in the critically ill. DESIGN: In this retrospective cohort study, data including age, gender, race, postoperative status, and Acute Physiology and Chronic Health Evaluation (APACHE) III scores were collected from the institutional APACHE III database. Baseline serum creatinine levels and body mass index were collected from the hospital laboratory database. The main outcomes measured were hospital mortality and intensive care unit length of stay. PATIENTS: Consecutive critically ill patients >18 yrs of age admitted to three ICUs from January 2003 to December 2006, excluding those who denied research authorization, did not have a baseline serum creatinine measured, were pregnant at the time of intensive care admission, had a history of chronic renal replacement, were in intensive care for <12 hrs, or were admitted for low-risk monitoring only. SETTING: Three intensive care units of two tertiary care hospitals. RESULTS: Of 11,291 patients who met the inclusion criteria, 1185 (10%) died in the hospital. Of the patients, 54% were male and 90% were white, with a mean age (+/-sd) of 63 +/- 17 yrs. Median body mass index was 27.3 (interquartile range [IQR], 23.5-32.1), median APACHE III score was 53 (IQR, 38-69), and median baseline serum creatinine was 1.1 (IQR, 0.9-1.4). When adjusted for APACHE III-predicted mortality, age, gender, postoperative state, and body mass index, low baseline creatinine was associated with increased mortality in a dose-response manner: odds ratio (OR) 2.59 (95% confidence interval [CI], 1.82-3.61) for baseline creatinine < or =0.6 mg/dL (p < .001) and OR 1.28 (95% CI, 1.03-1.60) for baseline creatinine 0.6-0.8 mg/dL (p = .023). Adjusted intensive care length of stay in survivors was 0.48 days (95% CI, 0-0.98) longer for patients with baseline creatinine < or =0.6 mg/dL (p = .058). CONCLUSION: Low baseline serum creatinine concentrations increase the risk of mortality in critically ill patients.     

Seasonal variation in estimated glomerular filtration rate based on serum creatinine levels in hypertensive patients

Seasonal variations in blood pressures should be kept in mind when controlling blood pressure in hypertensive patients. Seasonal variations in glomerular filtration rate (GFR) also may have a clinical significance. However, it is time-consuming to measure GFR directly. We therefore examined the seasonal variation in estimated glomerular filtration rate (eGFR) based on serum creatinine levels in hypertensive patients without CKD (eGFR ≥ 60 mL/min/1.73 m(2)) and those with chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73 m(2)). This study included 47 hypertensive patients without CKD (69 ± 11 yrs) and 55 hypertensive patients with CKD (76 ± 8 yrs). The eGFR was determined from the equation: eGFR = 194 × age(-0.287) × (serum creatinine)(-1.094) (× 0.739 if female). Overall, both groups of hypertensive patients demonstrated similar seasonal variations in eGFR. Importantly, hypertensive patients without CKD and those with CKD showed the lower eGFR in summer (June-August) (71.8 ± 13.2 and 37.2 ± 13.0 mL/min/1.73 m(2), respectively) compared with the eGFR in spring (March-May) (77.9 ± 13.0 and 43.0 ± 14.0 mL/min/1.73 m(2), respectively) (p < 0.05). The decrease in eGFR from spring to summer was similar for both types of hypertensive patients (without CKD, -6.1 ± 7.0; with CKD, -5.8 ± 5.2 mL/min/1.73 m(2)). However, the percent change in eGFR from spring to summer was greater in hypertensive patients with CKD (-13.8 ± 9.4 %) than in those without CKD (-7.7 ± 8.3 %) (p = 0.001). In conclusion, careful observation regarding renal function is needed for hypertensive patients with CKD during summer.     

Influence of dosage regimen on experimental tobramycin nephrotoxicity. A biochemical approach

Many factors play a role in aminoglycoside nephrotoxicity. To study the influence of dosage regimens, Wistar rats were injected for 8 days with a total daily dose of 10, 20, or 50 mg/kg tobramycin intraperitoneally either in one single (1) or in thrice (3) daily injections. The results were different according to the dose. With 10 or 20 mg/kg, serum creatinine did not increase. Alanine aminopeptidase activities decreased whatever the rhythm of administration. gamma-Glutamyl-transpeptidase and N-acetyl-beta-D-glucosaminidase activities were unchanged. Sphingomyelinase and cathepsin B activities were diminished with three injections and not affected with one injection. Renal tobramycin content was not significantly different with (1) or with (3). Lysosomal structural latency was decreased in rats treated three times a day. With 50 mg/kg, serum creatinine was significantly increased and was higher with one injection daily. Alanine aminopeptidase decreased with only one injection daily and gamma-glutamyl-transpeptidase was unchanged. N-acetyl-beta-D-glucosaminidase was increased with (1) and with (3). Sphingomyelinase and cathepsin B activities were significantly decreased. No differences were observed in rats treated once or thrice daily. Renal tobramycin content was similar with (1) and (3). The lysosomal structural latency was significantly decreased and to the same degree for both regimens. In conclusion, based on this study and on other related studies in the literature it is presently very difficult to determine the real relationship between dosage frequency and development of nephrotoxicity.     

Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions.

The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers.     

The influence of estimated creatinine clearance on plasma homocysteine in hypertensive patients with normal serum creatinine

OBJECTIVES: To examine the relation of estimated creatinine clearance (eCrCl) and plasma total homocysteine (tHcy) in hypertensive patients with a normal serum creatinine level. DESIGN AND METHODS: A total of 137 hypertensive patients (mean age 66.6 years, 69 men) with serum creatinine level 60 mL/min/1.73 m(2)). The CRI group was older (p<0.001), had higher tHcy (p<0.001), higher serum urea nitrogen (p<0.001), higher serum creatinine (p<0.001), lower eCrCl (p<0.001), and lower diastolic blood pressure (p=0.001). In univariate analysis, eCrCl had the strongest correlation with tHcy (r=-0.453, p<0.001). Significant correlations, ranging in decreasing order from r=-0.418, p<0.001 to r=-0.170, p=0.047, were also noted between tHcy and twelve other variables. In multivariate analysis, only eCrCl (p<0.001), usage of fibrate (p<0.001), serum level of vitamin B(12) (p=0.002), serum level of folic acid (p=0.009), and smoking (p=0.027) were independent predictors of tHcy. CONCLUSION: eCrCl is a strong independent predictor of tHcy in hypertensive patients with normal serum creatinine.     

The relationship of burn wound fluid to serum creatinine and creatinine clearance.

A case is presented with emphasis on creatinine clearance and burn wound closure. It suggests that the burn wound acts as an extrarenal site for creatinine loss. As a result, renal creatinine clearance may be falsely elevated while the burn wound is open, and closure of the burn wound may affect creatinine clearance.     

基于血清胱抑素C的肌酐清除率在急性肾损伤中的临床价值

目的 探讨基于血清胱抑素C(SCys C)的肌酐清除率(SCys C-CCr)对急性肾损伤(AKI)患者诊断以及预测AKI患者是否需要肾脏替代治疗(RRT)的价值.方法 收集2010年8月至2011年5月本院重症监护病房(ICU)入住超过3d的患者,以住ICU期间是否诊断为AKI将患者分为AKI组(21例)和非AKI组(30例),根据每日测定的SCys C和血清肌酐(SCr)分别计算肌酐清除率(SCys C-CCr和SCr-CCr),并统计尿量及急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分.比较两种方法计算的肌酐清除率在AKI中的诊断价值以及与RRT的关系.结果 AKI组入院时、确诊前2d、前1d及当日SCr-CCr和SCys C-CCr均较非AKI组显著下降.其中AKI组在诊断AKI前2d,SCys C-CCr( ml· min-1· 1.73 m-2)较入院时明显降低(70.6±8.4比114.8±15.8,P＜0.01),SCr-CCr( ml· min-1· 1.73 m 2)无明显变化(76.4±19.3比78.7±22.1,P＞0.05).受试者工作特征曲线(ROC曲线)分析显示,SCys C-CCr较SCr-CCr能更早发现AKI,AKI确诊前2d的曲线下面积(AUC)分别为0.859和0.664,敏感性分别为90.5％和47.6％,特异性分别为76.2％和81.0％.AKI组中6例行RRT者较15例未行RRT者入院时APACHEⅡ评分(分)更高(29.6±4.5比17.0±5.6,P＜0.05),24 h尿量(ml)更少(740±465比1780±1230,P＜0.05),而SCys C-CCr则无差异(50.4±11.2比53.0±8.4,P＞0.05).在AKI确诊当日,SCys C-CCr并不能很好地预测AKI患者是否需要行RRT(AUC =0.65).结论 SCys C-CCr敏感性较高,但特异性不高,对有AKI高危因素的患者有助于排除AKI,而在AKI诊断当日SCys C-Ccr并不能预测患者是否需行RRT治疗.     

A prospective randomised trial comparing individualised pharmacokinetic dosage prediction for aminoglycosides with prediction based on estimated creatinine clearance in critically ill patients

A prospective randomised trial was conducted in critically ill patients to evaluate a computer aided pharmacokinetic method of aminoglycoside dose prediction based on 3 measured plasma concentrations following the loading dose. The ability of this method to achieve therapeutic plasma aminoglycoside concentrations early in the course of treatment was compared with that of a nomogram approach based on creatinine clearance estimated using the formula of Cock-roft and Gault. Ninety-two percent of patients in the computer group achieved peak plasma concentrations within the optimum range of 6–10 mg/l at 48–72 h compared with 21% of control group patients (p=0.0009). The mean peak plasma concentration of 7.45 mg/l at 48–72 h in the computer group was closer to the target concentration of 8 mg/l than was the 5.14 mg/l in the control group (p=0.0004). There was no significant difference between the groups in measured indices of renal function, both groups showing an improvement in mean estimated creatinine clearance from the beginning to the end of the course of treatment. Dosing based on individualised pharmacokinetic data is therefore a more reliable method of achieving therapeutic blood concentrations early in the course of treatment than is nomogram based dosing. Other studies suggest that this should be associated with a reduction in mortality in severe infections.     

用肌酐亚氨水解酶偶联谷氨酸脱氢酶的酐酶法鉴定

目的 建立适合于自动化分析的人血清和尿肌酐亚氨水解酶偶联谷氨酸脱氢酶指示系统的酶促动力学测定方法。方法 在反应体系中加入异柠檬酸脱氢酶及其作用底物异柠檬酸，再生由主反应前氨消耗的NADPH和α－酮戊二酸，其后加入镁离子络合剂CyDTA和肌亚氨水解酶的启动试剂启动反应，在此同时NADPH和α－酮戊二酸的再生反应被终止，测定NADPH于340nm处吸光度的变化，计算样品中肌酐的浓度。结果 本法测定线性范围为40－2000μmol／L，批内和常规条件下的变异系数均小于5％，回收率为98．5％，与高效液相色谱法具有良好的相关性（r=0.9930)。乳糜、黄疸、溶血、酮体、乳酸盐、临床常用的治疗药物和高至2mmol/L的氨对测定没有干扰。结论 本法操作简便、精确，推荐作为常规测定方法。